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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 37 records · Page 2Linked to original sources
PubMed2005

Are anemic patients more sensitive to calcineurin inhibitors?

A calcineurin inhibitor (CNI) is characterized by high affinity binding to red blood cells. There is a possibility that hematocrit levels might affect the immunosuppressive effects of cyclosporine (CsA). The purpose of this study was to examine whether the treatment with CNI was more effective in preventing acute rejection in anemic compared with nonanemic patients and to find a suitable method to monitoring immunosuppression. Ninety-five living donor renal transplant recipients who were treated with CsA were divided into five groups depending on their Ht levels. The incidences of biopsy-proven acute rejection were 1/8 (12.5%), 8/31 (25.8%), 6/28 (21.4%), 10/22 (45.5%), and 2/6 (33.3%) for Ht < or = 25%, 25% < Ht < or = 30%, 30% < Ht < or = 35%, 35% < Ht < or = 40%, and 40% < Ht, respectively. In vitro IL-2 mRNA inhibition tests were performed to evaluate lymphocyte function after stimulation of whole-blood with phorbol myristate acetate and Ca-ionophore in the presence of various concentrations of CsA. Whole blood CsA levels causing 50% inhibition of IL-2 mRNA (IC50) were 256, 310, 175, and 55 ng/mL for Ht 50%, 40%, 30%, and 20%, respectively. It is speculated that plasma concentrations of CsA may increase at low Ht levels, because lower incidences of acute rejection and lower IC50 values of CsA were observed in the anemic state. When the dosage of CsA was adjusted to its whole-blood concentration, the anemic state is likely to enhance the immunosuppressive effect of CsA. A pharmacodynamic study, such as the IL-2 mRNA inhibition test, is preferable for CsA monitoring.

Anemia↗
PubMed2005

The effect of urinary protein excretion in post-renal transplant recurrent nephrotic syndrome on basiliximab pharmacokinetics and pharmacodynamics in a pediatric patient.

A pharmacokinetic and pharmacodynamic study of Basiliximab therapy has not been reported in recurrent post-renal transplant nephrotic syndrome. We assessed the effect of urinary protein in a focal segmental glomerulosclerosis patient. We measured the serum concentrations of basiliximab as well as the rate of activated CD25-positive T lymphocytes at fixed intervals in nephrotic versus eight nonnephrotic pediatric post-renal transplant patients. A significant reduction in the antibody concentrations was observed in focal segmental glomerulosclerosis. The CD25 expression rate showed a similar trend to the pharmacokinetic data. We conclude that cases of massive urinary protein excretion need special care to maintain immunosuppression in renal transplant using Basiliximab.

Adult↗
PubMed2005

Long-term results of tacrolimus therapy for renal transplantation in patients with diabetic nephropathy in Japan.

In Japan, the number of kidney transplants for the patients with diabetic nephropathy is limited because of an extreme organ shortage and poor patient and graft survival rates. We analyzed the 5-year outcomes in kidney transplant recipients treated with tacrolimus with (group 1; n = 53) and without a diagnosis of diabetic nephropathy (group 2; n = 1432). We also investigated outcomes in patients who received simultaneous pancreas and kidney transplants since 2000 (group 3; n = 15). Patients in group 1 were older than those in group 2, with a shorter duration of pretransplant dialysis (P = .0001). Five-year patient survival rates in groups 1 and 2 were 89.7% and 97.9%, respectively (P = .13), and 5-year graft survival rates were 89.6% and 94.8%, respectively (P = .44). The incidence of acute rejection within 3 months of transplantation was 28.3% in group 1 and 29.2% in group 2 (P = .98). Tacrolimus-based induction therapy was used in 13 of the 15 group 3 cases. Both kidney and pancreas grafts are surviving to date in all but one of the group 3 patients; one patient had the pancreas removed due to venous thrombosis at 7 days. It was concluded that tacrolimus-based therapy resulted in excellent 5-year outcomes in patients who had kidney transplantation because of diabetic nephropathy, despite the higher risks associated with this condition. Tacrolimus was also beneficial in association with simultaneous pancreas and kidney transplantation. These data encourage us to perform kidney transplantation in patients with diabetic nephropathy.

Adult↗
PubMed2005

Safety analysis after tacrolimus immunosuppression in renal transplant recipients in Japan: 5-year results in >1500 patients.

