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Summary This study was designed to compare the effects of wetsuit (WS) to swimsuit (SS) at identical relative velocities in a swimming flume. Thirteen triathletes performed a continuous progressive swimming test and submaximal steady state swimming tests with a WS and with a SS. Maximal oxygen uptake ( V ˙ O 2 max ) and the associated velocity at which the V ˙ O 2 max was achieved ( V V ˙ O 2 max ) were determined during the continuous progressive tests. Two 5 min swims (at 60% V V ˙ O 2 max (V60%) and 80% V V ˙ O 2 max (V80%)) were then conducted to measure V ˙ O 2 max , blood lactate concentration (LA), rating of perceived exertion (RPE), the energy cost of swimming (Cs), stroke rate (SR) and stroke length (SL). No difference was found in V ˙ O 2 max , but V V ˙ O 2 max with a WS was 5.4% higher than with a SS. V ˙ O 2 with a WS was lower than with a SS alone at V60%, but not at V80%. Cs with a WS was lower by 14.4% at V60% and 7.5% at V80% than with a SS. No differences were found in LA and RPE between suit conditions during both submaximal swims. Wearing a WS did not affect SL, but SR tended to be higher in a WS for both submaximal velocities. These results suggest that the benefits of wearing a WS are not only improvement in swimming performance and propulsion efficiency, but reduction in gross energy consumption in the swimming portion of triathlon races. Furthermore, when wearing a WS, incremental changes in SR rather than SL are associated with improved swimming performance.

本研究の目的は，シミュレーションモデル SWUM（Swimming hUman Model）によって水中ドルフィンキックの推進メカニズムを解明することであった．エリート競泳選手8名を対象にシミュレーション用入力データを算出し， SWUMを応用することでシミュレーション上に水中ドルフィンキックのダイナミクスを再現し，泳中の推進力と関節トルクを算出した．結果として，水中ドルフィンキックの推進力は主に足部で発揮され，推進力発揮には下肢だけではなく体幹でのトルク発揮が重要であることが明らかとなった．さらに，バタフライ泳者で腰痛が起こりやすい要因の 1つとして，水中ドルフィンキック泳中に体幹で大きな関節トルクを周期的に発揮していることが挙げられた．

The purpose of this study was to investigate the relationship between plantar flexion angle and underwater dolphin kick performance using a simulation model, SWUM (SWimming hUman Model), in which the entire body was represented as a series of elliptic cylinders. Three unsteady fluid forces (added mass force, normal and tangential resistive force), buoyancy and gravity acting on the elliptic cylinders were computed from the shape and density of the cylinders, and from the joint motion for one cycle. Eight elite competitive swimmers participated in this study. Their body characteristics were measured and input as the simulation data (the shape and density of the elliptic cylinders). The joint motion data for one cycle were obtained by the 2-D DLT method during the underwater dolphin kick. To recreate the dynamics of the underwater dolphin kick in the simulation, three fluid coefficients, used to calculate the three unsteady fluid forces, were identified to minimize the difference between measured and simulated swimming velocity by the least-squares method. This identification was conducted for each of the input data. Simulations of the increased plantar flexion angle in the knee extension phase were executed with the optimal fluid coefficients for each swimmer in order to analyze the change in swimming velocity and thrust generated by the feet. The conclusions can be summarized as follows : (1) Swimming velocity during the underwater dolphin kick increased due to the increment of the thrust generated by the feet after an increase in the plantar flexion angle. (2) It was suggested that flexibility of plantar flexion is important, although it is not a determinant of underwater dolphin kick performance. (3) Swimmers with low flexibility of plantar flexion tended to achieve a faster swimming velocity after increasing the plantar flexion angle.

The purpose of this study was to investigate the effects of water exercise at a day service facility and the effects of water exercise frequency on health-related quality of life (HRQL). Participants (n = 30) were randomly separated into three groups: two indicating exercise frequency, at once-weekly or twice-weekly, and a control group. One-hour exercise intervention sessions were carried out once or twice a week, accordingly, for 24 weeks. The water exercise session comprised a warm-up on land, activities of daily living (ADL) exercises, stretching, strength training, and relaxation in water. HRQL was evaluated using the Medical Outcomes Survey Short-Form 36 (SF-36) questionnaire, and ADL disability was assessed using the Functional Independence Measure. Significant differences were found between pre- and 6 months in both the once- and twice-weekly groups in HRQL (p

