Search PubMed⌕ Search

Biomedical subjects

Koichi Tanaka

Publications and source records attributed to Koichi Tanaka.

At least 55 records · Page 3Linked to original sources

Current role of liver transplantation for methylmalonic acidemia: a review of the literature.

To evaluate the current role of liver transplantation (LT) for methylmalonic acidemia (MMA), we reviewed the literature on outcomes of this treatment, and describe three of our own cases of living-donor liver transplantation (LDLT). The total number of LT cases identified was 18. Transplantation mode was deceased donor LT in 12, including five combined liver-kidney transplantations (CLKT) from deceased donors, and LDLT in six. Three hospital mortalities were noted, because of metabolic decompensation, sepsis and aspergillosis. Although mean postoperative serum MMA level decreased to 13.8% +/- 9.2% (range 1.25-26.1%) of preoperative levels, four patients (22.2%) had renal insufficiency after isolated LT and three (16.7%) had postoperative neurological disability. Continuing metabolic damage to the kidney and brain may occur even after successful LT. Further evaluation is required to determine the long-term suitability of this treatment modality.

Adolescent↗

Outcome of percutaneous transhepatic venoplasty for hepatic venous outflow obstruction after living donor liver transplantation.

PURPOSE: To evaluate retrospectively the outcome of percutaneous transhepatic venoplasty of hepatic venous outflow obstruction after living donor liver transplantation (LDLT). MATERIALS AND METHODS: The institutional Human Subjects Research Review Board approved the interventional protocol and the retrospective study, for which informed consent was not required. Before treatment, informed consent was obtained from the patient or the patient's parents in all cases. Of 26 consecutive patients (nine male, 17 female; median age, 9 years) suspected of having hepatic venous outflow obstruction after LDLT, 20 patients confirmed to have anastomotic outflow stenosis at percutaneous hepatic venography and manometry underwent venoplasty. Pressure gradients before and after venoplasty were evaluated by using a paired t test. Patients in whom obstruction recurred during follow-up were re-treated with venoplasty with or without expandable metallic stents. Patency was analyzed by using Kaplan-Meier analysis. RESULTS: The initial balloon venoplasty was technically successful in all 20 patients, all of whom had improved clinical findings. The pressure gradient +/- standard deviation was reduced from 14.6 mg Hg +/- 8.6 to 2.2 mg Hg +/- 2.4 (P < .001). Eleven patients had recurrent obstruction and were treated with balloon venoplasty; one of them underwent stent placement, as well as venoplasty. The primary (event-free) patency and 95% confidence interval (CI) at 3, 12, and 60 months after venoplasty were 0.80 (95% CI: 0.62, 0.98), 0.60 (95% CI: 0.38, 0.81), and 0.60 (95% CI: 0.38, 0.81), respectively. The primary assisted patency, maintained with repeated venoplasty and expandable metallic stents, was 1.00 at 60 months. CONCLUSION: Percutaneous venoplasty is an effective treatment for hepatic venous outflow obstruction after LDLT.

Adult↗

Living donor islet transplantation, the alternative approach to overcome the obstacles limiting transplant.

We performed the world's first successful living donor islet transplantation for unstable diabetes. A total of 408,114 islet equivalents were isolated from half a living pancreas and transplanted immediately to the recipient who was a 27-year-old female. The donor was a 56-year-old female in good health, mother of the recipient. The islets functioned immediately, and the recipient was weaned completely from insulin on the 22nd posttransplant day, and has maintained excellent glycemic control since. The donor was discharged on the 18th postoperative day with normal oral glucose tolerance test and without complications. Living donor islet transplantation could cure one insulin-dependent diabetes mellitus patients with a single donor. There are some advantages in the living donor islet transplantation: (a) living donor can alleviate the issue of donor shortage; (b) highly potent islets can be isolated from a living donor; and (c) the recipient can be treated with immunosuppressant and controlled blood glucose level tightly prior to the transplantation. These are important factors in overcoming the obstacles limiting islet transplantation. We believe that the living donor islet transplantation may become an additional option in treating insulin-dependent diabetes.

Adult↗

Immunosuppression for islet transplantation.

The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen is a significant breakthrough that allows the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year; however, the rate is reduced to 50% at 3 years, attributed to prolonged tacrolimus exposure. Recently, immunosuppression agents such as cyclosporine, mycophenolate mofetil, and the novel agent FTY 720 have been used instead of tacrolimus. Lymphocyte-depleting antibodies such as anti-thymocyte globulin, alemtuzumab, and hOKT3gamma 1 (ala, ala) have been launched, and a costimulatory blockade of anti-CD40 monoclonal antibodies and CTLA4-Ig will be attempted in the near future. Moreover, the potential of a novel immunosuppressing peptide could now be realized using new technology called the protein transduction system. In this review, we show some of the most recent contributions to the advancement of knowledge in this field.

