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N Shimoda

Publications and source records attributed to N Shimoda.

At least 19 recordsLinked to original sources
PubMed2004

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

Animals↗
PubMed2004

A case of plasmacytic hyperplasia arising in a kidney allograft salvaged with immunosuppression reduction alone.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation. Plasmacytic hyperplasia (PH) is thought of as the mildest form of PTLD; however, a graftectomy is necessary in most situations. We experienced an interesting case of PH arising in a kidney allograft, which could be relieved with a reduction in immunosuppression. A 27-year-old female underwent a living-related kidney transplantation. A 3-month non-episode protocol biopsy unexpectedly showed the devastating appearance of polymorphic plasma cell infiltration into the graft intersitium, compatible with PH. The PH was located in the graft by radiographic examinations. The infiltration of plasma cell disappeared completely on the 6-month graft biopsy specimen following immunosuppression reduction and the graft is functioning, although it was damaged by a subsequent acute rejection. Our present case indicates that some PTLD can be completely cured with a reduction in immunosuppression alone. The diagnostic modality for the evaluation of PTLD cell extinction is necessary to maintain graft function with adequate immunosuppression thereafter.

Adult↗
PubMed2003

Rectosigmoidal bladder utilizing an intussuscepted ileal segment: a surgical technique for urinary diversion.

A novel technique of urinary diversion was designed by interposition of an intussuscepted ileal segment between the ureters and the rectosigmoidal pouch, thus preventing ureteral reflux as well as stenosis at the uretero-enteric anastomosis, possible occurrence of urocolonic carcinoma, and frequent evacuation or incontinence. Since all the procedures were limited to the lower abdominal cavity, the surgical invasiveness was compatible with that of an ileal conduit. Our early experience in 15 patients showed that this technique can be considered for those in whom the urethra is not available.

Adult↗
PubMed2003

Total cystoprostatectomy in the treatment of locally advanced prostate carcinoma.

OBJECTIVE: Locally advanced prostate carcinoma frequently causes lower urinary tract symptoms and is a clinical challenge when radiation and/or hormone therapy fail. We investigated whether cystoprostatectomy with urinary diversion benefits patients with locally advanced prostate carcinoma in terms of quality of life and prognostic outcome. PATIENTS AND METHODS: Between 1989 and 2001, we performed 15 cystoprostatectomies for stage C-D1 prostate carcinoma with bladder neck involvement. Of these patients, 5 underwent ileal conduit, 8 rectal bladder, 1 Koch pouch, and 1 ureterocutaneostomy. All the patients received neoadjuvant and/or adjuvant hormonal therapy. In the same period, 28 patients underwent retropubic prostatectomies and 15 patients received hormone therapy alone for stage C-Dl disease. These patients were included as references. RESULTS: Lower urinary tract symptoms caused by bladder involvement were controlled well until the end of follow-up for all the patients in the cystoprostatectomy group. There was no statistically significant difference in QOL score assessed with the EORTC QLQ-C30 questionnaire between the prostatectomy group and the cystoprostatectomy group, while that in the hormone therapy group was lower than those in the surgery groups. There was no statistically significant difference in 5-year PSA-relapse-free survival among cystoprostatectomy, prostatectomy, and hormone therapy groups. Patients in the hormone therapy group died earlier than those in the prostatectomy group (p = 0.02), while those in the cystoprostatectomy group did not. CONCLUSION: These results suggest that total cystoprostatectomy with urinary diversion is a valid option, in terms of disease control and QOL, for prostate cancer patients whose tumor is infiltrating into the bladder.

Aged↗
PubMed2001

Sepsis increases the plasma membrane content of alpha1 and alpha2 isoforms of Na+-K+ adenosine triphosphatase in rat skeletal muscle.

