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Concern over environmental pollution generated by chemical fungicides has led to the introduction of alternative pest management strategies to chemical fungicide application. One of those strategies is the induction of plant defense response by an abiotic elicitor. In the present study, field-grown grapevines were subjected to electrical stimulation using a solar panel from two weeks before flowering to harvest in the 2016 and 2020 growing seasons. In both years, electrical stimulation decreased the incidence of gray mold and/or ripe rot on bunches and downy mildew on leaves of the field-grown grapevine. Transcription of a gene encoding β-1,3-glucanase but not class IV chitinase in leaves of potted grapevine seedlings was upregulated 20 days after electrical stimulation, suggesting that electrical stimulation acts as an abiotic elicitor of plant defense response to fungal diseases. The gene expression of PR1 but not PDF1.2 was upregulated in Arabidopsis plants subjected to electrical stimulation. On the other hand, PR1 gene expression was not induced in salicylic acid (SA)-insensitive Arabidopsis mutant npr1-5 subjected to electrical stimulation. Taken together, electrical stimulation is responsible for plant defense response through the SA-dependent defense pathway. These findings would help us develop a novel and innovative practical technique that uses electrical stimulation in integrated pest management.

Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.

Background Complications of peritoneal dialysis (PD) such as pain and catheter leakage are frequently reported. Delayed bowel perforation of a PD catheter is a rare adverse event but a serious complication associated with significant mortality. Bowel perforation of a PD catheter is difficult to differentiate from PD-related peritonitis and likely to result in a delay in diagnosis. Here, we report two cases of bowel perforation after PD catheter insertion by the stepwise initiation of PD using the Moncrief and Popovich technique (SMAP) and peritoneal wall anchor technique (PWAT). Case presentation The first case was a 53-year-old woman with end-stage renal disease (ESRD) due to diabetic nephropathy and a history of entero-adhesiolysis. She underwent PD catheter insertion by the SMAP with PWAT. Four months after PD catheter insertion, the catheter was found to perforate sigmoid colon. The second case was a 57-year-old woman with ESRD due to large polycystic kidney disease. She underwent the same procedure. After exteriorization of the catheter, she developed peritonitis due to perforation of the catheter tip into the bowel. Both patients were safely removed the catheter with uneventful recovery. Conclusion We reported two cases of a rare complication of PD catheter. The SMAP method, PWAT, enlarged kidneys and migration of the lower cuff may be risk factors of bowel perforation of a PD catheter.

A 27-year-old man visited our hospital with painless swelling of the left scrotum. Hematologic studies showed the following levels of lactate dehydrogenase, 3,171 IU/l ; alpha-fetoprotein, 2.2 ng/ml ; and β- human chorionic gonadotropin, 0.4 ng/ml, and abdominal computed tomography revealed a mass of 10×8 ×4 cm in the left testis, and that of 3.5×3.0×5.0 cm in the left renal hilar lymph node, without any other metastasis. Left high inguinal orchiectomy was performed, and histopathological examination revealed mixed form with seminoma and teratoma. He was diagnosed to have a left germ cell tumor with left renal hilar lymph node metastases, pT1, N3, M0, stage II C, indicating poor prognosis with IGCCC. The patient received four cycles of chemotherapy, COMPE regimen (CDDP, VCR, MTX, PEP, VP-16 [etoposide]). After lactate dehydrogenase, alpha-fetoprotein, and β -human chorionic gonadotropin all normalized, retroperitoneal lymph node dissection was performed. Histopathological examination revealed only a mature teratoma. Two and half years later, hematologic studies showed blast transformation. Bone marrow biopsy revealed acute myeloblastic lymphoma (M2). The patient received one cycle of AraC and daunorubicin, one cycle of high dose AraC, and three cycles of AraC and mitoxantrone. After chemotherapy, he has maintained a disease-free status for 11 years. In this case, etoposide, a topoisomerase II inhibitor, was the presumed cause of therapy-related acute myeloid leukemia. After administering chemotherapeutic agents especially etoposide, it is important to check blood count periodically for a long time.

Objective: To evaluate the clinical usefulness of effective renal plasma flow (ERPF) measured using preoperative mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of chronic renal insufficiency after nephrectomy. Methods: A total of 47 patients underwent preoperative MAG3 renal scintigraphy and subsequent unilateral nephrectomy. Correlations between the 5-year postoperative estimated glomerular filtration rate (eGFR) and the preoperative ERPF of the contralateral kidney (cERPF), ERPF of the diseased kidney (dERPF), total ERPF (tERPF), cERPF to dERPF ratio, serum creatinine (sCr) level, eGFR, as well as the influence of preoperative comorbidities (diabetes, hypertension) on the postoperative eGFR, were evaluated with both univariate and multivariate analyses. Results: Multiple linear regression analysis showed that preoperative cERPF significantly correlated with postoperative eGFR. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Multiple logistic regression analysis showed that only preoperative eGFR was a significant predicator of the development of advanced-stage chronic kidney disease (CKD). Conclusions: Preoperative MAG3 renogram is not superior to eGFR measurement as a prognostic indicator of long-term renal function after unilateral nephrectomy.

