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Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed2005

Analysis of neutral oligosaccharides for structural characterization by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry.

We have acquired multi-stage mass spectra (MSn) of four branched N-glycans derived from human serum IgG by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF-MS) in order to demonstrate high sensitivity structural analysis. [M+H]+ and [M+Na]+ ions were detected in the positive mode. The detection limit of [M+Na]+ in MS/MS and MS3 measurements for structural analysis was found to be 100 fmol, better than that for [M+H]+. The [M+H]+ ions subsequently fragmented to produce predominantly a Y series of fragments, whereas [M+Na]+ ions fragmented to give a complex mixture of B and Y ions together with some cross-ring fragments. Three features of MALDI-QIT-CID fragmentation of [M+Na]+ were cleared by the analysis of MS/MS, MS3 and MS4 spectra: (1) the fragment ions resulting from the breaking of a bond are more easily generated than that from multi-bond dissociation; (2) the trimannosyl-chitobiose core is either hardly dissociated, easily ionized or it is easy to break a bond between N-acetylglucosamine and mannose; (3) the fragmentation by loss of only galactose from the non-reducing terminus is not observed. We could determine the existence ratios of candidates for each fragment ion in the MS/MS spectrum of [M+Na]+ by considering these features. These results indicate that MSn analysis of [M+Na]+ ions is more useful for the analysis of complicated oligosaccharide structures than MS/MS analysis of [M+H]+, owing to the higher sensitivity and enhanced structural information. Furthermore, two kinds of glycans, with differing branch structures, could be distinguished by comparing the relative fragment ion abundances in the MS3 spectrum of [M+Na]+. These analyses demonstrate that the MSn technology incorporated in MALDI-QIT-TOF-MS can facilitate the elucidation of structure of complex branched oligosaccharides.

Carbohydrate Sequence↗
PubMed2005

Living donor liver transplantation with noninvasive ventilation for exertional heat stroke and severe rhabdomyolysis.

A 16-year-old male with exertional heat stroke (EHS) had extensive hepatocellular damage, severe rhabdomyolysis, renal failure, and coma. Hemodiafiltration was started on day 2 and living donor liver transplantation was performed on day 3. He received continuous mechanical ventilation with intubation before and after the surgery. As his mental status improved, he could not tolerate intubation, and he was extubated on postoperative day (POD) 26. He received facial noninvasive positive pressure ventilation until POD 50. Hemodiafiltration was discontinued on POD 52. He was discharged on POD 67 and is currently well more than a year after transplantation. A literature search indicates that this patient is the first long-term survivor (>1 year) after liver transplantation for exertional heat stroke.

Adolescent↗
PubMed2005

Comparison of cyclosporine microemulsion and tacrolimus in 39 recipients of living donor liver transplantation.

New immunosuppressive agents and regimens should be evaluated specifically in living donor liver transplant patients due to potential clinical and pharmacokinetic differences between deceased donor and living donor transplant recipients. The analysis presented here is the first direct comparison of clinical outcomes using cyclosporine microemulsion (CsA-ME) with monitoring of blood concentration at 2 hours postdose (C2) and tacrolimus-based immunosuppression in living donor liver transplantation. The analysis was conducted on the data provided by the 39 recipients of a living donor transplant out of the 495 patients enrolled in a 6-month, randomized, prospective, multicenter, open-label study (LIS2T). Patients were randomized to CsA-ME (C2 monitoring) or tacrolimus (monitoring of predose trough drug blood level [C0)]) and were administered corticosteroids with or without azathioprine. Twenty-three living-donor patients received CsA-ME and 16 received tacrolimus. By month 6, 9% of patients receiving CsA-ME and 19% of those receiving tacrolimus had lost their graft or died (not significant [NS]). Nine episodes of biopsy-proven acute rejection were reported: 4 in the CsA-ME group (17%) and 5 in the tacrolimus cohort (31%, NS). There were no significant differences in any safety parameter between groups. The most frequently reported serious adverse events were infections, which occurred in 14 patients in the CsA-ME group (61%) and 13 patients in the tacrolimus arm (81%, NS). Twelve patients in the CsA-ME arm (52%) and 5 in the tacrolimus arm (31%, NS) discontinued the study prematurely. In conclusion, CsA-ME C2 monitoring or tacrolimus both offer effective protection against rejection in living donor liver transplants while maintaining a good safety profile.

Adult↗
PubMed2005

Living donor liver transplantation for biliary atresia complicated by situs inversus: technical highlights.

Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties. Recently, some reports of successful diseased-donor liver transplantation in patients with BA complicated by SI have been published; however, few reports of that with LDLT exist. The technical difficulties involved with LDLT for such cases have not been described. Herein, we present 4 successful cases of LDLT for BA with SI. Complex anomalies associated with SI, such as a hepatic artery arising from the supraceliac aorta, a preduodenal portal vein, and absence of the retrohepatic inferior vena cava, increase the technical difficulties involved with the operation. Additional caution is required in LDLT because a living-donor graft has short vessels and the availability of vascular grafts from the donor is limited. In conclusion, LDLT for BA complicated by SI can be managed successfully with technical modifications and scrupulous attention. This series represents the largest reported group of patients with BA complicated by SI who underwent a successful LDLT procedure.

Abnormalities, Multiple↗
PubMed2005

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.

Adolescent↗
PubMed2005

Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs).

Recent dramatic improvements in clinical islet cell transplantation demonstrated by the Edmonton group have increased the demand for this treatment, and donor shortage could become a major problem. Utilization of marginal donors could alleviate the donor shortage, and non-heart-beating donors (NHBDs) might be good resources. The University of Pennsylvania group demonstrated that it was possible to isolate islets from NHBDs, and the group actually transplanted islets from NHBDs, for the first time. The patient became insulin-independent; however, there had been no more cases using NHBDs until our group initiated islet transplantations from NHBDs in Japan. In order to utilize NHBDs effectively, we modified the standard islet isolation method. These modifications included minimizing the warm ischemic time, the use of trypsin inhibition during isolation, carrying out density measurement before purification and the use of a less toxic islet purification solution. With these modifications we were able to transplant nine of ten islet preparations from ten NHBDs (90%), into five type-1 diabetic patients. The first transplantation was performed on April 7, 2004 (the first time in Japan), and this patient became insulin-independent after the second islet transplantation (first time in Japan). All patients showed improved glycemic control and reduced insulin requirements, without hypoglycemic events. We also performed living-donor islet transplantation, with our modified islet isolation protocol, on January 19, 2005. The improved islet isolation protocol enabled us to perform effective islet transplantations from NHBDs, and it also enabled us to perform the living-donor islet transplantation.

Animals↗
PubMed2005

Pharmacodynamic analysis of tacrolimus and cyclosporine in living-donor liver transplant patients.

BACKGROUND: The calcineurin inhibitors tacrolimus and cyclosporine (INN, ciclosporin) have been widely used to prevent allograft rejection after transplantation. We investigated pharmacodynamic properties of the 2 drugs and their clinical relevance in liver transplantation. METHODS: Forty de novo living-donor liver transplant patients participated in this study, and they were treated with either tacrolimus (N = 30) or cyclosporine (N = 10). We simultaneously measured blood drug concentrations and calcineurin phosphatase activity in peripheral blood mononuclear cells during the first 14 postoperative days. Nephrotoxicity and acute rejection were also examined in relation to the blood drug concentrations and calcineurin activity. RESULTS: Calcineurin activity was only partially inhibited by tacrolimus concentrations greater than 20 ng/mL, although it could be almost completely inhibited by cyclosporine concentrations greater than 700 ng/mL. According to a maximum effect model, the population mean estimates of the EC(50) (blood concentration that yields a half-maximal effect) for tacrolimus and cyclosporine were 26.4 ng/mL (95% confidence interval [CI], 15.7-37.1 ng/mL) and 200 ng/mL (95% CI, 127-274 ng/mL), respectively. Patients with nephrotoxicity in both groups had significantly higher trough concentrations compared with those without this adverse event. In addition, patients with acute rejection in the tacrolimus group had significantly lower trough concentrations and higher calcineurin activity than those without a rejection episode. CONCLUSIONS: The inhibitory effects on calcineurin activity in peripheral blood mononuclear cells differed between tacrolimus and cyclosporine in living-donor liver transplant patients. Pharmacodynamic assessment in combination with blood concentration monitoring may be useful for determining the individual therapeutic range of tacrolimus and cyclosporine.

Administration, Oral↗
PubMed2005

Human leukocyte antigens in Japanese patients with biliary atresia: retrospective analysis of patients who underwent living donor liver transplantation.

Biliary atresia (BA) is a neonatal obstructive cholangiopathy characterized by a fibrosclerosing obliteration of the extrahepatic bile duct. The aim of this study was to investigate the relationship between human leukocyte antigens (HLA) and susceptibility to BA. We retrospectively analyzed 392 Japanese patients with BA and without extrahepatic anomalies who underwent living donor liver transplantations at our institute. Healthy Japanese volunteers (n = 828) served as normal controls. A significant positive association was observed between BA and HLA-DR2 (39.0% of patients vs. 30.4% of controls, odds ratio = 1.46, p = 0.029). Two-locus analyses disclosed that DR2 was not independently associated with BA, but the increased frequency of HLA-A24 and -B52 reflected the linkage disequilibrium between -A24, -B52, and -DR2. Moreover, the frequency of the haplotype HLA-A24-B52-DR2 was significantly higher in patients with BA than in the general Japanese populations described in the literature (odds ratio = 2.20, p = 0.00124). These results indicate that the gene for BA susceptibility is in close linkage disequilibrium with the HLA-A24-B52-DR2 haplotype observed in the Japanese population. We speculate that a gene at the locus close to HLA plays an important role in the pathogenesis of BA.

