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Kota Takahashi

Publications and source records attributed to Kota Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition.

BACKGROUND: Complement 4d (C4d) deposition in the peritubular capillary (PTC) in the kidney allograft is a useful diagnostic marker for humoral rejection. C4d is produced not only by the classical pathway but also by the lectin pathway of the complement activation cascade. We have recently reported the in situ role of the later phase of the complement cascade in renal allografts with C4d deposition; however, the initial process prior to C4d deposition is yet to be resolved. METHODS: To clarify the early phases of the complement activation cascade, we evaluated the deposition of initial proteins of the above two pathways; IgG, IgM, mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine protease (MASP)-1 and MASP-2 in kidney allografts with PTC C4d deposition. RESULTS: Sixty kidney allograft specimens were divided into two groups on the basis of the presence of C4d deposition in PTC. The C4d-positive group (n = 18) included nine ABO-identical and nine ABO-incompatible cases, and the C4d-negative group (n = 42) had 34 ABO-identical and eight ABO-compatible (but not identical) cases. In the C4d-positive group, 16 of 18 cases showed diffuse H-ficolin and IgM deposition in PTC. In contrast, H-ficolin and IgM were not detected in PTC in the C4d-negative group. Other initial proteins were not detected in all cases. CONCLUSIONS: Our study suggested for the first time that the lectin pathway activated by H-ficolin may be involved in C4d deposition on PTC in the kidney allograft.

Adult↗
PubMed2006

Association between the dihydrotestosterone level in the prostate and prostate cancer aggressiveness using the Gleason score.

PURPOSE: To our knowledge the association between dihydrotestosterone in the prostate and prostate cancer aggressiveness has not yet been elucidated. We analyzed dihydrotestosterone levels in the prostate and Gleason score in patients diagnosed with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 81 patients with suspected prostate cancer underwent prostate biopsy. Serum samples were collected before biopsy. Dihydrotestosterone levels in prostatic tissue and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization. RESULTS: A total of 47 patients were diagnosed with stages T1 to T3N0M0 prostate cancer and 34 were diagnosed with no malignancy. Of the 47 patients 32 had a Gleason score of 6 or less and 15 had a score of 7 to 10. Dihydrotestosterone in prostatic tissue in patients with Gleason score 7 to 10 disease was significantly lower than in those with Gleason score 6 or less disease (p = 0.025). Gleason score correlated with the testosterone-to-serum dihydrotestosterone ratio (rs = 0.329, p = 0.038). CONCLUSIONS: Patients with Gleason score 7 to 10 prostate cancer have low dihydrotestosterone in the prostate, although there were no significant differences between patients with Gleason score 7 to 10 vs 6 or less prostate cancer with respect to serum androgens. Low dihydrotestosterone in cases of aggressive prostate cancer is probably sufficient to activate androgen receptor expression and propagate tumor growth.

Aged↗
PubMed2006

Role of connective tissue growth factor in fibronectin synthesis in cultured human prostate stromal cells.

OBJECTIVES: To clarify the correlation of connective tissue growth factor (CTGF) expression and fibronectin (FN) synthesis after transforming growth factor-beta-1 (TGF-beta1) stimulation in human prostate stromal cells. METHODS: Primary cultures of human prostate stromal cells were established from nine normal prostates by the explant method. The gene and protein expressions of CTGF and FN after TGF-beta1 treatment were examined. We also investigated the effect of CTGF blockade on TGF-beta1-induced FN synthesis by CTGF antisense oligodeoxynucleotide treatment. RESULTS: CTGF expression was detected in all nine prostate stromal cells by reverse transcriptase-polymerase chain reaction and immunoblotting. In prostatic tissues, CTGF expression was observed more strongly in epithelial cells than in the stromal area by immunohistochemistry. The upregulation of both CTGF and FN protein by TGF-beta1 treatment was demonstrated in a dose-dependent manner. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated FN synthesis. CONCLUSIONS: CTGF plays a crucial role in extracellular matrix production as a TGF-beta1 downstream mediator in human prostate stromal cells, suggesting that CTGF blockade is likely to be a therapeutic target against benign prostatic hyperplasia.

Cells, Cultured↗
PubMed2006

Kidney transplantation in pediatric recipients with mental retardation: clinical results of a multicenter experience in Japan.

