Roles of neural communication between the brain and thoracic ganglia in the selection and regulation of the cricket escape behavior.

To survive a predator's attack, prey animals must exhibit escape responses that are appropriately regulated in terms of their moving speed, distance, and direction. Insect locomotion is considered to be controlled by an interaction between the brain, which is involved in behavioral decision-making, and the thoracic ganglia (TG), which are primary motor centers. However, it remains unknown which descending and ascending signals between these neural centers are involved in the regulation of the escape behavior. We addressed the distinct roles of the brain and TG in the wind-elicited escape behavior of crickets by assessing the effects of partial ablation of the intersegmental communications on escape responses. We unilaterally cut the ventral nerve cord (VNC) at different locations, between the brain and TG, or between the TG and terminal abdominal ganglion (TAG), a primary sensory center of the cercal system. The partial ablation of ascending signals to the brain greatly reduced the jumping response rather than running, indicating that sensory information processing in the brain is essential for the choice of escape responses. The ablation of descending signals from the brain to the TG impaired locomotor performance and directional control of the escape responses, suggesting that locomotion in the escape behavior largely depends on the descending signals from the brain. Finally, the extracellular recording from the cervical VNC indicated a difference in the descending activities preceding the escape responses between running and jumping. Our results demonstrated that the brain sends the descending signals encoding the behavioral choice and locomotor regulation to the TG, while the TG seem to have other specific roles, such as in the preparation of escape movement.

Action selection based on multiple-stimulus aspects in wind-elicited escape behavior of crickets.

Escape behavior is essential for animals to avoid attacks by predators. In some species, multiple escape responses could be employed. However, it remains unknown what aspects of threat stimuli affect the choice of an escape response. We focused on two distinct escape responses (running and jumping) to short airflow in crickets and examined the effects of multiple stimulus aspects including the angle, velocity, and duration on the choice between these responses. The faster and longer the airflow, the more frequently the crickets jumped. This meant that the choice of an escape response depends on both the velocity and duration of the stimulus and suggests that the neural basis for choosing an escape response includes the integration process of multiple stimulus parameters. In addition, the moving speed and distance changed depending on the stimulus velocity and duration for running but not for jumping. Running away would be more adaptive escape behavior.

Spatial perception mediated by insect antennal mechanosensory system.

Animals perceive their surroundings using various modalities of sensory inputs to guide their locomotion. Nocturnal insects such as crickets use mechanosensory inputs mediated by their antennae to orient in darkness. Spatial information is acquired via voluntary antennal contacts with surrounding objects, but it remains unclear whether the insects modulate behaviors mediated by other sensory organs based on that information. Crickets exhibit escape behavior in response to a short air puff, which is detected by the abdominal mechanosensory organs called cerci and is perceived as a 'predator approach' signal. We placed objects of different shapes at different locations with which the cricket actively made contact using its antennae. We then examined the effects on wind-elicited escape behavior. The crickets changed their movement trajectory in response to nearby objects such as walls so that they could avoid collision with these obstacles even during the cercal-mediated behavior. For instance, when a wall was placed in front of the crickets so that it was detected by one antenna, the escape trajectory in response to a stimulus from behind was significantly biased toward the side opposite the wall. Even when the antenna on the free side without the wall was ablated, this collision avoidance was also observed, suggesting that the mechanosensory inputs from one antennae detecting an object edge would be sufficient to perceive the location of obstacle in front. This study demonstrated that crickets were able to use the spatial information acquired with their antennal system to modify their behavior mediated by other sensory organs.

Trade-off between motor performance and behavioural flexibility in the action selection of cricket escape behaviour.

To survive a predator's attack successfully, animals choose appropriate actions from multiple escape responses. The motor performance of escape response governs successful survival, which implies that the action selection in escape behaviour is based on the trade-off between competing behavioural benefits. Thus, quantitative assessment of motor performance will shed light on the biological basis of decision-making. To explore the trade-off underlying the action selection, we focused on two distinct wind-elicited escape responses of crickets, running and jumping. We first hypothesized a trade-off between speed and directional accuracy. This hypothesis was rejected because crickets could control the escape direction in jumping as precisely as in running; further, jumping had advantages with regard to escape speed. Next, we assumed behavioural flexibility, including responsiveness to additional predator's attacks, as a benefit of running. The double stimulus experiment revealed that crickets running in the first response could respond more frequently to a second stimulus and control the movement direction more precisely compared to when they chose jumping for the first response. These data suggest that not only the motor performance but also the future adaptability of subsequent behaviours are considered as behavioural benefits, which may be used for choosing appropriate escape reactions.

