Biomedical subjects

Yoichi Mizutani

Publications and source records attributed to Yoichi Mizutani.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Gene therapy using cationic multilamellar liposomes containing human interferon-beta gene against renal cell carcinoma].

The anticancer activity of cationic multilamellar liposomes containing human IFN-beta gene (IAB-1) against renal cell carcinoma (RCC) was examined. Concentrations of IFN-beta protein were measured by an enzyme-linked immunosorbent assay. The cytotoxic activity of IAB-1 against RCC cells and normal renal proximal tubule endothelial cells (RPTEC5899) was examined by the microculture tetrazolium dye assay. For the in vivo study, the NC65 RCC cell line was inoculated into severe combined immunodeficiency mouse. The RCC cells treated with IAB-1 secreted significant amounts of IFN-beta protein. Significant in vitro cytotoxic activity of IAB-1 against RCC cells was observed. In contrast, treatment of RCC cells with recombinant IFN-beta protein resulted in less cytotoxicity. No significant cytotoxicity was seen in RPTEC5899 cells. Apoptosis was observed in RCC cells treated with IAB-1. The size of NC65 RCC cancers transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposomes or recombinant IFN-beta protein. These findings show that IAB-1 may have significant antitumor activity against RCC, and suggest its potential clinical application for gene therapy against RCC.

Animals↗

PubMed2005

Differential response at the hGABP/E4TF1 site of retinoblastoma gene promoter in human testicular seminoma cells.

The tumor suppressor retinoblastoma gene (RB) is a well-known regulator of cell cycle progression, differentiation and apoptosis. Inactivation of this gene is closely associated with the development of many human malignancies. Previous studies of testicular germ cell tumors (TGCTs) revealed lower levels of RB mRNA and protein compared with normal testis tissue. In this study, we examined the mechanism behind the reduced expression of RB mRNA and protein in TGCTs. The mRNA and protein expression were down-regulated in JKT-1 human testicular seminoma cells, compared with other cell lines. Promoter activity from a construct without a hGABP/E4TF1-binding site was markedly reduced in A549 human lung adenocarcinoma cells, but not in JKT-1. Furthermore, promoter activity from a plasmid carrying a point mutation at the hGABP/E4TF1 site was reduced in A549 cells, but not altered in JKT-1 cells. These differential responses of RB promoter constructs raise the possibility that the hGABP/E4TF1 site does not act as a positive regulatory element in JKT-1 cells, and the RB gene might be down-regulated at the transcriptional level in JKT-1 cells.

Adenocarcinoma↗

PubMed2004

Downregulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance.

PURPOSE: Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers, including renal cell carcinoma (RCC). This study examined Smac/DIABLO expression in 78 healthy kidneys and 78 RCCs. MATERIALS AND METHODS: The level of Smac/DIABLO expression was quantified by Western blot analysis using nonfixed fresh frozen tissues. RESULTS: The expression of Smac/DIABLO was lower in RCC compared with the autologous normal kidney. Sixty-four (82%) of 78 of RCC expressed Smac/DIABLO, and 18% were negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC, 96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in stage III/IV. Smac/DIABLO expression inversely correlated with the grade of RCC. Patients with RCC expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression in the 5-year follow-up. Transfection with Smac/DIABLO cDNA enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -mediated and cisplatin-mediated cytotoxicity in RCC. CONCLUSION: The present study demonstrates for the first time that Smac/DIABLO expression was downregulated in RCC and that no Smac/DIABLO expression in RCC predicted a worse prognosis. In addition, transfection with Smac/DIABLO sensitized RCC to TRAIL/cisplatin-induced apoptosis. These results suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter, and that enhancement of Smac/DIABLO expression in RCC may potentiate immunotherapy and chemotherapy.

Adult↗

PubMed2004

Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in the process of lymphocyte-mediated cytotoxicity against malignant cells. Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, and circulating OPG has been implicated in the protection of cells from TRAIL-mediated apoptosis. Thus, OPG may protect tumor cells from lymphocyte-mediated cytotoxicity and, as a result, contribute to tumor progression. In the current study, the authors investigated this hypothesis in patients with bladder carcinoma. METHODS: Serum OPG levels for 185 patients with bladder carcinoma were determined using an enzyme-linked immunosorbent assay. These levels then were assessed for potential correlations with various disease characteristics and outcome measures. RESULTS: The mean serum OPG concentration in patients with bladder carcinoma was approximately 3 times greater than the mean concentration in healthy individuals, and among patients with bladder carcinoma, higher tumor stage and grade were found to be associated with increased serum OPG levels. Within the subpopulation of patients with superficial bladder carcinoma, after a follow-up period of 5 years, those who had low serum OPG levels tended to have a longer postoperative tumor-free interval compared with those who had high serum OPG levels. Furthermore, among patients with muscle-invasive bladder carcinoma, the 5-year disease-specific survival rate was greater for those who had low serum OPG levels than for those who had high serum OPG levels. CONCLUSIONS: To the authors' knowledge, the current study is the first to demonstrate that serum OPG concentration is correlated with both tumor stage and tumor grade and that elevated serum OPG levels are predictive of early recurrence in patients with bladder carcinoma. These findings suggest that serum OPG concentration may have utility as a prognostic parameter in this setting.

