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Biomedical subjects

M Ueda

Publications and source records attributed to M Ueda.

At least 37 records · Page 2Linked to original sources

Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.

Clearance of hepatitis B surface antigen (HBsAg) by lamivudine is achieved in only a small proportion of patients with chronic hepatitis B virus (HBV) infection. We investigated the effect of lamivudine on de novo HBV reactivation after living-donor liver transplantation when the number of HBV was expected to be very small. Thirty-eight HBV-naive recipients who received liver grafts from antibodies to core antigen-positive donors receiving hepatitis B immunoglobulin (HBIG) were studied. HBsAg appeared in nine cases (23.7 %) despite receiving HBIG for 12-71 months (mean: 35.1 months) after transplantation. Lamivudine treatment was started in six recipients during the acute phase of HBV reactivation. Five of the six recipients achieved complete clearance of HBsAg in sera at a median of 4.6 months (ranging from 21 to 330 days) after lamivudine administration. Although lamivudine was stopped in four cases, all remained negative for HBsAg. Our findings suggested that short-term lamivudine treatment during acute phase of HBV reactivation could achieve complete clearance of HBsAg in a significant number of liver transplant recipients.

Adolescent↗

A novel culture system for porcine odontogenic epithelial cells using a feeder layer.

The growth of cells in vitro can provide useful models for investigating their behaviour and improving our understanding of their function in vivo. Although the developmental regulation of enamel matrix formation has been comprehensively analysed, the detailed cellular characteristics of ameloblasts remain unclear because of the lack of a system of long-term in vitro culture. Therefore, the establishment of odontogenic epithelial cell lines has taken on a new significance. Here, we report on a novel porcine odontogenic epithelial cell-culture system, which has permitted serial culture of these cells. Epithelial cells were harvested from third molar tooth buds in the fresh mandibles of 6-month-old pigs, and seeded on dishes in D-MEM containing 10% FBS. Before the cells reached confluence, the medium was changed to LHC-9 to select the epithelial cells. When trypsinized epithelial cells were plated together with 3T3-J2 cells as a feeder layer, the epithelial cells grew from single cells into colonies. The colonies then expanded and became confluent, and could be sub-cultured for up to 20 passages. The long-term culture cells expressed mRNA for amelogenin and ameloblastin, as well as enamelysin (MMP-20), which is a tissue-specific gene product unique to ameloblasts. These results show that the system is capable of sustaining the multiplication of odontogenic epithelial cells with the characteristics of ameloblasts.

3T3 Cells↗

Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis.

OBJECTIVE: To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C). METHODS: The authors analyzed eight FAP ATTR Y114C patients. Six patients showed CNS symptoms associated with leptomeningeal amyloidosis. To examine the function of the blood-CSF barrier and blood-brain barrier (BBB), the authors performed CSF and MRI studies. The authors also performed a histopathologic study of autopsy specimens to examine the distribution of amyloid deposition in the CNS. RESULTS: CSF study showed high total protein concentrations and increased albumin CSF/serum concentration quotients (Qalb; an indication of blood-CSF barrier function). MRI with gadolinium (Gd) revealed enhancement from brainstem to spinal cord. Serial brain MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space (two patients). These findings suggested the blood-CSF barrier and BBB dysfunctions. Constructive interference in steady state (CISS) three-dimensional Fourier transformation (CISS-3DFT) sequence analysis demonstrated amyloid-induced funiculus structures joining the spinal cord and dura mater (one patient). Histopathologic study revealed intense amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. These distributions of amyloid deposition are unique compared to other TTR related leptomeningeal amyloidosis. CONCLUSIONS: Patients with familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C had CNS disorders related to amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition.

Adult↗

Chronic toxicity and carcinogenicity of dietary administered ammonium sulfate in F344 rats.

Chronic toxicity and carcinogenicity studies of ammonium sulfate, used as a food additive in fermentation, were performed in male and female Fisher 344 rats at dietary concentrations of 0%, 0.1%, 0.6% and 3.0% in a 52-week toxicity study and 0%, 1.5% and 3.0% in a 104-week carcinogenicity study. Treatment with ammonium sulfate caused significant increase in kidney and/or liver weights in males and females of the 3.0% diet group, but no effects were found on survival rate, body weights, and hematological, serum biochemical or histopathological parameters at any dose levels in the chronic toxicity study. Regarding carcinogenicity, ammonium sulfate did not exert any significant influence on the incidences of tumors in any of the organs and tissues examined. It was concluded that the no observed adverse effect level of ammonium sulfate was the 0.6% diet, which is equivalent to 256 and 284 mg/kg b.w./day in males and females, respectively, and the compound is non-carcinogenic under the conditions of the study.

