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Biomedical subjects

Norihiko Tsuchiya

Publications and source records attributed to Norihiko Tsuchiya.

At least 19 recordsLinked to original sources
PubMed2006

Radical nephroureterectomy as initial treatment for carcinoma in situ of upper urinary tract.

OBJECTIVES: Transitional cell carcinoma in situ (CIS) of the upper urinary tract is a relatively rare disease, and treatment guidelines remain to be defined. In this study, we evaluated the outcomes after radical nephroureterectomy as the initial therapy for upper urinary tract CIS. METHODS: Eight patients treated with radical nephroureterectomy after the diagnosis of upper urinary tract CIS from December 1999 to May 2004 were entered in this study. The diagnosis criteria included positive voided urinary cytology; negative multiple random biopsies of the bladder; negative radiographic studies, including retrograde pyelography and computed tomography; and serial positive cytology results in selective ipsilateral urine samples. RESULTS: The median follow-up period was 56 months. The presence of CIS was confirmed pathologically in all patients. Two patients had more invasive lesions (pT1 and pT2), although retrospective evaluation revealed no infiltrative lesions. Intravesical recurrence was found in 5 patients, whose median recurrence-free period was 16 months. These heterotopic urothelial recurrences did not affect patient survival, and all 8 patients were alive without disease at last follow-up. CONCLUSIONS: Although radical nephroureterectomy may be overtreatment for some patients with upper urinary tract CIS, excellent survival outcomes can be accomplished. In addition, the presence of concomitant invasive lesions, which cannot be identified on pretreatment examination in a substantial subset of patients with CIS, should be taken into account. Although the number of patients in this study was small, the results support the view that nephroureterectomy should remain a standard option for the initial treatment of this disease.

Aged↗
PubMed2006

Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients.

PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate an urothelium-specific null mutation of Pten in mice [FabpCrePten(flox/flox) (FPten(flox/flox)) mice]. Histologic examination revealed that all FPten(flox/flox) mice exhibited urothelial hyperplasia in which component cells showed enlarged nuclei and increased cell size. With time, 10% of FPten(flox/flox) mice spontaneously developed pedicellate papillary transitional cell carcinomas (TCC). This type of tumor also arose in FPten(flox/flox) mice treated with the chemical carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine. FPten(flox/flox) urothelial cells were hyperproliferative and showed increased activation of the survival signaling molecules Akt and extracellular signal-regulated kinase. In humans, 53% of primary bladder cancer patients exhibited decreased or absent expression of PTEN protein in either the cytoplasm or nucleus of tumor cells. In early bladder cancers, PTEN expression was repressed in 42% of superficial papillary TCC but in only 8% of cases of carcinoma in situ (CIS). In advanced bladder cancers, PTEN protein was significantly reduced (particularly in the nucleus) in 94% of cases, and this decrease in PTEN correlated with disease stage and grade. Thus, PTEN deficiency may contribute to bladder cancer both by initiating superficial papillary TCC and by promoting the progression of CIS to advanced invasive and metastatic forms.

Animals↗
PubMed2006

Circadian pharmacokinetics of mycophenolic Acid and implication of genetic polymorphisms for early clinical events in renal transplant recipients.

BACKGROUND: We investigated the mycophenolic acid (MPA) chronopharmacokinetics and the relation between MPA circadian exposure and the incidence of acute rejection (AR). The association between selected genetic polymorphisms and clinical events or MPA circadian exposure was also studied. METHODS: Thirty recipients were studied one month after renal transplantation. Mycophenolate mofetil (MMF) was administered twice a day at a single dose of 0.5 g in four patients, 0.75 g in eight patients, and 1 g in 18 patients. RESULTS: The daytime area under the concentration-time curve (AUC0-12) was larger than the nighttime AUC0-12 (55.09 vs. 50.54 microg.hr/ml, P=0.049). The Cmax and tmax of MPA after the morning dose were respectively higher and shorter than those after the night dose. Seven patients (23.3%) had AR episodes. The MMF single dose per body weight (12.46 mg/kg in patients with AR vs. 16.99 in patients without AR), daytime and nighttime AUC0-12 (32.41 vs. 62.00 and 24.44 vs. 57.88 microg.hr/ml) and morning trough level of MPA (1.03 vs. 3.83 microg/ml) were significantly lower in patients with AR than in those without AR. The percentage of patients requiring diminished dose of MMF due to diarrhea was higher among patients with the multidrug resistance 1 (MDR1) C3435T T allele than among those with the CC genotype (P=0.049). CONCLUSION: MPA pharmacokinetics showed circadian variations, and a lower MPA AUC in both daytime and nighttime was associated with the occurrence of AR in the early stage after renal transplantation. The MDR1 C3435T polymorphism might be associated with diarrhea due to MPA.

