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Y Tokunaga

Publications and source records attributed to Y Tokunaga.

At least 127 records · Page 7Linked to original sources
PubMed1994

Cytomegalovirus infection in living related liver transplantation: rapid diagnosis by human monoclonal antibody staining of blood leucocytes.

Symptomatic cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following orthotopic liver transplantation. Early detection and prompt treatment with appropriate medicine are crucial for successful outcome. As an early detection method, we used the CMV antigenemia test which is based on immunocytochemical detection of CMV immediate early antigens in blood leucocytes. CMV immediate early antigens were detected in blood leucocytes with direct immunoperoxidase technique using a horseradish peroxidase (HRP)-conjugated F(ab')2 fragment of human monoclonal antibody (humab C7), designated HRP-C7. Of the 37 living related liver transplantations we performed on pediatric patients between June 1990 and August 1992, we experienced four cases (10.8%) of symptomatic CMV infection: three CMV hepatitis and one CMV peritonitis. They were all treated successfully with a combination of ganciclovir and immunoglobulins. In ABO-incompatible cases ganciclovir was administered prophylactically. Early detection using this method is though to have led to these successful outcomes. It is concluded that HRP-C7 staining of blood leucocytes is useful for the rapid diagnosis of CMV infection.

ABO Blood-Group System↗
PubMed1994

Portal vein graft in living related hepatic transplantation.

In living related hepatic transplantation, sclerotic small portal vein and thrombosis can impede standard end to end anastomosis of the graft portal vein and the recipient portal vein. We have described herein the successful use of the donor ovarian vein as the portal vein graft. It offers a safe and simple modality that can avoid unnecessary wound to the living donor.

Adolescent↗
PubMed1993

Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer.

The nm23 gene is a potential metastasis-suppressor gene originally identified in a murine melanoma line. Several investigators have reported the probable inverse association of nm23 expression with disease prognosis and/or metastasis. Since there are now 2 known isotypes of human nm23, namely nm23-HI and -H2, we immunohistochemically examined expression of these isotypes in human breast-cancer tissues using monoclonal antibodies (MAbs) specific for each isotype protein. We also analyzed expression of c-erbB-2 in the same collection of cancer tissues, in order to examine the significance of nm23 expression in comparison with c-erbB-2 expression. Of 130 tumors from breast-cancer patients, 73 (56%) and 69 (53%) positively expressed nm23-HI and -H2 respectively. Expression of c-erbB-2 was positive in 36 (28%). Expression of nm23-HI, but not nm23-H2, was inversely associated with lymph-node metastasis (p < 0.01). Expression of c-erbB-2 was associated with Tnm stage, tumor size and lymph-node metastasis (p < 0.01, p < 0.05 and p < 0.05 respectively). Overall survival was better (p = 0.014) in patients in whom expression of nm23-HI was positive than in those in whom it was negative. In multivariate analyses using a Cox's proportional-hazards regression model with 9 variables, nm23-HI showed the fourth greatest contribution to patient survival following lymph-node metastasis, Tnm stage and menopausal status. No significant contribution was shown for c-erbB-2 expression. nm23-HI, but not nm23-H2, may perform a role in disease prognosis in addition to its participation in cancer metastasis. It may have value for predicting long-term survival of human breast-cancer patients.

Adult↗
PubMed1993

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody.

In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2a), C3H/He (H-2k), and C3H/HeN (H-2k) strains were highly susceptible, whereas the C57BL/6N (H-2b), C57BL/10Sn (H-2b), BALB/cAnN (H-2d), AKR/N (H-2k), CBA/JN (H-2k), C3H/HeJ (H-2k), and MRL/lpr (H-2k) strains were low susceptible, and the DBA/2N (H-2d) as well as C3H/BiKi (H-2k) strains were resistant. In particular, mice of the H-2k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC x 2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC x 2 or TC x 3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC x 3. The low susceptible and the resistant mice that received TC x 2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC x 3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H-2 locus in our new EAO model.

Animals↗
PubMed1993

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. II. Analysis on susceptibility to EAO induction using F1 hybrid mice and adoptive transfer system.