The flow field around a swimmer has been assumed to be steady or quasi-steady in the estimation of flow force acting on hand/arm in spite of its extremely unsteady characters, because the convenient means for measuring the flow field has been lacking. A sophisticated technique called the PIV (Particle Image Velocimetry) was developed and enabled us to estimate the unsteady flow field. The PIV technique can visualize the unsteady flow field and can detect the vortex behavior around a hand. On the other hand, motion analysis has been widely used in the field of biomechanics of sport. This method can also be expected to evaluate the swimmer's complicated motion. Our study is to clarify the relationship between the vortex behavior and the motion of a hand in crawl swimming. Two methods were combined to know the generating mechanism of swimming thrust. Measurements were made for two subjects ; one is a female Olympic swimmer (subject 1) and the other a male with no competitive career (subject2). The trajectory of the plam of the subject 1 was S-shaped motion. From the change of the palm inclination angle, it was suggested that the palm of the subject 1 reversed the orientation of the circulation. On the other hand, the palm of subject 2 did not reverse the orientation of the circulation. It is plausible that subject 2 does not generate any strong and coherent vortices. From the results of visualization of flow field, subject 1 generates strong vortices or vortex pair after the phase turned from in-sweep to out-sweep. In addition, the shed vortex pair follows a jet flow in the direction of the flume flow. In contrast, subject 2 did not shed any vortex pairs. It was confirmed that the hand motion in swimming was closely related to the vortex generation and also to the thrust.

This study investigated thermal swimsuits (TSS) effects on body temperature and thermal insulation of prepubescent children during moderate-intensity water exercise. Nine prepubescent children (11.0+/-0.7 yrs) were immersed in water (23 degrees C) and pedalled on an underwater cycle-ergometer for 30 min with TSS or normal swimsuits (NSS). The rectal temperature (Tre) was maintained slightly higher with TSS than with NSS. The total insulation (Itotal) was significantly higher with TSS. The DeltaTre, Deltamean body temperature (Tb), and tissue insulation (Itissue) in the NSS condition were correlated with % body fat, which indicated that the insulation layer of subjects with low body fat was thinner than that of obese subjects, and tended to decrease body temperature. Wearing TSS increased Itotal, thereby reducing heat loss from subjects' skin to the water. Consequently, subjects with TSS were able to maintain higher body temperatures. In addition, TSS is especially advantageous for subjects with low body fat to compensate for the smaller Itissue.

To compare the activity of lower extremity muscles during land walking (LW), water walking (WW), and deep-water running (DWR), 9 healthy young subjects were tested at self-selected low, moderate, and high intensities for 8 sec with two repetitions. Surface EMG electrodes were placed on the tibialis anterior (TA), soleus (SOL), medial gastrocnemius (GAS), rectus femoris (RF), and biceps femoris (BF). During DWR, the SOL and GAS activities were lower than LW and WW. The BF activities were higher during DWR than LW and WW. It was considered that the lower activity of SOL and GAS depended on water depth, and higher activity of BF occurred by greater flexion of the knee joint or extension of the hip joint during exercise.

A study was conducted to identify the effect of a computer-assisted swimming instruction (CASI) program on children's learning motivation and learning strategy. Twenty children learning to swim in a private swimming club participated. The subjects were classified into an experimental group that used the CASI program before each swimming lesson and a control group that merely participated in the ordinary swimming lesson at the pool. Learning motivation, learning strategy, and 50-m swimming performance for the front crawl and breaststroke were investigated before and after the swimming lesson. The experimental group showed significantly higher fulfilment-oriented motivation (p

This study investigated the effect of a thermal swimsuit (TSS) on children's thermal sensation and formative evaluation during elementary school swimming classes. In addition, application of the TSS in different environmental conditions in an outdoor swimming pool and children's physical characteristics were studied. The study participants were 62 sixth-grade elementary children, who were divided into two groups (experimental: n=32, control: n=30). The investigation consisted of a pre-test, and a post-test after three days of TSS intervention. A questionnaire survey concerning children's thermal sensation and formative evaluation of the class was conducted after each class. It was found that on days when the weather was cold, the experimental group significantly attenuated the cold sensation and showed higher motivation and interest in the class. Additionally, the TSS was able to decrease the number of students who could not continue swimming in the water because of coldness. These results indicated that swimming classes could be held even in a cold environment when the TSS was used. Furthermore, it was suggested that application of the TSS as a teaching aid would compensate for the thinner physique of children.

