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Biomedical subjects

K Nonomura

Publications and source records attributed to K Nonomura.

At least 19 recordsLinked to original sources
PubMed2004

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias.

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.

Adult↗
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↗
PubMed2003

Diminished penile expression of vascular endothelial growth factor and its receptors at the insulin-resistant stage of a type II diabetic rat model: a possible cause for erectile dysfunction in diabetes.

Erectile dysfunction (ED) is commonly experienced in men with diabetes mellitus. Vascular endothelial growth factor (VEGF) has been extensively documented for its pathogenic significance in different complications of diabetes. We hypothesized that expressions of VEGF, its receptors and its signaling pathway Akt may be drastically altered in diabetic penile tIssues and their alterations may modulate penile expression of the molecules that are believed to play a role in diabetic ED. Otsuka Long-Evans Fatty (OLETF) rats, a type II (non-insulin-dependent) diabetes mellitus, were used at the insulin-resistant stage of type II diabetes (20 weeks of age). We determined protein and mRNA expressions of VEGF, its receptors, Akt, nitric oxide synthase isoforms, and apoptosis-related molecules in the penis using immunohistochemistry, Western blotting, in situ hybridization, and real-time quantitative PCR analyses. The penile sections were also submitted to the Tdt-mediated dUTP nick end labeling assay for apoptosis. OLETF rats showed marked reductions in penile expression of VEGF, its two receptors and Akt. In OLETF rat penises, endothelial and neuronal nitric oxide synthase isoforms were expressed less abundantly. Furthermore, while anti-apoptotic markers, Bcl-2 and phosphorylated Bad, were down-regulated, pro-apoptotic markers, active caspase-3 and Bax, were up-regulated, resulting in the appearance of apoptotic cells in the penile tIssues of OLETF rats. The VEGF signaling system would work less well in diabetic penile tIssues as a result of the reduced expression, leading to diminished endothelial production of nitric oxide and apoptosis-related erectile tIssue damage. We propose that the abnormalities of the VEGF signaling system in the penis may play a role in the pathophysiology of diabetic ED.

Animals↗
PubMed2001

The centromere composition of multiple repetitive sequences on rice chromosome 5.

The large-scale primary structure of the centromeric region of rice chromosome 5 was analyzed, the first example in a cereal species. The yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC) contigs aligned on the centromere of rice chromosome 5 (CEN5) covered a distance of more than 670 kb. Strong suppression of genetic recombination, one of the features of a functional centromere, occurred along the contig region. The most remarkable feature of CEN5 is the composition of the multiple repetitive elements. Oryza-specific RCS2 short tandem repeats were clustered along less than 100 kb at one end of the contig. At least 15 copies of the conserved domain of the 1.9 kb RCE1 centromeric repeats, which are similar to the long terminal repeats (LTRs) of gypsy-type retrotransposon RIRE7, were dispersed mainly in 320 kb stretches next to RCS2 tandem clusters. Many copies of the LTR-like sequences of RIRE3 and RIRE8, another gypsy-type retrotransposon, were also found throughout the contig. On the other hand, the gagpol region was less conserved in the contig. These results indicate that the rice centromere is composed of multiple repetitive sequences with the RCS2 tandem cluster probably being situated as the core of a functional centromere of some hundreds of kilobases to megabases in length.

Base Sequence↗
PubMed2001

Laparsocopic ureteroureterostomy for retrocaval ureter.

Two cases of retrocaval ureter are reported that were successfully treated by a laparoscopic approach. Case 1 was a 20-year-old woman who presented with symptoms of a right ureter stone. Case 2 was a 23-year-old woman who had suffered from recurrent right flank pain with gross hematuria. A transperitoneal approach was used for case 1, and a retroperitoneal approach was used in case 2. Both were successfully treated with laparoscopic ureteroureterostomy using an intracorporeal suture technique. Laparoscopic surgery should be the first choice for retrocaval ureter not only because of the minimal invasiveness but also because of the cosmetic advantage compared to conventional open surgery. Further technical and instrumental advances are essential for intracorporeal suturing.

Adult↗
PubMed2001

Pre-emptive renal transplantation in children.

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

Acute Disease↗
PubMed2001

Intravenous digital subtraction angiography and helical computed tomography in evaluation of living renal donors.