Tacrolimus was approved in Japan in April 1996 for the prevention of allograft rejection in patients receiving kidney transplants. There has been a concern that immunosuppressive therapy may be associated with cardiovascular and metabolic complications, including hyperlipidemia, hypertension, and posttransplant diabetes mellitus. A multicenter (59 institutions) study was conducted in Japan in patients who underwent renal transplantation and received tacrolimus immunosuppression. Patients were followed for >5 years, from April 1996 to December 2002. Of the 1569 patients enrolled, 1542 were evaluated. In this analysis, graft survival rate and medication usage patterns of antihyperlipidemics, antihypertensives, insulin, and oral hypoglycemics were observed for >5 years in patients receiving tacrolimus immunosuppression. The graft survival rates of patients requiring antihyperlipidemic therapy and experiencing acute rejection were significantly lower compared with all other patients (P < .05). The risk of graft rejection was significantly greater in patients with cardiovascular complications requiring antihyperlipidemics or antihypertensives. Graft survival was significantly lower in patients with acute rejection and antihyperlipidemic therapy than in other patients.

Follow-Up Studies↗
PubMed2005

Improvement of quality of life in tacrolimus-based pediatric renal transplant recipients and their caregivers, including donors.

INTRODUCTION: To date, no reports have concurrently investigated the quality of life (QOL) of both pediatric renal transplant recipients and their caregivers. We conducted a survey at nine institutions in Japan with regard to changes in QOL before and after renal transplantation. METHODS: We chose 68 pediatric renal transplant recipients whose surgery was followed by tacrolimus-based immunosuppressive therapy. Both patients and their caregivers were asked to complete self-rating questionnaires. For the patients' surveys, we used 29 questions relevant to pediatric patients, which were excerpted from Kidney Disease Quality of Life (Japanese version). The SF-36 (Japanese version) was taken by their caregivers. RESULTS: Fifty-six patients (82.4%) responded to the questionnaires. The mean age at renal transplantation and at the time of the survey was 11.1 and 15.3 years old, respectively. The general questions of the patients' survey indicated a significant QOL improvement in each of the subscales (such as physical functioning and vitality) after transplantation as compared to prior. In the questions pertaining to kidney diseases, significant QOL improvement was observed in many subscales, such as symptoms/problems and effects of kidney disease. Of the 54 caregivers (79.4%) who answered SF-36 questionnaires, 47 (87.0%) were living donors. After renal transplantation surgery for the children, a significant improvement of QOL was seen in the subscales for caregivers' mental well-being. However, a significant decrease was observed for QOL in regard to physical health.

Adolescent↗
PubMed2005

Successful results after 5 years of tacrolimus therapy in ABO-incompatible kidney transplantation in Japan.

In Japan, living donor kidney transplantation accounts for about 80% of all kidney transplants. This is in contrast to the United States and Europe, where transplantation of organs from cadaveric or brain-dead donors is more common. This study analyzed the results of 5 years of experience with tacrolimus in Japan, focusing on the efficacy of the drug in improving patient and graft survival in patients who underwent transplantation with ABO-incompatible kidney grafts. Of the 1542 evaluable patients, 1281 patients received grafts from living donors. Of these, 177 patients received kidneys from ABO-incompatible donors and 981 patients received kidneys from ABO-compatible donors. Graft survival rates in ABO-incompatible recipients ranged from 90.7% at 1 year to 80.5% at 5 years. Subsequent graft survival rates in ABO-compatible recipients were 98.1% and 92.9%, respectively (P < .001 between groups). Patient survival rates at 5 years were 93.2% in ABO-incompatible recipients and 98.1% in ABO-compatible recipients. The rejection rate for kidneys from ABO-compatible donors was 27.8%, while for ABO-incompatible donors the rejection rate was 45.2%. The excellent outcome from this study demonstrates that even suboptimal ABO-incompatible donors can be used successfully as a source of kidneys when using tacrolimus as the immunosuppressive regimen. This may go some way to addressing the shortage of kidney donors in Japan.

ABO Blood-Group System↗
PubMed2005

Successful treatment of 115 pediatric renal transplant recipients with tacrolimus-based immunosuppressive therapy: a 7-year multicenter study in Japan.

The safety and efficacy of tacrolimus (Tac)-based immunosuppressive treatments were studied in 115 pediatric renal transplant recipients (mean follow-up period, approximately 20 months). The acute rejection rate was 22.7% 6 months after transplantation and the steroid-resistant acute rejection rate was 6.4%. The 5-year patient and graft survival rates were 98.6% and 95.9%, respectively. Major adverse effects included infection, ie, cytomegalovirus (CMV) antigenemia (41.7%), renal dysfunction (29.6%), and impaired glucose tolerance (20.9%). The incidences of these adverse events were significantly decreased among patients who had undergone transplantation after March 2000 (n = 43), namely, 30.2%, 18.6%, and 11.6%, respectively.

Adult↗
PubMed2005

Primary osteosarcoma of the thoracic spine: report of an unusual elderly patient with autopsy findings.