Animals↗

[Usefulness of ultrasonically activated scalpel for pulmonary resection in video-assisted thoracoscopic surgery].

We evaluated the reliability and efficacy of the ultrasonically activated scalpel (Harmonic Scalpel) for pulmonary resection in video-assisted thoracoscopic surgery (VATS). Fifty-six cases of primary or metastatic lung cancer with history of lobectomy or segmentectomy from July 2003 to June 2006 were investigated. The ultrasonically activated scalpel was used to separate aborted lobulation and segment in the surgery. The outcome of the operation using the ultrasonically activated scalpel revealed the mean operation time of 224.5 minutes and mean blood loss volume of 116.7 ml. The chest drainage catheter was removed at the postoperative day 3.4 and hospitalization lasted 10.4 days on average. By means of statistical analysis, no significant differences were noted when compared with the cases using surgical stapler to separate the lobules or segments of the lungs. Histopathological results showed destruction of alveolar structures and denaturation of cells at the cut surface of the resected lung through the use of the ultrasonically activated scalpel. This method resulted in good lung expansion and preservation of the residual lung volume. Furthermore, it prevented postoperative air leakage by appropriate treatment to the cut surfaces of the residual lung. Indeed, the method appears to be useful in the separation of lung tissues in severe aborted lobulation and segmentectomy by VATS.

Aged↗

Fine structural survey of the intermediate subnucleus of the nucleus tractus solitarii and its glossopharyngeal afferent terminals.

The intermediate subnucleus of the nucleus tractus solitarii (imNTS) receives somatosensory inputs from the soft palate and pharynx, and projects onto the nucleus ambiguus, thus serving as a relay nucleus for swallowing. The ultrastructure and synaptology of the rat imNTS, and its glossopharyngeal afferent terminals, have been examined with cholera toxin-conjugated horseradish peroxidase (CT-HRP) as an anterograde tracer. The imNTS contained oval or ellipsoid-shaped, small to medium-sized neurons (18.2 x 11.4 microm) with little cytoplasm, few cell organelles and an irregularly shaped nucleus. The cytoplasm often contained one or two nucleolus-like stigmoid bodies. The average number of axosomatic terminals was 1.8 per profile. About 83% of them contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), while about 17% contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). The neuropil contained small or large axodendritic terminals, and about 92% of them were Gray's type I. When CT-HRP was injected into the nodose ganglion, many labeled terminals were found in the imNTS. All anterogradely labeled terminals contacted dendrites but not somata. The labeled terminals were usually large (2.69+/-0.09 mum) and exclusively of Gray's type I. They often contacted more than two dendrites, were covered with glial processes, and formed synaptic glomeruli. A small unlabeled terminal occasionally made an asymmetric synaptic contact with a large labeled terminal. The large glossopharyngeal afferent terminals and the neurons containing stigmoid bodies characterized the imNTS neurons that received pharyngeal afferents.

Afferent Pathways↗

Projections to the alimentary canal from the dopaminergic neurons in the dorsal motor nucleus of the vagus of the rat.

The motility of the alimentary canal is regulated not only by neurons that contain acetylcholine or adrenaline, but also by nonadrenergic noncholinergic neurons. There are many neurons containing dopamine in the dorsal motor nucleus of the vagus (DMV). We examined the projections of these dopaminergic neurons to the alimentary canal with double-labeling immunohistochemistry for tyrosine hydroxylase (TH) and the retrograde tracer cholera toxin subunit b following its injection into the subdiaphragmatic esophagus, the cardia, the pylorus, the duodenum, the jejunum, and the ascending colon. Almost all double-labeled neurons were found in the half of the DMV caudal to the area postrema. In the caudal half of the DMV, about 58% of the TH-immunoreactive neurons projected to the cardia, about 36% projected to the pylorus, and about 28% projected to the subdiaphragmatic esophagus. Only a few TH-immunoreactive neurons projected to the duodenum, the jejunum, or the ascending colon. As a whole, less than 10% of the neurons in the DMV that projected to the alimentary canal showed TH-like immunoreactivity. These results suggest that some of the dopaminergic neurons in the DMV might regulate the activities of the stomach and the subdiaphragmatic esophagus.

