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Biomedical subjects

Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 127 records · Page 7Linked to original sources
PubMed2004

Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor liver transplantation.

Operational tolerance (graft acceptance in an immunosuppression (IS)-free environment) after living-donor liver transplantation (LDLT) could occur by our elective protocol in some patients. There is, nevertheless, no reliable parameter to monitor patients who may discontinue IS without a risk of rejection. To identify such parameters, we systemically phenotyped peripheral blood mononuclear cells from operationally tolerant patients. An increase was observed in the frequency of CD4+CD25high+ cells, B cells and Vdelta1/Vdelta2 gammadeltaT-cells ratio in operationally tolerant patients (Gr-tol; n = 12), compared with those from age-matched volunteers (Gr-vol; n = 24) or patients on IS (Gr-IS; n = 19). The frequency of NK cells was decreased in Gr-tol, compared with those in Gr-IS or Gr-vol. The frequency of NKT cells was decreased after LDLT, compared with that in Gr-vol. Although the contribution of those subsets to the tolerant state remains elusive, the results may provide important clues for reliable indicators of tolerance after LDLT.

Adolescent↗
PubMed2004

Primary structure details of haptoglobin alpha chain proteins from human plasma samples are resolved by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight multiple-stage tandem mass spectrometry sequencing.

MALDI QIT ToF MS(n) analyses lead to the rapid identification of protein structural details, as readily interpretable spectra after peptide fragmentations were obtained showing ion signals with high abundance even with sample amounts in the low femtomole range. In our studies we show that the Hp alpha 1F form that contained a C-terminal arginine residue was found to be the only contributing component to spot 149. By contrast, spots 77 and 79 were found to consist of two haptoglobin forms each. Spot 77 consists of Hp alpha 1S and deamidated Hp alpha 1F, whereas spot 79 consists of Hp alpha 1F and of Hp alpha 1S that contains a C- terminal arginine residue. The use of ion traps, enabling the acquisition of MSn spectra serves as a powerful peptide sequencing method for the analysis of both, genetic differences and post-translational modification events as the main reason for the observed spot pattern in the 2-D gels of haptoglobin proteins.

Amino Acid Sequence↗
PubMed2004

Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects.

OBJECTIVE: It has been demonstrated that ghrelin plays a major role in the regulation of GH secretion and food intake. These actions make ghrelin a strong candidate for the treatment of GH deficiency, anorexia and cachexia. However, only preliminary studies have been performed to assess ghrelin administration in humans. In this study, we have conducted a double-blind, randomized, placebo-controlled trial to investigate the pharmacokinetics, safety, and endocrine and appetite effects of ghrelin in young healthy volunteers. DESIGN: Eighteen male volunteers were randomly assigned into three groups of six subjects: low- and high-dose ghrelin groups, who received intravenous injections of 1 and 5 microg/kg ghrelin (acylated form) respectively, and a placebo group who were injected with mannitol instead of ghrelin. RESULTS: Acylated ghrelin disappeared more rapidly from plasma than total ghrelin, with elimination half life (t(1/2)) of 9-13 and 27-31 min respectively. The number of subjects that experienced adverse effects did not significantly differ among the three groups, and all adverse effects were transient and well tolerated. Both the low and high doses of ghrelin strongly stimulated GH release (peak plasma concentration (C(max,0-90 min)): 124.2+/-63.9 and 153.2+/-52.2 ng/ml for 1 and 5 microg/kg ghrelin respectively). Slight alterations of blood glucose and insulin levels after the injection were observed. Although not statistically significant, ghrelin administration tended to increase hunger sensation in a dose-dependent manner. CONCLUSIONS: These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.

Adult↗
PubMed2003

Identification of a subunit of a novel Kleisin-beta/SMC complex as a potential substrate of protein phosphatase 2A.