Administration, Oral↗

Promotion of thyroid carcinogenesis by para-aminobenzoic acid in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.

Sulfonamide analogues of para-aminobenzoic acid (PABA), a precursor of folate synthesis, have beneficial effects as antifolate, but thyroid peroxidase inhibition has been reported as a side effect that results in promotion of rat thyroid carcinogenesis. In the present study, effects of PABA itself on F344 rat thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN) were evaluated. In experiment 1, rats in groups 1-4 received a single subcutaneous injection of DHPN at 2800 mg/kg, and groups 5 and 6 received vehicle saline alone. From 1 week after DHPN initiation, rats in groups 2, 3, 4, and 6 were fed basal diet containing 0.25%, 0.5%, 1.0%, and 1.0% PABA, respectively, for 40 weeks. Rats in groups 1 and 5 received basal diet alone throughout the experiment. The final incidence of thyroid follicular cell adenomas and adenocarcinomas was significantly (p < 0.05 or 0.01) increased in groups 3 and 4 as compared to group 1. No thyroid tumors were found in groups 5 and 6. In experiment 2, animals in group 1 were fed basal diet alone, while groups 2 and 3 were given 0.5% and 1.0% PABA in the diet, respectively, for 2 weeks. Thyroid weights in group 3, and serum thyroid stimulating hormone level and proliferative activity of follicular cells in groups 2 and 3 were significantly (p < 0.05 or 0.01) elevated. In addition, the serum thyroxine level in group 3 was significantly (p < 0.05) depressed. These results clearly indicate that PABA exerts promotion/progression effects on rat thyroid carcinogenesis as a result of hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.

4-Aminobenzoic Acid↗

Dialysis-related amyloidosis of the temporomandibular joint.

Dialysis-related amyloidosis (DRA) is a serious complication occurring most commonly in patients undergoing long-term hemodialysis. We describe a case of amyloidosis of the bilateral temporomandibular joint (TMJ) that developed after long-term hemodialysis therapy.

Aged↗

Portal vein complications in the long-term course after pediatric living donor liver transplantation.

The frequency and the outcome of patients with portal vein (PV) complications in the long-term course after pediatric living donor liver transplantation (LDLT) have rarely been reported. Between June 1990 and September 2003, 527 pediatric patients underwent primary LDLT with left lobe grafts, among which 479 patients with functioning grafts at 3 months after LDLT were included in this analysis. The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and body weight from 3.1 kg to 62.4 kg (median: 9.6 kg). Biliary cirrhosis was the most common cause for LDLT (81%). The PV was anastomosed with or without a vein graft. Thirty-nine patients (8%) showed a PV complication (stenosis: 16; obstruction: 17; thrombus: 2; twist: 3). Their ages ranged from 4 months to 17 years, 3 months (median: 1 year) and their body weight from 3.8 kg to 44.8 kg (median: 8.5 kg) at operation. PV complications were detected between 4 and 116 months (median: 14 months) after the transplant. Splenomegaly and decreased platelet counts were observed in more than 90% of the patients with a PV complication. In 27 patients (71%), interventional venoplasty was successful. Eleven patients had obstruction of the PV (2.3%) including three who showed cirrhosis; one with severe pulmonary hypertension; one death after retransplantation; and one alive after retransplantation. Moderate fibrosis was found in two patients at 3 and 2 years after the procedure, one of whom had the complication of a moderate intrapulmonary shunt. Early detection of PV stenosis with these two markers can lead to successful angioplasty and avoid graft loss.

Adolescent↗

New protocol of immunosuppression for liver transplantation across ABO barrier: the use of Rituximab, hepatic arterial infusion, and preservation of spleen.

