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Biomedical subjects

Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 163 records · Page 9Linked to original sources

Lens culinaris agglutinin-A-reactive alpha-fetoprotein as a marker for liver atrophy in fulminant hepatic failure.

Liver atrophy is frequently found at autopsy of patients with fulminant hepatic failure (FHF). Imaging studies in patients with FHF demonstrate that estimation of total liver volume correlates with prognosis. In this study, in order to determine serum markers for evaluating liver atrophy, we measured the weight of whole livers resected from 31 transplant recipients with FHF, and assessed the relation between the liver weights and several prognostic markers. The level of liver atrophy was evaluated by calculating the ratio of the removed whole liver weight to the body weight of each recipient, and 16 major variables including several serological markers were analyzed among those recipients. We found that the serum Lens culinaris agglutinin-A-reactive alpha-fetoprotein (AFP-L3) levels were significantly higher in patients with FHF than in those with other liver diseases. In FHF patients, the serum AFP-L3 level at the onset of encephalopathy was significantly higher in cases with mild atrophy than in those with severe atrophy (P<0.05). Notably, the residual liver volume was significantly correlated with the serum AFP-L3 level (Pearson's correlation coefficient=0.63), but not with AFP. In conclusion, AFP-L3 is a possible serum marker for evaluating liver atrophy and/or liver regeneration in patients with FHF.

Journal Article↗

Apoptosis and retinal projections in the dorsal lateral geniculate nucleus after monocular deprivation during the later phase of the critical period in the rat.

The visual cortex in the rat is matured physiologically by postnatal day 30, but the visual system retains the potential to be reorganized until postnatal day 45. Therefore, we defined the period from postnatal days 28-45 as the 'late critical phase'. To examine whether monocular deprivation during the late critical phase gives rise to neuronal apoptosis in the dorsal lateral geniculate nucleus (dLGN), we used the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method and anterograde tracing. The number of apoptotic cells in the dLGN after monocular deprivation at postnatal day 28 showed little difference from control at postnatal day 29, but was significantly increased to more than fourfold of control ipsilaterally to the monocular deprivation at postnatal day 35 and to more than 10-fold of control bilaterally at postnatal day 40. In the control, there were almost no apoptotic neurons in the dLGN on either side at postnatal day 40. In the nucleus ipsilateral to the monocular deprivation, approximately half the apoptotic neurons were found in an area that did not receive a retinal projection. These findings suggest that the biological process of increased apoptosis in the dLGN of rats that received monocular deprivation in the late critical phase may be different from that in the early critical phase. The increased number of apoptotic cells in the dLGN in the late critical phase may not be simply the result of monocular deprivation.

Animals↗

Endoscopic management of postoperative biliary complications in donors for living donor liver transplantation.

BACKGROUND & AIMS: Biliary leakage and stricture are serious complications that occur in donors whose liver is resected for living donor transplantation. We assessed the usefulness of endoscopic nasobiliary drainage and endoscopic biliary stenting, respectively, in repairing biliary leakage and stricture. METHODS: Between July 1999 and December 2001, a total of 276 donors underwent liver resection (left side, 118; right side, 158) for living donor transplantation at Kyoto University Hospital. Seven (2.5%) donors developed biliary leakage, which required endoscopic nasobiliary drainage; 3 of these donors also had biliary stricture. RESULTS: All 7 patients who developed biliary leakage were the right-lobe donors. Endoscopic retrograde cholangiography identified the site of the biliary leakage in all 7 of the donors. In 6 of these donors, the biliary leakage resolved within an average of 15 days after an endoscopic nasobiliary drainage tube was placed. In the seventh donor, the biliary leakage resolved after percutaneous transhepatic biliary drainage was performed. Three patients developed biliary stricture that required endoscopic biliary stenting. The angles between common hepatic duct and the left hepatic duct were more acute in patients with stricture than in those without stricture (62 degrees vs. 119 degrees). CONCLUSIONS: Biliary complications requiring endoscopic treatment developed exclusively in donors for right-lobe living donor transplantation. Endoscopic retrograde cholangiography is a favorable modality for diagnosing and treating postoperative biliary complications in donors for living donor liver transplantation.

Adult↗

Long-term effects of liver transplantation on bone mineral density in children with end-stage liver disease: a 2-year prospective study.

