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Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 109 records · Page 6Linked to original sources

Distribution and ultrastructure of dopaminergic neurons in the dorsal motor nucleus of the vagus projecting to the stomach of the rat.

Almost all parasympathetic preganglionic motor neurons contain acetylcholine, whereas quite a few motor neurons in the dorsal motor nucleus of the vagus (DMV) contain dopamine. We determined the distribution and ultrastructure of these dopaminergic neurons with double-labeling immunohistochemistry for tyrosine hydroxylase (TH) and the retrograde tracer cholera toxin subunit b (CTb) following its injection into the stomach. A few TH-immunoreactive (TH-ir) neurons were found in the rostral half of the DMV, while a moderate number of these neurons were found in the caudal half. Most of the TH-ir neurons (78.4%) were double-labeled for CTb in the half of the DMV caudal to the area postrema, but only a few TH-ir neurons (5.5%) were double-labeled in the rostral half. About 20% of gastric motor neurons showed TH-immunoreactivity in the caudal half of the DMV, but only 0.3% were TH-ir in the rostral half. In all gastric motor neurons, 8.1% were double-labeled for TH. The ultrastructure of the TH-ir neurons in the caudal DMV was determined with immuno-gold-silver labeling. The TH-ir neurons were small (20.4 x 12.4 microm), round or oval, and contained numerous mitochondria, many free ribosomes, several Golgi apparatuses, a round nucleus and a few Nissl bodies. The average number of axosomatic terminals per section was 4.0. More than half of them contained round synaptic vesicles and made asymmetric synaptic contacts (Gray's type I). Most of the axodendritic terminals contacting TH-ir dendrites were Gray's type I (90%), but a few contained pleomorphic vesicles and made symmetric synaptic contacts (Gray's type II).

Animals↗

Efficacy of anterior segment drainage reconstruction in right-lobe liver grafts from living donors.

BACKGROUND: The efficacy of additional venous reconstruction in the anterior segment has not been fully investigated for graft congestion in right-lobe liver grafts. METHODS: Posttransplant graft venous congestion in the anterior segment was evaluated using magnetic resonance imaging in right-lobe living-donor liver transplantation. Additional venous reconstruction was categorized into two types: reconstruction of tributaries from segment 5 or 8 (n=11) and reconstruction of the middle hepatic vein (MHV) (n=9). Forty-five grafts only with right-sided hepatic vein(s) including the right hepatic vein served as controls. RESULTS: No significant difference in congestion score of the anterior segment was observed between grafts with V5/8 and standard grafts 1 month after transplantation despite the patency of reconstruction. Only grafts with the MHV showed no congestion (P <0.01). CONCLUSIONS: Drainage reconstruction of tributaries from the anterior segment produces only suboptimal benefits when evaluated radiologically. The addition of the main trunk of the MHV with its surrounding communication has the best effect on the congestion of the anterior segment.

Adult↗

Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation.

BACKGROUND: Transplantation of hepatic grafts from ABO-incompatible donors is controversial because of the risk of hyperacute rejection mediated by preformed anti-ABO antibodies. The aim of the present study was to evaluate the outcome of liver transplants performed with ABO-incompatible living-donor livers and to detect risk factors for development of complications. METHODS: From June 1990 to February 2000, 66 patients, 10 months to 55 years old (median, 2 years old), received 68 ABO-incompatible living-donor liver grafts. The antibody titer and clinical course were followed prospectively during a period ranging from 3 to 11 years. RESULTS: The 5-year patient survival was 59%, 76%, and 80% for ABO-incompatible, ABO-compatible, and ABO-identical grafts, respectively (P<0.01). In patients <1 year old, > or =1 to <8, > or =8 to <16, and and > or =16 years old, 5-year survival was 76%, 68%, 53%, and 22%, respectively. The incidence of intrahepatic biliary complications and hepatic necrosis in ABO-incompatible living-related grafts (18% and 8%, respectively) was significantly (P<0.0001) greater than in ABO-compatible and ABO-identical grafts (both 0.6% and 0%, respectively). Predictive risk factors for increased mortality and morbidity were age greater than 1 year and elevated anti-ABO titers before transplantation. CONCLUSIONS: ABO-incompatible liver transplantation was carried out with relative safety in infants <1 year old but was not satisfactory in children >1 year in long-term follow-up. Patients aged >8 years remain at considerable risk of early fatal outcome because of hepatic necrosis, and new strategies to prevent antibody-mediated rejection are required.