BACKGROUND: There are few published reports on kidney transplantation (KT) in physically handicapped patients with mental retardation. The aim of this study is to clearly identify the outcome of KT in these patients and clarify whether handicapped patients can be candidates for KT. METHODS: Our study identified 25 multiply handicapped transplant recipients from 8 institutions. Causes of mental retardation were chromosomal abnormality in 5 patients, genetic syndrome in 10 patients, developmental brain anomaly in 2 patients, and other or unknown causes in 8 patients. Primary diseases leading to end-stage renal disease were congenital urinary tract anomaly in 12 patients, focal segmental glomerulosclerosis in 3 patients, cystic kidney disease in 3 patients, and other in 7 patients. RESULTS: Twenty-three patients received living-related transplants from a parent and 2 patients received cadaver transplants. Twenty-two patients were on peritoneal dialysis therapy, 2 patients were on hemodialysis therapy at the time of KT, and 1 patient underwent preemptive KT. Eleven acute rejection episodes occurred in 8 patients. All episodes were completely reversed with treatments that included mainly methylprednisolone pulse therapy. Posttransplantation lymphoproliferative disorder occurred in 2 patients. Follow-up data showed that all grafts were functioning during a mean observation period of 41.1 months (range, 4 to 187 months). All persons providing primary support for patients were satisfied with the KT and believed that quality of life was improved in both transplant recipients and themselves. CONCLUSION: Results indicate that KT is not contraindicated in handicapped patients, but cannot determine which patients are unsuitable to undergo KT.

Adolescent↗
PubMed2006

Correlation between pharmacological efficacy of cyclosporine A and tacrolimus, evaluated by lymphocyte immunosuppressant-sensitivity test (LIST) with MTT assay procedure in renal transplant recipients.

The dose of calcineurin inhibitors in renal transplantation has been adjusted, based on the therapeutic drug monitoring data. However, the data do not always correlate with clinical drug efficacy. In vitro response of peripheral-blood mononuclear cells to immunosuppressive drugs is reported to correlate with the recipient-response to therapeutic efficacy of the drug. We report, here, usefulness of a lymphocyte immunosuppressant sensitivity test for the estimation of individual drug sensitivity in renal transplant recipients. The LIST we have developed includes MTT assay procedures without the use of radioisotope-labeled compounds, which is convenient for general hospital use. Utilizing this procedure, we compared the pharmacological efficacy between cyclosporine A and tacrolimus in 41 renal transplant recipients.

Adult↗
PubMed2006

Efficacy of extracorporeal shockwave lithotripsy with patients rotated supine or rotated prone for treating ureteral stones: a case-control study.

PURPOSE: To improve the therapeutic efficacy of extracorporeal shockwave lithotripsy (SWL) for ureteral stones by attempting semilateral/rotated approaches. There has been no study that shows the advantage of rotated positions. PATIENTS AND METHODS: Two hundred forty-eight (group 1) and 156 (group 1R) patients with proximal-ureteral stones were treated by the Dornier Lithotriptor U15/50 in the supine and rotated-supine position, respectively. When residual calculi remained in the middle-distal ureter, group 1 subjects underwent subsequent sessions in the ordinary prone position, and Group 1R patients were treated in the rotated-prone position. Sixty-two (group 2) and 60 (group 2R) patients with primary middle-ureteral stones were treated in the prone and rotated- prone position, respectively, while 110 (group 3) and 98 (group 3R) patients with distal-ureteral stones were treated in the prone and rotated-prone position, respectively. RESULTS: Although the stone-free rate was not different in group 1 (94.8%) and 1R (97.4%), the number of sessions required for Group 1R patients to be stonefree (mean 1.49) was less than for Group 1 patients (mean 1.74; p=0.023). Group 1R patients tolerated a higher shockwave intensity than group 1 patients for sessions in the proximal ureter (p=0.042). The stone-free rate for Groups 1 and 1R for booster sessions in the middle- distal ureter was 85.4% and 100%, respectively (p=0.059). The stone-free rate for groups 2R (95.0%) and 3R (98.0%) was higher than that for groups 2 (83.9%) and 3 (89.1%) (p=0.046; p=0.011). CONCLUSION: These effortless modifications bring about a superior outcome when treating ureteral calculi with SWL.

Adult↗
PubMed2006

Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25 in successful ABO-incompatible kidney transplantation without splenectomy.