Biliary Atresia↗
PubMed2005

Successful liver transplantation for congenital absence of the portal vein complicated by intrapulmonary shunt and brain abscess.

A 27-day-old boy had convulsion associated with brain abscesses and severe hypoxemia at the age of 3 months. Congenital absence of the portal vein (CAPV) and some associated anomalies were detected by radiological examinations. Brain abscess and hypoxemia were thought to be serious complications resulting from CAPV and were successfully corrected by living donor liver transplantation at the age of 4 months. This is the first report of a successful transplantation indicated for intrapulmonary shunt and brain abscess in an infant with CAPV.

Abnormalities, Multiple↗
PubMed2005

Role of bcl-2 mRNA in homeostatic proliferation in circulating T-cells in human liver transplant patients after T-cell depletion.

BACKGROUND: Prolonged T-cell depletion after liver transplantation leads to life-threatening infections. Members of the anti-apoptotic Bcl-2 gene family can maintain T-cell viability. T-cell numbers and their Bcl-2 expression following living donor liver transplantation (LDLT) were analyzed in 108 surviving and 13 deceased recipients. MATERIALS AND METHODS: Bcl-2 mRNA levels and phenotypic changes of T-cells were examined by quantitative PCR and by measuring expression of CD45RO and CCR7. RESULTS: Based on the restoration of peripheral T-cell numbers, the 108 surviving recipients were classified into three groups. All recipients showed T-cell depletion, down to approximately 30% of pretransplant levels within 3 h of graft reperfusion. In Group I, the T-cell numbers were rapidly restored to pretransplant levels, within 5 days, with a rapid decrease in Bcl-2 mRNA levels immediately after LDLT. In Group II, the T-cell numbers were restored to normal levels by 19 days, with down-regulation of Bcl-2 mRNA. In Group III, the T-cell numbers were maintained at low levels for much longer, with high levels of Bcl-2 mRNA. In all three groups of recipients, there was statistically significant (r = -0.78) inverse correlation between T-cell numbers and Bcl-2 mRNA. CONCLUSIONS: For successful transplantation, homeostatic restoration of T-cells must occur as soon as possible. Evaluation of peripheral T-cell numbers and of Bcl-2 expression may have therapeutic potential in identifying those transplant patients who face increased risk of infection.

Adolescent↗
PubMed2005

Rapid quantitation of immunoglobulin G antibodies specific for blood group antigens A and B by surface plasmon resonance.

BACKGROUND: The measurement of immunoglobulin (Ig) G blood group A/B antibody(anti-A/B) levels is important for ABO-unmatched organ recipients because the effective removal of the antibodies improves their prognosis. Currently existing methods to detect IgG anti-A/B suffer limitations owing to high costs, low throughput, and poor adaptability to automation. STUDY DESIGN AND METHODS: We have developed a rapid means to quantitate IgG anti-A/B by surface plasmon resonance (SPR). To investigate the accuracy, a serially diluted plasma sample from a donor was measured with the SPR method. Moreover, IgG anti-A/B titers in 45 healthy volunteers were measured both by the SPR and by the standard tube test (TT) method, as were plasma samples from two ABO-unmatched organ recipients. RESULTS: The change in titers when the same plasma was diluted was precisely reflected by the SPR method. The coefficients of correlation between SPR and TT methods for IgG anti-A and anti-B were 0.85 and 0.56, respectively. The SPR values also paralleled the TT values, which showed a decline in titers after the removal of antibodies by double-filtration plasmapheresis or plasma exchange. CONCLUSION: This SPR method can be used to measure IgG anti-A/B titers in the plasma very quickly and quantitatively.

ABO Blood-Group System↗
PubMed2005

Intraoperative blood loss during living donor liver transplantation: an analysis of 635 recipients at a single center.