ABO Blood-Group System↗

Periportal edema and necrosis as diagnostic histological features of early humoral rejection in ABO-incompatible liver transplantation.

Humoral rejection caused by antidonor blood group A/B antibodies is one of the most important obstacles for successful ABO-incompatible liver transplantation. However, no specific morphologic features of liver biopsies to distinguish humoral rejection from other conditions such as ischemia or sepsis have been satisfactorily documented. To histologically clarify the early changes in humoral rejection, we studied 41 cases of living donor ABO-incompatible liver transplantation whose allograft biopsies during the first episode of suspected acute rejection were available within the first postoperative month. Postoperative isohemagglutinin IgM titers were x64 or more in 21 patients (51%; high-titer group) and less than x64 in 20 cases (49%; low-titer group). In the high-titer group, elevation of postoperative titers x64 or more occurred within postoperative days 5.7 +/- 4.1 (range: 1-17). An increase in the incidence of cholangitis was observed in the high-titer group (90% vs. 30%, P <.0001), as well as poorer overall graft survival than in the low-titer group (38% vs. 70%, P <.05). Seven biopsies obtained from the high-titer group within 3 days after the onset of elevation of the antibody titers and one biopsy obtained at the peak of the antibody titers demonstrated periportal edema and necrosis, neither of which was found in the low-titer group. All grafts of these patients caused massive hepatocyte necrosis or severe biliary complications. In conclusion, a high morbidity rate of ABO-incompatible liver transplantation is associated with high postoperative levels of antibody titers. Periportal edema and necrosis observed during elevation of antibody titers can be regarded as histological indications of early changes in severe humoral rejection.

ABO Blood-Group System↗

Arteriopathy in chronic allograft rejection in liver transplantation.

Chronic rejection is an important cause of liver allograft failures. The allograft undergoing chronic rejection shows affected large- and medium-sized muscular arteries with homing of foamy macrophages and enlargement of the intimal area. The objective of this study was to elucidate the pathogenesis of the intimal lesion that causes obliterative arteriopathy by identifying the origin of the foamy macrophages and mesenchymal cells present in the intimal area. Nine allografted livers (6 male and 3 female patients) from sex-mismatched donors undergoing chronic rejection were studied by combined staining of the macrophages or the mesenchymal cells in the intimal area with immunohistochemistry and in situ hybridization using a probe for the human Y chromosome. By using the specimens from female donor allografts transplanted to male recipients, it was found that 62 +/- 11% of CD68+ foamy macrophages and 71 +/- 4% of smooth muscle actin-positive mesenchymal cells in the intimal lesions and a few interstitial myofibroblasts were positive for the Y chromosome probe. This indicated that they were derived from the recipients. In conclusion, the thickening intimal lesion seen in obliterative vasculopathy in liver allografts consists of the foamy macrophages and mesenchymal cells of recipient origin. These circulating recipient cells migrated to the areas in advance of remodeling arteries.

Adolescent↗

End-to-side portocaval shunting for a small-for-size graft in living donor liver transplantation.