Adult↗
PubMed2006

Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer.

PURPOSE: The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. PATIENTS AND METHODS: One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. RESULTS: Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). CONCLUSION: The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

Aged↗
PubMed2006

Outcome of right hand-assisted retroperitoneoscopic living donor nephrectomy.

OBJECTIVES: To compare the results of right and left hand-assisted retroperitoneoscopic living donor nephrectomy (HARDN) and assess the usefulness and feasibility of right HARDN. METHODS: A total of 68 HARDNs performed from July 2001 to February 2005 in Akita University Medical Center were entered into this study. Of these, 12 cases were right-sided HARDN. The reasons for selecting right HARDN were wandering right kidney in 4, multiple left renal arteries in 3, lower glomerular function presenting in the right kidney in 2 patients, and left renal stone, right renal cyst, and right renal aneurysm in 1 patient each. We compared the perioperative and postoperative results of the 12 right-sided HARDNs with those of the 56 left HARDNs. RESULTS: No significant differences were found between the two groups in the demographic data (ie, age, sex, number of renal arteries), except for the body mass index. None of the right HARDNs resulted in major complications or open conversion, but two left HARDNs required conversion to open surgery. No difference was found between the two groups regarding estimated blood loss, warm ischemia time, or time to oral intake, although the right HARDN group had a longer mean operative time. No significant differences were found in the recipient's postoperative graft function or in the frequency of delayed graft function. CONCLUSIONS: Right HARDN provided almost similar perioperative and postoperative outcomes compared with those of left HARDN. Our results indicate that right HARDN is a choice for living donor nephrectomy because of its technical feasibility, safety, and minimal invasiveness, which are comparable to those of left HARDN.

Adult↗
PubMed2006

Bladder acellular matrix grafting regenerates urinary bladder in the spinal cord injury rat.

OBJECTIVES: To assess the feasibility of bladder acellular matrix (BAM) grafting onto the bladder of rats with spinal cord injury (SCI). METHODS: Female Wistar rats, weighing 100 to 150 g, were divided into four groups: neurologically intact groups with sham operation or BAM grafting and SCI rats with or without BAM grafting (grafted groups, n = 15 each; nongrafted groups, n = 5 each). The BAM was prepared from other normal rat bladder tissue. During BAM surgery, the rats underwent partial cystectomy, followed by BAM grafting as a bladder augmentation. The SCI was created by compressing the spinal cord at the 10th thoracic level. BAM grafting in SCI rats was performed 2 to 3 weeks after SCI. At 2, 4, and 12 weeks after grafting, cystometry was performed with the rats under pentobarbital anesthesia, and the bladders were subsequently harvested and immunostained with anti-PGP9.5, uroplakin III, and alpha-smooth muscle actin antibodies (n = 5 each time). For comparison, similar examinations were performed in the nongrafted groups (n = 5 each). RESULTS: Regenerated urothelium, smooth muscles, and nerve fibers in the grafted BAM appeared at 2, 4, and 12 weeks, respectively, in both intact and SCI rats. Immunohistologic examination showed that these regenerated tissues inherited each characteristic of the host bladder tissue. The grafted BAM itself also showed the proper storage function of distensibility in the intact and SCI groups receiving BAM. CONCLUSIONS: Our data have indicated that BAM grafting is feasible, even in animals with spinal injury, suggesting that BAM may be one of the alternatives for patients with a neurogenic bladder who require augmentation enterocystoplasty in clinical situations.

Animals↗
PubMed2006

Cavernous nerve regeneration by biodegradable alginate gel sponge sheet placement without sutures.