Background: Fulminant myocarditis involves various serious arrhythmias that sometimes have lethal consequences. The purpose of the present study was to investigate the electrocardiogram findings, arrhythmogenicity and abnormalities of the cardiac conduction system in children with fulminant myocarditis. Methods and Results: Between 1999 and 2008, 7 consecutive patients (mean age: 7 years) who suffered from fulminant myocarditis were included in the study. A 12-lead electrocardiogram, Holter monitoring and signal-averaged electrocardiograms were performed and compared between the acute, convalescent, and recovery phases in the 4 surviving patients. Also, electrophysiologic assessment was carried out during the convalescent phase. Five out of 7 patients developed complete atrioventricular block, 3 developed ventricular tachycardia, 2 had cardiac arrest, 2 developed sinus tachycardia, 1 developed ventricular fibrillation, 1 had advanced atrioventricular block, and 1 developed sick sinus syndrome. Among the surviving patients, all arrhythmias resolved during the convalescent and remote phases. No atrial or ventricular arrhythmias were induced in any patients during the programmed stimulation study. In the convalescent phase, no arrhythmias could be induced and there were no signs of any conduction abnormalities on electrophysiological assessment. Conclusions: Close follow-up should be performed to observe for the occurrence of any new arrhythmias and/or a decrease in cardiac function in children with fulminant myocarditis. (Circ J 2011; 75: 932-938)

Background This study was performed to investigate the incidence of arrhythmias in patients with Kawasaki disease (KD). Methods and Results Electrophysiologic studies (EPS) were performed in 40 patients (mean age: 10.3±5.1 years; 30 males, 10 females) with KD who had severe to moderate coronary artery disease. Clinical arrhythmias were documented in 4 patients (premature ventricular contractions, ventricular tachycardia, atrioventricular block, and ventricular fibrillation). Dual atrioventricular nodal pathways were demonstrated in 3 patients. Nonsustained atrial fibrillation was induced in 1 patient. The AH interval was prolonged in 2 patients. The Wenckebach rate was 164±37 beats/min, and 4 of the patients had a decreased Wenckebach rate. The maximum and corrected sinus node recovery times were 997±257 ms and 281±130 ms, respectively, and 7 patients were thought to be abnormal. The sino-atrial conduction time was 108±64 ms, and 2 patients had prolonged conduction times. Conclusions Although there was no relationship between coronary stenosis or obstruction and the EPS parameters, the incidence of abnormal sinus node and atrioventricular node function is apparently higher in KD patients than in the normal population. These functional abnormalities may possibly be caused by myocarditis or an abnormal microcirculation in the sinus node and atrioventricular node artery. In some patients, myocardial ischemia may provoke malignant ventricular arrhythmia. (Circ J 2008; 72: 274 - 280)

This study was designed to evaluate the usefulness of real-time 3-dimensional echocardiography (RT-3DE) for evaluating coronary artery morphology in patients with Kawasaki disease.The diagnosis of coronary artery morphology in the acute phase of the disease is of prime importance for evaluating the likelihood of cardiovascular sequelae. Occasionally, visualization of the right coronary artery and bifurcated regions, including the circumflex artery, has proved challenging with traditional echocardiographic methods.A total of 111 patients with Kawasaki disease were studied. Coronary aneurysms were detected in 8 patients (4 had giant aneurysms), and coronary dilation was found in 11 patients. Coronary artery visualization was evaluated and scored as 1 of 4 grades, 0 to 3 points, for both 2-dimensional echocardiography (2DE) and RT-3DE. Evaluation criteria for each coronary artery were defined according to the American Heart Association classification of coronary angiographic features. Total scores for each patient and for individual coronary branches were compared between 2DE and RT-3DE.The total scores for coronary artery visualization were, respectively, showing a significantly higher score for RT-3DE than for 2DE (P.01). A mural thrombus could be clearly delineated in the giant coronary aneurysms by RT-3DE.RT-3DE is superior to 2DE for coronary artery visualization. This diagnostic system is expected to improve the screening of coronary artery abnormalities in Kawasaki disease.