Circulating Aminoterminal Propeptide of Type III Procollagen as a Biomarker of Cardiovascular Events in Patients Undergoing Hemodialysis.

AIM: Type Ⅲ collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type Ⅲ procollagen (PⅢNP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. METHODS: Serum PⅢNP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64±11 years; dialysis duration, 11.5±7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. RESULTS: During the follow-up for 4.7±1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PⅢNP concentration (1 U/mL; hazard ratio, 1.616; P=0.0001). The median serum PⅢNP concentrations were higher in patients with cardiovascular events than in those without (2.30±0.19 U/mL vs 1.30±0.03 U/mL; P＜0.0001). When the patients were assigned to subgroups based on serum PⅢNP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P=0.0001) in the subgroup of serum PⅢNP ≥1.75 U/mL than in that of serum PⅢNP ＜1.75 U/mL (31.9% vs 88.2%). CONCLUSIONS: Serum PⅢNP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

Post-molting development of wind-elicited escape behavior in the cricket.

Arthropods including insects grow through several developmental stages by molting. The abrupt changes in their body size and morphology accompanying the molting are responsible for the developmental changes in behavior. While in holometabolous insects, larval behaviors are transformed into adult-specific behaviors with drastic changes in nervous system during the pupal stage, hemimetabolous insects preserve most innate behaviors whole life long, which allow us to trace the maturation process of preserved behaviors after the changes in body. Wind-elicited escape behavior is one of these behaviors and mediated by cercal system, which is a mechanosensory organ equipped by all stages of nymph in orthopteran insects like crickets. However, the maturation process of the escape behavior after the molt is unclear. In this study, we examined time-series of changes in the wind-elicited escape behavior just after the imaginal molt in the cricket. The locomotor activities are developed over the elapsed time, and matured 24h after the molt. In contrast, a stimulus-angle dependency of moving direction was unchanged over time, meaning that the cercal sensory system detecting airflow direction was workable immediately after the molt, independent from the behavioral maturation. The post-molting development of the wind-elicited behavior was considered to result not simply from maturation of the exoskeleton or musculature because the escape response to heat-shock stimulus did not change after the molt. No effect of a temporal immobilization after the imaginal molt on the maturation of the wind-elicited behavior also implies that the maturation may be innately programmed without experience of locomotion.

Possible Inhibitory Effect of Erythropoiesis-Stimulating Agents at the Predialysis Stage on Early-Phase Coronary Events after Hemodialysis Initiation.

BACKGROUND: We examined whether the use of erythropoiesis-stimulating agents (ESAs) to correct anemia at the predialysis stage could inhibit early-phase coronary events after hemodialysis initiation. METHODS: We enrolled 242 patients with chronic kidney disease who had received continued medical treatments and initiated maintenance hemodialysis from 1 September 2000 to 31 December 2014 at Toujinkai Hospital. Patients with a previous history of blood transfusion or any cardiovascular events or interventions were excluded. The coronary events were followed for 1 year after initiation of hemodialysis. RESULTS: Coronary events occurred in 51 of 242 patients: 10 patients had acute coronary syndrome [9 with percutaneous coronary intervention (PCI), 1 without intervention], and 41 had elective coronary revascularization (38 PCI and 3 coronary artery bypass graft). ESA was administered in 118 of 242 patients (48.8%). In stepwise logistic analysis, coronary events were positively associated with nonuse of ESA at the predialysis stage (odds ratio 2.66, p = 0.005) and diabetes mellitus (odds ratio 5.33, p < 0.001). When dividing the patients into 4 subgroups by blood hemoglobin (Hb) level (8.5 g/dl) and the use/nonuse of ESA, coronary event-free survival rates were higher (p = 0.005) in those with Hb ≥8.5 g/dl, ESA+ (86.6%, n = 82) and tended to be higher (p = 0.055) in those with Hb <8.5 g/dl, ESA+ (86.1%, n = 36) than in patients with Hb <8.5 g/dl, ESA- (68.6%, n = 86) in a Kaplan-Meier analysis. CONCLUSIONS: The use of ESA to correct anemia at the predialysis stage may inhibit early-phase coronary events after hemodialysis initiation.