Adult↗

PubMed2004

Prognostic significance of orotate phosphoribosyltransferase activity in bladder carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU), an antitumor agent, is used clinically against a variety of malignancies, including bladder carcinoma. 5-FU is a prodrug, and orotate phosphoribosyltransferase (OPRT) is the principal enzyme that converts 5-FU directly into an active antitumor metabolite, 5-fluoro-2'-deoxyuridine 5'-monophosphate. In addition, OPRT is the key enzyme in the de novo DNA and RNA synthetic process. To the authors' knowledge, little is known regarding the significance of OPRT in various malignancies, including bladder carcinoma. The authors analyzed the activity levels of OPRT in 60 bladder carcinomas and evaluated the association between the level of OPRT activity and the stage and grade status of bladder carcinoma. They also examined the prognostic significance of OPRT activity in patients with bladder carcinoma and the correlation between OPRT activity levels in bladder carcinoma cells and the sensitivity of those cells to 5-FU. METHODS: OPRT activity levels in nonfixed, fresh-frozen specimens of bladder carcinoma and normal bladder were determined enzymatically using a 5-FU phosphorylation assay. The sensitivity of bladder cells to 5-FU was assessed using a microculture tetrazolium dye assay. RESULTS: The activity levels of OPRT were approximately 7.5-fold higher in bladder carcinoma specimens compared with the activity levels in normal bladder specimens. OPRT activity in muscle-invasive bladder carcinoma was 2-fold higher compared with the activity in superficial bladder carcinoma (classified as Ta and T1). In addition, the activity of OPRT in T1 bladder carcinoma was 2-fold higher compared with the activity in Ta bladder carcinoma. The level of OPRT activity in Grade 3 bladder carcinoma was 6-fold and 2-fold higher compared with the activity in Grade 1 and Grade 2 bladder carcinoma, respectively. Patients who had Ta and T1 bladder carcinoma with low OPRT activity had a longer postoperative tumor free period compared with patients who had bladder carcinoma with high OPRT activity in the 3-year follow-up. There was a positive association between the activity levels of OPRT and thymidylate synthase/thymidine kinase, which are the key enzymes in the de novo/salvage DNA synthetic process. OPRT activity in bladder carcinoma cells was correlated positively with their sensitivity to 5-FU. CONCLUSIONS: to the authors' knowledge, the current study is the first to demonstrate that OPRT activity levels in bladder carcinoma were higher compared with its activity in the normal bladder tissues and that OPRT activity levels were correlated positively with the stage and grade of bladder carcinoma. In addition, high OPRT activity levels in patients with superficial bladder carcinoma predicted early recurrence and high sensitivity to 5-FU. These results suggest that the level of OPRT activity may be used both as a prognostic parameter and as a predictive indicator for 5-FU efficacy in patients with bladder carcinoma and that OPRT may be a molecular therapeutic target in bladder carcinoma.

Adult↗

PubMed2004

Neuroselective current perception threshold evaluation of bladder mucosal sensory function.

OBJECTIVE: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders. METHODS: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three different CPTs were obtained from each test site using a constant alternating current sinusoid waveform electrical stimulus presented at 2000Hz, 250Hz and 5Hz stimulation frequencies, which could selectively reflect the functions of the large myelinated fibers (A-beta-fiber), the small myelinated fibers (A-delta-fiber), and the unmyelinated fibers (C-fiber), respectively. RESULTS: As the determination of CPT values on the finger skin, the CPT values in the bladder could be determined using the neuroselective measures in all patients but three who had no sensory response (absence of sensation) caused by complete spinal injury. In the 8 patients with detrusor hyperreflexia due to incomplete spinal cord injury (supra-sacral lesion), the bladder CPT value (4.0+/-1.9) at 5Hz was significantly lower (p<0.01) than that in the controls (26.2+/-17.7). In the neurogenic bladders determined to be underactive (n=11, including post pelvic surgery, post infra-sacral level spinal cord injury and diabetes patients), the higher CPT values of bladder mucosal sensory functions were found at 5Hz (p<0.05), 250Hz (p=0.07), and 2000Hz (p<0.05) compared to the controls. CONCLUSIONS: Quantitative neuroselective measurement of CPT values in the human bladder mucosal function was feasible. Hypersensitivity or hyposensitivity of the urinary sensory function could be determined using the CPT values in comparison to control. The quantitative neuroselective estimation of the bladder sensory functions in different types of sensory peripheral nerve fibers may contribute to the appropriate selection of therapeutic strategy in patients with urinary sensory dysfunction.