In children with end-stage liver disease, little is known regarding the long-term effects of liver transplantation on bone. In this 2-year prospective study, we evaluated the effects of liver transplantation on bone mineral density (BMD) and on other parameters of bone metabolism in 30 consecutive children with biliary atresia who underwent liver transplantation after failed Kasai operation. Tacrolimus and steroids were used as immunosuppressants. BMD of the first through fourth lumbar spine (L1-4) was measured by dual-energy radiographic absorptiometry (QDR-2000, Hologic) and expressed in Z-values. Before transplantation, Z-values of BMD, height, and weight were low in all patients (-3.4 +/- 0.34, -2.0 +/- 0.28, and -1.67 +/- O.16 [mean +/- SEM], respectively). Low BMD states were associated with low levels of serum 25-hydroxyvitamin D and serum levels of insulin-like growth factor-I (IGF-I), one of the most potent anabolic skeletal growth factors. Liver transplantation resulted in marked improvement in BMD values as well as in height and body weight: 24 months after transplantation, recovery was achieved in each parameter (0.16 +/- 0.30, -0.29 +/- 0.23, and 0.42 +/- 0.18, respectively). BMD recovery first was observed 3 months after transplantation. Moreover, these favorable effects of transplantation were accompanied by increases in serum levels of 25-hydroxyvitamin D and IGF-I. We conclude that liver transplantation effectively reverses the low bone mass status and growth retardation of children with end-stage liver disease.

Adolescent↗

The utility of marginal donors in liver transplantation.

The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed.

Fatty Liver↗

Enhanced expression of enterocyte P-glycoprotein depresses cyclosporine bioavailability in a recipient of living donor liver transplantation.

We evaluated levels of intestinal expression of absorptive-barrier P-glycoprotein (PGP) and cytochrome P-450 IIIA4 (CYP3A4) and immunosuppressant therapy in a patient who underwent living donor liver transplantation (LDLT) and received a second living donor liver transplant after chronic rejection of the first. PGP and CYP3A4 expression were measured using part of a Roux-en-Y limb. After the first LDLT, the concentration-dose ratio of orally administered tacrolimus was 159.8 +/- 125.3 (average +/- SD of 32 different days), similar to the average for 46 recipients of living donor liver transplants in our hospital (161.3 +/- 88.1). However, the recipient required very large oral doses of cyclosporine (703.9 +/- 385.4 mg/d, average +/- SD of 13 different days) after the second LDLT. Although intestinal PGP level was increased markedly at the second LDLT, CYP3A4 level was decreased. In addition, levels of messenger RNA expression of several gene products related to the local inflammation, such as cyclooxygenase 2, interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha, were increased. These results suggest that hepatic failure after LDLT, including chronic rejection and/or cholangitis, was accompanied by upregulation of intestinal PGP expression, which could depress the bioavailability of the immunosuppressant.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Small-for-size graft in living donor liver transplantation: how far should we go?

With the extensive use of living donor liver grafts in adult patients, controversy over small-for-size syndrome has escalated in recent years. Although several symptoms have been suggested as manifestations of the syndrome, small-for-size syndrome remains difficult to diagnose because these symptoms are neither specific nor inevitable. The occurrence of small-for-size syndrome also seems to depend on a number of recipient and graft factors. Potential pathogenic mechanisms include persistent portal hypertension and portal overperfusion. At present, several techniques are being explored in an attempt to ameliorate the impact of small-for-size syndrome. Recent experience suggests that the occurrence of small-for-size syndrome is multifactorial and that complications relating to small-for-size grafts should be examined in relation to a variety of graft, recipient, and technical factors.

Body Constitution↗

New ELISA system for myeloid-related protein complex (MRP8/14) and its clinical significance as a sensitive marker for inflammatory responses associated with transplant rejection.

BACKGROUND: C-reactive protein (CRP), a useful marker for inflammatory diseases, is not always sensitive to inflammatory reaction in the liver or other tissues. The aim of this study was to develop a sensitive and specific method for detecting inflammatory responses associated with transplant rejection. METHODS: We developed a new, highly sensitive ELISA system for the measurement of serum human myeloid-related protein complex (MRP8/14), using monoclonal antibodies against MRP8/14, and applied it to specimens obtained from patients undergoing small intestine or liver transplantation. RESULTS: This assay could detect MRP8/14 concentrations as low as 2 micro g/L. Within-run CVs were 3.7-6.1% and between-day CVs were 5.6-8.7% for MRP8/14 concentrations of 117-3300 micro g/L. Mean recovery was 104% (range, 80-128%). We observed a marked increase in serum MRP8/14 postoperatively in most recipients of transplants, followed by an increase in CRP 1-7 days after the increase in the complex. The increase in serum MRP8/14 occurred simultaneously with permeation of lymphocytes into the transplanted tissues as a result of rejection of the graft tissues. CONCLUSIONS: Accurate measurement of serum MRP8/14 provides a useful clinical diagnostic method tool for detecting inflammation associated with rejection of transplanted tissues.

Acute Disease↗

Forecasting of blood tacrolimus concentrations based on the Bayesian method in adult patients receiving living-donor liver transplantation.