HYPOTHESIS: Increased Na(+)-K(+) adenosine triphosphatase (ATPase) activity in skeletal muscle during sepsis is caused by transient increases in enzyme content within the plasma membrane. DESIGN: Randomized controlled study. SETTING: University laboratory. INTERVENTION: Eighty-eight adult male Wistar rats were randomly assigned to undergo cecal ligation and puncture (CLP) or sham operation. MAIN OUTCOME MEASURES: Gastrocnemius muscles were harvested 6, 12, 24, and 48 hours after operation and Na(+)-K(+) ATPase activities were measured spectrofluorimetrically. Messenger RNA (mRNA) levels for the alpha1 and alpha2 isoforms of Na(+)-K(+) ATPase were determined by Northern blot analysis. Crude membranes, internal membranes, and purified plasma membranes were isolated from gastrocnemius muscles and protein levels of alpha1 and alpha2 isoforms were determined by Western blot analysis. RESULTS: Na(+)-K(+) ATPase activity in the CLP group was significantly higher compared with the sham group 24 hours after operation (P<.05). However, there were no differences between the sham and CLP groups 6, 12, or 48 hours after operation. No significant differences between the CLP and sham groups were noted in mRNA levels for Na(+)-K(+) ATPase alpha1 and alpha2 isoforms. Western blot analysis revealed that the plasma membrane (but not internal membrane or crude membrane) content of alpha2 and alpha1 isoforms from the CLP group was significantly increased compared with the sham group 24 hours after operation (P<.05). CONCLUSIONS: Na(+)-K(+) ATPase activity increases 24 hours after CLP in gastrocnemius muscle and then declines. This increase is caused by increased Na(+)-K(+) ATPase protein levels in the plasma membrane.

Animals↗
PubMed2001

Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administration.

BACKGROUND: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. METHODS: The blood concentration-time curve was studied in 10 living-related kidney transplant recipients, aged 18-51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. RESULTS: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0-27.2% for preoperative and 6.4-22.0% for postoperative area under the curve, respectively. CONCLUSION: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment.

Administration, Oral↗
PubMed2001

Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.

Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.

Aged↗
PubMed2001

[A case of retroperitoneal fibrosis responding to steroid therapy].

A 73-year-old man presented with acute renal failure due to bilateral hydronephroses. Urography and CT scan revealed stenosis and medial deviation of the bilateral ureters surrounded by a soft tissue mass at the level of the 4-5th lumber vertebrae. Under a diagnosis of retroperitoneal fibrosis, bilateral nephrostomies were temporarily placed and prednisolone administration was initiated at a dose of 20 mg/day. Ureteral passage markedly improved within 2 weeks in association with a decrease in size of the retroperitoneal soft tissue mass. The steroid therapy was continued for 4 months with decreasing dosing schedule. The patient has been doing well without any signs of recurrence for 3 months after the cessation of the steroid therapy.

Aged↗
PubMed2000

Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect.

The CYP17 gene (CYP17) codes for the cytochrome P450c17alpha enzyme, which mediates two key steps in the sex steroid synthesis. There is a polymorphism (a T-to-C substitution) in the 5'-untranslated region, which may influence the transcription level of CYP17 mRNA. There is a continuing controversy as to whether the variant allele is associated with a subset of breast cancer or polycystic ovary syndrome. In prostate cancer research, there are contradictory data concerning the CYP17 risk allele. We explored the association between CYP17 polymorphism and a risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. This study included 252 prostate cancer patients, 202 BPH patients, and 131 male controls. A 451-bp fragment encompassing the polymorphic site was amplified by PCR, treated with restriction enzyme MspA1, and electrophoresed on an agarose gel. The MspA1-undigested allele with the published sequence and the MspA1-digested variant allele were designated as A1 and A2, respectively. There was a significant difference (P < 0.05) in the genotypes between prostate cancer patients and male controls, and between BPH patients and male controls. Men with the A1/A1 CYP17 genotype had an increased risk of prostate cancer [odds ratio (OR), 2.57; 95% confidence interval (CI) = 1.39-4.78] and BPH (OR, 2.44; 95% CI = 1.26-4.72) compared with those with the A2/A2 genotype. Men with the A1/A2 genotype had an intermediate increased risk of prostate cancer (OR, 1.45; 95% CI = 0.84-2.54) and BPH (OR, 1.60; 95% CI = 0.89-2.87) compared with those with the A2/A2 genotype. The trend of an increasing risk of prostate cancer and BPH with an increasing number of the A1 allele was statistically significant (prostate cancer versus male control, P = 0.003; OR, 1.57; 95% CI = 1.16-2.12; BPH versus male control, P = 0.008; OR, 1.55; 95% CI = 1.12-2.13). There was no significant association between the CYP17 genotype and the tumor status (grade and stage) of prostate cancer. Our results suggest that the A1 allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and BPH, with a gene dosage effect. However, the CYP17 genotype does not seem to influence the disease status in prostate cancer.