Protein phosphatase 2A (PP2A) holoenzymes consist of a catalytic C subunit, a scaffolding A subunit, and one of several regulatory B subunits that recruit the AC dimer to substrates. PP2A is required for chromosome segregation, but PP2A's substrates in this process remain unknown. To identify PP2A substrates, we carried out a two-hybrid screen with the regulatory B/PR55 subunit. We isolated a human homolog of C. elegans HCP6, a protein distantly related to the condensin subunit hCAP-D2, and we named this homolog hHCP-6. Both C. elegans HCP-6 and condensin are required for chromosome organization and segregation. HCP-6 binding partners are unknown, whereas condensin is composed of the structural maintenance of chromosomes proteins SMC2 and SMC4 and of three non-SMC subunits. Here we show that hHCP-6 becomes phosphorylated during mitosis and that its dephosphorylation by PP2A in vitro depends on B/PR55, suggesting that hHCP-6 is a B/PR55-specific substrate of PP2A. Unlike condensin, hHCP-6 is localized in the nucleus in interphase, but similar to condensin, hHCP-6 associates with chromosomes during mitosis. hHCP-6 is part of a complex that contains SMC2, SMC4, kleisin-beta, and the previously uncharacterized HEAT repeat protein FLJ20311. hHCP-6 is therefore part of a condensin-related complex that associates with chromosomes in mitosis and may be regulated by PP2A.

Adenosine Triphosphatases↗
PubMed2003

ATP hydrolysis is required for cohesin's association with chromosomes.

BACKGROUND: A multi-subunit protein complex called cohesin is involved in holding sister chromatids together after DNA replication. Cohesin contains four core subunits: Smc1, Smc3, Scc1, and Scc3. Biochemical studies suggest that Smc1 and Smc3 each form 50 nm-long antiparallel coiled coils (arms) and bind to each other to form V-shaped heterodimers with globular ABC-like ATPases (created by the juxtaposition of N- and C-terminal domains) at their apices. These Smc "heads" are connected by Scc1, creating a tripartite proteinaceous ring. RESULTS: To investigate the role of Smc1 and Smc3's ATPase domains, we engineered smc1 and smc3 mutations predicted to abolish either ATP binding or hydrolysis. All mutations abolished Smc protein function. The binding of ATP to Smc1, but not Smc3, was essential for Scc1's association with Smc1/3 heterodimers. In contrast, mutations predicted to prevent hydrolysis of ATP bound to either head abolished cohesin's association with chromatin but not Scc1's ability to connect Smc1's head with that of Smc3. Inactivation of the Scc2/4 complex had a similar if not identical effect; namely, the production of tripartite cohesin rings that cannot associate with chromosomes. CONCLUSIONS: Cohesin complexes whose heads have been connected by Scc1 must hydrolyze ATP in order to associate stably with chromosomes. If chromosomal association is mediated by the topological entrapment of DNA inside cohesin's ring, then ATP hydrolysis may be responsible for creating a gate through which DNA can enter. We suggest that ATP hydrolysis drives the temporary disconnection of Scc1 from Smc heads that are needed for DNA entrapment and that this process is promoted by Scc2/4.

Adenosine Triphosphatases↗
PubMed2003

Cells of origin of vagal motor neurons projecting to different parts of the stomach in the rat: confocal laser scanning and electron microscopic study.

Parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) innervate the stomach by way of the gastric and hepatic branches of the vagus nerve. To investigate whether single neurons of the DMV provide collateral innervations to various parts of the stomach, we injected the retrograde tracer Fluoro-Gold (FG) into the cardia and the retrograde tracer cholera toxin subunit b (CTb) into the antrum or the pylorus of the same animal. Both retrogradely FG-labeled and CTb-labeled neurons were found throughout the DMV. Almost all CTb-labeled neurons (97%) were double-labeled with FG after injection of FG into the cardia and CTb into the antrum, while only a few CTb-labeled neurons (11%) were double-labeled with FG after injection of FG into the cardia and CTb into the pylorus. Thus, the cardia and the antrum received collateral projections, but the pylorus received projections mainly from different neurons in the DMV. These results indicate that different neurons in the DMV activate either the cardia or the pyloric sphincter muscles. We also labeled, retrogradely, the neurons projecting to the cardia and the pylorus in the DMV with cholera toxin-conjugated horseradish peroxidase (CT-HRP) to examine their ultrastructural characteristics. Although the neurons projecting to the cardia (21.6x15.0 microm, 248.0 microm2 per section) were significantly smaller than the neurons projecting to the pylorus (27.5x15.9 microm, 323.2 microm2 per section), their ultrastructural appearances were similar. Both types of neurons were small-to-medium sized, round or oval in shape, and generally had a small amount of cytoplasm containing a few Nissl bodies and a round nucleus. The average number of axosomatic terminals per section was low in the neurons projecting to the cardia (2.3) and the neurons projecting to the pylorus (3.0). Almost all axon terminals contacting these motor neurons contained round synaptic vesicles and made asymmetric synaptic contacts (Gray's type I).