OBJECTIVES: The present study was carried out to evaluate the accuracy of helical computed tomography (CT) and intravenous digital subtraction angiography (IV-DSA) on anatomical assessment of renal vasculature for living renal donors. METHODS: Forty-two healthy potential renal donors were prospectively evaluated and 35 subsequently underwent donor nephrectomy after helical CT and IV-DSA evaluation. The vascular and non-vascular findings were compared between the findings on helical CT, IV-DSA and surgery. RESULTS: Ten prehilar branches and five accessory renal arteries were found at nephrectomy. Overall, operative findings agreed with the findings by IV-DSA in 89% and by helical CT in 83%. In delineating accessory arteries, IV-DSA had a sensitivity of 60% and specificity of 97%, whereas helical CT had a sensitivity of 40% and specificity of 100%. In delineating prehilar branches, IV-DSA had a sensitivity of 90% and specificity of 100%, whereas helical CT had a sensitivity of 70% and specificity of 100%. Accessory arteries and prehilar branches that were not detected by helical CT or IV-DSA, were less than 2 mm in diameter and did not require vascular reconstruction. Renal veins were delineated in 63% by IV-DSA, whereas they were clearly imaged by helical CT in all cases, including a case with a circumaortic renal vein. Non-vascular findings were obtained in 64% by helical CT, including two renal tumors. None of these findings were obtained by IV-DSA. CONCLUSION: Helical CT and IV-DSA provide comparably sufficient information on renal artery vasculature. However, helical CT provides significantly more information on venous and non-vascular findings as a single-imaging modality.

Adult↗
PubMed2001

Testicular-sparing surgery for the prepubertal testicular tumor. Experience of two cases with large cell calcifying Sertoli cell tumors.

PURPOSE: We review prepubertal germ cell tumors of testis in our institute and the Japanese registry and present 2 cases with a large cell calcifying Sertoli cell tumor (LCCSCT) and discuss the possibility of testis-sparing surgery. MATERIALS AND METHODS: Incidence, age, pathology and clinical stages of prepubertal germ cell tumors are surveyed for 30 years at our department and 10 years of the malignant tumor registry of the Japanese Society of Pediatric Surgery. Two representative prepubertal boys with LCCSCT are presented. One of them was treated by partial orchiectomy. RESULTS: The majority of testicular germ cell tumors in the prepubertal age were composed of embryonal cell carcinoma/yolk sac tumors or teratoma, occurred in preschool age, were limited to clinical stage I and did not metastasize irrespective of histology. Benign behavior which included recovery from hormonal derangement, no tumor recurrence and negative antisperm antigen was observed in 2 cases with LCCSCT who underwent either radical orchiectomy or partial orchiectomy. CONCLUSION: Partial orchiectomy should be considered as a standard option in prepubertal schoolboys with a testicular mass if surgically feasible. This surgical treatment is safe and preserves fertility and is psychologically advantageous. It is not recommended for yolk sac tumors that may recur, however they are rare in prepubertal boys and can be differentiated preoperatively by prudent evaluation.

Adolescent↗
PubMed2000

Neurosurgery at Fujita Health University, Japan.

Neurosurgery at the Fujita Health University began in 1972 with Dr. Tetsuo Kanno. In 1973, he was joined by Dr. Kazuhiro Katada and in the year 1976, an independent neurosurgery department was established with Dr. Kanno as the Chief of Neurosurgery. Under his guidance the department continued to grow and by 1978, a neurosurgical residency program recognised by the Japanese Board of Neurosurgery was established. Integration of laboratory research and clinical experience is the hallmark of this program. The current philosophy is directed towards subspecialization and academic training. This article provides a brief overview of the rapid development of a Neurosurgical Centre to reach international acclaim under the guidance of Prof. Tetsuo Kanno.

Hospitals, University↗
PubMed2000

Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases.

Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide++ + dihydrochloride] is widely used as a specific inhibitor of the Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) family of protein kinases. This study examined the inhibition mechanism and profile of actions of Y-27632 and a related compound, Y-30141 [(+)-(R)-trans- 4-(1-aminoethyl)-N-(1H-pyrrolo[2, 3-b]pyridin-4-yl)cyclohexan-ecarboxamide dihydrochloride]. Y-27632 and Y-30141 inhibited the kinase activity of both ROCK-I and ROCK-II in vitro, and this inhibition was reversed by ATP in a competitive manner. This suggests that these compounds inhibit the kinases by binding to the catalytic site. Their affinities for ROCK kinases as determined by K(i) values were at least 20 to 30 times higher than those for two other Rho effector kinases, citron kinase and protein kinase PKN. [(3)H]Y-30141 was taken up by cells in a temperature- and time-dependent and saturable manner, and this uptake was competed with unlabeled Y-27632. No concentrated accumulation was found, suggesting that the uptake is a carrier-mediated facilitated diffusion. Y-27632 abolished stress fibers in Swiss 3T3 cells at 10 microM, but the G(1)-S phase transition of the cell cycle and cytokinesis were little affected at this concentration. Y-30141 was 10 times more potent than Y-27632 in inhibiting the kinase activity and stress fiber formation, and it caused significant delay in the G(1)-S transition and inhibition of cytokinesis at 10 microM.