In the development of adult-to-adult living donor liver transplantation (LDLT), the small-for-size graft has been associated with poor clinical outcome. Persistent portal hypertension or portal venous overperfusion are considered to be causative factors, and partial diversion of portal flow to systemic circulation may be effective for avoiding injuries that occur in the small-for-size (SFS) graft. Recently, we constructed an end-to-side portocaval shunting using 1 of the portal branches and anastomosed the other branch with the portal vein of the graft in 2 cases of LDLT recipients transplanted with a SFS graft. With the suppression of portal hypertension, as well as sufficient portal flow to the graft, the recipients recovered successfully with favorable graft function. This new and simple technique may be able to be used as a feasible and effective method to attenuate the SFS syndrome.

Adolescent↗

Enhanced responses in matrix-assisted laser desorption/ionization mass spectrometry of peptides derivatized with arginine via a C-terminal oxazolone.

We have developed a novel method for enhancing the response of a peptide in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) by activating the C-terminal carboxyl group through an oxazolone with which is coupled an amine containing a functional group to help ionize the peptide. The reactions consist of dehydration with acetic anhydride to give an oxazolone, followed by aminolysis with an appropriate amino acid derivative such as arginine methyl ester. The MALDI signal of Ac-Tyr-Gly-Gly-Phe-Leu-Arg-OMe, thus converted from leucine-enkephalin, was detected while completely excluding the responses of arginine-deficient peptides coexisting in the reaction mixture. Some less intense peaks corresponding to a few sequential degradation products, also terminated with the arginine derivative, were also observed. The side-chain groups potentially that are reactive were conveniently protected by acetylation simultaneous with the C-terminal activation, and those that remained unprotected were reduced to virtually negligible proportions when the reaction was conducted in a peptide solution of concentration less than 1 mM. The greatly increased responses of such arginine-terminated peptides could possibly be exploited to discern the C-terminal tryptic peptide of a protein that is otherwise almost insensitive to MALDI-MS in general. The simplicity of the post-source decay spectrum of enkephalin derivatized by arginine methyl ester characteristically accentuated z- and b-type ions, and this should facilitate sequencing of such derivatized peptides. Remaining problems with practical applications of this approach are discussed.

Amino Acid Sequence↗

Subcapsular hematoma after right-lobe living-donor liver transplantation.

Because right-lobe living-donor liver transplantation was introduced in adult-to-adult liver transplantation to mitigate the problems of small-for-size grafts, some technical controversies have been reported. This report describes a case of graft subcapsular hematoma due to parenchymal injury. A 53-year-old woman underwent a right-lobe living-donor liver transplantation for acute-on-chronic liver failure due to primary biliary cirrhosis. A huge subcapsular hematoma was discovered by routine Doppler echogram examination on the first posttransplantation day. Relaparotomy findings revealed that rotation of the graft for the hemostasis procedure during the transplant operation had induced a compression injury to the graft by the xiphoid process. It was speculated that a small laceration in the graft parenchyma led to the major subcapsular hematoma. This experience suggests that the graft liver must be handled with special care to prevent potential mechanical injury.

Echocardiography, Doppler↗

Successful surgical ligation under intraoperative portal vein pressure monitoring of a large portosystemic shunt presenting as an intrapulmonary shunt: report of a case.

We report a rare case of patent ductus venosus (PDV) with collapsed intrahepatic portal branches and an intrapulmonary shunt. Excellent improvement of the intrahepatic portal vein flow was achieved by ligating the large ductus venosus under intraoperative portal vein pressure (PVP) monitoring. A 3-year-old boy being followed up for hypergalactosemia at a local hospital was found to have mild lip cyanosis, exertional dyspnea, clubbed fingers, and mild liver dysfunction with high levels of transaminase and ammonia. Cardiac catheterization indicated an intrapulmonary shunt with a ratio of 33%. Abdominal ultrasonography and computed tomography showed remarkable communication between the portal vein and the inferior vena cava. We performed laparotomy and successfully ligated the PDV under PVP monitoring. The PVP did not increase until the catheter was removed 7 days postoperatively. The patient's liver function test results returned to normal within 2 weeks. His serum galactose level was 0 mg/dl after drinking milk, and his SpO2 in room air and exertional dyspnea also improved. He was discharged 18 days after his operation, without any complications. We propose that ligation of a PDV under PVP monitoring could be a treatment of choice, bearing in mind that PDV is associated with collapsed intrahepatic portal branches.