We have previously reported that Salvador homologue 1 (SAV1), a component of the Hippo pathway, is significantly down-regulated in high-grade clear cell renal cell carcinoma (ccRCC) due to 14q copy number loss, and that this down-regulation contributes to the proliferation and survival of renal tubular epithelial cells through activation of Yes-associated protein 1 (YAP1), a downstream target of the Hippo pathway. However, the impact of SAV1 loss on the proliferation and survival of kidney cells in vivo remained to be determined. To address this issue, we generated kidney-specific Sav1-knockout (Cdh16-Cre;Sav1(fl/fl) ) mice. Sav1 deficiency enhanced the proliferation of renal tubular epithelial cells in Cdh16-Cre;Sav1(fl/fl) mice, accompanied by nuclear localization of Yap1, suggesting suppression of the Hippo pathway. Sav1 deficiency in renal tubules also caused structural and cellular abnormalities of the epithelial cells, including significant enlargement of their nuclei. Furthermore, Cdh16-Cre;Sav1(fl/fl) mice developed both glomerular and tubular cysts. Although lining cells of the glomerular cysts showed no atypia, those of the tubular cysts showed variations in cell size and nuclear shape, which became more severe as the mice aged. In aged Cdh16-Cre;Sav1(fl/fl) mice, we observed focal disruption of proximal tubules and perivascular lymphocytic infiltration. In conclusion, Sav1 is required for the maintenance of growth, nuclear size and structure of renal tubules under physiological conditions, and its deficiency leads to the acquisition of enhanced proliferation of renal epithelial cells through suppression of Hippo signalling.

Purpose: β2-Microglobulin (β2M), a soluble protein secreted by cancer and host inflammatory cells, has various biological functions, including antigen presentation. Because aberrant expression of β2M has been reported in human renal cell carcinoma, we investigated the effects of β2M overexpression on cancer cell growth and analyzed its molecular signaling pathway. Experimental Design: We established clonal cell lines that overexpressed β2M in human renal cell carcinoma (SN12C) cells and then examined cell growth in vitro and in vivo and studied the β2M-mediated downstream cell signaling pathway. Results: Our results showed that β2M expression positively correlates with (a) in vitro growth on plastic dishes and as Matrigel colonies, (b) cell invasion and migration in Boyden chambers, and (c) vascular endothelial growth factor (VEGF) expression and secretion by cells. We found, in addition, that β2M mediates its action through increased phosphorylation of cyclic AMP–responsive element-binding protein (CREB) via the protein kinase A-CREB axis, resulting in increased VEGF expression and secretion. In convergence with this signal axis, β2M overexpression also activated both phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. β2M overexpression induced accelerated growth of SN12C in mouse subcutis and bone. Interrupting the β2M signaling pathway using small interfering RNA led to apoptosis with increased activation of caspase-3 and caspase-9 and cleaved poly(ADP-ribose) polymerase. Conclusions: Our results showed for the first time that the β2M-protein kinase A-CREB-VEGF signaling axis plays a crucial role in support of renal cell carcinoma growth and progression and reveals a novel therapeutic target.

A 45-year-old man on long-term hemodialysis (HD) was incidentally discovered to have a pheochromocytoma and underwent successful resection. This patient was normotensive, and had no symptoms suggesting pheochromocytoma. The plasma concentrations of total adrenomedullin (AM-T) and mature AM (AM-m) were higher than those in normal controls. To elucidate the source of AM, we measured plasma AM levels by immunoradiometric assay before and 3 weeks after surgery in addition to plasma adrenaline, noradrenaline and dopamine. AM expression was also assessed by immunoblot and immunohistochemical analyses on normal adrenal and tumor tissues. After surgery, elevated plasma adrenaline levels returned to the normal range; however, the levels of AM-T and AM-m remained almost the same as the preoperative values. Furthermore, although AM was expressed in both normal adrenal and tumor tissues, the AM expression level was less in tumor. In this case, it was suggested that elevation in plasma AM level might be a factor associated with normotensive blood pressure; however, adrenal pheochromocytoma was not a major source of circulating AM. To our knowledge, this is the first case of pheochromocytoma in patient with HD associated with AM in the literature.