Animals↗

Living donor liver transplantation for noncirrhotic inheritable metabolic liver diseases: impact of the use of heterozygous donors.

BACKGROUND: In living donor liver transplantation (LDLT), the liver donor is almost always a blood relative; therefore, the donor is sometimes a heterozygous carrier of inheritable diseases. The use of such carriers as donors has not been validated. The aim of the present study was to evaluate the outcome of LDLT for noncirrhotic inheritable metabolic liver disease (NCIMLD) to clarify the effects of using a heterozygous carrier as a donor. METHODS: Between June 1990 and December 2003, 21 patients with NCIMLD underwent LDLT at our institution. The indications for LDLT included type II citrullinemia (n = 7), ornithine transcarbamylase deficiency (n = 6), propionic acidemia (n = 3), Crigler-Najjar syndrome type I (n = 2), methylmalonic acidemia (n = 2), and familial amyloid polyneuropathy (n = 1). Of these 21 recipients, six underwent auxiliary partial orthotopic liver transplantation. RESULTS: The cumulative survival rate of the recipients was 85.7% at both 1 and 5 years after operation. All surviving recipients are currently doing well without sequelae of the original diseases, including neurological impairments or physical growth retardation. Twelve of the 21 donors were considered to be heterozygous carriers based on the modes of inheritance of the recipients' diseases and preoperative donor medical examinations. All donors were uneventfully discharged from the hospital and have been doing well since discharge. No mortality or morbidity related to the use of heterozygous donors was observed in donors or recipients. CONCLUSIONS: Our results suggest that the use of heterozygous donors in LDLT for NCIMLD has no negative impact on either donors or recipients, although some issues remain unsolved and should be evaluated in further studies.

Acidosis↗

Derivatization for stabilizing sialic acids in MALDI-MS.

While matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is useful in oligosaccharide analysis, the sialic acid, or N-acetylneuraminic acid (NANA), moiety of an oligosaccharide is liable to dissociation in- or postsource during mass measurement. In this study, we tried to stabilize the moiety by amidation, as in the case of peptides (Sekiya, S.; Wada, Y. Tanaka, K. Anal. Chem. 2004, 76, 5894-5902), and found 4-(4,6-dimethoxy-1,3,5-triazin-2yl)-4-methylmorpholinium chloride to be a desirable condensing agent. Amidation stabilized the glycosidic bond with NANA and suppressed its preferential cleavage by in-source decay, postsource decay, or collision-induced dissociation. In addition, the suppressed dissociation considerably improved the yield of the B/Y type ions for structural analysis by MS/MS. These results demonstrate that amidation is an effective derivatization to reinforce the structural analysis of sialylated oligosaccharides by MALDI-MS. In addition, amidation with (15)N-labeled ammonium chloride decreases the mass shift from the acid to amide form to just 0.013, reducing the complexity of mass spectral interpretation and database searching.

Amination↗

Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.

Rejection remains a major barrier to successful bowel transplantation, in spite of improved immunosuppressive techniques. Therefore, new, more effective, immunosuppressants, with fewer side effects, are needed. Biodegradable microspheres containing tacrolimus (FK506) were used in an experimental porcine small bowel transplantation. Twenty pigs underwent transplantation and were divided into four groups according to the immunosuppressive regimen. Group A (n = 5): no immunosuppression; group B (n = 6): 0.2 mg/kg per day of FK506; group C (n = 3): 1.0 mg/kg per day of FK506; group D (n = 6): 0.04 mg/kg per day of FK506 contained in biodegradable microspheres. Rejection was diagnosed macroscopically by endoscopic examination and histologically by biopsy specimen analysis. The mean survival time and standard deviation (SD) were 8.8+/-3.5, 11.0+/-1.4, 9.7+/-2.5 and 28.6+/-22.5 days for groups A, B, C, and D, respectively, with a statistically significant difference found between group D, on the one hand, and groups A, B and C, on the other. The mean trough blood concentration of FK506 was 10.5+/-2.2, 27.9+/-6.0 and 10.5+/-3.5 ng/ml in groups B, C and D, respectively. In groups A and B, all pigs died of rejection, without infection. In group C, all died of infection, without rejection. In contrast, none of the pigs in group D developed rejection or infection. Our results clearly show that the drug delivery system using biodegradable microspheres that contain FK506 is effective for controlling rejection with fewer side effects in the porcine small bowel transplantation.

Animals↗

Percutaneous transhepatic balloon dilation of portal venous stenosis in patients with living donor liver transplantation.