Animals↗
PubMed2003

Outcomes for pediatric liver retransplantation from living donors.

BACKGROUND: The only therapeutic option for patients with a failing allograft is retransplantation. Living donor liver transplantation (LDLT) is a well-accepted therapeutic option for end-stage liver disease, but retransplantation from a living donor (Re-LDLT) has not previously been discussed. METHODS: A total of 547 LDLTs were performed in 519 children (<18 years old) at Kyoto University Hospital from June 1990 to October 2002. During the same study period, a total of 28 Re-LDLTs were performed in 27 recipients (Re-LDLT performed twice in 1 patient). Patient survival was analyzed with respect to various preoperative factors, such as functional status, pretransplantation apheresis, cause of primary graft failure, interval from primary to subsequent transplants, and laboratory values of total bilirubin and creatinine. RESULTS: Kaplan-Meier survival rate from the date of Re-LDLT to 1 year was 47.6%. Functional status, pretransplantation apheresis, interval to Re-LDLT, and bilirubin and creatinine levels all exerted an adverse impact on survival after Re-LDLT. Pathologically proven major causes of primary graft failure were chronic rejection (n=10, 35.7%), chronic cholangitis (n=6, 21.4%), and vascular complications (n=7, 25.0%). Among these causes, vascular complications displayed the strongest adverse impact on survival, compared with chronic cholangitis and chronic rejection (1-year survival was 35.7% in vascular complications; 66.7% in chronic cholangitis; and 60.0% in chronic rejection). CONCLUSIONS: Re-LDLT can save patients with a failing allograft. To achieve better results after Re-LDLT, further investigations are necessary to understand the factors leading to poor outcome after Re-LDLT.

Adolescent↗
PubMed2003

Endoscopic management of biliary strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation.

BACKGROUND: The aims of this study were to characterize the features of the biliary strictures that occur after duct-to-duct biliary reconstruction during right-lobe living-donor liver transplantation (LDLT) and to evaluate the feasibility of correcting such stricture endoscopically by inserting an "inside stent," that is, a short internal stent, above the sphincter of Oddi. METHODS: Biliary stricture occurred in 26 (35.6%) of 73 consecutive patients who underwent right-lobe LDLT with duct-to-duct biliary reconstruction from July 1999 through October 2001 and survived for more than 3 months. Of the 26 patients who had biliary stricture, 22 were referred for endoscopic retrograde cholangiography (ERC) and 4 for percutaneous cholangiography. RESULTS: ERC disclosed biliary stricture in 19 (86.4%) of the 22 patients who underwent the procedure. One patient had an unbranched stricture, 16 had a fork-shaped stricture, 1 had a trident-shaped stricture, and 1 had a stricture with more than three branches. Fourteen (73.7%) of the patients with strictures were treated endoscopically by inserting inside stents ranging from 7 F to 12 F in size, three underwent a Roux-en-Y hepaticojejunostomy to repair their stricture, and two were closely observed as outpatients. Of the 14 patients who were treated with the inside-stent, only 1 had acute cholangitis immediately after the procedure and underwent a Roux-en-Y hepaticojejunostomy. The other 13 patients who were treated with the inside stent have not required surgical repair for as long as an average of 586 days. CONCLUSION: Endoscopic placement of an inside stent is useful for treating biliary strictures in patients who have undergone right-lobe LDLT with duct-to-duct reconstruction.