BACKGROUND: In Japan, ABO-incompatible (ABO-I) kidney transplantation began in 1989; these transplantations have flourished because of the lack of cadaveric donors, and more than 600 cases were performed up to 2004. Splenectomy has been considered to be necessary for successful ABO-I kidney transplantation, and the majority of pre-conditioning protocols include splenectomy in Japan. However, we have lost some grafts due to antibody-mediated rejection (AMR) accompanying explosive elevation of anti-A/B antibody (Ab) titer even though the patients had a low pre-operative Ab titer. PATIENTS AND METHODS: We utilized two doses of anti-CD20, rituximab, simply combined with mycophenolate mofetil (MMF)/low-dose steroid desensitization started 1 month before surgery in ABO-I kidney transplantation. Two sessions of pre-operative Ab removal by double filtration plasmapheresis or plasma exchange were carried out. We performed six ABO-I kidney transplantations without splenectomy. Anti-A/B Ab titers were more than 16 to 32 times before treatment. We did not plan any post-operative repeated Ab removal or intravenous immunoglobulin G (IVIG). RESULTS: Pre-operative anti-A/B Ab titers were successfully reduced to less than eight times in all cases. Except for one case in which we had to remove the graft due to aspiration pneumonia and methicillin-resistant staphylococcus epidermidis (MRSE) sepsis, the other five cases did not experience antibody-mediated rejection (AMR). An additional session of post-operative Ab removal and/or IVIG was not necessary. In all patients, B cells (CD19+, CD20+, CD21+) and activated T cells (CD25+) were selectively suppressed, although CD3+, CD4+ and CD8+ cell populations remained stable, thus we call our protocol "pinpoint targeted immunosuppression." Plasma immunoglobulin level was also successfully suppressed, especially after 6 weeks of surgery. CONCLUSION: Anti-CD20/MMF desensitization is safe and allows successful ABO-I kidney transplantation without splenectomy.

ABO Blood-Group System↗
PubMed2006

Present status of ABO-incompatible kidney transplantation in Japan.

BACKGROUND: We have been making continuous efforts in ABO-incompatible kidney transplantation since 1989 to expand the opportunities for kidney transplantation from living donors in Japan. PATIENTS AND METHOD: From the Japanese registry, we reviewed the long-term patient and graft survival of ABO-incompatible kidney transplantation. This survey focused on 564 patients who received ABO-incompatible kidney grafts from January 1989 to December 2003 in whom monitoring follow-up could be achieved in 60 institutions all over Japan. The mean age of 367 (65%) male and 197 (35%) female patients at surgery was 34.5 yr. Pre-operative anti-A/B antibody (Ab) removal and splenectomy (n = 553, 98%) were routinely performed combined with triple or quadruple immunosuppression using calcinurine inhibitor (CNI), anti-metabolites and steroids with or without deoxyspurgualin (DSG) or anti-lymphocyte Abs. RESULTS: The overall patient survival rate at 1, 3, 5 and 10 yr after transplantation was 94, 91, 88 and 81%, with overall graft survival rates of 86, 82, 74 and 53%, respectively. The graft survival rate was significantly higher in patients aged 29 and younger compared with those aged 30 and older. Children aged 15 or younger in particular have shown excellent graft survival rates at 1, 3, 5 and 10 yr of 90, 90, 86 and 76%, respectively. Patients with anticoagulation therapy (n = 285) showed a significantly higher graft survival rate than those without anticoagulation (n = 213), with 10-yr graft survival rates of 59 vs. 48%. There were no significant differences between A and B incompatibility with respect to clinical outcomes. There were also no significant difference in numbers of human leukocyte antigen mismatches, induction and maintenance CNI (cyclosporin A (CYA) vs. tacrolimus) and donor/recipient relationships with respect to the outcomes. We divided the patients into five groups according to the transplanted year periods. The outcome of the most recent 124 cases since 2001 had dramatically improved, with 2-yr graft survival of 94%, and there is a significant difference between the groups in 2001 onwards and the other four groups. CONCLUSION: This study confirms that the long-term outcome of ABO-incompatible living kidney transplantation is excellent and is similar to that of ABO-compatible cases. Recent data show that short-term graft survival has also improved. ABO-incompatible kidney transplantation is a radical, but safe and effective, treatment choice for end-stage renal disease.

ABO Blood-Group System↗
PubMed2006

Obstruction of the ileal ureter by mesenteric vessels occurring 5 years after total ureteral substitution for bilateral ureteral stenosis due to systemic lupus erythematosus.

We previously reported a case of bilateral ureteral stenosis accompanied by systemic lupus erythematosus, which was successfully managed by total ureteral reconstruction using a segment of the ileum. Herein, we describe an unusual complication in the same patient, which we experienced 5 years after the ileal-ureteral substitution. Left-sided back pain repeated together with transient obstruction of the ileal ureter interposed between the right and left renal pelvis. Consequently, exploratory laparotomy revealed that left colic vessels oppressed and caused obstruction, and the obstructed ileal ureter was released by reconstitution of these vessels instead of re-anastomosis of the ileal ureter. Left hydronephrosis and related back pain disappeared postoperatively. The number of patients with an indication of ileal-ureteral substitution is increasing for various disorders, and thus, the present report gives additional suggestions for the follow up of patients with ileal ureter.