In our novel murine model of experimental autoimmune orchitis (EAO) induced by two or three injections of viable syngeneic testicular germ cells (TC) alone, significant differences in susceptibility to the induction of EAO were found, and the disease susceptibility did not seem to be associated with a particular H-2 haplotype. The H-2 identical background disparate (highly susceptible x low susceptible)F1 hybrids, (C3H/He x C3H/HeJ)F1 and (C3H/HeJ x C3H/He)F1 mice, were highly susceptible to the induction of EAO. The H-2 identical background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x C3H/BiKi)F1 and (C3H/BiKi x C3H/He)F1 mice, were low susceptible to the induction of EAO. Both the H-2 and background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x DBA/2N)F1 and (DBA/2N x C3H/He)F1 mice, were equally resistant to EAO induction. In the susceptible hybrids, both delayed footpad reaction (DFR) and antibody responses to TC increased. On the other hand, in the resistant hybrids, the levels of anti-TC antibodies were elevated but the DFR to TC remains depressed. This suggests that the antibody production and induction of DFR may be under different genetic controls and that cellular immunity plays an important role in this EAO induction. In order to search for the mechanistic basis for low susceptible C3H/HeJ and resistant C3H/BiKi mice, these mice received orchitis-inducible spleen cells (SPCs) from C3H/He mice. C3H/HeJ mice were highly susceptible to passive EAO. In contrast, disease-resistant C3H/BiKi mice failed to develop passive EAO. In addition, we examined whether or not regulatory cells capable of preventing the disease induction were generated in low susceptible C3H/HeJ and resistant C3H/BiKi mice immunized with TC. Transfer of SPCs from TC-immunized C3H/HeJ and C3H/BiKi mice into C3H/He mice before the EAO challenge had no suppressive effect on subsequent disease induction.

Animals↗
PubMed1993

Living related liver transplantation across ABO blood groups with FK506 and OKT3.

In living related liver transplantation (LRLT), the use of graft livers across ABO blood groups is unavoidable since the organ donor is usually one of the recipient's parents. This report presents our initial experiences with LRLT, focusing on ABO-incompatible cases. From June 1990 to May 1992, we successfully performed a series of 34 LRLT on children (15 males and 19 females) ranging in age from 7 months to 15 years. Overall recipient survival rates were 90% (25/28) in elective LRLT and 50% (3/6) in emergency LRLT. These cases were classified into three groups: ABO blood group-identical (n = 21), compatible (n = 10), and incompatible (n = 3). The immunosuppressive regimen consisted of FK506 and low-dose steroids in the first two groups. In the incompatible cases, exchange transfusion was performed to decrease anti-A and/or -B antibody titers before LRLT, and prophylactic OKT3 was added to FK506 and steroids after LRLT. No significant difference in recipient and graft survival was observed among the groups. In the identical group, no rejection episodes have been observed thus far. Rejection occurred in two out of the ten compatible cases. Among the incompatible cases, one recipient had mild rejection and was treated. The remaining two recipients have had no rejection episodes thus far. Although all three recipients had cytomegalovirus (CMV) infection, they were successfully treated with ganciclovir, and no lethal infection has developed in any of these cases. The present results suggest that graft livers from living related donors across ABO blood groups can function well with FK506, low-dose steroids, and prophylactic OKT3 without causing lethal complications.

ABO Blood-Group System↗
PubMed1993

Surgical techniques and innovations in living related liver transplantation.