Background Catheter ablation inside the Koch's triangle has a risk for complete atrioventricular block. Methods and Results The anatomic size of the coronary sinus (CS) and His bundle (HB) in children and the distance between them was studied using a 3-dimensional electroanatomical mapping system (CARTO). Fifty-three children (mean age, 11.8±3.7 years) without congenital heart disease (ie, 24 with atrioventricular re-entrant tachycardia, 18 with atrioventricular nodal re-entrant tachycardia, 7 with atrial tachycardia, 2 with ventricular tachycardia and 2 with atrial flutter) were studied. The size of the HB recording area was 148±97 mm2 and the size of the CS was 66±44 mm2. The size of the CS and the distance between the HB and CS (18±7 mm) were proportional to body weight, body length and body surface area. All patients underwent catheter ablation, including 25 ablations inside Koch's triangle. Catheter ablation was successful in 52 patients without any atrioventricular nodal injury. Conclusions The CS size and the distance between the HB and CS increased proportionally with children's growth. To know the distance from the HB to the ablation point is useful in avoiding atrioventricular node injury, and information about the length of Koch's triangle may provide supportive information when applying radiofrequency energy inside Koch's triangle without needing to use the CARTO system in children, but this merits further investigation. (Circ J 2007; 71: 1918 - 1921)

Background This study was performed to investigate the frequency and importance of supraventricular arrhythmia and sinus node (SN) dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods and Results Eight patients with CPVT (mean age: 16.8±8.1 years) underwent an electrophysiological study. SN recovery time (1,389±394 ms) was slightly prolonged, and 4 of 8 patients had abnormal values. Atrial flutter (AF) was induced by low-rate atrial pacing in 2 patients and by isoproterenol infusion in 1 patient. Atrial fibrillation (Af) was induced by isoproterenol infusion in 2 patients. One patient presented with Af during the follow-up period, and 2 of 4 patients with AF/Af presented with increased SN recovery time. Conclusions Patients with CPVT frequently have associated with SN dysfunction, and inducible atrial tachyarrhythmias, which indicate that the pathogenesis of CPVT is limited not only to the ventricular myocardium, but also to broad regions of the heart, including the SN and atrial muscle. (Circ J 2007; 71: 1606 - 1609)

Background The purpose of this study was to determine the appropriate recommendations for weaning off cardiopulmonary support (CPS) in children with fulminant myocarditis. Methods and Results Four consecutive patients diagnosed with fulminant myocarditis who were treated with CPS were enrolled (mean age: 9 years). The relationships between timing of weaning from CPS and various factors, including bleeding episodes, platelet count, serum concentration of the MB isoform of creatine kinase (CK-MB), echocardiographic findings, and the mixed venous blood oxygen saturation (SvO2), were retrospectively analyzed. All patients had CPS performed safely for a mean duration of 53.1 h without exchange of the circuit. Three of the 4 patients had a bleeding episode before discontinuation. The minimum platelet count occurred during weaning in all 4 patients. The peak serum CK-MB concentration when initiating CPS was higher than the peak value on the day of weaning. Echocardiographic findings before stopping CPS were similar to those after weaning. The SvO2 was 62.5% when initiating CPS and 71.3% before weaning. Conclusions In children with fulminant myocarditis CPS can be used without exchanging the circuit and can be discontinued before bleeding episodes become symptomatic, with improvement in the biomarkers and SvO2 on weaning off CPS. (Circ J 2007; 71: 1551 - 1554)

Background: We assessed our experiences in performing a laparoscopic nephrectomy, with regard to complications and the learning curve, during a 4-year period. Methods: Between November 2000 and October 2004, a total of 78 laparoscopic nephrectomies were performed at our institution (37 radical nephrectomies, 30 nephroureterectomies and 11 simple nephrectomies). The patient charts were retrospectively reviewed to identify any operative and postoperative complications, and also to evaluate the operating time. Results: A total of eleven complications (14.1%) occurred in our series (nine operative and two postoperative complications). All operative complications were due to vascular injuries (n = 9), five (2.6%) of which required an open conversion. The operating time and the rates of complications decreased significantly as the surgeons’ experiences increased. Conclusion: A laparoscopic nephrectomy could be performed as safely as previously reported. In addition, the learning curve for a laparoscopic nephrectomy appeared to be good over the initial 50 procedures at our institution.

The in vitro metabolism of amrubicin by rat and human liver microsomes and cytosol was examined. The main metabolic routes in both species were reductive deglycosylation and carbonyl group reduction in the side-chain. In vitro metabolism of amrubicinol by rat and human liver microsomes and cytosol was also examined and the main metabolic route of this active metabolite was reductive deglycosylation. Metabolism of amrubicin in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol and quercetin. Generation of amrubicinol was inhibited only by quercetin. The results indicate that metabolism of amrubicin is mediated by NADPH-cytochrome P450 reductase, NADPH:quinone oxidoreductase and carbonyl reductase. In addition, generation of amrubicinol is mediated by carbonyl reductase. Metabolism of amrubicinol in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol. The results indicate that metabolism of amrubicinol is mediated by NADPH-cytochrome P450 reductase and NADPH:quinone oxidoreductase. To investigate the influence of cisplatin on the metabolism of amrubicin and amrubicinol, human liver microsomes and cytosol were pre-incubated with cisplatin. This did not change the rates of amrubicin and amrubicinol metabolism in either human liver microsomes or cytosol.