3T3 Cells↗
PubMed1999

Reappraisal of Tc-99m DMSA scintigraphy for follow up in children with vesicoureteral reflux.

We reviewed Tc-99m DMSA scintigraphy in children with vesicoureteral reflux (VUR) in order to assess whether repeated Tc-99m DMSA scans are necessary for the follow up of these patients. Ninety-seven children who were followed up for more than one year (1-7.4 years, average 2.8 years) after the first DMSA scan were included in the study. Fifty-one patients had been diagnosed as primary VUR and 46 as secondary VUR. Age at the first examination ranged from 0 to 14 years (average 5.1 years). Planar images were taken 2 hours after injection. The % renal uptake per injected dose (%RU) was calculated from posterior images. Kidneys in 11 patients (11.3%) changed morphologically during the follow up. Of these, new photon deficient areas (PD) were detected in only 4 patients (4.1%). All of these 4 patients had neurogenic bladder and were managed with self-catheterization. Of the remaining 7 patients, cortical thinning progressed in 5 patients (5.2%) and PDs resolved in 3 patients (3.1%). In one of these 7 patients, PD resolved in one kidney and cortical thinning progressed in the contralateral kidney. Of 97 patients reviewed, % RU decreased more than 20% during the follow up in 6 patients (6.2%). All were diagnosed as secondary VUR due to neurogenic bladder. %RU decreased only in the contracted kidneys at the initial scan. Two of them underwent renal transplantation because of severe renal failure. In conclusion, new PD rarely developed and % RU decreased in only a few patients during the follow up of children with VUR. Repeated Tc-99m DMSA scintigraphy therefore seems to have little benefit in the follow up of children with VUR. It should be performed in selected patients with high risk of urinary tract infection or renal failure.

Adolescent↗
PubMed1999

Changes in renal blood flow in response to sympathomimetics in the rat transplanted and denervated kidney.

BACKGROUND: Renal denervation and re-innervation may affect vascular responses to sympathomimetics, which may play a role in the maintainance of renal blood flow (RBF) following renal transplantation. The purpose of the present study was to elucidate pharmacological alteration of the renal sympathetic response following kidney transplantation. Using the rat kidney transplantation model, we focused on responses to various sympathomimetics in order to investigate the effects of sympathetic denervation and functional remodulation mechanisms in the transplanted kidney. METHODS: Male isogenic rats underwent unilateral kidney denervation or kidney transplantation accompanied by unilateral native nephrectomy. Renal blood flow was evaluated using a laser Doppler flow meter following bolus injection of 50 microg/kg dopamine and continuous infusion of 60 microg/min phenylephrine (PE) at 0, 30, 60, 90 and 240 days after transplantation as well as at 30 days after denervation. RESULTS: Bolus injection of dopamine (50 microg/kg) induced an initial reduction in RBF (that of alpha-adrenoceptors) followed by a long-lasting increase in RBF (that of beta-adrenoceptors) in the native kidney. In grafted or denervated kidneys, the dopamine-induced decrease in RBF mediated by alpha-adrenoceptors was markedly enhanced while the increase in RBF mediated by an action of dopamine on beta-adrenoceptors was blunted. The effects of the post-transplant period on vascular responses to dopamine were significant, but not completely synchronized with the native kidney, even at 240 days. Continuous infusion of PE (60 microg/min) produced a gradual increase in RBF in the native kidney, whereas a sudden reduction (i.e. breakthrough in autoregulation) was observed in the denervated and transplanted kidney. CONCLUSIONS: The responses to sympathomimetics in the grafted kidney were shifted towards flow reduction (i.e. enhanced vasoconstriction via stimulation of alpha-adrenoceptors and blunted vasodilatation via stimulation of beta-adrenoceptors. This functional impairment was recovered in a time-dependent manner. In addition, the hemodynamic autoregulation system in the kidney deteriorated following transplantation or denervation.

Animals↗
PubMed1999

Impact of congenital narrowing of the bulbar urethra (Cobb's collar) and its transurethral incision in children.