Adult↗

PubMed2004

Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUND: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.

Aged↗

PubMed2004

Possible contribution of prostatic anterior fibromuscular stroma to age-related urinary disturbance in reference to pressure-flow study.

Recently, we reported that the anterior fibromuscular stroma (AFMS) of the prostate has significant different innervation compared with the other glandular regions of the prostate. In healthy volunteers (n = 12) using transrectal ultrasound (US), or TRUS, monitoring during voiding, we observed dynamic change (p < 0.0001) of the thickness of the AFMS during voiding. The aim of this study was to reveal the possible functional contribution of the AFMS to micturition, as well as the age-related voiding dysfunction. In the patients (n = 56) with voiding dysfunction who underwent both pressure-flow study (PFS) for determining obstruction and TRUS monitoring during voiding, we measured the ultrasonic dynamic change of the lower urinary tract during voiding. In old men with voiding dysfunction, ultrasonic measurements of dynamic change in the AFMS (p < 0.01) as well as the opening urethra (p < 0.05) could contribute to diagnosing of the anatomical localization of obstructive lesions. The poor movement of AFMS could account for the age-related urinary disturbance in the patients without benign prostatic enlargement and without bladder neck obstruction.

Aged↗

PubMed2004

Hand-assisted retroperitoneoscopic radical nephrectomy and nephroureterectomy.

In laparoscopic operations for renal tumor and upper urinary-tract transitional-cell carcinoma (TCC), three approaches - the transperitoneal, retroperitoneal, and transperitoneal hand-assisted - have been reported. We have performed hand-assisted retroperitoneoscopic radical nephrectomy (RN) since 1999 and nephroureterectomy (NU) since 2000. The surgical techniques and the operative results of 95 cases of RN and 54 cases of NU are described and analyzed. These procedures were effective and safe for renal tumors and upper urinary-tract TCC.

Carcinoma, Transitional Cell↗

PubMed2004

Significance of orotate phosphoribosyltransferase activity in renal cell carcinoma.

PURPOSE: The anticancer agent 5-fluorouracil (5-FU) is clinically used against various cancers, including renal cell carcinoma (RCC). It is a prodrug and orotate phosphoribosyltransferase (OPRT) is the principal enzyme that directly converts 5-FU to the active anticancer metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate. In addition, OPRT is the key enzyme in the de novo DNA and RNA synthetic process. Little is known about the significance of OPRT in various cancers, including RCC. We investigated the activity of OPRT in 83 RCCs and evaluated the association between the level of OPRT activity and the stage/grade of RCC. The relationship between OPRT activity in RCC cells and their sensitivity to 5-FU was also examined. MATERIALS AND METHODS: OPRT activity in nonfixed, fresh frozen RCC and normal kidney was determined enzymatically by the 5-FU phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. RESULTS: The activity of OPRT was approximately 8.5-fold higher in RCC than in normal kidney. OPRT activity in stage III/IV RCC was 3-fold higher than in stage I/II RCC. The level of OPRT activity in grade 3 RCC was 3-fold higher than that in grade 1/2 cancer. Patients with RCC with low OPRT activity had longer postoperative disease specific survival than those with high activity at 5-year followup. OPRT activity in RCC cells positively correlated with their sensitivity to 5-FU. CONCLUSIONS: To our knowledge this is the first study to demonstrate that OPRT activity in RCC was higher than that in normal kidney and OPRT activity positively correlated with RCC stage/grade. In addition, higher OPRT activity in RCC predicted worse prognosis and higher sensitivity to 5-FU. These results suggest that the level of OPRT activity may be used as a prognostic parameter and predictive indicator for 5-FU efficacy in RCC and OPRT may be a molecular therapeutic target in RCC.

Adult↗

PubMed2004

Enhanced sensitivity of bladder cancer cells to cisplatin mediated cytotoxicity and apoptosis in vitro and in vivo by the selective cyclooxygenase-2 inhibitor JTE-522.