Several basic metal oxide catalysts were tested for the synthesis of 1,3-disubstituted urea from ethylene carbonate (EC) and amine. Among the catalysts used, CaO has been found to be an excellent recyclable catalyst for the reaction. It has been suggested that strongly basic property of CaO results in its high activity. Disubstituted ureas are obtained from propylamine and butylamine with high yields at 100 °C. Slightly higher reaction temperatures are necessary for obtaining good yields from amines having larger molecular weights and urea is not produced from dibutylamine as a secondary amine. Propylene carbonate can be used instead of EC for the reaction. A reaction mechanism was proposed, which involves reaction between EC and amine giving a carbamate followed by catalytic reaction between the carbamate and amine, yielding 1,3-disubstituted urea. It is suggested that the latter reaction is the rate-determining step. On the basis of this reaction mechanism, the synthesis of unsymmetric urea was also examined. 2-Hydroxyethyl butylcarbamate is selectively produced from EC with butylamine in the absence of the catalyst at a low temperature and reacts with benzylamine producing 1-butyl-3-benzylurea along with symmetric dialkyl ureas.

Congenital hydronephrosis is one of the most common anomalies found in humans and may cause renal failure in childhood. Half of the cases are due to obstruction at the ureteropelvic junction (UPJ). Here we report that mice lacking Id2, an inhibitor of basic helix-loop-helix (bHLH) transcription factors, exhibit hydronephrosis mimicking the characteristics of human cases such as unilaterality and male preponderance. Hydronephrosis was found even in Id2+/- mice. The penetrance was 67.2% in Id2-/- males, 48.8% in Id2+/- males, 28.0% in Id2-/- females and 20.0% in Id2+/- females. Distortion or high insertion of the ureter at the UPJ was frequently observed and these morphological changes were evident in late embryogenesis. Histologically, the muscle layer, where Id2 is normally expressed, was hypertrophic and/or irregular at the UPJ. Furthermore, gene expression analysis suggested that BMP4 (bone morphogenetic protein 4), which is known to be involved in the development of hydronephrosis, appears to function as an upstream factor of Id2. Our results thus raise the possibility that Id2 is a gene responsible for the pathogenesis of hydronephrosis in man.

The most serious problem regarding a laparoscopic partial nephrectomy is how to perform bloodless excision without causing renal ischemia in a limited working space. We report the case of a 65-year-old man with left small renal cell carcinoma in the posterior mid zone who underwent a laparoscopic partial nephrectomy through a retroperitoneal approach by carrying out the ligation of the tumor-feeding artery, but without clamping the renal pedicle. Both preoperative abdominal computed tomography (CT) and intraoperative ultrasonography revealed the tumor to be fully encapsulated. The tumor-feeding artery could be exposed by dissection from the renal hilum and, after an arterial ligation, tumor resection with a safety margin was smoothly performed with minimal bleeding. Postoperatively, CT revealed a limited defect of the renal parenchyma and excretory pyelography showed no urine leakage or urinary tract obstruction. The preoperative and postoperative creatinine levels were 0.66 and 0.69 mg/dL, respectively. As a result, a tumor-feeding artery ligation with a laparoscopic partial nephrectomy for left renal cell carcinoma in the posterior mid zone is considered to be an effective surgical modality which avoids renal ischemia and pelvic heat injury.

Background: To assess the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal transitional cells in patients with bladder cancer, who have undergone radical cystectomy. Methods: Measurements of the nuclear areas of cancer and normal transitional cells were carried out on the histological slides of 73 patients with bladder cancer. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the cause-specific survival of the patients was examined. Results: The median values of MNA and NAI in the 73 patients were 39 µm2 and 1.2, respectively. Cause-specific survival rates of the patients were calculated according to stage (T1–2 vs T3–4), grade (grade 2 vs grade 3), MNA (

We studied 24 patients with severe coronary artery lesions to assess myocardial perfusion and left ventricular contractile reserve simultaneously using low-dose dobutamine quantitative electrocardiographically gated single-photon emission computed tomography in patients with Kawasaki disease. Low-dose dobutamine infusion was started after an injection of technetium-99m tetrofosmin at rest. Myocardial contractile reserve was evaluated using the post-stress and low-dose dobutamine images, and myocardial perfusion was evaluated using the stress and rest images. Quantitative electrocardiographically gated single-photon emission computed tomography during low-dose dobutamine infusion is a useful and safe method for the combined evaluation of myocardial contractile reserve and myocardial perfusion.