Adolescent↗
PubMed2003

Operative morbidity of living liver donors in Japan.

BACKGROUND: Deaths of living liver donors have been reported in western countries, whereas the morbidity and mortality of such donors in Japan, one of the leading countries for living liver transplantation, have not been reported in detail. We aimed to review the operative morbidity and mortality of such donors in Japan. METHODS: 1853 donors of 1852 living liver transplants done in 46 liver transplant centres, and registered in the database of the Japanese Liver Transplantation Society, were assessed for eight donor-related factors of morbidity and mortality. Data for 1841 donors were analysed. FINDINGS: No perioperative mortality was recorded since inception of the liver transplantation programme in Japan from Nov 13, 1989, to April 11, 2002. 244 postoperative complications were reported in 228 (12%) donors. The frequency of complications was significantly higher in donors of the right liver lobe than in those involving the lateral segment, and left lobe graft (p<0.0001, and p<0.0001, respectively). Postoperative hospital stay was significantly longer in donors of the right lobe (mean 19.7 [SD 13.0]) than in those of the lateral segment (14.2 [7.6]), left lobe (14.0 [6.5]), and left lobe and caudate lobe (16.3 [12.1]). Re-operation related to donor hepatectomy was done in 23 donors. INTERPRETATION: By contrast with western countries, no perioperative mortality was recorded in living liver donors in Japan. However, a proportion of these donors developed serious complications. This morbidity should be reduced to maintain zero mortality in living liver donors.

Adolescent↗
PubMed2003

Living-donor liver transplantation with monosegments.

BACKGROUND: Living-donor liver transplantation is now an established technique to treat children with end-stage liver disease. Implantation of left-lateral segment grafts can be a problem in small infants because of a large-for-size graft. We report 10 cases of transplantation using monosegment grafts from living donors. METHOD: Of 506 children transplanted between June 1990 and June 2002, 10 patients (median age 196 days, median weight 5.9 kg) received monosegment living-donor liver transplants. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. RESULTS: Graft and patient survival was 80.0%. There were no differences in donor operation time and blood loss between monosegmentectomy and left-lateral segmentectomy (n=281). Monosegmental transplantation had a high incidence of vascular complications (20.0%). CONCLUSION: Monosegmental living- donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.

Adult↗
PubMed2003

A role of Helicobacter pylori infection in the development of duodenal ulcer after adult living-related liver transplantation.

Gastrointestinal bleeding caused by peptic ulcer disease is one of the serious complications of living-related liver transplantation (LRLT). The aim of this study was to clarify the factors involved in peptic ulcer formation in adult LRLT recipients. Forty consecutive adult LRLT recipients without a history of peptic ulcer disease were studied. Twenty-five patients (62.5%) tested positive for Helicobacter pylori. After LRLT, duodenal ulcer (DU) developed in six patients, and all of them tested positive for H. pylori. In contrast, none of the H. pylori-negative patients developed DU. Preoperative serum gastrin levels in patients with DU were significantly higher than in those without DU, irrespective of H. pylori infection. Preoperative pepsinogen I levels in patients with DU were significantly higher than in those without DU with H. pylori infection. These data suggest involvement of H. pylori infection in the development of DU after LRLT. Eradication of H. pylori may prevent the development of DU after LRLT particularly in patients with hypergastrinemia and high serum pepsinogen I.

Adult↗
PubMed2003

Immunohistochemical characterization of cardiac vagal preganglionic neurons in the rat.

