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Biomedical subjects

Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 145 records · Page 8Linked to original sources

Living-related liver transplantation for Alagille syndrome.

Alagille syndrome (AGS) is an autosomal dominant genetic disorder characterized by chronic cholestasis, congenital heart disease, peculiar facies, butterfly-like vertebrae, and posterior embryotoxon. Liver dysfunction is the common presentation of AGS, and liver transplantation may be indicated. This study examines the outcome of living-related liver transplantation (LRLT) for AGS. Twenty patients with AGS (median age 5.0 years, range 0.6-12.9) underwent LRLT at Kyoto University Hospital between June 1990 and February 2002. Five potential donors were excluded because of paucity of intrahepatic bile ducts diagnosed by preoperative liver biopsy and one because of a hepatic vascular anomaly. The overall 5-year patient survival was 80.4%. Three patients died as the result of the following: complications related to surgery, heart failure caused by progressive pulmonary artery stenosis, and a graft with unsuspected bile duct paucity. Liver dysfunction was improved in all successful cases, and catch-up growth occurred in 90% of patients. LRLT is an efficacious treatment modality for AGS if donors are selected by cautious evaluation to rule out unsuspected bile duct paucity.

Alagille Syndrome↗

Rac- and meso-3,3'-Bis(3,5-dimethylphenyl)-3H,3'H-2,2'-biindenylidene-1,1'(2H,2'H)-dione.

In the rac isomer of the title compound, C(34)H(28)O(2), the two C-Ph(dimethylphenyl) bond axes make an angle of 58.7 (1) degrees. There is no short contact between the two 3,5-dimethylphenyl rings, although the dihedral angle between them is 4.93 (7) degrees. The meso isomer has a center of symmetry at the middle of the C=C bond, and the two C-Ph(dimethylphenyl) bond axes are antiparallel to one another.

Journal Article↗

Significant role of middle hepatic vein in remnant liver regeneration of right-lobe living donors.

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.

Adult↗

Living-donor liver transplantation: 12 years of experience in Asia.

Living-donor liver transplantation has provided a solution to the severe lack of cadaveric grafts for the replacement of livers afflicted with end-stage cirrhosis, fulminant disease, or inborn errors of metabolism. The pioneering experience in Japan in the early 1990s helped open wide the avenues of a new branch of science that is technically demanding and whose benefits are clearly dramatic. The need for alternative sources of liver grafts was common to the entire Asian region and, fortunately, the option of obtaining partial liver grafts from live donors had already become tenable. By the second half of the past decade, living-donor liver transplant programs had been successfully established in Hong Kong, Taiwan, and Korea. More than 1,500 cases have been performed over a 12-year period. This report describes the cumulative experience in living-donor liver transplantation in Asia on the basis of data from five major liver transplant centers.

Asia↗

Living-donor liver transplantation for hepatocellular carcinoma.

In cadaveric liver transplantation, the Milan criteria have been accepted as the selection criteria for hepatocellular carcinoma (HCC) patients in considering organ allocation. However, the situation is different in living-donor liver transplantation (LDLT), in which the donor has a strong preference for altruism. The authors describe herein their experience with LDLT for HCC patients using their patient selection criteria. From February 1999 to March 2002, right lobe LDLT was performed in 56 patients with HCC. The authors' exclusion criteria included only those with extrahepatic metastasis or vascular invasion detected during preoperative evaluation. Thirty patients (54%) were in tumor, node, metastases stage IVa and 25 patients (45%) did not meet the Milan criteria at the time of LDLT. The follow-up period was 1 to 39 months (median, 11 months). The overall survival rates at 1 and 3 years were 73% and 55%, respectively, and the latter was significantly lower than that of adult right lobe LDLT without HCC (71% at 3 years). Fourteen patients died because of postoperative complications without tumor recurrence. Thirty-six patients survived without recurrence and six patients had recurrence. Among the six patients with recurrence, four had survived for 11 to 36 months after LDLT. In the analysis of patients who survived longer than 3 months after transplantation, 19 of 20 within the Milan criteria survived without recurrence. However, 15 of 20 patients beyond the criteria also survived without recurrence for 3 to 33 months (median, 12 months) and three of five patients with recurrence were alive for 11 to 36 months (median, 20 months). Histopathologic grading and microscopic portal venous invasion had significant negative impact on tumor recurrence. LDLT was an effective treatment for uncontrollable hepatocellular carcinoma. Because many patients who did not meet the Milan criteria survived without tumor recurrence after transplantation, different patient selection criteria are necessary in LDLT to save those with advanced HCC.