INTRODUCTION: An ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) is a challenge. Until 2000 systemic multidrug immunosuppression and splenectomy was the gold standard with poor results. Application of local administration with prostagrandin E1 (PGE1) and steroids via a portal vein (PV) catheter dramatically improved the survival from 20% to 60% but PV thrombus became a problem (35%). To solve it, an hepatic arterial (HA) catheter was used instead of a PV catheter and splenectomy was omitted. Although the PV thrombus problem was resolved, the ABO antibody titers significantly increased, and two cases of uncontrollable humoral rejection (HR) were experienced. In this study, Rituximab was introduced instead of splenectomy to decrease the antibody. We report the efficacy of prophylaxis with Rituximab for ABO-I LDLT. METHODS: Eight patients received. Rituximab at 2 to 14 days before LDLT. During the operation, the spleen was preserved. Methylpredonisolone and PGE1 were administered via an HA catheter for 2 to 3 weeks after LDLT in addition to an immunosuppressive regimen consisting of tacrolimus and steroids. Antibody titers were measured serially. RESULT: There was no clinical HR. Two patients died of complications unrelated to HR. The antibody titer decreased compared to patients without splenectomy/rituximab. B cells (CD19) were depleted from peripheral blood for up to 3 months. Cytomegalovirus infections were decreased compared to patients with splenectomy (P = .085). CONCLUSION: Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.

ABO Blood-Group System↗

Insulin independence of unstable diabetic patient after single living donor islet transplantation.

BACKGROUND: Current success in islet transplantation will lead to a donor shortage. Living donor islet transplantation could be an alternative approach to expand the potential donor pool. In this study we describe the first successful living donor islet transplantation for unstable diabetes, performed at Kyoto University Hospital on January 19, 2005. METHODS: The donor was a healthy 56-year-old woman and mother of the recipient. The recipient was a 27-year-old woman with insulin-dependent diabetes since the age of 15 years. She experienced frequent hypoglycemic unawareness episodes. Her blood glucose concentration was difficult to control and C-peptide level was negative after glucagon stimulation. She needed an average 28 of units of insulin per day. The donor underwent a distal pancreatectomy and islets were isolated from the resected pancreas graft. The total islet yield was 408,114 islet equivalents and isolated islets were immediately transplanted into the recipient's liver. RESULTS: After transplant, the blood glucose level of the recipient was tightly controlled without hypoglycemic episodes. She was discharged on day 37 with a normal oral glucose tolerance test (OGTT). The recipient remained insulin-independent for >3 months, since day 22 posttransplant. The donor's postoperative clinical course was uneventful. She was discharged on postoperative day 18 and returned to her job within 1 month. CONCLUSIONS: We report the first successful living donor islet transplantation for the treatment of unstable diabetes. We believe that living donor islet transplantation may become an option in the treatment of insulin-dependent diabetes.

Adult↗

Simple evaluation of engraftment by secretory unit of islet transplant objects for living donor and cadaveric donor fresh or cultured islet transplantation.

BACKGROUND: Evaluation of engraftment is important to assess the success of islet transplantation. Recently we developed secretory unit of islet transplant objects (SUITO) index for simple evaluation of engraftment. Assuming that normal subjects aged <40 years have 100% pancreatic beta-cell function, SUITO index was calculated by the formula: 1500 x fasting C-peptide immunoreactivity [ng/dL]/(fasting blood glucose [mg/dL] - 63). In this study, we compared the efficacy of islet transplantation from cadaveric and living donors using the SUITO index. METHODS: We performed eight islet transplantations with non-heart-beating donors (NHBDs) into five patients. Two patients received fresh islets once, one patient received fresh islets twice, one patient received cultured islets once, and one patient received cultured islets twice plus fresh islets once. In addition, one patient received fresh islets from a living donor. We calculated the SUITO index from postoperative days 3 to 30 for each case. RESULTS: Mean SUITO index after one fresh islet transplant was 11.7 +/- 1.0, after two fresh islet transplants was 28.5 +/- 3.4, after one cultured islet transplant was 2.1 +/- 0.4, after two cultured islet transplant was 12.1 +/- 1.9, and after two cultured islet transplant plus one fresh islet transplant was 26.7 +/- 1.7. The mean SUITO index after single living donor islet transplant was 40.7 +/- 2.6, which was significantly higher compared with all other groups. Insulin independence was obtained when the SUITO index was >26, which might reflect that 26% beta-cell mass was required for insulin independence. CONCLUSION: SUITO index is useful to evaluate islet engraftment and to predict the possibility of insulin independence.

Blood Glucose↗

Selective and efficient culturing of retinal pigment epithelial cells using a feeder layer.