Low parathyroid hormone levels after parathyroidectomy reduce cardiovascular mortality in chronic hemodialysis patients.

BACKGROUND: The aim of the study is to elucidate whether parathyroid hormone (PTH) levels after parathyroidectomy affect the prognosis of patients with secondary hyperparathyroidism. SUBJECTS AND METHODS: Two hundred and ninety-five patients, who underwent PTx without autotransplantation from July 1998 to December 2011, were divided into the low (n = 148) and high (n = 147) PTH groups, using the median value of each mean value of intact PTH after surgery (16.6 pg/mL). After observation for 5.00 years, we evaluated demographic factors, influences of postoperative mineral metabolism, magnitude of uremia, and vitamin D receptor activators on their prognosis, with the multivariate Cox proportional hazard model. RESULTS: While overall survival rates in the high and low PTH groups were 54.9 and 74.2 %, respectively (P = 0.1500), cardiovascular survival rates were 71.6 and 94.4 %, respectively (P = 0.0256). The hazard ratio for cardiovascular mortality in the high PTH group (≥16.6 pg/mL) was 3.132 (P = 0.0470), and those in groups with the median age more than 59 years and with cardiovascular disease were 2.654 (P = 0.0589) and 3.377 (P = 0.0317), respectively. The intact PTH level 6 days after surgery and the mean postoperative intact PTH value showed a strong correlation (Spearman ρ = 0.9007, P < 0.0001, y = 0.4725x + 30.395, R 2 = 0.51798). CONCLUSION: The present study suggests that maintaining low PTH levels after parathyroidectomy reduces cardiovascular mortality and improves the prognosis. Total parathyroidectomy (more than 4 glands) without autotransplantation seems to be one of the treatment options for managing severe secondary hyperparathyroidism.

Effects of intravenous l-carnitine on myocardial fatty acid imaging in hemodialysis patients: responders or non-responders to l-carnitine.

We investigated whether chronic intravenous administration of l-carnitine could improve myocardial fatty acid imaging in patients on maintenance hemodialysis. We enrolled 72 hemodialysis patients who had impaired myocardial fatty acid imaging and left ventricular dysfunction not based on coronary lesion. l-Carnitine (1,000 mg) was intravenously administered after dialysis for 1 year to 36 participants (Carnitine group), while not in the other 36 participants (Control group). Single-photon emission computed tomography (SPECT) using an iodinated fatty acid analogue, BMIPP, was performed. Uptake on SPECT images was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. During follow-up, 19 participants were discontinued from the study, and 53 participants (65 ± 12 years: 27 carnitine, 26 control) were analyzed. The mean BMIPP summed scores 1 year after carnitine administration did not differ from that before in the carnitine group, nor from that in the control group. However, improved SPECT (Changes in BMIPP summed scores <-20%) was found in 7 (25.9%) participants in the carnitine, whereas in 2 (7.7%) in the control group. Multivariate logistic analysis showed the improved SPECT was inversely associated with baseline serum albumin levels (1 g/L: odds ratio, 0.669); the cut-off was 35 g/L. Chronic intravenous l-carnitine might improve myocardial fatty acid imaging in a selected group of hemodialysis patients with hypoalbuminemia.

Improvement of myocardial fatty acid metabolism by oral nicorandil in hemodialysis patients without coronary artery disease.

BACKGROUND: We investigated the potential of oral nicorandil to improve myocardial fatty acid metabolism assessed by single-photon emission computed tomography (SPECT) using (123)I-ß-methyliodophenyl pentadecanoic acid (BMIPP) in hemodialysis patients without obstructive coronary artery disease (CAD). METHODS: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive CAD, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years); 50 with oral administration of nicorandil (15 mg/d, nicorandil group) and 50 without (control). BMIPP SPECT was performed every year after angiography. Uptake on SPECT was graded in 17 segments on a five-point scale (0 normal, 4 absent) and assessed as BMIPP summed scores (SS). RESULTS: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients. Myocardial uptake of BMIPP in SPECT improved in the nicorandil group compared with the control group from 2 years of administration. In Kaplan-Meier survival analyses, free survival rate from cardiac death was higher in patients with a BMIPP SS improvement rate of ≥20% compared to those with ≥0% <20% or with <0% BMIPP SS improvement rate. At multiple logistic analysis, a ≥20% BMIPP SS improvement rate was positively associated with serum albumin concentration and oral nicorandil. CONCLUSIONS: Long-term oral nicorandil may inhibit cardiac death by improving myocardial fatty acid metabolism in hemodialysis patients without obstructive CAD.