BACKGROUND: Living-donor liver transplantation (LDLT) has been an important option in the treatment of patients with end-stage liver disease. Massive intraoperative blood loss can occur during LDLT, necessitating blood transfusion. The purpose of this study was to present blood loss data from the recipients of LDLT, to assess the effect of massive intraoperative blood loss on prognosis, and to assess the reliability of preoperative information in predicting intraoperative blood transfusion requirements in LDLT. STUDY DESIGN AND METHODS: A total of 635 patients who underwent LDLTs between January 1995 and March 2002 at a university hospital were retro- spectively investigated. The volume of blood loss, prognosis, and preoperative variables were analyzed statistically. RESULTS: Intraoperative blood loss ranged from 5.15 to 1980 mL per kg (mean, 136 mL/kg). Massive blood loss negatively affected survival not only immediately after operation (high blood loss [HBL]:low blood loss [LBL] ratio, 85.5%:93.9% at 1 month) but also over the long term (HBL:LBL, 61.4%:76.8% at 5 years). Preoperative risk factors for massive blood loss were determined to be recipient age (<1 years), weight (<10 kg), C-reactive protein (>2 mg/dL), hematocrit (<30%), total bilirubin (>20.0 mg/dL), direct bilirubin (>16.0 mg/dL), and blood urea nitrogen levels (>30.0 mg/dL). CONCLUSIONS: The risk factors associated with massive intraoperative blood loss during LDLT were identified. This is the first analysis of blood loss during LDLT at a single center. Massive blood loss is a predictor of poor prognosis in LDLT patients.

Age Distribution↗
PubMed2005

Auxiliary partial orthotopic living donor liver transplantation: Kyoto University experience.

Auxiliary partial orthotopic liver transplantation (APOLT) was initially indicated as a potentially reversible fulminant hepatic failure and non-cirrhotic metabolic liver disease to compensate for enzyme deficiency without complete removal of the native liver. We expand our indication of APOLT for small-for-size grafts to support the function of implanted grafts during the early post-operative period, and for ABO-incompatibility to sustain a patient's life if the patient has a graft failure. We retrospectively reviewed 31 patients undergoing APOLT from living donor. The indication of APOLT was fulminant hepatic failure in 6, non-cirrhotic metabolic liver disease in 6, small-for-size grafts in 13 and ABO-incompatible cases in 6. The cumulative survival rate for APOLT at 1 and 5 years was 57.9% and 50.6%, and 78.8% and 73.8% for standard LDLT. None of the patients who underwent transplantation with APOLT for fulminant hepatic failure had long-term patient survival. The incidence of acute cellular rejection was higher in APOLT (58.1%) than standard LDLT (35.0%). Biliary complication was higher and the need for retransplantation was greater in APOLT than standard LDLT (p < 0.01). The results suggest that the indications of APOLT should be reconsidered in view of the risk for complications and retransplantation.

ABO Blood-Group System↗
PubMed2005

Impact of right lobe with middle hepatic vein graft in living-donor liver transplantation.

Technical improvements in adult-to-adult living-donor liver transplantation (LDLT) have led to the use of right-lobe grafts to overcome the problems encountered with 'small-for-size grafts'. The major controversy remains that the venous drainage from anterior segment substantially depends on tributaries of the middle hepatic vein (MHV), and deprivation of such tributaries may critically influence the postoperative graft function. Right-lobe grafts with MHV could resolve the potential problem of congestion in anterior segment. From December 2000 to January 2004, we performed 217 right-lobe LDLTs for adult patients. Of these, 40 patients received a right lobe with MHV graft (18.4%). The overall cumulative 3-year graft survival rate of a right lobe with (n = 40) and without MHV (n = 177) was 86.2% and 74.8% (p = NS). The proximal side of the MHV and the drainage vein of segment IV to the MHV (the left medial superior vein) were preserved in 24 patients. All of them needed venous interposition graft for anastomosis. All patients had a patent right hepatic vein (RHV) and MHV anastomosis during the follow-up period. We adopted the right lobe with MHV graft in 40 LDLT cases. Vein graft is essential for safe MHV anastomosis in cases which preserve proximal side of the MHV.

Adult↗
PubMed2005

Cell permeable peptide of JNK inhibitor prevents islet apoptosis immediately after isolation and improves islet graft function.

Although application of the Edmonton protocol has markedly improved outcomes for pancreatic islet transplantation, the insulin independence rate after islet transplantation from one donor pancreas has proven to remain low. During the isolation process and subsequent clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. Pancreas preservation with the two-layer method (TLM) has proven to improve transplant results by protecting isolated islets against apoptosis through the mitochondrial pathway. However, pancreas storage with TLM cannot protect against activation of c-Jun NH2-terminal kinase (JNK) in isolated islets. This study investigated whether delivery of a JNK inhibitory peptide (JNKI) via the protein transduction system can prevent apoptosis of islet cells immediately after isolation. For efficient delivery of the (JNKI into isolated islets, we synthesized JNKI as a C-terminal fusion peptide with the 11-arginine protein transduction domain (11R-JNKI). 11R efficiently delivered the JNKI into isolated islets and 11R-JNKI prevented islet apoptosis immediately after isolation and improved islet graft function. These findings suggest that peptide drugs could be useful for the prevention of the impairment of islet cells and lead to improvement in the outcomes for pancreatic islet transplantation.

Amino Acid Sequence↗