Cardiac vagal preganglionic neurons (CVN) control cardiac activity by negative chronotropic, dromotropic and inotropic effects. We attempted to characterize the distribution and neuronal properties of the CVN by using double labeling with the retrograde tracer cholera toxin B subunit (CTb) and immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) or nitric oxide synthase (NOS). Injection of CTb into the sinoatrial ganglia resulted in many retrogradely labeled of neurons in the dorsal motor nucleus of the vagus (DMV), the compact (AmC), semicompact (AmS), loose (AmL), external (AmE) formations of the nucleus ambiguus, and the intermediate zone (IZ) between DMV and the nucleus ambiguus. Almost all CTb-labeled neurons showed ChAT immunoreactivity in the DMV, AmC, AmS, AmL and IZ, but most of the CTb-labeled neurons showed no ChAT immunoreactivity in the AmE. Most of the CTb-labeled neurons were double-labeled with CGRP immunoreactivity in the AmC, AmS and AmL, but a few double-labeled neurons were found in the DMV, IZ and AmE. A few CTb-labeled neurons were double-labeled with NOS immunoreactivity only in the DMV. No TH-immunoreactive neurons were found among the CVN. These results indicate that there are four kinds of neurons among the CVN: non-cholinergic CVN in the AmE, cholinergic and CGRP-containing CVN in the AmC, AmS and AmL, and cholinergic or cholinergic and NOS-containing CVN in the DMV.

Animals↗
PubMed2003

Background and clinical impact of tissue congestion in right-lobe living-donor liver grafts: a magnetic resonance imaging study.

BACKGROUND: Although right-lobe liver grafts from living donors have been widely accepted as an option for adult patients, impact of middle hepatic vein (MHV) deprivation is a recent controversy. METHODS: Fifty recipients of right-lobe living-donor liver grafts without MHV or drainage reconstruction in anterior segment were evaluated for posttransplant tissue congestion with T2-weighted magnetic resonance imagings. Age of recipients and donors ranged from 19 to 69 (median 50) and 19 to 64 (46) years, respectively. Graft-to-recipient weight ratio ranged from 0.74% to 1.66% (1.06%). Cavoplasty was provided during right hepatic vein reconstruction to avoid anastomotic stricture. RESULTS: Congestion was observed in 88% of segments V and 85% of segments VIII in the first month. Congestion positively correlated with anatomic dependency on MHV. Also, donors were significantly older in age in grafts with more congestion. However, congestion improved within several months in most grafts. Graft congestion was associated neither with morbidities nor with graft loss except for temporary correlation with ascites production in the third and fourth posttransplant weeks. CONCLUSION: A significant proportion of right-lobe liver grafts without MHV experience morphologic congestion of the anterior segment in the early phase after transplantation, which is dependent on venous anatomy and donor age. However, the congestion spontaneously resolves in most cases. These results suggest that reconstruction of drainage vein(s) from the anterior segment is not necessary for all grafts provided good outflow through compensatory routes is secured. Additional reconstruction may be indicated in grafts with marginal size, anatomy, and quality.

Drainage↗
PubMed2003

Surgery-related morbidity in living donors of right-lobe liver graft: lessons from the first 200 cases.

BACKGROUND: Living-donor liver transplantation (LDLT) using the left lateral segment or left-lobe graft has been widely accepted, but currently, right-lobe grafts are more commonly used in many LDLT programs with yet unknown risks for donors. METHODS: We investigated our initial 200 donors of righ-lobe grafts to focus on the incidence and variety of surgery-related morbidity. Changes in liver function tests were also analyzed to clarify the relation with donor age, steatosis of the liver, and residual liver volume (RLV). Complications were surveyed for a median period of 28.7 months. RESULTS: In all the donors, liver enzymes and bilirubin were normalized within 1 month. Enzymes on day 1 were significantly higher in donors with older age, macrovesicular steatosis, and larger RLV. Bilirubin on day 1 was significantly higher in donors with smaller RLV. Biliary enzyme was not normalized in the majority at 1 month after donation. Seventy-five complications occurred in 69 donors. Biliary complications were most common, which consisted of 26 bile leakages (13%) and 3 biliary strictures (1.5%) in 27 donors. No significant dependence of the incidence was observed either for donor age (>or=50 years), body mass index (BMI) (>or=25 kg/m2), estimated RLV (<40%), or medical history. None of the complications led either to mortality or to long-term sequelae. CONCLUSIONS: Complications occurred in a significant proportion of right-lobe donors irrespective of donor age, BMI, estimated RLV, and medical history. Living-liver donor surgery requires more care in right-lobe transplants.

Adolescent↗