Abnormalities, Multiple↗

Delayed bronchial stenosis after blunt chest trauma with right aortic arch.

We report a case of delayed bronchial stenosis after blunt chest trauma with right aortic arch. A 21-year-old male passenger was involved in a traffic accident. He was brought to an emergency hospital with severe chest pain and dyspnea, and diagnosed with multiple rib fractures, right hemopneumothorax and chylothorax. He was treated with chest tube drainage and the symptoms subsided. About 9 weeks later, he complained of exertional dyspnea and was referred to our hospital. Bronchoscopy demonstrated circumferential stenosis of the right main bronchus approximately 1 cm distal to the carina. Thoracic computed tomography and magnetic resonance imaging revealed the right aortic arch. Successful resection of the bronchial stenotic lesion was performed followed by end-to-end anastomosis through midsternotomy due to the associated right aortic arch. Postoperative bronchoscopy revealed that the site of the anastomosis was patent and his symptoms were relieved.

Adult↗

Tacrolimus therapy according to mucosal MDR1 levels in small-bowel transplant recipients.

To clarify the clinical applicability of intestinal absorptive barriers, we have quantified messenger ribonucleic acid (mRNA) expression levels of multidrug resistance 1 (MDR1) protein and cytochrome P450 (CYP) 3A4 in intestinal biopsy specimens from 2 small-bowel transplant recipients. Postoperative immunosuppressive therapy was started with intravenous and oral administrations of tacrolimus and a small amount of steroids. The daily dosage of tacrolimus was modified mainly on the basis of trough levels. After confirmation that the enterocyte MDR1 level was decreasing, tacrolimus was administered via the oral route only. The mRNA levels in the biopsy specimens varied widely throughout the period. With high-dose steroid-pulse treatment, the enterocyte mRNA expression of CYP3A4, but not of MDR1, was markedly enhanced. The mRNA levels of MDR1, but not CYP3A4, correlated well with the concentration/oral dose ratio and the oral dosage of tacrolimus. The good progress after transplantation in both cases suggested that monitoring the change in expression of MDR1 mRNA in the graft intestine might be helpful for understanding the pharmacokinetic profile and determining when to change the route of tacrolimus administration in small-bowel transplant recipients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease.

Auxilliary partial orthotopic liver transplantation (APOLT) was introduced initially as a tentative or permanent support for patients with potentially reversible fulminant hepatic failure and has extended its indication to congenital metabolic disorder of the liver that has otherwise normal functional integrity. Postoperative management of APOLT is complicated because of functional portal flow competition between the native and graft liver. The native portal vein diversion to the graft is sometimes indicated to prevent functional competition; however, it is still an open question whether this technique can be theoretically indicated for APOLT patients. The authors report a on patient with ornithine transcarbamylase deficiency who received APOLT from a living donor without native portal vein diversion. Because of functional portal vein competition between the native and graft liver, the patient had to have portal vein diversion, portal vein embolization, and finally native hepatectomy to induce the graft regeneration after APOLT. After the experience of the current case, primary portal vein diversion for APOLT with noncirrhotic metabolic liver disease patients to prevent functional portal flow competition is recommended.

Anastomosis, Surgical↗

Living related liver donor transplantation: techniques and caution.

LDLT is often performed under less than ideal circumstances, such as limited graft mass, aberrant vascular and biliary anatomy, limited sources of venous grafts, and a recipient in a state of deterioration. The margin for error is small in both recipients and donors. Every step of the surgery needs to be planned and performed in a meticulous and synchronized manner. Small errors or absences of coordination can lead to unexpected complications. In addition, use of a segmental graft requires the knowledge of the safety margin of hepatic adaptation to nonphysiologic situations for the safety of both recipient and donor. Scientific and clinical evidences for precise individualization of the tactics are still not sufficient. Further accumulation of knowledge and experience is awaited for the safest performance of this evolving surgery.