26,26,26,27,27,27-Hexafluoro-1α,25(OH) 2 vitamin D 3 , a hexafluorinated analog of 1α,25(OH) 2 vitamin D 3 , has been reported to be several times more potent than the parent compound with respect to some vitamin D actions. The reason for enhanced biological activity in the bones, kidneys, and small intestine appears to be related to F 6 -1α,25(OH) 2 vitamin D 3 metabolism to ST-232 (26,26,26,27,27,27-hexafluoro-1α,23 S ,25-trihydroxyvitamin D 3 ), a bioactive 23 S -hydroxylated form that is resistant to further metabolism. We compared the disposition and metabolism of [1β- 3 H]F 6 -1α,25(OH) 2 vitamin D 3 and [1β- 3 H]1α,25(OH) 2 vitamin D 3 in parathyroid glands of rats intravenously administered with labeled compounds at a dose of 10 μg/kg. In the [1β- 3 H]F 6 -1α,25(OH) 2 vitamin D 3 -dosed group, radioactivity was highly detected in the kidneys, parathyroid glands, and the small intestine. The radioactivity in the parathyroid glands remained high until 48 h postdosing, with values of 2.5, 8.4, and 14.6 times higher at 6, 24, and 48 h postdosing than after dosing with [1β- 3 H] 1α,25(OH) 2 vitamin D 3 . In the group given [1β- 3 H]F 6 -1α,25(OH) 2 vitamin D 3 , the unchanged compound was mainly detected with a small amount of ST-232 at 6 h postdosing. At the 24- and 48-h time points, over half of the radioactivity was observed as ST-232, and additionally, ST-233, the 23-oxo form, accounted for a small amount at the 48-h time point. The present study demonstrated local retention of [1β- 3 H]F 6 -1α,25(OH) 2 vitamin D 3 and the bioactive metabolite ST-232 in parathyroid glands after intravenous administration. The findings may indicate one of the reasons for the higher potency of F 6 -1α,25(OH) 2 vitamin D 3 than 1α,25(OH) 2 vitamin D 3 in parathyroid.

In vitro metabolism studies were conducted to assess drug-drug interactions between perospirone, an antipsychotic agent, and concomitantly administered drugs--biperiden, flunitrazepam, haloperidol, and diazepam--using human liver microsomes. The metabolism of perospirone in the presence of 100 microg/ml drugs was decreased to 45-73% of that in their absence, whereas no effects were observed with any of the drugs at 1 microg/ml or lower. The effects of perospirone on the metabolism of concomitantly administered drugs were also assessed, and no inhibitory effect was observed. Thus, the metabolism of perospirone and concomitantly administered drugs did not demonstrate any marked mutual inhibition in the human liver microsomes. On the other hand, the perospirone metabolism was markedly reduced by ketoconazole indicating a major role for CYP 3A4. Based on the inhibition constant (Ki) for perospirone metabolism and the plasma unbound concentration of ketoconazole, in vivo perospirone clearance was estimated to be reduced to 64-90% of the control level. Thus careful attention should be paid to the possibility of increase in unchanged perospirone concentration when perospirone is co-administered with drugs that are known as CYP3A4 inhibitors, including macrolide antibiotics and other imidazole antifungals.

(S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethyl]-6,7-dihydro-1 H,5 H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate (SM-18400) was given intravenously to rats and dogs and its pharmacokinetics was investigated. By LC/MS/MS analysis, the major metabolite in the rat serum was identified as N-acetylated SM-18400 (SM-NAc). In rats, AUC ratio of SM-NAc to SM-18400 was approximately 50%. However, 71% of the dose was excreted as unchanged SM-18400 and only 9.8% as SM-NAc in the urine and bile, indicating that the contribution of N-acetylation clearance (CL(NAc)) to the total clearance (CL(tot)) is limited to 10-30% in rats. No SM-NAc or other metabolites were detected in the dog serum, urine or bile. The in vitro intrinsic clearance (CL(int), ml/min/mg cytosolic protein) of N-acetyltransferase (NAT) activities of dog liver cytosol towards SM-18400 and hepatic N-acetylation clearance (CL(NAc), ml/min/kg body weight) estimated by well-stirred model were both only 5% of the respective rat value, well reflecting the relative in vivo CL(NAc)/CL(tot) ratios. CL(int) values for human liver cytosol samples (n = 4) and estimated CL(NAc) were all less than 18% and 7% of the rat, respectively. Based on these results, we concluded that the CL(NAc)/CL(tot) of human would be small enough to avoid major inter-individual variance in SM-18400 pharmacokinetics due to N-acetylation polymorphism. In addition, even a human liver cytosol sample lacking polymorphic NAT2 activity as determined by sulfamethazine (SMZ) N-acetylation analysis, proved capable of acetylating SM-18400, suggesting that NAT2 is not the major enzyme responsible for N-acetylation of SM-18400 in human. This fact would also reduce the risk of N-acetylation polymorphism playing a role in clinical use of this drug.