OBJECTIVES: Alginate, a biodegradable polysaccharide, may be applied to facilitate nerve regeneration. We attempted to regenerate excised cavernous nerves by filling the gap with a biodegradable alginate gel sponge sheet without sutures. METHODS: Bilateral cavernous nerves of male Wistar rats were excised to make an approximately 2-mm gap. A piece of freeze-dried alginate sheet was then placed over the gap to cover each stump without suturing (alginate group). We also performed sham operations (sham group) and bilateral nerve excision alone (excision group). RESULTS: Erection was confirmed visually by mating behavior in 9%, 36% and 73% of alginate rats at 2, 4, and 12 weeks, respectively. In contrast, no excision rats had an erection. At 12 weeks postoperatively, electrical stimulation of the pelvic plexus increased intracavernous pressure in the sham group and alginate rats with restored erectile function. However, no increase occurred in the excision group. In a retrograde neural tracing study with FluoroGold at 12 weeks, rich FluoroGold-positive cells were observed in the sham group and alginate rats with restoration, but very few were found in the excision group. Double-labeled immunochemistry with anti-S-100 and beta-tubulin III antibodies showed that the neural gap was connected with the regenerated nerve fibers at 12 weeks. CONCLUSIONS: The results of our animal study have demonstrated that by simply filling the nerve gap using an alginate sheet, the cavernous nerve can be regenerated and erectile function may be restored.

Absorbable Implants↗
PubMed2006

Hand assisted retroperitoneoscopic living donor nephrectomy in elderly donors.

PURPOSE: We assessed the influence of HARDN on residual donor kidney and allograft function, invasiveness and morbidity in elderly living donors. MATERIALS AND METHODS: A total of 89 living donors underwent nephrectomy before September 2004 at our institution. The 18 donors who were 65 years or older included 4 of 27 with ODN and 14 of 62 with HARDN. RESULTS: In older (65 years or older) donors mean operative time, mean blood loss and warm ischemia time in the HARDN group did not differ from those in the ODN group. None of the donors had major complications. Older donors with HARDN had a tendency toward a shorter hospital stay than those with ODN. Postoperative serum creatinine in older donors with HARDN was higher than that in younger donors with HARDN, while there was no difference in postoperative serum creatinine between older donors with HARDN and those with ODN. The frequency of allograft losses tended to be higher in older than in younger kidneys (4 of 18 vs 5 of 71, p = 0.054). However, most allograft losses did not seem to be related to surgical technique. CONCLUSIONS: Although further studies, especially with long-term followup, are necessary, HARDN is suggested to be safe and minimally invasive surgery even in elderly donors and to be comparable to open surgery in terms of morbidity, the residual donor kidney and allograft function.

Adult↗
PubMed2006

Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal aberration of testicular germ cell tumors.

It is known that many genomic and genetic alterations caused by aging or environmental factors are responsible for cancer development and progression. XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The objective of this study was to investigate the association of genomic alterations and the susceptibility of testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4 microsatellite markers in a subgroup of 50 patients. Patients with at least one Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated with the Gln allele against the Arg homozygote was more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no significant difference in the genotype distribution between TGCT patients and the controls. In AI analysis, the frequency of AI was significantly higher in tumors with at least one Gln allele than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development and progression of TGCT through genomic instability.

Chromosome Aberrations↗
PubMed2005

Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus.

BACKGROUND: The present study investigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus-based immunosuppression based on clinical characteristics, tacrolimus pharmacokinetics, and genetic polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus. METHODS: Seventy nondiabetic adult kidney recipients were studied. Patients with continuous high plasma glucose levels, over 6.5 mg/dl of hemoglobin A1c, or requiring insulin and/or oral antidiabetic agents for more than 3 months after transplantation 6 months postoperatively were diagnosed as having PTDM. Twelve genomic polymorphisms were assessed. RESULTS: Six months after transplantation, 10 recipients (14.3%) developed PTDM. Positive risk factors were age (P=0.019) and body mass index (P=0.038). There were no significant differences in acute rejection rate, total steroid doses, tacrolimus pharmacokinetics or its related to genetic polymorphisms between the two groups. The frequency of PTDM was significantly higher in patients with the vitamin D receptor (VDR) TaqI t allele than in those with the TT genotype (P=0.013). On multivariate analysis, age over 50 years (odds ratio 9.28, P=0.003) and the presence of the VDR TaqI t allele (odds ratio 7.05, P=0.048) were correlated with the development of PTDM. CONCLUSION: The incidence of PTDM was 14.3% in our cohort. Age over 50 years was a risk factor. The presence of the VDR TaqI t allele may also be a risk factor for PTDM, suggesting that genotyping of diabetes-related polymorphisms is a possible method of predicting a patient's risk for developing PTDM and would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals.

Adiponectin↗
PubMed2005

Association of BCL10 germ line polymorphisms on chromosome 1p with advanced stage testicular germ cell tumor patients.