STUDY DESIGN: A case report of primary osteosarcoma of the spine in an elderly patient. OBJECTIVE: The histopathological features of osteosarcoma vary widely, often leading to diagnostic difficulties particularly when there is little evidence of osteoid formation. The report describes the difficulty in the diagnosis of osteosarcoma of the thoracic vertebra. SETTING: Department of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medicine, Fukui, Japan. METHOD: A 78-year-old man presented with paraparesis and underwent urgent anterior excision of a primary spinal tumor emanating from the T10 vertebra followed by artificial vertebral replacement. The patient eventually died of disseminated disease of vertebral osteosarcoma. RESULTS: Samples from the T10 vertebral tumor showed neoplastic growth of atypical spindle-shaped cells, with foci of storiform-like proliferation. The tissue also demonstrated positive immunohistochemical staining for vimentin and alpha-smooth muscle actin and a tentative diagnosis of leiomyosarcoma was made. However, a metastatic nodule of the chest wall at autopsy showed focal osteoid formation, a finding not seen in the primary tumor. CONCLUSION: Early detection and accurate diagnosis is important for improving not only patient prognosis but also the quality of life. We should always consider this rare entity, particularly in elderly patients who present with back pain and vertebral collapse.

Actins↗
PubMed2005

Retroperitoneal lymphocele associated with lumbar spine fracture: report of an unusual case.

DESIGN: To describe a case of retroperitoneal lymphocele as an extremely rare complication after lumbar spine fracture. OBJECTIVE: To discuss the possible mechanism of development of retroperitoneal lymphocele following blunt trauma to the ureter and lumbar spine. SETTING: Fukui University Hospital, Fukui, Japan. RESULTS: A 71-year-old man presented with severe intractable low back pain caused by a huge retroperitoneal lymphocele, which was considered to be related to an occult L4 vertebral fracture and a blunt ureteral injury. The retroperitoneal lymphocele also caused significant instability at L3-4 level, thus requiring surgical resection followed by interbody fusion. CONCLUSION: Physicians should be aware that such unusual retroperitoneal lymphocele might develop even after a blunt ureteral injury or a minor lumbar spine fracture.

Aged↗
PubMed2005

A case of canine apocrine sweat gland adenoma, clear cell variant.

A cutaneous mass at the base of the retroauricular region of a 4-year-old, female Golden Retriever was examined pathologically. Histologically, the mass formed multiple nodules consisting of a proliferation of large clear cells with abundant cytoplasm. Mitotic figures among the neoplastic cells were very sparse. The large clear cells were intensely positive for cytokeratins (AE1/AE4, cytokeratin 8 and 18) and moderately positive for lysozyme and contained periodic acid-Schiff-positive granules in the cytoplasm. In addition, small flat cells lined the islands of neoplastic large clear cells, and these were strongly positive for alpha-smooth muscle actin and vimentin, and some were positive for cytokeratin (AE1/AE4), suggesting they were myoepithelial cells. No local recurrence or metastasis has been recognized during the 18 months since surgical excision. On the basis of these findings, the present tumor was diagnosed as apocrine sweat gland adenoma, clear cell variant. There have been few previous reports of canine apocrine adenomas showing a clear cell morphology.

Adenoma, Sweat Gland↗
PubMed2005

Two cases of feline malignant craniopharyngioma.

Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.

Animals↗
PubMed2005

Effects of long-term treatment with mizoribine in patients with proliferative lupus nephritis.

AIM: Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. METHOD: Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 +/- 10 (100 - 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 +/- 5.5 (70 - 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. RESULTS: All patients were females, mean age 43.0 +/- 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). CONCLUSION: From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.

Adult↗
PubMed2004

Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis.

A total of 12 clinically ill cats previously diagnosed as feline infectious peritonitis (FIP) were treated with a combination of recombinant feline interferon and glucocorticoid. A complete remission (over 2 years) and a partial remission (2 to 5 months) were observed in four (33.3%) and four (33.3%) cases, respectively. Those that survived for more than 2 years were all older cats (6 to 16 years old) with the effusive form of FIP.

Animals↗
PubMed2004

Cyclosporine nephrotoxicity: how does it affect renal allograft function and transplant morphology?