The purpose of this study was to develop a Computer Assisted Instruction (CAI) web site for elementary school swimming class, and to clarify the effect of different CAI contents. BBS (Bulletin Board System, textual information) which the children could contribute their question freely and a multimedia contents (movie information) were made for the CAI web-contents. Three elementary schools (5th-6th grade) participated in this study. Questionnaire survey was conducted to analyze the effect of the CAI web site. Both contents received positive attitude from the children. Comparing the results between BBS and multimedia utilization, children answering “Useful to have new findings on swimming” was significantly higher than using multimedia contents (BBS: 19.2%, multimedia: 61.5% P

The starting technique is one of the most important factors for sprint performance in competitive swimming. Take-off velocity and take-off angle determine the horizontal take-off velocity and flight distance in the aerial phase. The most appropriate take-off angle for start performance has not been investigated, although the importance of take-off velocity is well known. The purpose of this study was to clarify the effects of take-off angle on take-off velocity, flight distance and block time during swim-start. Twelve elite competitive swimmers performed three different types of start trial. In the experimental starting trials, swimmers were instructed to take off from the starting block higher (High) and lower (Low) than the usual grab start trial (Normal). The starting motions of subjects were recorded by a high-speed camera (Photron FAST-CAM PCI, 250 fps) and the 2D-DLT method was used for calculating the kinematic variables. The starting movement was modeled by a pendulum model, and the take-off velocity was resolved to the rotational component and the extensional component. A decrement of the take-off angle resulted in an increment of rotational component, extensional component of take-off velocity. Therefore, the decrement of flight distance with decrement of the take-off angle resulted in fewer disadvantages for start performance. In addition, there was no correlation between take-off angle and the block time in Normal trials. Considering the importance of horizontal take-off velocity, which is in the direction of swimming, take-off angle should be approximately 0 degree in the aerial phase.

Introduction: The purpose of the present study was to compare the incidence of inguinal hernias after conventional and minilaparotomy (minilap) radical retropubic prostatectomy (RRP). Patients and Methods: In this retrospective study, we review our experience with 70 consecutive patients with prostate cancer who underwent prostatectomy from April 1995 through March 2001. Of these, 35 patients had conventional RRP, and 35 patients had minilap RRP. Results: Conventional RRP and minilap RRP groups were similar in body mass index (mean 24.4 and 23.5), operative time (mean 260 and 241 min), previous lower abdominal operation record (mean 37.1 and 25.7%), and post-prostatectomy anastomotic strictures (mean 11.4 and 14.3%). The volume of the estimated blood loss was significantly less for minilap RRP (mean 1,220 ml) than for conventional RRP (mean 1,666 ml; p = 0.0194). The incidence of postoperative inguinal hernias was 17.1% (6 of 35), 2.9% (1 of 35), and 3.2% (1 of 31) in conventional RRP, minilap RRP, and unoperated groups, respectively. The incidence of inguinal hernias after minilap RRP was significantly lower than after conventional RRP (p = 0.0464). Seven patients with postoperative inguinal hernias had a high incidence of postoperative strictures (42.9%), while 63 patients without hernia had a low incidence (9.5%). There was a significant difference in developing postoperative strictures between patients with hernia and those without (p = 0.0124). While postoperative stricture and operative technique were different in the hernia and hernia-free groups on univariate analysis, multivariate logistic analysis revealed that the operative technique was an independent factor for the occurrence of inguinal hernias (p = 0.0419). Conclusion: Minilap RRP compares favorably with conventional RRP in view of the postoperative inguinal hernia development.

Lymphoepithelioma-like carcinoma (LELC) in the bladder is uncommon with a reported incidence of 0.4%–1.3% of all bladder carcinomas. In Japan, some occurrences of LELC have been reported in the renal pelvis and ureter but only two in the bladder. A bladder tumor was identified in a 70-year-old man suffering from macroscopic hematuria for 2 months. Sections of the transurethral tumor resection showed invasive high-grade urothelial carcinoma. The patient was diagnosed with local invasive bladder tumor, and cystectomy with ileal conduit formation was performed. The final pathological evaluation was predominant LELC with urothelial carcinoma. We present a new case of LELC in the bladder and performed a review of all published cases of LELC in the urinary tract to obtain its characteristics and prognostic guide.

The purpose of the present study is to investigate the role of X-linked inhibitor of apoptosis protein (XIAP) in the regulation of apoptosis induced by cisplatin in human prostate cancer cell line (LNCaP). We examined the effects of cisplatin on cell growth and apoptosis in LNCaP by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1), flow cytometric analyses, and caspase-3 activity assay. In addition, to clarify the roles of the XIAP, we established clonal cell lines that overexpressed XIAP. The effects of cisplatin on the XIAP expression in the induction of apoptosis in LNCaP were examined by RT-PCR and immunoblot analyses. Although the growth rates were reduced in a dose- and time-dependent manner by cisplatin in LNCaP sublines, the anti-proliferative effects of cisplatin were significantly decreased in XIAP stably overexpressing cell lines. In addition, we found that cisplatin-induced apoptosis following activation of caspase-3, and that the overexpression of XIAP inhibited apoptosis by attenuating caspase-3 activity. Interestingly, treatment of LNCaP cells with 10 and 100 muM cisplatin for 48 h significantly decreased the expression of XIAP at both the protein and mRNA levels in a dose-dependent manner. Furthermore, 10-muM cisplatin treatment of LNCaP decreased XIAP mRNA and protein in a time-dependent manner. These results suggest that cisplatin induces apoptosis by the inhibition of XIAP expression, and that XIAP plays an important role in the regulation of cisplatin-induced apoptosis in LNCaP cells. The ability of cisplatin to down-regulate XIAP may be an important mechanism in chemosensitivity.