The association between four BCL10 single nucleotide polymorphisms at codons 5, 8, 162, and intron 1 and the susceptibility or progression for germ cell tumors (GCTs) was investigated in 73 testicular GCT patients and 72 controls. GCT patients with metastatic disease were more likely to have a variant type allele of the polymorphisms at codon 5 (age-adjusted odds ratio (aOR)=6.25; 95% CI=1.09-35.83; P=0.040) and codon 8 (aOR=4.63; 95% CI=1.35-15.93; P=0.015) than those with the localized disease. Therefore, BCL10 polymorphisms at codons 5 and 8 may play a role in the progression to advanced stage GCTs.

Adaptor Proteins, Signal Transducing↗
PubMed2005

CYP3A5 gene polymorphism and risk of prostate cancer in a Japanese population.

The CYP3A5 gene (CYP3A5) encodes the cytochrome P450 3A5, which catalyzes the 6beta-hydroxylation of testosterone. We explored association between the CYP3A5 A6986G polymorphism and a risk of prostate cancer in 260 prostate cancer patients, 199 BPH patients and 212 male controls. The CYP3A5 gene polymorphism did not influence significantly a risk of developing of prostate cancer in general. However, compared with males with the GG genotype, those with the AA genotype had a 0.23-fold decreased risk of developing low-grade prostate cancer (P=0.023), and a 0.31-fold decreased risk of developing localized (stages A-C) prostate cancer (P=0.044). The CYP3A5 A6986G polymorphism may be specifically associated with a decreased risk of low-grade or early stage prostate cancer.

Aged↗
PubMed2005

An A/G polymorphism of core 2 branching enzyme gene is associated with prostate cancer.

The expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1 (C2GnT) is associated with development and progression of malignancy. Sequence analysis showed that the codon 152 of C2GnT has a polymorphism having GTT encoding valine or ATT encoding isoleucine. By examining the polymorphism in prostate cancer and benign prostatic hyperplasia patients, we found that the C2GnT G allele was more frequently observed in the prostate cancer group (p=0.015) than the control group. Men with the GG genotype had a 3.60-fold increased risk of prostate cancer, and men with the AG genotype had a 1.58-fold increased risk of prostate cancer compared with those with the AA genotype. The G allele was found to have a gene dosage effect for prostate cancer risk. No such risk was associated for benign prostatic hyperplasia. These results demonstrate that C2GnT A/G polymorphism is associated with the susceptibility to prostate cancer in a Japanese population.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2005

Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection.

PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

Animals↗
PubMed2005

Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis.

PURPOSE: We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). MATERIALS AND METHODS: Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. RESULTS: Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). CONCLUSIONS: In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.

Adolescent↗
PubMed2005

Successful renal transplantation in the right iliac fossa 2 years after serious deep venous thrombosis in a patient with systemic lupus erythematosus.

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.

Adult↗
PubMed2005

CA repeat polymorphism in the insulin-like growth factor-I gene is associated with increased risk of prostate cancer and benign prostatic hyperplasia.

Insulin-like growth factor-I (IGF-I) plays an important role in prostate growth, hyperplasia, and carcinogenesis. Circulating IGF-I levels may be modulated by a genetic cytosine-adenine (CA) repeat polymorphism in the promoter region of IGF-I. The association of the polymorphism with the risk of prostate cancer and benign prostatic hyperplasia (BPH) was explored in 303 patients with prostate cancer, 219 patients with BPH and 262 controls. The number of CA repeats ranged from 15 to 22 in case and control subjects. The 19-CA-repeat allele (19-allele) was more frequently observed in both the prostate cancer and BPH patients compared with the controls (prostate cancer versus control: P<0.001; BPH versus control: P=0.001). Compared with non-carriers of the 19-allele, men homo-zygous for the 19-allele had a significantly increased risk of prostate cancer [age-adjusted odds ratio (aOR) = 3.36, 95% confidence intervals (CI) = 1.30-8.67, P=0.012] or BPH (aOR = 3.53, 95% CI = 1.32-9.46, P=0.012), and those heterozygous for the 19-allele also had an intermediate increased risk of prostate cancer (aOR = 1.78, 95% CI = 1.25-2.53, P=0.001) or BPH (aOR = 1.66, 95% CI = 1.14-2.43, P=0.009). A gene dosage effect for the aORs was found with an increasing number for the 19-allele (P<0.001 in prostate cancer and P=0.001 in BPH). No significant association was found between the presence of the 19-allele and the tumor stage and grade at the time of diagnosis. In conclusion, the 19-allele of IGF-I appears to increase the risk of prostate cancer and BPH with a gene dosage effect in the Japanese population.

Alleles↗