OBJECTIVE: To evaluate Bayesian prediction of blood tacrolimus concentrations in adult patients receiving living-donor liver transplantation (LDLT) using previously obtained population pharmacokinetic parameters. PATIENTS AND METHODS: Data were retrospectively collected from 47 adult patients receiving LDLT who were not included in the estimation of population pharmacokinetic parameters. Blood tacrolimus concentrations were predicted without or with the empirical Bayesian method using sparse samples obtained in the previous week. Predictive performance of the concentrations was evaluated by the mean prediction error (ME), mean absolute prediction error (MAE) and root mean square error (RMSE) as well as the percentage of successful predictions (percentage of absolute prediction error less than 3 microg/L, %PRED3). RESULTS: Concentrations predicted by the population mean pharmacokinetic parameter values coincided well with observed concentrations during the period of tacrolimus infusion immediately after the operation. For concentrations during subsequent oral therapy with tacrolimus, predictability by the population mean pharmacokinetic parameter values alone was not satisfactory. Bayesian forecasting using one or two blood concentrations obtained in the previous week significantly decreased (p<0.05) MAE and RMSE compared with predictions based on the population mean pharmacokinetic parameters on postoperative days 21 and 28, but not on day 14. During postoperative days 15-21, %PRED3 was increased to 68.6% or 71.2% with the Bayesian method using one or two blood concentrations, respectively, from 44.9% with the population mean pharmacokinetic parameter values. CONCLUSION: The present study demonstrated the applicability of the Bayesian method with use of one or two samples for prediction of blood tacrolimus concentrations in adult patients receiving LDLT.

Administration, Oral↗

Bridging use of plasma exchange and continuous hemodiafiltration before living donor liver transplantation in fulminant Wilson's disease.

A 15-year-old girl presented with acute hepatic failure showing ascites and hepatic encephalopathy, accompanied by hemolytic anemia. She was diagnosed as having fulminant Wilson's disease (FWD). Plasma exchange (PE), continuous hemodiafiltration (CHDF) and D-penicillamine administration were started immediately. Copper [24,000 microg] was removed by PE and CHDF over three days, which relieved the jaundice and the consciousness disorder. A successful liver transplant followed. FWD progresses rapidly and often liver transplantation is the only possible therapy. In this case, PE and CHDF were an effective therapy bridge until liver transplantation.

Adolescent↗

[Neoadjuvant chemotherapy with nedaplatin and UFT for oral squamous cell carcinomas].

The purpose of this study was to evaluate the effect of preoperative combination chemotherapy with nedaplatin and UFT for oral squamous cell carcinomas. Eleven patients were enrolled in this study (four men and seven women, with a mean age of 66.3 years). They received oral UFT (300 or 400 mg/day, total 2,100-24,600 mg with an average of 10,700 mg) from the initial diagnosis to the day before surgery. They also received an administration of nedaplatin (80 or 100 mg/m2) about four weeks before the planned surgery. The locoregional response rate (complete response and partial response) was 36.4%, and histological examination of surgical specimens revealed a response rate of 40%. There was no relationship between total dose of UFT and either clinical or histological response. Three patients showed severe neutropenia under 1,000/m3 and all recovered with (two patients) or without (one) the use of G-CSF. No other severe side effect was recognized. From the results of this study it is suggested that this combination therapy is useful for preoperative patients with oral squamous cell carcinoma, and that it is possible for them to undergo the therapy on an out-patient basis.

Aged↗

The fission yeast pfh1(+) gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase.

The Cdc24 protein plays an essential role in chromosomal DNA replication in the fission yeast Schizosaccharomyces pombe, most likely via its direct interaction with Dna2, a conserved endonuclease-helicase protein required for Okazaki fragment processing. To gain insights into Cdc24 function, we isolated cold-sensitive chromosomal suppressors of the temperature-sensitive cdc24-M38 allele. One of the complementation groups of such suppressors defined a novel gene, pfh1(+), encoding an 805 amino acid nuclear protein highly homologous to the Saccharomyces cerevisiae Pif1p and Rrm3p DNA helicase family proteins. The purified Pfh1 protein displayed single-stranded DNA-dependent ATPase activity as well as 5' to 3' DNA helicase activity in vitro. Reverse genetic analysis in S.pombe showed that helicase activity was essential for the function of the Pfh1 protein in vivo. Schizosaccharomyces pombe cells carrying the cold-sensitive pfh1-R20 allele underwent cell cycle arrest in late S/G2-phase of the cell cycle when shifted to the restrictive temperature. This arrest was dependent upon the presence of a functional late S/G2 DNA damage checkpoint, suggesting that Pfh1 is required for the completion of DNA replication. Furthermore, at their permissive temperature pfh1-R20 cells were highly sensitive to the DNA-alkylating agent methyl methanesulphonate, implying a further role for Pfh1 in the repair of DNA damage.

Adenosine Triphosphatases↗