The authors successfully performed a series of 33 living related liver transplantations (LRLT) on children (15 males and 18 females, ranging from 7 months to 15 years of age) from June 1990 to May 1992, with the informed consent of their parents and the approval of the Ethics Committee of Kyoto University. Before operation, six of the children required intensive care, another 14 were hospitalized, and 13 were homebound. Donors (12 paternal and 21 maternal) were selected solely from the parents of the recipients on the basis of ABO blood group and graft/recipient size matching determined by computed tomography scanning. Procurement of graft was performed using ultrasonic aspirator and bipolar electrocautery without blood vessel clamping and without graft manipulation. All donors subsequently had normal liver function and returned to normal life. The left lateral segment (16 cases), left lobe (16 cases), or right lobe (one case) were used as grafts. The partial liver graft was transplanted into the recipient who underwent total hepatectomy with preservation of the inferior vena cava using a vascular side clamp. Twenty-seven of 33 recipients are alive and well with the original graft and have normal liver function. The patient survival rate was 89% (24/27) in elective cases and 50% (3/6) in emergent cases. The other six recipients had functioning grafts but died of extrahepatic complications. Complications of the graft were minimal in all cases. Hepatic vein stenosis, which occurred three times in two cases, was successfully treated by balloon dilatation. In cases with sclerotic portal vein, the authors anastomosed the portal vein of the graft to the confluence of the splenic vein and the superior mesenteric vein without a vascular graft, after experiencing a case of vascular graft thrombosis. After hepatic artery thrombosis occurred in one of the initial seven recipients whose arterial anastomosis was done with surgical loupe, microsurgery was introduced for hepatic artery reconstruction. There has been no occurrence of thrombosis since then. The current results with LRLT suggested that the meticulous management of surgical factors at each stage of the LRLT procedure is crucial for successful outcome. Living related liver transplantation is a promising option for resolving the graft shortage in pediatric liver transplantation and may be regarded as an independent modality to supplement cadaver donation.

Adolescent↗
PubMed1993

Metallic expanding biliary stents in malignant obstruction. Cases with stent in stent.

We reviewed a total of 13 stent (Gianturco-Rosch biliary Z-stent) placements in 11 patients with biliary obstruction due to malignancy and report the cases treated with the stent-in-stent technique for treatment of stent occlusion due to tumor ingrowth. Causes of biliary obstruction included cholangiocarcinoma (four cases), hepatic hilar metastasis of gastrointestinal carcinoma (five cases), and pancreatic carcinoma (two cases). After transient percutaneous transhepatic biliary drainage (PTBD), the stents were successfully inserted by transhepatic route in all patients without any serious complication that needed further surgical intervention. Almost all patients were freed from the external PTBD tube about a week after stent placement and discharged from the hospital with improvement in quality of life as well as normal serum bilirubin levels. The technical advantages of stent placement include ease of insertion and the ability to drain both right and left biliary systems from a single transhepatic route by arranging the stents in a variety of configurations. Furthermore, it provides a second chance of stent placement when the previous stent has been occluded by tumor ingrowth.

Aged↗
PubMed1993

Experience with FK506 in living-related liver transplantation.

The new immunosuppressive agent FK506 was used with steroids to treat 22 pediatric patients who received living-related partial liver transplantation. Seventeen recipients survived and 5 died between one and 16 months after transplantation. Three of the 5 patients who died had required intensive care preoperatively. Autopsy findings showed no evidence of rejection. There was no episode of rejection that required retransplantation in any of the patients. Liver allograft dysfunction, which was suspected to be a rejection response, was encountered in 2 recipients with ABO-nonidentical but compatible grafts. However, their clinical and biochemical findings were ameliorated upon steroid pulse therapy or upon augmented FK506 administration without additional potent immunosuppressive agents. Steroid treatment has been discontinued in all surviving patients at 1-9 months after transplantation. Infectious complications encountered in 9 patients included 2 bacterial, 5 viral, and 2 fungal infections. One recipient died of fungal pneumonia. Abnormal increase of serum creatinine level was confined to the complicated patients. Hypertension was a temporary adverse reaction in the early postoperative period, and only one patient needed an antihypertensive drug at 2 months after transplantation. Acute pancreatitis with hyperamylasemia was observed in one patient who was treated successfully with reduction of FK506 administration. Tremor was observed in 8 patients, itching in 4, insomnia in 2, and vomiting in one. Hirsutism, gingival hypertrophy, and lymphoma were not observed. FK506 was highly effective in living-related partial liver transplantation not only in terms of immunosuppressive potential but also because it produced fewer adverse effects.

Adolescent↗
PubMed1993

The effects of cold preservation on steatotic graft viability in rat liver transplantation.