Adult↗

Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

Afferent Pathways↗

Factors influencing liver regeneration following living-donor liver transplantation of the right hepatic lobe.

BACKGROUND: As a result of the shortage of cadaveric livers for adults, many institutes perform living-donor liver transplantation (LDLT) using right-lobe grafts. It is important to learn whether regeneration of the graft is compromised by division of middle hepatic vein (MHV) tributaries. Accordingly, we studied the effect on graft regeneration of transection of the MHV tributaries and other factors, including graft versus body weight ratio (GRBW). METHODS: Of 100 adult recipients having undergone right-lobe LDLT, 30 6-month survivors were studied. Liver regeneration was assessed by volumetry based on the computed tomography (CT). A regeneration index was defined as the ratio of the graft volume 6 months after LDLT to the preoperative value. The dominance of the MHV tributaries over the right hepatic vein in venous drainage of the anterior segment was evaluated by preoperative CT using a 5-point scale. RESULTS: The regeneration index of the posterior segment was significantly greater than that of the anterior segment (Wilcoxon signed rank test, P=0.01). The relatively poor regeneration of the anterior segment compared with the whole graft was associated with preoperatively dominant MHV tributaries (Spearman rank correlation: R=-0.44, P=0.01). The only significant determinant of the whole-graft regeneration, however, was GRBW (stepwise regression: Y=-0.80X+0.2, R(2)=0.70, P<0.0001). CONCLUSIONS: Despite deprivation of MHV tributaries, a graft will regenerate to meet the metabolic demand, and a smaller graft for the recipient is capable of regenerating to a greater extent.

Adolescent↗

Matrix-assisted laser desorption/ionization- quadrupole ion trap-time of flight mass spectrometry sequencing resolves structures of unidentified peptides obtained by in-gel tryptic digestion of haptoglobin derivatives from human plasma proteomes.

Two-dimensional gel electrophoresis-separated and excised haptoglobin alpha2-chain protein spots were subjected to in-gel digestion with trypsin. Previously unassigned peptide ion signals observed in mass spectrometric fingerprinting experiments were sequenced using the matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight (MALDI-QIT-TOF) mass spectrometer and showed that the haptoglobin alpha-chain derivative under study was cleaved by trypsin unspecifically. Abundant cleavages occurred C-terminal to histidine residues at H23, H28, and H87. In addition, mild acidic hydrolysis leading to cleavage after aspartic acid residues at D13 was observed. The uninterpreted tandem mass spectrometry (MS/MS) spectrum of the peptide with ion signal at 2620.19 was submitted to database search and yielded the identification of the corresponding peptide sequence comprising amino acids (aa) aa65-87 from the haptoglobin alpha-chain protein. Also, the presence of a mixture of two tryptic peptides (mass to charge ratio m/z 1708.8; aa40-54, and aa99-113, respectively), that is caused by a tiny sequence variation between the two repeats in the haptoglobin alpha2-chain protein was resolved by MS/MS fragmentation using the MALDI-QIT-TOF mass spectrometer instrument. Advantageous features such as (i) easy parent ion creation, (ii) minimal sample consumption, and (iii) real collision induced dissociation conditions, were combined successfully to determine the amino acid sequences of the previously unassigned peptides. Hence, the novel mass spectrometric sequencing method applied here has proven effective for identification of distinct molecular protein structures.

Alleles↗

An approach to quantitative proteome analysis by labeling tryptophan residues.

This report describes a method for quantification and sequence identification of individual proteins in complex mixtures. The method is based on labeling with the chemical reagent 2-nitrobenzenesulfenyl chloride (NBSCl) in conjunction with tandem mass spectrometry. In this method, selective introduction of the 2-nitrobenzenesulfenyl (NBS) moiety onto tryptophan residues is achieved, and a 6 Da mass differential is generated using (13)C(6)-labeled NBSCl (NBSCl-(13)C(6)) and (12)C(6)-labeled NBSCl (NBSCl-(12)C(6)). The 6 Da mass differential between the NBS-(12)C(6)-labeled and the NBS-(13)C(6)-labeled peptides assigns a mass signature to all tryptophan-containing peptides in any pool of proteolytic digests for protein identification through peptide mass mapping. Using this strategy, we compared the protein expression in rat sera using a normal (control) rat (Crj:Wistar) and a hyperglycemic rat (GK/Crj). The stable isotope dilution techniques used in this method provide highly accurate relative quantification. The NBS approach offers a widely applicable means of analyzing protein mixtures derived from biological samples, and the method described here presents an effective and simplified approach to proteome analysis.