Chronic CSA nephrotoxicity is the second most important diagnosis responsible for the late graft failure. CSA associated arteriolopathy (CAA) is a well-known lesion of chronic CSA nephrotoxicity. The clinicopathological characteristics and the significance of CSA nephrotoxicity have changed following reduction in CSA doses and implementation of monitoring of blood levels. Seventy-four CAA patients on CSA therapy were classified as functioning (n=30) or loss groups (n=44). There was no significant difference in severity of CAA. The concomitant lesion of chronic rejection, but not the severity of CAA, was the most important risk factor for graft loss. Among 54 recipients with focal segmental glomerulosclerosis lesions (FGS), 32 (59%) were diagnosed as CAA associated glomerulopathy (CAG). Eighteen of the 32 CAG patients lost their grafts upon follow-up. Decreasing the CSA dosage to maintain lower blood levels than the usually optimal concentrations, but not discontinuation of CSA, has been useful to retard the progression of graft dysfunction in half of 15 isolated pure CAG patients. Patients with increasing daily proteinuria exceeding 2 grams lost their graft function despite CSA reductions. CAA is not a specific lesion of chronic CSA nephrotoxicity; the FGS lesion is also a nonspecific lesion often seen in renal allografts. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. The FGS lesion accompanying CAA is considered to be CSA-associated glomerulopathy. These data contribute to therapeutic plans for renal transplant patients during long-term CSA treatment.

Arterioles↗
PubMed2004

Clinical success of Neoral absorption profile.

We investigated the clinical benefits of cyclosporine microemulsion preconcentrate (CyA-MEPC; Neoral) in 16 de novo renal transplant recipients. The dose of CyA-MEPC was managed from AUC(0-4h), with serial target values of AUC(0-4h) at 5000-->4000-->3000-->2000 ng. hr/mL. The frequency of acute rejection episodes was 25%. The decreased renal function reached a low value of 12.5%, and creatinine was stable. Therefore, setting the target AUC(0-4h) value in the early phase at 5000 ng.hr/mL is an effective strategy to prevent acute rejection episodes. The single dose of Neoral given immediately after the renal transplant was 6 mg/kg (making a daily dose of 12 mg/kg). Thereafter, the dose-normalized AUC(0-4h) was set at a constant value to 4 weeks posttransplant. At week 4, the single dose was decreased to 4 mg/kg twice daily (a daily dose of 8 mg/kg). From these studies a daily dose of 12 mg/kg is suggested to be the appropriate amount for the first dose immediately after transplant. The renal biopsy performed at 6 months posttransplant showed neither cyclosporine-induced renal impairments, nor findings of chronic rejection, suggesting that 2000 ng.hr/mL is an appropriate target AUC(0-4h) value in the maintenance phase. These results suggest that it is possible to set the target value of C2 monitoring in the maintenance phase to a value slightly lower than that proposed from other studies.

Adult↗
PubMed2004

Increased cell proliferation of mouse fibroblast NIH-3T3 in vitro induced by excretory/secretory product(s) from Opisthorchis viverrini.

Infection by Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. However, the mechanism by which the parasite is involved in carcinogenesis is not clear. In addition to the direct damage of the bile duct epithelium via direct contact with O. viverrini, the excretory/secretory (ES) product(s) released from the parasites may play important roles in this process. We therefore investigated the responses of a fibroblast cell line, NIH-3T3, to ES product(s) released from O. viverrini by using a non-contact co-culture technique. In this culture system, the parasites in the upper chamber had no direct contact with the NIH-3T3 cells in the lower chamber of the culture plate. The results indicated a marked increase in NIH-3T3 cell proliferation in the non-contact co-culture condition with either 0% or 10% calf serum in the medium compared with that without parasites. ES product(s) increased cell proliferation by stimulating the expression of phosphorylated retinoblastoma (pRB) and cyclin D1, the key proteins in driving cells through the G1/S transition point of the cell cycle. This led to the induction of cells going into the S-phase of the cell cycle. ES product(s) also changed the morphology of NIH-3T3 cells to a refractive and narrow shape, which allowed the cells to proliferate in the limited culture area. For the first time, we have been able to demonstrate increased cell proliferation induced by the ES product(s) from O. viverrini; this finding may clarify how O. viverrini ES product(s) affect human bile duct epithelium during cholangiocarcinogenesis.

Animals↗
PubMed2004

Phylogenetic relationships among medically important yeasts based on sequences of mitochondrial large subunit ribosomal RNA gene.

Sequences of the mitochondrial large subunit ribosomal RNA (mtLsurRNA) gene of medically important yeasts were analysed. Sixteen strains of eight species including two varieties were subjected to sequencing. Sequencing enabled us to recognize the differences between all the species and varieties. Alignment analysis revealed that these sequences consisted of three clusters: the Candida albicans group, the C. glabrata group, and the basidiomycetous group. It is possible, therefore, that the mtLsurRNA gene is one of the targets not only for species identification but also for phylogenetic analysis of closely related yeasts. The dendrogram of each group, obtained from this gene, supports the previous study of yeasts based upon the chromosomal genes.

Base Sequence↗