Aged↗
PubMed2000

Signaling mechanisms of glucagon-like peptide 2-induced intestinal epithelial cell proliferation.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) stimulates intestinal epithelial growth with high potency and specificity. However, the intracellular signaling pathways responsible for the growth-stimulatory action of GLP-2 are not clearly understood. Here we report possible signaling pathways mediating GLP-2's proliferative actions in the human intestinal epithelial cell line Caco-2. MATERIALS AND METHODS: Caco-2 cells were subcultured under serum-deprived conditions in the presence or absence of GLP-2 (10 microM) and varying concentrations of inhibitors of three candidate kinases: genistein, a global tyrosine kinase inhibitor; LY294002, a phosphatidylinositide (PI) 3-kinase inhibitor; and PD 098059, a mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitor. Proliferation was assessed using [(3)H]thymidine incorporation. Relative abundance of the phosphorylated forms of two specific mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, was assessed by Western blotting. RESULTS: GLP-2-treated cells demonstrated a greater than 10-fold increase in proliferation. This response was inhibited by genistein, LY294002, and PD 098059 in a dose-dependent fashion. A significantly greater abundance of the phosphorylated forms of both ERK-1 and ERK-2 was present in cells within 5 min of treatment with GLP-2. CONCLUSIONS: GLP-2 stimulates the proliferation of Caco-2 cells in vitro. This increase in Caco-2 proliferation in response to GLP-2 may be due, at least in part, to the involvement of both the PI 3-kinase and the MAPK pathways.

Caco-2 Cells↗
PubMed2000

Proviral insertions in the zebrafish hagoromo gene, encoding an F-box/WD40-repeat protein, cause stripe pattern anomalies.

The zebrafish, Danio rerio, has three types of pigment cells (melanophores, xanthophores and iridophores) and, in adult fish, these cells are organized into a stripe pattern. The mechanisms underlying formation of the stripe pattern are largely unknown. We report here the identification and characterization of a novel dominant zebrafish mutation, hagoromo (hag), which was generated by insertional mutagenesis using a pseudotyped retrovirus. The hag mutation caused disorganized stripe patterns. Two hag mutant alleles were isolated independently and proviruses were located within the fifth intron of a novel gene, which we named hag, encoding an F-box/WD40-repeat protein. The hag gene was mapped to linkage group (LG)13, close to fgf8 and pax2.1. Amino acid sequence similarity, conserved exon-intron boundaries and conserved synteny indicated that zebrafish hag is an ortholog of mouse Dactylin, the gene mutated in the Dactylaplasia (Dac) mouse [1]. The Dac mutation is dominant and causes defects in digit formation in fore- and hindlimbs. This study revealed that the hag locus is important for pattern formation in fish but is involved in distinct morphogenetic events in different vertebrates.

Amino Acid Sequence↗
PubMed2000

Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population.

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.

3' Untranslated Regions↗
PubMed2000

Genetic analysis of the signal-sensing region of the histidine protein kinase VirA of Agrobacterium tumefaciens.