PURPOSE: Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in various cancer cells. Several anticancer agents also mediate apoptosis and may share the common intracellular pathways leading to apoptosis with COX-2 inhibitors. We reasoned that combination treatment of bladder cancer cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide) synergizes with anticancer agents in cytotoxicity and apoptosis against bladder cancer cells in vitro and in vivo. MATERIALS AND METHODS: Cytotoxicity was determined by the microculture tetrazolium dye assay. RESULTS: Combination treatment of T24 bladder cancer cells with JTE-522 and cis-diamminedichloroplatinum (II) (CDDP) resulted in a synergistic cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CDDP was shown to be due to apoptosis. Treatment of T24 cells with JTE-522 decreased expression of the anti-apoptotic molecule Bcl-2. The in vivo significant growth inhibitory effect of JTE-522 and CDDP against the T24 line heterotransplanted in SCID mice was also observed. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with the selective COX-2 inhibitor JTE-522 and CDDP results in synergistic cytotoxicity and apoptosis in vitro and in vivo. These findings support the potential clinical application of a combination of JTE-522 and CDDP for the treatment of bladder cancer as a new form of therapy with more selective cytotoxicity and fewer collateral side effects.

Animals↗

PubMed2004

Oncogenic role of NALP7 in testicular seminomas.

To isolate novel molecular targets for treatment of testicular germ cell tumor (TGCT), we performed genome-wide expression profile analysis of testicular seminomas using a cDNA microarray. We here report identification of NACHT, leucine-rich repeat and PYD containing 7 (NALP7 ), that was significantly transactivated in testicular seminomas. Subsequent semi-quantitative RT-PCR and northern blot analyses confirmed an approximately 3.3-kb transcript that was expressed exclusively in testis, although the expression level of this gene in normal testis was much lower than in tumor cells, suggesting an important role of this gene in germ-cell proliferation. Immunohistochemical analysis using anti-NALP7 polyclonal antibody detected the endogenous NALP7 protein in the cytoplasm of embryonal carcinoma cells and testicular seminoma tissues. Transfection of small interfering RNA (siRNA) for NALP7 significantly reduced the NALP7 expression and resulted in growth suppression of testicular germ-cell tumors. These findings imply that NALP7 may play a crucial role in cell proliferation, as well as testicular tumorigenesis, and it appears to be a promising candidate for development of targeted therapy for TGCTs.

Animals↗

PubMed2004

Retroperitoneoscopic heminephroureterectomy for children with duplex anomaly: Initial experience.

OBJECTIVES: To evaluate the feasibility of retroperitoneoscopic heminephroureterectomy for children with duplex anomaly. METHODS: Retroperitoneoscopic heminephroureterectomy was performed in five children (four girls and one boy) with complete duplication of the ureter, of whom four (age range 1-5 years; mean age 3.3 years) had upper pole ectopic megaureters and one (3 years old) had an upper pole megaureter with ureterocele. In the patient with ureterocele, distal ureterectomy and ureterocelectomy were performed by Pfannenstiel incision. RESULTS: The mean operation time was 346 min (range 270-450 min) in the four patients with ectopic megaureter and 420 min (330 min for heminephroureterectomy) in the patient with ureterocele. The mean estimated blood loss was 43 mL (range 5-100 mL) in the four patients with ectopic megaureter and 40 mL in the patient with ureterocele. No postoperative complications were observed. Postoperative intravenous pyelography showed normal pyelogram and renal function of the preserved lower pole in all cases. CONCLUSIONS: Retroperitoneoscopic heminephroureterectomy for children is feasible, safe and has good postoperative results, including cosmetic results. However, the operation time needs to be reduced.

Child, Preschool↗

PubMed2004

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk.

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.

Aged↗

PubMed2003

The significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor activity in renal cell carcinoma.

BACKGROUND: Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PDECGF) and has angiogenic activity. Little is known about the significance of TP/PDECGF activity in patients with renal cell carcinoma (RCC). The authors examined the enzymatic activity of TP in 66 RCC specimens and investigated the association between the level of TP activity and the stage/grade status of patients with RCC. Furthermore, the authors examined the correlation between TP/PDECGF activity and prognosis. METHODS: TP activity levels in nonfixed, fresh-frozen RCC specimens and in specimens of normal kidney were determined using a thin-layer chromatography assay. RESULTS: The activity of TP was approximately 3.5-fold greater in RCC specimens compared with normal kidney specimens. TP activity in patients with Stage III-IV RCC was 2.6-fold greater compared with TP activity in patients with Stage I-II RCC. In addition, the level of TP activity was correlated with a higher grade of RCC. Patients who had RCC with low TP activity had a longer postoperative disease-specific survival compared with patients who had RCC with high TP activity in the 5-year follow-up. CONCLUSIONS: The current study is the first to demonstrate a correlation between levels of TP activity and both disease progression and a higher grade of RCC. It also is the first to show that elevated TP activity in patients with RCC predicts a poor prognosis. The results suggest that high TP/PDECGF activity may be associated with the malignant potential of RCC and that TP/PDECGF may be a molecular therapeutic target in patients with RCC.