BACKGROUND: The techniques to isolate and purify retinal pigment epithelial (RPE) cells from small piece of autologous tissues are extremely difficult, and it is important to develop an efficient cell culture technique for RPE cells. The purpose of this study was to investigate the effect of 3T3-J2 cells and conditioned medium from 3T3-J2 cells on the proliferation of cultured RPE cells. METHODS: RPE cells from pigmented rabbits and a human RPE-derived cell line, ARPE-19, were used. First, the effects of co-culturing RPE cells with 3T3-J2 cells on the growth of the cells were analyzed. Second, the effects of the conditioned medium from 3T3-J2 cells on the proliferation of both types of cells were investigated. And third, the effects of the conditioned medium on RPE cell culture from a surgically removed choroidal neovascular (CNV) membrane were investigated. RESULTS: The 3T3-J2 cells increased the proliferation of both rabbit RPE cells and ARPE-19 cells. The number of rabbit RPE cells cultured in a mixture of the conditioned medium from 3T3-J2 cells was significantly higher than that in the reported optimal condition, and a similar tendency was observed for ARPE-19 cells. The results from enzyme-linked immunosorbent assay showed the presence of PDGF-AB, VEGF and IGF-I in the conditioned medium. The conditioned medium also promoted selective growth of human RPE cells from CNV. DISCUSSION: The results from this study present the conditions for efficient and selective culture of primary RPE cells.

3T3 Cells↗

Differentiation of transplanted mesenchymal stem cells in a large osteochondral defect in rabbit.

BACKGROUND: Although accumulating evidence shows that mesenchymal stem cells (MSC) are a promising cell source for articular cartilage repair, the fate of transplanted MSC has not been extensively studied. METHODS: To monitor their persistence and differentiation, we labeled uninduced MSC with a fluorescent dye, PKH26, and transplanted them, in a poly-glycolic-acid scaffold, to full-thickness defects made in the weight-bearing area of rabbit femoral trochleae with hyaluronate sheets. The fate of the labeled cells was monitored for up to 8 weeks. RESULTS: Two weeks after transplantation, immature cartilage containing collagen type II had formed. By 8 weeks, this cartilage had thinned and immunolabeling for collagen type II gradually disappeared from the basal region, which became positive for collagen type I. Most chondrocytes within the regenerated cartilage were PKH26-positive and, therefore, derived from transplanted MSC, whereas osteoblasts within the regenerated bone were a mixture of donor- and host-derived cells. The thickness of the cartilage became thinner up to 8 weeks and then remained stable up to 42 weeks after surgery. DISCUSSION: These results showed that uninduced MSC were able to survive osteochondral defects and differentiated according to the environment, making a major contribution to initial cartilage formation and a partial contribution to bone regeneration.

Animals↗

Retinoic acid suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma.

BACKGROUND: Activation of telomerase is crucial for the continued growth and progression of cancer cells. In a previous study, we showed that telomerase is frequently activated in skin tumours. OBJECTIVE: Because retinoic acid (RA) plays an important role in the growth and differentiation of keratinocytes and as RA has some preventive and therapeutic effects on human skin cancers, we examined the effect of RA on the telomerase activity of HSC-1 human cutaneous squamous cell carcinoma cells. RESULTS: Treatment of HSC-1 cells with all-trans RA (ATRA) significantly suppressed their telomerase activity. The suppression of telomerase activity was obvious at day 4 and was maximal at day 5 after the start of treatment with RA. This suppression was reversible as removal of ATRA allowed the recovery of telomerase activity. The suppression of telomerase activity correlated with the decreased expression of mRNA of human telomerase catalytic subunit (hTERT), the rate-limiting determinant of enzyme activity. The production of c-myc and of Sp1 proteins, transcription factors regulating hTERT expression, was not suppressed in HSC-1 cells by ATRA, but phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and of the serine/threonine kinase Akt was significantly suppressed. Phosphorylation of the epidermal growth factor receptor, which regulates hTERT expression in HSC-1 cells, was not altered by ATRA. CONCLUSIONS: These data indicate that RA is effective in inhibiting telomerase activity in HSC-1 cells. Suppression of ERK1/2 and Akt activation is presumed to be involved in the RA-induced suppression of hTERT.