OBJECTIVES: We described the clinical manifestation and outcome after transurethral incision (TUI) of a congenital narrowing of the bulbar urethra (Cobb's collar). MATERIALS AND METHODS: Over a period of 11 years a total of 74 boys, from 3 months to 16 years old with a mean age of 5 years, were subjected to TUI. A febrile urinary tract infection (UTI) was the most common symptom in 40 cases, enuresis in 15, urinary incontinence in 11, hematuria in 9, antenatally diagnosed dilated urinary tract in 4 and others in 9. Concurrent bladder instability was detected by cystometry in 27/31 boys older than 3 years with suspicious bladder urgency. When the bulbar narrowing was detected by cystourethroscopy under 8 Fr, the lesion was simultaneously incised by using an infantile resectoscope (Olympus 10 Fr with a knife electrode or Storz 10 F with a cold knife). RESULTS: Vesicoureteral refluxes (VURs) occurred in 39 cases (53%) and it was diminished in 11 and improved in 25 after TUI. Of the 40 cases, 38 (95%) were free from UTI after TUI. For enuresis and urinary incontinence, 14/15 and all 11, respectively, thrived after TUI and the anticholinergic supplement. Although 61 cases were primarily cured with no complications, insufficient cutting and recurrence of the stricture required an additional TUI in 13 cases for whom the knife electrode was mostly used. Overall clinical improvement was obtained in 71/74 (93%) cases after TUI. CONCLUSION: Meticulous cystourethroscopy is indispensable for detecting a clinically significant bulbar narrowing. TUI of the lesion is useful as a primary treatment in the majority of cases even with concurrent VUR and unstable bladder. A cold knife is preferable to electrocautery in incising this fine anterior urethral lesion.

Adolescent↗
PubMed1998

Experience with kidney transplantation in children and adolescents.

BACKGROUND: Paediatric kidney transplantation has different aspects in adults in terms of underlying primary renal disease, surgical technique, perioperative care and graft prognosis. Significant urological problems are present in a high percentage of paediatric recipients. This study was undertaken to characterize paediatric kidney transplantation as performed at our institutes. METHODS: Twenty-eight patients (age range 4-17 years, 10 girls, 18 boys) were included in this study. We analyzed (1) urologic procedures performed prior to or simultaneously with transplantation, (2) intraoperative changes in haemodynamics, (3) postoperative complications and (4) acute allograft rejection and graft prognosis. RESULTS: Of 4 patients with lower urinary tract abnormalities (neurogenic bladder in 3, posterior urethral valve in 1), 2 underwent augmentation ileocystoplasty prior to transplantation. The Mitrofanoff procedure as a diversion for neourethra was also performed in 2 of the 4 patients. All these 4 patients were managed with clean intermittent catheterization. Central venous pressure changes before and after graft vessel declamping were much greater in patients with body weight below 25 kg than in those above 25 kg. Five surgical complications and 6 infections were encountered postoperatively and hypertension was lasting in 6. Thirteen patients experienced 19 periods of acute allograft rejection. All of the 24 patients in the cyclosporin era (1986-) overcame rejections and they are all alive with good graft function. CONCLUSIONS: As long as proper pretransplant patient evaluation and management, and intensive perioperative care are undertaken, good prognosis of renal allograft can be achieved in young patients.

Adolescent↗
PubMed1998

Kidney transplantation in patients with neurovesical dysfunction.

BACKGROUND: Five renal recipients with neurovesical dysfunction (NVD) were retrospectively reviewed focusing on anatomical and urodynamic abnormalities of the lower urinary tract and their management prior to kidney transplantation. METHODS: The underlying anomalies in these 5 patients were a posterior urethral valve (1 with an imperforate anus; n = 2), meningomyelocele (n = 2) and a congenital short urethra with an imperforate anus (n = 1). Their urinary tracts were evaluated prior to transplantation with voiding cystourethrography, urethrocystoscopy, cystometrography and electromyography of the external urethral sphincter to identify a possible focus of urinary tract infection, urine storage and voiding function. RESULTS: All 5 patients had NVD proven by urodynamic studies or by documentation of urinary retention in the absence of mechanical outlet obstruction. Bilateral high grade vesicoureteral reflux was noted in all patients, requiring ureteroneocystostomy. Clean intermittent catheterization (CIC) was ultimately employed for bladder emptying in all patients. Two patients with poor bladder compliance underwent augmentation cystoplasty before transplantation. The Mitrofanoff procedure was used in 2 patients with structural urethral abnormalities to access the bladder for catheterization. After eradication of possible sources of infection and establishment of a low-pressure urine storage system with bladder emptying by CIC, kidney transplantation was performed. Following kidney transplantation, all of the recipients were asymptomatic for urinary tract infections using CIC. Although 1 patient lost his graft due to chronic rejection, the other 4 other patients have good renal function. CONCLUSION: Kidney transplantation in patients with NVD can be performed provided that their urinary tract problems are properly resolved.

Adolescent↗