Animals↗

Varicose bleeding after liver transplantation in a patient with severe portosystemic shunts.

Recipients for liver transplantation often have portosystemic shunts due to portal hypertension. It is an important problem whether such shunts should be ligated during operations. Ligating the shunts seems of benefit for increasing portal blood flow to the liver, but it is sometimes difficult technically, and it is invasive to the patient. We experienced a recipient with huge portosystemic shunts and no esophageal varices before living-related liver transplantation. Some shunts were ligated during operation to increase portal blood flow to the graft. Unfortunately, the patient suffered severe bleeding from esophagogastric varices after he underwent retransplantation owing to accidental liver failure. Based on our experience, extreme care should be exercised to avoid varicose bleeding after ligating the portosystemic shunts of liver transplantation patients.

Adult↗

Role of a novel oncogenic protein, gankyrin, in hepatocyte proliferation.

BACKGROUND: Gankyrin is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma. However, little is known about the physiological role of gankyrin in the cell-cycle progression of normal noncancerous hepatocytes at present. We investigated the possible involvement of gankyrin in hepatocyte proliferation and examined the expression of gankyrin in the liver of patients with fulminant hepatic failure (FHF). METHODS: We examined the potential cell-cycle dependence of gankyrin expression in primary hepatocytes after mitogenic stimulation. Gankyrin expression level was also measured in the liver tissue of patients with FHF, as a model of active proliferation of human hepatocytes associated with liver regeneration. RESULTS: In primary hepatocytes, gankyrin was expressed in the G1/S phase of the cell cycle at 48 h after mitogenic stimulation, which coincided with the phase of cyclin D1 RNA upregulation and RB1 protein downregulation. Using a quantitative reverse transcription polymerase chain reaction assay, we showed that gankyrin mRNA in the liver tissue of patients with FHF was expressed abundantly compared with that in healthy individuals (median, 109.7 [interquartile range; IQR, 49.0-186.4] vs median, 22.4 [IQR, 1.4-77.3] copies per sample, respectively). CONCLUSIONS: The upregulation of gankyrin correlates with cell-cycle progression in normal hepatocyte proliferation. Thus, gankyrin may play a role in cell-cycle progression in normal hepatocytes. Moreover, gankyrin may have a role in the pathophysiology of FHF.

Adolescent↗

A case of inflammatory pseudotumor of the liver hilum successfully treated with aggressive hepatectomy.

Inflammatory pseudotumor (IPT) of the liver is a rare, benign tumor. When the tumor involves the hepatic hilum, however, the clinical course of the patient becomes problematic because of obstructive jaundice and portal hypertension. Complete removal of the tumor sometimes is difficult when the hepatic hilum is extensively involved, and liver transplantation becomes necessary for such an unresectable tumor. This report concerns a 7-year-old boy who presented with obstructive jaundice and portal hypertension owing to an inflammatory pseudotumor of the hepatic hilum and was treated successfully with aggressive hepatectomy, vascular reconstructions of both the portal vein and the hepatic artery, and biliary reconstruction. The patient was discharged after 39 days of hospitalization. Eight months later, portal vein obstruction was detected and treated successfully with percutaneous transhepatic balloon dilatation of the obstructed site. The liver has continued to function well for 11 months after the tumor resection.

Bile Ducts↗

Quantitative PCR to evaluate small amounts of BCL2 mRNA in human peripheral T cells: implication of equimolar target and competitor end products.

BACKGROUND: It is difficult to reliably and reproducibly quantitate small amounts of mRNA by conventional PCR. The method we describe here enabled us to more accurately quantitate a small amount of BCL2 mRNA in human peripheral T cells. METHODS: The sample was amplified in four tubes containing three-fold serial dilutions of competitor so that when the PCR products in the four tubes were totaled, the number of target and competitor components were approximately equal. An unknown concentration of target molecules should be assessed only within a narrow range, requiring that several reactions be performed for each sample. RESULTS AND CONCLUSION: With this method, conventional PCR machines can be used to perform quantitative PCR on very small amounts of BCL2, and would be especially useful for samples that contain substance(s) that affect PCR amplification efficiency.

Adolescent↗

Five- and 10-year survival rates after surgery for biliary atresia: a report from the Japanese Biliary Atresia Registry.