Following the administration of [Carbonyl-14C]perospirone ([CO-14C]perospirone) and [isothiazolyl-3-14C]perospirone ([TH-14C]perospirone) to male-pigmented rats at a single oral dose of 10 mg/kg, serum radioactivity reached maxima of 499 ng eq./g and 446 ng eq./g, respectively, at 1 hour, then decreased rapidly to below 2 ng eq./g at 168 hours, and radioactivity in eyeballs reached maxima of 576 ng eq./g and 3449 ng eq./g, respectively, at 24 hours, then decreasing slowly to become 120 ng eq./g and 314 ng eq./g at 26 weeks. Apparent elimination half-lives of radioactivity in eyeballs were 197 and 126 days for [CO-14C]perospirone and [TH-14C]perospirone, respectively. With radioluminograms, radioactivity was detected specifically in the uvea, reaching maxima at 168 hours for [CO-14C]perospirone and at 24 hours for [TH-14C]perospirone. In addition to unchanged compound, many metabolites were found in serum and eyeballs, but those were also detectable in SD albino rats and cynomolgus monkeys. Among radioactive components in eyeballs after administration of [CO-14C]perospirone, ratios of ID-15036 and MX11 followed by unchanged compound and MX9 are high. After administration of [TH-14C]perospirone, ID-11614 accounted for nearly half of the radioactivity. Values decreased in line with radioactivity in eyeballs over time and 26 weeks only a few polar metabolites could be detected.

Purpose: The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). Procedures: Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. Results: In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV (P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. Conclusions: FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy. (Mol Imag Biol 2002;4:99–104)

Vanadium pentoxide is used as a catalyst and a ferrovanadium alloy ingredient in automotive steels and in jet engines and airframes. In addition, vanadium is found in fuel oils. Thus, occupational exposures to vanadium pentoxide and trioxide may occur during the cleaning of oil-fired ship boilers, and from oil-fired power station boilers. Occupational exposure to vanadium pentoxide induces green tongue, asthmatic symptoms and albuminuria with cast. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In this study, we exposed rat renal brush border membrane vesicles (BBMV) to vanadium pentoxide and examined their citrate uptake characteristics. The preincubation of BBMV with 1 mM V2O5 for 8 hours significantly inhibited citrate uptake compared with that of BBMV without V2O5, preincubation. These findings indicate that the preincubation of BBMV with vanadium pentoxide results in a time-dependent inhibition of citrate uptake by BBMV. These findings might contribute to nephrotoxicity in vanadium exposure.

1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity levels following intrahepatic arterial administration of (14)C-SM-11355 suspended in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were monitored in six animals, with tissue distribution studied after 1 day, 4 and 13 weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic circulation from Lipiodol, resulting in very low levels of Pt compounds in plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after the administration with proportions excreted for Pt and radioactivity up to 30-60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the administration, predominately as intact SM-11355. The concentrations were highest in the left lobe of the liver, the administration site, but levels in the remainder of the liver were also markedly higher than those in plasma and other tissues. 4. The results strongly support the concept that SM-11355 targets the liver with highly selectivity and sustained release of Pt compounds.

Retroperitoneal cystic lymphangioma is a rare benign tumor. Most patients eventually experience some symptoms that necessitate therapeutic intervention. Excision is the treatment of choice, and some cases of laparoscopic resection have been reported. We report another case of a huge retroperitoneal cystic lymphangioma that was successfully excised laparoscopically with the SAND balloon catheter. Large cystic lymphangioma was downsized by puncturing and aspirated with the SAND balloon catheter. Laparoscopic surgical technique should be considered for treatment of selected cystic lesions of retroperitoneal origin.

Objectives. To assess the diagnostic accuracy of the World Health Organization (WHO) grading system for renal cell carcinoma (RCC) in terms of nuclear size evaluation. Furthermore, the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal tubular cells, is investigated. Methods. Measurement of the nuclear areas of cancer and normal tubular cells was performed on the histologic slides from the 76 patients with RCC, and the distribution of MNA and NAI was compared among the WHO grades. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the progression-free and cause-specific survival of the patients was examined. Results. MNA for cancer cells and NAI significantly increased according to the grade. NAI was 1.0 or less in 9 of the 10 patients with G1 tumors and more than 1.0 in 12 of the 13 patients with G3 tumors, whereas the NAI ranged widely from 0.53 to 2.0 in 53 patients with G2 tumors. By multivariate analysis, including grade and TNM categories, NAI and MNA were independent variables for survival in all the patients as well as for cancer progression in localized disease. Conclusions. WHO G2 RCCs are actually composed of tumors with varying nuclear size, and the prognosis of the patients with G2 tumors varied as well. NAI could provide improved prognostic information for the patients with RCC, especially in G2 cases.