Clinical experience suggests that grafts obtained from steatotic livers result in primary nonfunction more frequently than those from nonsteatotic livers. To date, however, only a few studies have been done to verify the accuracy of this observation. To investigate the effects of cold preservation on steatotic liver viability, liver grafts obtained from rats fed with a choline-deficient diet were transplanted after periods of cold preservation. Recipient survival rates with normal liver grafts were 8/8 (100%) and those with steatotic liver grafts were 7/8 (88%) (P > 0.05) after 1-hr preservation with UW solution. After 9-hr preservation, however, these rates decreased significantly to 0/8 (0%) with steatotic grafts (P < 0.01), but were not significantly decreased with normal grafts. LDH levels in the effluent at the time of transplantation were 133 IU/L (1-hr) and 512 IU/L (9-hr) in normal livers, but in steatotic livers these were elevated to 598 and 3141 IU/L, respectively (P < 0.01). Recovery rates of hepatic blood flow measured by laser Doppler flowmeter after revascularization were 99% (1-hr) and 96% (9-hr) in normal grafts, but in steatotic grafts they were 98% (1-hr) and 63% (9-hr, P < 0.01). In addition, the oxidative phosphorylation ability of liver mitochondria obtained from steatotic grafts was decreased significantly after cold preservation. The present results suggest that steatotic liver grafts are prone to lose their viability more easily than normal liver grafts after prolonged periods of cold preservation due to a combination of causes.

Animals↗
PubMed1993

Interstitial radiofrequency hyperthermia for brain tumors--preliminary laboratory studies and clinical application.

An interstitial radiofrequency (RF) hyperthermia system for brain tumor was evaluated in cranial phantoms and cat brains. An intracranial RF applicator and thermocouple microprobes were emplaced in the brain and a headband-type flexible extracranial electrode fixed over the scalp. An 8 MHz RF capacitive-type heating machine provided power. The temperature distribution was measured by thermography. In phantom and animal studies, the RF power had good penetration into the tissue and generated uniform and easily controllable high-temperature fields within the intracranial cavity. There was little change in temperature near or in the cranium itself. Six cases of human malignant glioma were treated with this interstitial RF hyperthermia system, achieving therapeutic temperature without adverse effects.

Adult↗
PubMed1993

Living-related liver transplantation for biliary atresia.

We reviewed our initial experience of 29 living-related liver transplantations (LRLT) for children with biliary atresia in terms of postoperative complications and management to analyze the factors that may influence the outcome. All patients underwent an initial portoenterostomy at 17-134 days of age. The age distribution at the time of LRLT ranged from 6 months to 12 years, following revised portoenterostomy 0 to 3 times, and with (n=5) or without enteric stoma (n=24). Living-related donors provided the partial liver grafts weighing 170 to 630 g according to recipient size. Twenty-six of the 29 recipients are alive and well with follow-up between 1 and 27 (mean=14) months. Three patients died of extrahepatic complications including aspiration asphyxia, Candida infection and lymphoproliferative disorder. Four of 5 children with enteric stoma had 9 incidences of postoperative complication, while only 4 incidences occurred in 4 out of 24 children without stoma (p=0.007). Children hospitalized at the time of transplantation seemed to have early postoperative complications more frequently than home-bound children (p=0.06). The present results indicated that LRLT could offer satisfactory outcome for children in whom repeated Kasai's operation could not attain adequate biliary diversion and for those who developed cirrhosis despite good initial bile drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗
PubMed1993

Characterization of cholecystokinin receptors on the human gallbladder.