PURPOSE: The aim of this study was to elucidate the epidemiology and short- and long-term results of biliary atresia in Japan analyzing the data of the Japanese Biliary Atresia Registry (JBAR). METHODS: In 1989, the Japanese Biliary Atresia Society started a nationwide registry, JBAR, to investigate all aspects of biliary atresia. A total of 1,381 patients, 863 girls, 507 boys, and 11 unknown, were registered between 1989 and 1999. JBAR includes an initial and follow-up questionnaires. Using these patients' data, the incidence, sex distribution, associated anomalies, the type of obstruction, the type of operation, and the surgical results were evaluated. The 5- and the 10-year results of 735 patients who were registered initially in or before 1994 also were analyzed. RESULTS: The incidence of biliary atresia was 1 in 9,640 live births. One hundred sixty-four patients (11.9%) had type I atresia of the common bile duct, 34 (2.5%) had type II atresia of the hepatic ducts, and 1,162 (84.1%) had type III atresia at the porta hepatis. Congenital associated anomalies were found in 19.6% of the patients including 33 cases associated with polysplenia. Impact of the age at operation on bile flow was not clear until 90 days of age, and after 90 days the bile flow rate worsened. The original Roux-en-Y procedure had been used in more than 50% of the patients since 1995. In 1999, 96% of the patients underwent the original Roux-en-Y procedure or the Roux-en-Y with an intestinal valve, and only 3 patients (3.5%) underwent other modifications. There were no significant differences in either the rate of disappearance of jaundice or the incidence of cholangitis among these 3 procedures. Of the 735 patients registered in or before 1994, 19 patients (2.6%) were lost to follow-up. The 5-year survival rates of patients registered in 1989, 1990, 1991, 1992, 1993, and 1994 were 62%, 64.5%, 61.3%, 59.0%, 58.7%, and 52.7% without liver transplantation (LTx), and 69.4%, 74.2%, 75.2%, 79.5%, 78%, and 78.3% with LTx, respectively. Although the overall 5-year survival rate changed from 69.4% to 78.3%, the difference was not statistically significant. According to the 10-year follow-up results of the 108 patients initially registered in 1989, 72 (66.7%) and 57 (52.8%) survived with and without the aid of LTx, respectively. CONCLUSIONS: The overall 5- and 10-year survival rates were 75.3% (553 of 734) and 66.7% (72 of 108), respectively. In spite of the increasing number of survivors after LTx, there was no significant improvement in the 5-year survival rate. It was shown that the JBAR system was functioning well with only 19 patients lost to follow-up among the 743 patients registered from 1989 to 1994.

Anastomosis, Roux-en-Y↗

Monosegmental living-donor liver transplantation for infantile hepatic hemangioendothelioma.

Infantile hepatic hemangioendothelioma (IHHE) is a rare vascular tumor that presents before the age of 6 months. The patients with IHHE suffer from high-output congestive heart failure caused by major arteriovenous fisutulas in the liver, which leads to respiratory compromise and results in a high mortality rate despite medical treatments. A case of 4-month-old baby with liver failure caused by IHHE is reported. The baby received an urgent liver transplantation from a living donor. A monosegmental graft was used to mitigate graft-to- recipient size mismatching. The surgical procedure of monosegmental living donor liver transplantation also is discussed.

Hemangioendothelioma↗

Circulating antibody to hepatitis B core antigen does NOT always reflect the latent hepatitis B virus infection in the liver tissue.

Accumulating evidence suggests the presence of latent hepatitis B virus (HBV) infection in the liver of individuals negative for HBV surface antigen (HBsAg) but positive for antibodies to HBV core antigen (anti-HBc) at low titer. It remains unclear, however, whether positive anti-HBc in the serum invariably reflects latent HBV infection. In this study, we examined the presence of HBV genomes in the liver tissue of 33 donors and 30 recipients of living-related liver transplantation with positive for anti-HBc together with time course changes in their anti-HBc titer. None of these anti-HBc-positive healthy donors or recipients was positive for HBV-DNA nor anti-HBc at high titer (200 dilution) in their sera. However, HBV-DNA was detected in the liver tissue of 24 of 33 healthy anti-HBc-positive donors (72.7%) and five of 30 anti-HBc-positive recipients (16.7%). Interestingly, anti-HBc was continuously positive in all healthy donors tested. In contrast, anti-HBc titers in 75% of recipients, who were positive for anti-HBc at the time of liver transplantation, gradually decreased after the operation, and finally became negative after the mean follow up period of 9.0 months (range 1.2-45.1). Notably, HBV-DNA was never detected in the liver of those recipients who were transiently positive for anti-HBc. In conclusion, our findings suggested the possibility that presence of circulating anti-HBc does not always reflect the presence of HBV genomes in the liver tissue of anti-HBc-positive patients.

Journal Article↗