Anastomosis, Surgical↗

CYP3A5*1-carrying graft liver reduces the concentration/oral dose ratio of tacrolimus in recipients of living-donor liver transplantation.

OBJECTIVES: Tacrolimus is widely used for immunosuppressive therapy after organ transplantation, but its pharmacokinetics shows such great interindividual variation that control of its blood concentration is difficult. We have previously reported that an intestinal P-glycoprotein (MDR1) contributes to this variation as an absorptive barrier, but the role of hepatic metabolism is not clear. METHODS: In this study, we have evaluated the genotypes of MDR1 and cytochrome P450 (CYP) 3A in donor and recipient, and the influence of polymorphisms on mRNA expression and the tacrolimus concentration/dose (C/D) ratio in recipients of living-donor liver transplantation (LDLT). RESULTS: The expression level of MDR1 and tacrolimus C/D ratio were not affected by either MDR1 C3435T or G2677T/A. The CYP3A4*1B genotype was not detected, but the CYP3A5*3 genotype had an allelic frequency of 76.3%. The mRNA level of CYP3A5 was significantly reduced by the *3/*3 genotype, and the tacrolimus C/D ratio was decreased in recipients engrafted with partial liver carrying CYP3A5*1/*1 genotype. An analysis of the combination of intestinal MDR1 level and liver CYP3A5 genotype revealed that the tacrolimus C/D ratio was lower in the group with higher MDR1 levels regardless of CYP3A5 genotype during postoperative week 1. CONCLUSIONS: These results indicate that in recipients of LDLT, the pharmacokinetics of tacrolimus is influenced by flux via P-glycoprotein in the intestine during the first week; after that, it is mostly the hepatic metabolism that contributes to the excretion of tacrolimus, and carriers of the CYP3A5*1/*1 genotype require a high dose of tacrolimus to achieve the target concentration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Early graft failure due to a veno-occlusive disease after a pediatric living donor liver transplantation.

A 10-month-old boy with biliary atresia after Kasai procedure underwent a living donor liver transplantation (LDLT). Five days after the LDLT, high fever and increased ascites followed by poor bile drainage was accompanied by elevation of serum liver enzymes. Liver biopsy showed occlusion of the central veins by fibro-edematous endothelium and submassive necrosis of the parenchyma. Veno-occlusive disease (VOD) was suspected, and re-LDLT was urgently performed because of deterioration of hepatic failure. There are few cases of VOD after liver transplantation and this is the first one in an infant after LDLT.

Graft Occlusion, Vascular↗

The role of apheresis therapy in living donor liver transplantation.

Liver transplantation is a radical therapy for end-stage liver disease. The severe shortage of transplantable organs is, however, a big problem, not only in liver transplantation but also other organ transplants. Although in Japan, transplantation of organs obtained from brain-dead donors (BDD) has been allowed since October 1997, to date only 27 BDD have been obtained. It has become difficult to procure liver grafts from BDD, therefore we must use liver grafts from living donors. The living-donor liver transplantation (LDLT) program started in 1990 in Japan, and is still the major form of liver transplantation because of the scarcity of cadaveric donors. In the Department of Transplant Surgery, Kyoto Hospital (Kyoto, Japan), the accumulated number of LDLT cases exceeded 955 up to October 2003. In order to perform LDLT under safer conditions, apheresis plays a major role in Japan due to the prevalence of LDLT where later retransplantation is difficult. Clinical indications of apheresis for LDLT are mainly use as a bridge before transplantation, and liver support after transplantation. We describe the effect of apheresis therapy for LDLT patients with nephritic and hepatic problems.

Blood Component Removal↗