Anomalous origin of the right coronary artery is a relatively rare coronary artery anomaly which is known to cause myocardial ischemia and sudden death. Association of anomalous origin of the right coronary artery with congenital bicuspid aortic valve is even rarer with only a few cases being reported previously. We describe, for the first time, MDCT findings of anomalous origin of the right coronary artery associated with congenital bicuspid aortic valve.

Objectives. To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. Methods. The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). Results. Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. Conclusions. The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

Postmenopausal osteoporosis is caused mainly by a deficiency of oestrogen with rapid bone loss. To target oestrogen to the bone effectively, we have synthesized and evaluated the effects of a novel hybrid compound of oestrogen and bisphosphonate, SM-16896. The tissue distribution pattern and pharmacological potential are reported. Although the affinity for calf uterine oestrogen receptor was very low (IC50: 73.3 μM; 1/25000 of that of 17β-oestradiol (2.84 nM)), SM-16896 showed oestrogenic activity. SM-16896 (1 μM) induced a 4.5-fold transcriptional activity in rat osteosarcoma UMR-106 cells compared with vehicle-treated control, when we used the expression vector for human oestrogen receptor and a CAT reporter plasmid containing an oestrogen-responsive element. The distribution of SM-16896 after a subcutaneous administration to 7-week-old female rats was examined by radioluminography using 3H-labelled SM-16896. At 30 min after the administration, significant radioactivity was detected in the bone. At 24 h after administration, a high level of radioactivity was detected in the bone, but in the uterus it was only at a background level. Daily subcutaneous administration of 0.5 mg kg−1 SM-16896 for 12 weeks (five times per week) to 13-week-old ovariectomized rats suppressed the ovariectomized-induced reduction in bone mineral density. A bone mineral density ratio of 120% was maintained compared with sham-operated rats, whereas a relatively low suppression of uterine weight was observed (about 50% loss compared with sham-operated rats). In the same experiment, the implantation of a 17β-oestradiol time-release pellet (0.25 mg/pellet/90 days) almost completely suppressed the reduction of both the bone mineral density and uterine tissue weight. It is likely that the effect of SM-16896 on bone was due to its oestrogenic activity, since 1.0 mg kg−1 SM-18108, the bisphosphonate moiety of this compound, had no effect on bone in 7-week-old ovariectomized rats. The results suggest that SM-16896, a bisphosphonate-conjugated oestrogen, showed a preference profile in the uterus and bone due to its characteristic distribution pattern compared with the natural oestrogen analogue 17β-oestradiol. Thus, bisphosphonate-conjugated oestrogens have the potential to improve patient compliance in oestrogen therapy by minimizing adverse effects and reducing the frequency of medication.

Bland-White-Garland syndrome (BWG) is a rare disorder that includes abnormalities of the coronary arteries that cause severe myocardial ischemia or infarction in infancy. In this case report, we describe an infant with BWG evaluated by dual single photon emission computed tomography using thallium-201 and I-123 beta-methyl-p-iodophenyl-pentadecanoic acid before and after surgery.

BACKGROUND To evaluate the clinical usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) compared with histopathological grading, clinical stage and serum prostatic specific antigen (PSA) level in the detection and characterization of prostate cancer. METHODS Forty-four patients with histologically proven prostate cancer and five control subjects with benign prostatic hyperplasia (BPH) were prospectively investigated with FDG-PET prior to treatment. RESULTS By visual inspection, FDG accumulation was positive in 28 patients with prostate cancer (sensitivity 64%), whereas all were negative in the control group. FDG-PET in three patients with lymph node metastases did not show any high intrapelvic accumulations corresponding to metastatic sites. Among 12 patients with multiple bone metastases which were detected with 99m-HMDP bone scintigraphy, nine (75%) showed moderate to high FDG accumulation at the sites of bone metastases. Quantitatively, FDG accumulation in prostate cancer was significantly higher than in BPH and there was a tendency for FDG uptake of tumors to be higher with higher histological Gleason grades. Furthermore, FDG uptake in tumors with lymph node and/or bone metastasis was significantly higher than that of localized stages. However, the correlation between PSA and FDG uptake in the prostate cancer was very weak for clinical relevance. CONCLUSIONS Although FDG-PET was not sensitive enough to detect prostate cancer in clinical use, it is suggested that glucose metabolism in prostate cancer tended to be higher in patients with tumors of advanced stages.