Adolescent↗
PubMed2006

Primitive neuroectodermal tumor of the adrenal gland.

We report a rare case of primitive neuroectodermal tumor arising from adrenal gland in adulthood, diagnosed preoperatively as having non-functional adrenocortical adenoma. Laparoscopic adrenalectomy was performed. Immunohistological examination revealed the definite diagnosis as primitive neuroectodermal tumor of the adrenal gland. Although primitive neuroectodermal tumor is a highly malignant neoplasm, there is no evidence of local recurrence and distant metastasis 16 months after surgery.

12E7 Antigen↗
PubMed2006

Idiopathic retroperitoneal fibrosis associated with IgG4-positive-plasmacyte infiltrations and idiopathic chronic pancreatitis.

Idiopathic retroperitoneal fibrosis (IRPF) is an inflammatory fibrosclerosing condition, leading to renal failure by obstruction of the ureters. Idiopathic chronic pancreatitis associated with marked inflammatory infiltrates has recently been referred to as autoimmune pancreatitis (AIP), and infiltrating plasmacytes carrying immunoglobulin-gamma type 4 (IgG4) are relevant to its pathogenesis. The case is described herein of IRPF associated with subclinical pancreatitis that was most probably AIP in a 70-year-old man. Biopsy specimens of the retroperitoneal pseudotumor revealed a marked lymphoplasmacytic infiltration with dense fibrosis. Infiltrating plasma cells were immunoreactive for anti-IgG4 antibodies. Subsequent systemic examinations showed an extremely elevated serum IgG4 level and pancreatitis concordant with AIP. Following oral steroid administration, the serum IgG4 level normalized, although the appearance of the pseudotumor did not alter. Some AIP cases have been associated with idiopathic fibrosclerosing disorders including IRPF, but histological evidence of IgG4-related IRPF has rarely been provided.

Aged↗
PubMed2006

Stepping-stones to the further advancement of androgen-deprivation therapy for prostate cancer.

Androgen-deprivation therapy has remained the critical therapeutic option for patients with advanced prostate cancer for over 60 years. Patients with poorly differentiated prostate cancer have low dihydrotestosterone levels in the prostate. After androgen-deprivation therapy, dihydrotestosterone levels in the prostate remain at approximately 25% of the level measured before therapy. The addition of a nonsteroidal anti-androgen to luteinizing hormone-releasing hormone analog or surgical castration significantly reduces the risk of all causes of death by 8%, which translates into a small, but significant, improvement in the 5-year survival of 2.9% over castration alone. The biologically aggressive prostate cancer cells may have an androgen receptor with heightened sensitivity to low dihydrotestosterone levels from the early stage of androgen-dependent disease. It is necessary to consider the androgen environment and the status of the androgen receptor in the prostate in order to improve the clinical efficacy of androgen-deprivation therapy and the quality of life of patients.

Androgen Antagonists↗
PubMed2005

Transforming growth factor-beta1 regulates cell growth and causes downregulation of SMemb/non-muscle myosin heavy chain B mRNA in human prostate stromal cells.

OBJECTIVES: SMemb/non-muscle myosin heavy chain B (SMemb/NMMHC-B) is most abundantly expressed in proliferating smooth muscle cells and correlates with phenotypic changes from a contractive to a proliferative type. The stromal cells of the prostate play a crucial role in the regulation of prostatic growth and function. The aim of this study was to investigate the effects of the multifunctional cytokine transforming growth factor-beta1 (TGF-beta1) on SMemb/NMMHC-B mRNA expression and stromal cell growth. The expression of the SM2 isoform of smooth muscle myosin heavy chain (SMMHC) mRNA was also examined. MATERIAL AND METHODS: Primary cultures of prostate stromal cells were established by means of an explant method from eight normal prostates. The effects of TGF-beta1 on stromal cell growth were determined by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay. SMemb/NMMHC-B and SM2 mRNA expression were analyzed quantitatively by means of real-time polymerase chain reaction. RESULTS: In the absence of TGF-beta1, cells expressed alpha-smooth muscle actin and vimentin. After TGF-beta1 treatment, the expression of alpha-smooth muscle actin increased and cells also expressed desmin. TGF-beta1 at concentrations of 1.0, 5.0 and 10 ng/ml suppressed cell growth by 72%, 62% and 56%, respectively, downregulated SMemb/NMMHC-B mRNA expression by 71%, 52% and 38%, respectively and upregulated SM2 mRNA expression 2.1-, 3.0- and 5.3-fold, respectively. CONCLUSIONS: These results demonstrate that TGF-beta1 modulates the smooth muscle cell phenotype from a proliferative to a contractile type and that the inhibitory effects of TGF-beta1 on stromal cell growth correlate with downregulation of the SMemb/NMMHC-B gene.