Adult↗

PubMed2003

Glycine ameliorates lung reperfusion injury after cold preservation in an ex vivo rat lung model.

BACKGROUND: The role of glycine has not been investigated in lung ischemia-reperfusion injury after cold preservation. Furthermore, the role of apoptosis after reperfusion following cold preservation has not been fully understood. METHODS: Lewis rats were divided into three groups (n=6 each). In the GLY(-) and GLY(+) groups, isolated lungs were preserved for 15 hr at 4 degrees C after a pulmonary artery (PA) flush using our previously developed preservation solution (ET-K; extracellular-type trehalose containing Kyoto), with or without the addition of glycine (5 mM). In the Fresh group, isolated lungs were reperfused immediately after a PA flush with ET-K. They were reperfused for 60 min with an ex vivo perfusion model. Pulmonary function, oxidative stress, apoptosis, and tumor necrosis factor (TNF)-alpha expression were assessed after reperfusion. RESULTS: Shunt fraction and peak inspiratory pressure after reperfusion in the GLY(-) group were significantly higher than those in the GLY(+) and Fresh groups. Oxidative damage and apoptosis in the alveolar epithelial cells of the GLY(-) group, assessed by immunohistochemical staining and quantification of 8-hydroxy-2'-deoxyguanosine and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method, were significantly higher than those of the GLY(+) and Fresh groups. There were correlations among shunt fraction, oxidative damage, and apoptosis. There was no expression of TNF-alpha messenger RNA in all groups evaluated by the reverse transcription-polymerase chain reaction. CONCLUSIONS: Glycine attenuates ischemia/reperfusion injury after cold preservation by reducing oxidative damage and suppressing apoptosis independent of TNF-alpha in this model. The suppression of apoptosis might ameliorate lung function after reperfusion.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Bladder capacity at the time of enuresis.

OBJECTIVES: To evaluate bladder capacity at the time of enuresis and compare the daytime capacity of enuretics with that of controls. METHODS: The functional bladder capacity (FBC), which was the maximal endurable capacity in the daytime, the ordinary bladder capacity (OBC), which was the capacity at ordinary urinary sensation in the daytime, and the enuretic bladder capacity (EBC), which was the capacity at the time of enuresis, were measured in 67 patients with monosymptomatic nocturnal enuresis. The EBC was measured using a diaper and enuresis alarm. The FBC, OBC, and nocturnal bladder capacity, which was the maximal voided volume in the nighttime, were also measured in 67 controls. RESULTS: The FBC was not significantly different between enuretics and controls. The EBC in enuretics was significantly smaller than the nocturnal bladder capacity in controls. In enuretics, the EBC was significantly smaller than the FBC and was similar to the OBC. In controls, no statistically significant differences were found between the FBC and the nocturnal bladder capacity. CONCLUSIONS: In enuretics, the bladder capacity during sleep was significantly smaller than the daytime functional capacity. In controls, on the other hand, the bladder capacity during sleep did not differ from the daytime functional capacity. Our understanding of the bladder capacity in enuretics may need to change in view of this result. The inability to hold urine during sleep may be an important cause of nocturnal enuresis.

Adolescent↗

PubMed2003

Preliminary report of association of chronic diseases and erectile dysfunction in middle-aged men in Japan.

OBJECTIVES: To investigate the effect of chronic diseases on erectile dysfunction (ED) in Japanese middle-aged men using the International Index of Erectile Function, 5-item version (IIEF-5). METHODS: The subjects consisted of 640 healthy men and 396 men with chronic disease who responded to the IIEF-5 questionnaire (mean age 43.6 +/- 8.3 years, range 30 to 59). The incidence and severity of ED were calculated in three age groups (30 to 39, 40 to 49, and 50 to 59 years). RESULTS: The incidence of hypertension, cardiac disease, diabetes mellitus, and chronic renal failure was associated with the incidence and severity of ED, as was age. In stepwise multivariate logistic regression analysis, cardiac disease was the strongest independent risk factor (odds ratio [OR] 6.5), followed by diabetes mellitus (OR 5.9), chronic renal failure (OR 3.9), hypertension (OR 2.0), and age (OR 1.8). CONCLUSIONS: The results of this study demonstrated that the risk of ED increases with the presence of cardiac disease, diabetes mellitus, chronic renal failure, and hypertension in middle-aged men in Japan.

Adult↗