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Background: Pelvic lymph node dissection (PLND) is an important staging method for men with clinically localized prostate cancer. We report our experience with staging PLND and the impact of lymph node metastasis on long-term prognosis. Methods: One hundred forty-eight consecutive patients who underwent staging PLND for clinically localized prostate cancer were retrospectively studied. Patients were evaluated for the presence and number of lymph node metastases, treatment (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with respect to disease progression and survival. The mean follow-up period was 52.9 months (range, 2.3 to 165.8 months). Results: Thirty-two patients (21.6%) had pelvic lymph node metastases, the incidence of which markedly decreased from 32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease progression and cancer death were significantly shorter in patients with positive lymph nodes (P < 0.001). In stage D1 disease, patients who underwent a radical prostatectomy tended to be free of progression longer than those receiving radiotherapy or conservative therapy (P= 0.0546). Other factors, such as early endocrine therapy, the extent of lymph node involvement and the Gleason score of the primary tumor did not predict disease progression or survival. Conclusion: These data suggest a decreasing trend in the incidence of lymph node metastasis in the PSA era. Although longer disease-free intervals were observed in radical prostatectomy-treated patients, the impact of an aggressive approach to stage D1 disease awaits further studies.

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent.

Background This study investigated the relationships between the numeric aberrations of chromosome 17 and p53 expression, the proliferating cell nuclear antigen labeling index (PCNA-LI) and histopathology, to determine their prognostic significance in bladder cancer. MethodsUsing in situ hybridization (1SH) with a biotin-labeled chromosome-specific DNA probe, the copy number of pericentromeric sequences in chromosome 17 were detected within interphase nuclei in formalin-fixed paraffin-embedded sections from 59 nonmetastasized transitional cell carcinomas (TCCs) of the urinary bladder. Expression of p53 and PCNA-LI were determined in serial sections by an immunohistochemical method. Results The percentage of hyperdiploid cells for chromosome 17 correlated with p53 overexpression (P< 0.002), PCNA-LI (P< 0.002), increasing tumor grade (P< 0.002) and advanced pathologic stage (P< 0.002). The average percentage of hyperdiploid cells was lower in tumors with negative p53 expression than in tumors with p53 overexpression (P< 0.002). Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P

Morphological similarities between renal oncocytomas and 'oncocytic' renal cell carcinomas (RCCs) make a differential diagnosis in many cases difficult. A series of 41 renal oncocytomas has been analysed by microsatellite markers from chromosomes 1, 2, 3p, 6q, 8p, 9, 10, 13q, 14q, 17, and 21, alterations of which are known to be involved specifically in non-papillary and chromophobe RCCs. Only eight of the 41 renal oncocytomas showed loss of heterozygosity (LOH). LOH at chromosomes 1 and 14 occurred in four tumours each and at chromosomes 2, 8, and 9 in one tumour each. Combined LOH at chromosomes 1, 9, and 14 and also at chromosomes 1 and 14 occurred in one case each. No LOH was seen at any other genomic sites. The lack of combination of LOH at specific chromosomal sites differentiates renal oncocytomas from other renal cell tumours with overlapping phenotypes. Applying the microsatellite assay described here, the diagnosis can be established within 2 days, from fresh as well as from paraffin-embedded material.

The metabolism of amrubicin hydrochloride (SM-5887), a novel antitumor agent, was investigated in rats and dogs after intravenous administration of 14C-labeled SM-5887. 1. Nine metabolites in rat urine, ten metabolites in rat bile, six metabolites in dog urine and eleven metabolites in dog bile were observed after intravenous administration of 14C-SM-5887. Major radioactive components in rat urine were amrubicinol (SM-5887-13-OH) and the unchanged SM-5887, and those in dog urine were M-2 and Met B. Major radioactive components in bile of rats and dogs were polar metabolites, such as M-1 and M-2. 2. In rat tissues, ma jor radioactive components were nonpolar or less polar metabolites, such as Met B and SM-5887-13-OH, and the unchanged SM-5887. 3. The structures of the nonpolar or less polar metabolites (SM-5887-13-OH and Met A ?? Met D) were determined by comparing them to the authentic samples using HPLC and mass spectrometry. The identified metabolites were an alcoholic derivative (SM-5887-13-OH), deoxyaglycones (Met A and Met B) formed by reductive glycosidic cleavage, an aglycone (Met B) formed by glycosidic cleavage and a deaminated derivative (Met D). Two polar metabolites (M-4 and M-6) were also identified as the conjugates of SM-5887-13-OH with glucuronic acid. The other polar metabolites (M-1 ?? M-3, M-5 and M-7), which were assumed to be conjugates based on their high polarities, could not be identified due to their low stabilities.