PURPOSE: To retrospectively evaluate the long-term effectiveness of percutaneous transhepatic balloon dilation of portal venous stenosis in patients who have undergone living donor liver transplantation. MATERIALS AND METHODS: Institutional review board approval and informed consent were not required. From June 1996 to August 2003, obstructed portal venous blood flow was diagnosed in 45 patients (21 male, 24 female) with a history of living donor liver transplantation; patients ranged in age from 9 months to 61 years (mean, 9.2 years). All stenoses occurred in the extrahepatic portal vein near the anastomosis of the portal vein. All dilation procedures were performed with percutaneous transhepatic puncture of the intrahepatic portal vein and subsequent balloon dilation of the stenosis. Patients who experienced recurrent stenosis underwent another balloon dilation session. Intravascular metallic stents were not deployed because of the possible need for repeated transplantation. The authors used paired t tests to compare patients successfully treated with one venoplasty procedure and those requiring repeated venoplasty, with regard to age and stenosis diameter percentages before and after the initial procedure. RESULTS: Percutaneous balloon dilation was technically successful in 35 of 45 patients. In the remaining 10 patients, portal venous thrombotic occlusion precluded access to the mesenteric side of the portal vein. Twenty-five patients were successfully treated with a single session of balloon dilation (group 1). Results at follow-up ultrasonography revealed restenosis in 10 of 35 patients. Recurrent stenosis was resolved by means of repeated balloon dilation in nine patients (group 2). There were no significant differences between groups 1 and 2 in age (P = .87) or in stenosis diameter percentages before (P = .053) or after (P = .95) the initial procedure. CONCLUSION: Percutaneous transhepatic balloon dilation seems to be an effective method for treatment of portal venous stenosis after living donor liver transplantation.

Adolescent↗

Hepatitis B virus infection in lymphatic tissues in inactive hepatitis B carriers.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originating from the viral particles present in the serum. METHODS: We assessed HBV genome, replicative forms, and viral integrants in the liver, serum, peripheral blood mononuclear cells (PBMC), and lymph nodes of 21 inactive HBV carriers who tested positive for antibodies against the HBV core antigen (anti-HBc). RESULTS: Of the 21 anti-HBc positive individuals, HBV-DNA was detected in liver samples of 15 (71.4%), in the lymph nodes of 11 (52.4%), and in PBMC of three (14.3%). However, none of the detected HBV genomes from lymphatic tissues included the replicative forms of HBV. In one case, integrated HBV was present in the lymphatic tissues and the host-viral junction was present in the intronic sequences of chromosome 17. CONCLUSIONS: These data suggest that human lymphatic tissues cannot support viral replication in anti-HBc positive inactive HBV carriers, while retaining the viral genome as an integrated form.

Adult↗

Multicentric reticulohistiocytosis associated with rheumatoid arthritis.

Due to the fact that both multicentric reticulohistiocytosis (MRH) and rheumatoid arthritis (RA) are destructive arthritic and skin disorders, it is often difficult to differentiate one from the other. Here, we report the case of a 67-year-old Japanese woman who had been diagnosed as suffering from RA 20 years ago, and who developed MRH. MRH may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis.

Aged↗

Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain.

We investigated some neurochemical changes that take place in the spinal cord dorsal horn in a mouse model of neuropathic cancer pain. The model was produced by inoculation of Meth-A sarcoma cells to the vicinity of the sciatic nerve, which resulted in growth of a tumor mass embedding the nerve. Hind paw-lifting, a behavioral sign of spontaneous pain, was at maximum on Day 18, but decreased thereafter. The decrease was likely caused by progression of motor paralysis. On Day 18, thermal and mechanical pain thresholds of the affected paw were significantly increased. Histologically, the sciatic nerve presented damages to both unmyelinated and myelinated fibers on Day 18, which were more pronounced on Day 25. In the spinal cord, c-Fos-positive cells were significantly increased in the superficial and deep layers on Day 18. The number of c-Fos-positive cells in the superficial layer correlated with the duration of paw-lifting. The increase in c-Fos-positive cells was still present on Day 25 despite decreased paw-lifting. Substance P and calcitonin gene-related peptide were up-regulated on Day 18 but down-regulated on Day 25. A marked up-regulation of dynorphin A (DynA) was present on Day 18 and persisted through Day 25. Our model caused progressive damage to the sciatic nerve and presented spontaneous pain-behavior while the paw became hyposensitive to mechanical and thermal stimuli. Since the up-regulation of DynA in the dorsal horn persisted and paralleled the increase in c-Fos-positive cells, the release of DynA may be associated with spontaneous pain in our model.

Animals↗