The membrane-bound sensor protein kinase VirA of Agrobacterium tumefaciens detects plant phenolic substances, which induce expression of vir genes that are essential for the formation of the crown gall tumor. VirA also responds to specific monosaccharides, which enhance vir expression. These sugars are sensed by the periplasmic domain of VirA that includes the region homologous to the chemoreceptor Trg, and the phenolics are thought to be detected by a part of the cytoplasmic linker domain, while the second transmembrane domain (TM2) is reported to be nonessential. To define regions of VirA that are essential for signal sensing, we introduced base-substitution and deletion mutations into coding regions that are conserved among the respective domains of VirA proteins from various Agrobacterium strains, and examined the effects of these mutations on vir induction and tumorigenicity. The results show that the Trg-homologous region in the periplasmic domain is not essential for the enhancement of vir gene expression by sugars. Most mutations in the TM2 domain also failed to influence enhancement by sugars and reduced the level of vir induction, but a mutation in the TM2 region adjacent to the cytoplasmic linker abolished induction of the vir genes. In the linker domain, sites essential for vir induction by phenolics were scattered over the entire region. We propose that a topological feature formed by the linker domain and at least part of the TM2 may be crucial for activation of a membrane-anchored VirA protein. Complementation analysis with two different VirA mutants suggested that intermolecular phosphorylation between VirA molecules occurs in vivo, and that two intact periplasmic regions in a VirA dimer are required for the enhancement of vir induction by sugars.

Agrobacterium tumefaciens↗
PubMed2000

An accessory spleen mimicking a nonfunctional adrenal tumor: a potential pitfall in the diagnosis of a left adrenal tumor.

We describe a case of accessory spleen mimicking a left adrenal tumor. A 66-year-old woman was referred to our hospital because of a suspected left adrenal mass detected by US. A laparoscopic adrenalectomy was performed, and examination of the surgical specimen revealed that the resected adrenal gland contained no tumorous lesion. A further investigation of the intraperitoneal space revealed an accessory spleen. This indicates that urologists should be aware of the possible existence of accessory spleens when left adrenal tumors are suspected on CT and MRI.

Adrenal Gland Neoplasms↗
PubMed1999

Distribution characteristics of entrapped recombinant human erythropoietin in liposomes and its intestinal absorption in rats.

Recombinant human erythropoietin (Epo) is frequently administered by intravenous (i.v.) injection for the clinical treatment of renal anemia. Oral (per os; p.o.) administration is desired as an alternative route to i.v. administration, and liposomes have been chosen as a drug carrier. We found previously that after a p.o. administration to rats of Epo entrapped in liposomes before gel filtration, the Epo was absorbed, but variability in the number of days of appearance and in the levels of pharmacological effects, i.e. , the peak of circulating reticulocyte counts (RTC), was observed. The purpose of the present study was to examine the distribution characteristics of Epo in liposomes and intestinal absorption of liposomal Epo in rats by using purified Epo entrapped in liposomes after gel filtration (Epo/liposomes). The distribution characteristics of Epo/liposomes were determined by measuring the Epo in liposomes by a radioimmunoassay, high-performance liquid chromatography and zeta potential measurements. We observed that the protein part of Epo was mostly entrapped in liposomes, and was not adsorbed by the liposomal membrane at middle and high Epo p.o. doses, but the zeta potential of the Epo/liposomes increased negatively with the increase in the Epo p.o. doses. These results suggest that the sialic acid part of Epo entrapped in liposomes may project out from liposomes, depending on the entrapped Epo concentration. Little Epo was adsorbed or penetrated into liposomes when it was added to empty liposomes. After the p. o. administration of Epo/liposomes, the peak of RTC appeared at a 2-day delay on day 6, without variation and without dose dependency in comparison with that after i.v. administration. These results suggest that one of the reasons for the variability may be because the non-entrapped Epo and/or Epo/liposomes itself affected the intestinal absorption of Epo/liposomes. In conclusion, Epo/liposomes without nonentrapped Epo may be clinically useful for the oral administration of Epo.

Administration, Oral↗
PubMed1999

Zebrafish genetic map with 2000 microsatellite markers.

The zebrafish is the first vertebrate organism used for large-scale genetic screens seeking genes critical to development. These screens have been quite successful, with more than 1800 recessive mutations discovered that speak to morphogenesis of the vertebrate embryo. The cloning of the mutant genes depends on a dense genetic map. The 2000 markers we present here, using microsatellite (CA) repeats, provides 1.2-cM average resolution. One centimorgan in zebrafish is about 0. 74 megabase, so, for many mutations, these markers are close enough to begin positional cloning by YAC walks.

Animals↗