BACKGROUND: Several studies examined in vivo and in vitro biologic activity of the human gallbladder in response to cholecystokinin (CCK). However, few studies have demonstrated directly the interaction of CCK with receptors on the human gallbladder, which is responsible for this biologic activity. METHODS: To characterize CCK receptors on human gallbladder tissue, gallbladders were removed from human donor grafts that were being used for liver transplantation. The gallbladders were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay. RESULTS: Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH, and temperature. The binding was inhibited only by cholecystokinin-related peptides including CCK-8 (IC50 10 +/- 1.0 nmol/L) (mean +/- SD), des(SO3) CCK-8 (IC50 0.9 +/- 0.2 mumol/L), and gastrin-17-I (IC50 9.0 +/- 2.0 mumol/L) or specific CCK receptor antagonist L-364,718. Computer analysis of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(SO3) CCK-8 (EC50 1.2 +/- 0.7 mumol/L) and gastrin-17-I (EC50 4.5 +/- 2.4 mumol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 +/- 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction. The dose-response curve for CCK-8 alone to induce gallbladder contraction was not significantly different from those caused by CCK-8 plus 1 mumol/L tetrodotoxin or 1 mumol/L atropine. CONCLUSIONS: These results characterized the CCK receptors on smooth muscle of human gallbladder as sulfate dependent and causing gallbladder contraction.

Autoradiography↗
PubMed1993

Characterization of cholecystokinin receptors on the human sphincter of Oddi.

BACKGROUND: The present in vitro study investigated the interaction between cholecystokinin (CCK) and receptors on human sphincter of Oddi tissue obtained from donated human livers that were being transplanted. METHODS: Radiolabeled ligands with cholecystokinin receptor specificity, autoradiography, and crystal scintillation counting were used to directly characterize cholecystokinin receptors on tissue sections. RESULTS: The binding of 125I-BH-CCK-8 to the tissue was saturable, specific, and dependent on time, pH, and temperature. Saturable binding of 125I-BH-CCK-8 was localized on the smooth muscle layer, and binding was inhibited only by cholecystokinin-related peptides. Computer analysis of 125I-BH-CCK-8 binding indicated the presence of two classes of binding sites, one with a high affinity and the other with a low affinity for CCK-8. CCK-8 caused relaxation (half-maximal concentration, 6 nmol/L) and carbachol caused contraction (half-maximal concentration, 10 nmol/L) of circular, cross-sectional strips of the tissue. Longitudinal strips were less responsive. The relative 125I-BH-CCK-8 binding inhibition potency of CCK-8 agreed closely with its relative ability to cause sphincter relaxation. Tetrodotoxin (1 mumol/L) and atropine (1 mumol/L) caused a rightward shift of the dose-response curve for CCK-8-stimulated sphincter relaxation. CONCLUSIONS: The present results indicate that cholecystokinin receptors on the human sphincter of Oddi are sulfate dependent and mediate sphincter relaxation.

Atropine↗
PubMed1993

Hepatic vein reconstruction of the graft in partial liver transplantation from living donor: surgical procedures relating to their anatomic variations.

BACKGROUND: The surgical procedures to reconstruct the hepatic veins differ according to their anatomic variations to obtain the optimal graft volume for the recipient. This is an overview of the procedures used in our 25 living related liver transplantations. METHODS: The donor/recipient body weight ratio ranged widely from 1.2:1 to 9.6:1 (5.3 +/- 0.5:1, mean +/- SEM). RESULTS: The graft weight/recipient body weight was 2.40% +/- 0.21%. Graft components, which were determined by the optimal graft volume, and their drainage veins were the following: (1) segments 2 and 3 (S2+3) were used in 13 cases, 11 with the left hepatic vein (LHV) and two with the LHV and a partial drainage vein of S3; (2) S2+3 and a part of S4 in eight cases, seven with LHV and one with LHV and a partial drainage vein of S4; (3) S2+3+4 in three cases, with the common trunk of LHV and middle hepatic vein in all cases; and (4) S5+6+7+8 in one case with right hepatic vein. In two of three cases in which the graft had two drainage veins, the two vessels were reformed to have a common anastomotic orifice by the back-table plastic surgery procedure. In the other case in which the procedure could not be performed, two separate anastomoses of the individual vessels were performed successfully. Although stenosis of the reconstructed hepatic veins occurred four times in two cases at 3 months or more after transplantation, all incidences could be completely repaired by balloon dilation. CONCLUSIONS: These results show that, with careful consideration of the hepatic vein reconstruction, pediatric patients can receive optimal volume grafts from living donors.

Adolescent↗