Carcinoma, Squamous Cell↗

Body posture during sleep and disc displacement in the temporomandibular joint: a pilot study.

Many possible factors associated with internal derangement of the temporomandibular joint (TMJ) have been discussed, but the causal factors remain unproven. The present study aimed to investigate habitual body posture during sleep (HBP) of patients with anterior disc displacement (ADD) in the TMJ. The sample comprised 87 patients (12 males, 75 females) aged 13-68 years (mean 25 years) and diagnosed by magnetic resonance imaging as having unilateral or bilateral ADD in the TMJ. The HBPs were classified into five categories: supine, prone, right lateral, left lateral, and no-dominant positions. Of the 50 patients with the unilateral ADD, 33 (66%) had the ipsilateral HBP to the affected joint while none (0%) had the contralateral HBP. This contrast showed that the HBP was a possible contributing factor to the ADD. It was suggested that HBP allows the ipsilateral condyle to displace posteriorly and this posterior position causes relative ADD.

Adolescent↗

Bowen's carcinoma of the scrotal skin associated with human papillomavirus type 82.

We have previously cloned human papillomavirus type 82 (HPV-82) from a vaginal intraepithelial neoplasia, but it is not known whether HPV-82 can induce a cutaneous lesion. A large erosive nodule developed on the scrotum of a 50-year-old Japanese patient. Histopathologically, the lesion was composed of two distinct parts; one part showing changes characteristic of Bowen's disease in the epidermis, and the other showing elongated rete ridges and proliferation of atypical basaloid cells in the dermis. These parts were partially connected, giving the diagnosis of Bowen's carcinoma. Immunohistochemically, HPV capsid antigen was detected only in the nuclei of a few cells on the upper part of the epidermis. HPV-82 was identified in the lesion by blot hybridization and viral DNA was demonstrated in the lesion by in situ hybridization. HPV-82 has tropism for both the skin and the genital regions.

Blotting, Southern↗

Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea.

AIM: To elucidate the pathogenic mechanism of amyloid formation in corneal amyloidosis with trichiasis. METHODS: Ophthalmological examination was performed in nine patients to determine secondary corneal amyloidosis with trichiasis. Congo red staining and immunohistochemistry using anti-human lactoferrin antibody were used for biopsied corneal samples. For genetic analyses, single strand conformation polymorphism (SSCP), direct DNA sequence analysis, and polymerase chain reaction (PCR) induced mutation restriction analysis (IMRA) were employed to detect lactoferrin gene polymorphism. RESULTS: All patients had had trichiasis at least for 1 year, and all amyloid-like deposits were found in one eye with trichiasis. Ophthalmological examination revealed that eight patients showed gelatinous type of amyloid deposition and one showed lattice type of amyloid deposition. Studies of biopsied corneal samples with Congo red stain revealed positive staining just under the corneal epithelial cells. Immunoreactivity of anti-human lactoferrin antibodies was recognised in all tissues with positive Congo red staining. Lactoferrin gene analysis revealed that seven patients were heterozygotic and two were homozygotic for lactoferrin Glu561Asp. The frequency of the polymorphism in the patients was significantly different from that in 56 healthy control subjects. CONCLUSION: Lactoferrin Glu561Asp is a key polymorphism related to facilitating amyloid formation in corneal amyloidosis with trichiasis.

Adolescent↗

Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson's disease.

AIM: To evaluate the reliability of [(123)I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson's disease (PD). PATIENTS/METHODS: A series of 391 outpatients showing one or more parkinsonian-like symptoms was longitudinally followed up for accurate clinical diagnosis. MIBG scintigraphy was performed in the patients and 10 normal controls of similar age. The heart to mediastinum uptake ratio was calculated in each person, and the values were considered abnormal if they were greater than two standard deviations below the control mean. RESULTS: MIBG uptake was decreased in most patients with PD (87.7%), and was seen in all advanced cases with Hohen-Yahr stage III or more; the sensitivity and specificity of scintigraphy for detecting PD were 87.7% and 37.4%, respectively. Surprisingly, over half of the patients without PD (66.5%) also exhibited low uptake, resulting in considerable overlap in the ratios between PD and the other disorders. CONCLUSION: MIBG scintigraphy is a sensitive, but not specific, test for PD. Low MIBG uptake does not necessarily indicate PD, but is essential for diagnosing advanced PD.

3-Iodobenzylguanidine↗