Clinical potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention in hemodialysis patients.

BACKGROUND/AIMS: The assessment of myocardial fatty acid metabolism impairment by single-photon emission computed tomography (SPECT) using (123)I-ß-methyliodophenyl-pentadecanoic acid (BMIPP) might predict the risk of cardiac death in hemodialysis patients. We investigated the potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention (PCI) in this population. METHODS: We evaluated 128 hemodialysis patients who had obtained coronary revascularization by PCI (90 men and 38 women, 66 ± 9 years). Participants for the analysis were randomly assigned to either the nicorandil (n = 63) or control group (n = 65). BMIPP SPECT was performed every year after coronary revascularization by PCI. Uptake on SPECT was graded in 17 segments on a 5-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores (SS). RESULTS: The incidence of cardiac death was lower (p = 0.004) in the nicorandil group (7/63, 11.1%) than in the control group (21/65, 32.3%) during a mean follow-up of 2.7 ± 1.4 years. BMIPP SS reduction rates improved in the nicorandil group compared with the control group from 3 years of administration. In Kaplan-Meier analyses, free survival rate of cardiac death was higher in patients with a ≥20% BMIPP SS reduction rate as compared with those with a <20% BMIPP SS reduction rate (p = 0.0001). In multiple logistic analysis, oral administration of nicorandil was associated with ≥20% reduction rates of BMIPP SS (odds ratio 2.823, p = 0.011). CONCLUSION: Long-term oral administration of nicorandil may improve impaired myocardial fatty acid metabolism after coronary revascularization by PCI in hemodialysis patients.

Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND AND AIMS: To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. METHODS: Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. RESULTS: The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. CONCLUSION: Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.

Oral nicorandil for prevention of cardiac death in hemodialysis patients without obstructive coronary artery disease: a propensity-matched patient analysis.

BACKGROUND/AIMS: We examined the potential of oral administration of nicorandil for protecting against cardiac death in hemodialysis patients without obstructive coronary artery disease. METHODS: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive coronary lesions, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years), including 50 who received oral administration of nicorandil (15 mg/day, nicorandil group) and 50 who did not (control). The efficacy of nicorandil in preventing cardiac death was investigated. RESULTS: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients, including 6 due to acute myocardial infarction, 11 due to heart failure, and 8 due to sudden cardiac death. The incidence of cardiac death was lower (p < 0.001) in the nicorandil group (4/50, 8%) than in the control (21/50, 42%). On multivariate Cox hazard analysis, cardiac death was inversely associated with oral nicorandil (hazard ratio, 0.123; p = 0.0002). On Kaplan-Meier analysis, cardiac death-free survival rates at 5 years were higher in the nicorandil group than in the control group (91.4 vs. 66.4%). CONCLUSION: Oral nicorandil may inhibit cardiac death of hemodialysis patients without obstructive coronary artery disease.

Enhancement of the sensitivity of renal cell carcinoma cells to fas-mediated cytotoxicity and apoptosis by the selective cyclooxygenase-2 inhibitor JTE-522.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in a variety of cancer cells. We reasoned that combination treatment of renal cell carcinoma (RCC) cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 synergizes with anticancer agents in cytotoxicity and apoptosis against RCC cells. METHODS: The cytotoxicity of the selective COX-2 inhibitor JTE-522 and other anticancer agents against the RCC cell lines and the normal renal cell line was determined by the microculture tetrazolium dye assay. RESULTS: JTE-522 was cytotoxic against the Caki-1 RCC cell line. JTE-522 and anti-Fas monoclonal antibody (CH-11) exhibited a synergistic cytotoxic effect against Caki-1 cells. In contrast, JTE-522 in combination with 5-fluorouracil, adriamycin, cis-diamminedichloroplatinum, or interferon-alpha, all commonly used clinically, resulted in an additive cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CH-11 was shown to be due to apoptosis. CONCLUSIONS: The present study demonstrated that the selective COX-2 inhibitor JTE-522 had a cytotoxic effect on RCC and that synergistic cytotoxicity against RCC was obtained with JTE-522 in combination with anti-Fas monoclonal antibody. These results suggest that selective COX-2 inhibitors in combination with immunotherapy may be useful in treating patients with RCC.