Cell Count↗
PubMed2005

A new concept of accommodation in ABO-incompatible kidney transplantation.

This work focuses on the mechanism of acute antibody-mediated rejection leading to graft loss and the mechanisms of accommodation permitting graft survival in ABO-incompatible kidney transplantation. As previously noted, accommodation occurs only with (i) post-transplant suppression of glycosyltransferase, a product of ABO histo-blood group genes in the graft and (ii) prevention of antigen-antibody reactions and delayed hyperacute rejection due to reduced antigenicity of enzyme-regulated histo-blood group antigens. This article discusses the mechanism of ABO histo-blood group glycosyltransferase suppression. Accommodation is always established in successful ABO-incompatible organ grafts and ABO-minor mismatch bone marrow transplantation. In the former, accommodation develops even though ABO histo-blood types of the recipient and the donor are incompatible. In the latter, infusion of donor-derived bone marrow causes the recipient's blood to be eventually replaced by blood of the donor's type. However, the recipient's organs retain their original tissue type. In successful bone marrow engraftment, accommodation is established regardless of ABO-incompatibility. In organ transplantation the recipient's ABO histo-blood type regulates the graft's ABO histo-blood type, while in bone marrow transplantation the new ABO histo-blood type from the donor suppresses and regulates the ABO histo-blood type in recipient organs. In other words, bone marrow-derived histo-blood type regulates the histo-blood type of the organs.

ABO Blood-Group System↗
PubMed2005

The morphological compensatory change of peritubular capillary network in chronic allograft rejection.

To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non-pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non-pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non-pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.

Adult↗
PubMed2005

A prospective trial of steroid withdrawal after renal transplantation treated with cyclosporine and mizoribine in children: results obtained between 1990 and 2003.

A prospective trial of adrenocorticostertoid (steroid) withdrawal after pediatric renal transplantation was begun in 1990. Ninety-four pediatric renal transplant recipients were enrolled in our multicenter study. Immunosuppressive therapy with cyclosporine (CyA), methylprednisolone (MPL), and mizoribine (MZ) was started after transplantation. MPL was reduced to administration on alternate days in 69 patients (73.4%) and was withdrawn in 27 patients (28.7%). Rejection episodes occurred in nine patients (33.3%) after withdrawal of MPL. It occurred within 3 months after withdrawal of MPL in two patients and more than 6 months in the others. Among them, two patients lost the grafts. Thirteen-year patient survival rate and graft survival rate were 94.6 and 83.1%, respectively. Forty-four of the 94 patients reached their final height. Mean final height was 155.0 cm in males and 146.3 cm in females and their height standard deviation score was -2.6 s.d., the same as that at the time of transplantation. Management of growth retardation before transplantation and further reduction in the steroid dose after transplantation will increase the final height of children with chronic renal failure.

Adolescent↗
PubMed2005

Immunosuppressive efficacy of mycophenolate mofetil when compared with azathioprine and mizoribine against peripheral lymphocytes from renal transplant recipients.

Mycophenolate mofetil is currently used instead of azathioprine in clinical transplantation. However, comparative studies for the immunosuppressive potency of anti-metabolites used for organ transplantation have not been well documented. We compared the pharmacological efficacy of mycophenolic acid (MPA), 6-meraputopurine (6-MP), and mizoribine (MZ) for inhibiting purine synthesis of peripheral blood mononuclear cells (PBMCs) in vitro by a mitogen assay procedure. PBMCs were obtained from 18 renal transplant recipients before operation and 18 healthy subjects. The inhibitory efficacy of 6-MP against concanavalin A-induced PBMC blastogenesis exhibited large variations between subjects in both recipients and healthy subjects. In contrast, the pharmacological efficacy of MPA on PBMC blastogenesis showed the smallest inter-individual variation of all the purine synthesis inhibitors examined. Furthermore, the effects of MPA were almost similar in the recipients and healthy subjects. The pharmacological efficacy of MZ against PBMC blastogenesis was weaker than that of the other two agents and the inter-individual variation of MZ IC50 against PBMCs of the patients was larger than that of MZ IC50 against PBMCs of healthy subjects. Reproducible immunosuppressive efficacy of MPA compared with other purinesynthesis inhibitors could be expected from the viewpoint of MPA pharmacodynamics against PBMCs in renal transplantation.

Adult↗