Imprint cytologic features of chromophobe renal cell carcinoma morphologically resembling renal oncocytoma: is this an oncocytic variant of chromophobe renal cell carcinoma?

In this article, we report a case of 76-year-old woman with a rare variant of chromophobe renal cell carcinoma (CRCC). Cytologically, renal tumor cells obtained from imprint cytology were isolated or arranged in small or monotonous population cells with abundant granular cytoplasm. Neoplastic cells showed regular and uniformly shaped small round to oval nuclei with smooth margin. Binucleation was occasionally seen. Immunocytochemically, the cytoplasm of almost all tumor cells was diffusely positive for vimentin and CK 7. Histologically, the cytoplasm was abundant granular eosinophilic and composed of solid cell sheets or pseudoacinar structures. Additionally, tumor cells showed infiltration into some small renal veins covered by a single layer of endothelial cells. These cytological and histological features entirely resembled those of renal oncocytoma. We performed the analysis of von Hippel-Lindau (VHL) gene mutation, 3p loss of heterozygosity (LOH), and fluorescence in situ hybridization (FISH) on chromosomes 7, 10, 13, 17, and 21. As a result, we confirmed monosomy of chromosomes 7, 10, 13, and 17, and these findings corresponded to the diagnosis of CRCC. Finally, we present a case of renal tumor morphologically resembling renal oncocytoma but genetically showing CRCC. We suggest that oncocytic variant of CRCC may actually exist.

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis.

X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase-inhibitory IAP family member and a negative regulator of various apoptotic stimuli. Thus, XIAP overexpression in cancer cells may select for tumor cell survival following various cytotoxic therapeutic modalities. The anatomical staging system in renal cell carcinoma (RCC) currently provides good prognostic information, albeit insufficient. We hypothesize that overexpression of XIAP in RCC may serve as a molecular prognostic marker in RCC and improve the staging of RCC. This study examined the protein level of XIAP in lysates from surgical specimens of 109 patients with RCC and 109 normal kidney specimens from the same patients. The level of XIAP expression was quantified by Western blot analysis using non-fixed fresh frozen tissues of RCCs and normal kidneys. Results indicated that the mean level of XIAP expression was higher in RCC compared to autologous normal kidney, and the XIAP expression level in 38/109 (35%) of RCC was more than 2-fold greater than that in normal kidney tissue. In Stage I/II RCC, the mean XIAP expression level was almost identical to that detected in normal kidney, whereas XIAP expression in Stage III/IV was 2.5-fold higher than that in Stage I/II RCC. Levels of XIAP expression also correlated with the grade of RCC. Patients with RCC with low XIAP expression had a longer postoperative disease-specific survival as compared to those with high expression in the 5-year follow-up. The suggested role of XIAP in the regulation of resistance in apoptosis was examined in vitro following treatment of RCC cell lines with XIAP antisense oligonucleotide and the cells were sensitized to both Fas-mediated and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The present study demonstrates at the protein level that XIAP is overexpressed in RCC, and that high XIAP expression in RCC predicted a worse prognosis. In addition, XIAP antisense oligonucleotide sensitized RCC to Fas/TRAIL-induced apoptosis. These results suggest that XIAP expression in RCC may be used as a prognostic parameter, and that downregulation or inhibition of XIAP expression in RCC may reverse immune resistance.

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.

[A case of spontaneous rupture of the urinary bladder followed by pneumomediastinum].

A 67-year-old male admitted to our hospital with a complaint of gross hematuria and lower abdominal pain. He was being followed up at our hospital for prostate cancer with multiple bone metastases. He was diagnosed with spontaneous rupture of the urinary bladder by abdominal computed tomography. Chest X-ray and chest computed tomography also showed pneumomediastinum. An urgent operation revealed a rupture of the urinary bladder 3 cm in length. We briefly reviewed 122 cases of spontaneous rupture of the urinary bladder reported in the Japanese literature.