The purpose of this study was to investigate the effect of rest periods on energy system contribution during interval swimming and whether the energy system contribution varied depending on the swimmer's specialty, such as swimmers who specialize in the 100 m or 200 m. Seven highly-trained male varsity swimmers performed three different tests: a 10-min continuous test (CON), 10 × 1-min interval test with rest periods of 20 s (INT20) and 10 × 1-min interval test with rest periods of 30 s (INT30). Swimming velocity during all tests was set to maintain a blood lactate of 4 mM determined by progressive swimming. The relative aerobic and anaerobic energy system contribution was evaluated from accumulated oxygen uptake and oxygen deficit. Aerobic energy system contribution in CON, INT20, and INT30 was 93.3 ±1.1, 81.0 ±10.4, and 67.4 ±8.5%, and anaerobic contribution was 6.7 ±1.1, 19.0 ±10.4, and 32.6 ±8.5%, respectively. There were significant differences (p

A 64-year-old Japanese man suffering from IgD lambda myeloma and renal failure requiring chronic hemodialysis was treated with thalidomide. Serum IgD concentration was 4,050 mg/dl and myeloma cells constituted 95.6% of nucleated cells in bone marrow at the start of treatment. These parameters improved markedly to 1,590 mg/dl and 22.0%, respectively, in the 4 months immediately prior to his death due to pneumonia. Thalidomide caused peripheral neuropathy and constipation at a dose of 100 mg daily in the first week of treatment, but adverse effects resolved upon dose reduction. Thalidomide represents a valid therapeutic option for some myeloma patients receiving hemodialysis.

Lower pole renal stones are well known to show a poor stone clearance rate after extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Marietta, Georgia). In the current study we analyzed several anatomical factors as predictors of lower pole stone clearance that may be used to indicate the usefulness of ESWL in such patients.Between January 1993 and October 2000, 63 patients with a unilateral single lower pole stone of 2 cm. or less were included in the study. Excretory urography was done to determine the lower infundibulopelvic angle, caliceal pelvic height, lower infundibular length and diameter, lower infundibular length-to-diameter ratio and number of lower pole minor calices. Stone-free status was assessed by x-ray.The overall stone clearance rate was 54% (34 of 63 patients). While caliceal pelvic height, lower infundibular diameter, length, length-to-diameter ratio and number of minor calices were different in the stone-free and residual stone groups on univariate analysis, multivariate logistic analysis revealed that the lower infundibular length-to-diameter ratio, diameter and number of minor calices were independent predictors of successful stone clearance. The 13 patients (20.6%) who showed all 3 favorable anatomical factors (lower infundibular length-to-diameter ratio less than 7, diameter greater than 4 mm. and a single minor calix) achieved an impressive 84.6% stone clearance rate. In patients with only 1 or 2 favorable factors the stone clearance rate was still greater than 60%. In contrast, the stone clearance rate was only 6.7% in the 15 patients who showed none of these factors.From this study it is apparent that successful ESWL is highly sensitive to the anatomy of the lower pole of the kidney. If a patient with a lower pole stone has at least 1 of the favorable factors identified in this study, ESWL may be advocated as first line therapy with a greater than 60% prospect of a successful outcome. Other treatment options should be considered in those without any of these predictive factors.

Background: Adrenomedullin (AM) has pluripotent activities and is involved in the regulation of vasomotor tone, cell differentiation and embryogenesis. However, the expression and pathophysiological role of AM has not been determined in human renal cell carcinoma (RCC). Methods: Twenty-six RCC specimens and three cultured human RCC cell lines (A498, SN12C and KPK-13) were analyzed. Expression of AM was determined by immunohistochemistry and reverse transcription–polymerase chain reaction (RT-PCR) analysis. The correlation between AM expression and microvessel count (MVC) in RCC specimens was examined to determine if AM plays a role in tumor angiogenesis. The correlation between the expression of AM and vascular endothelial growth factor (VEGF) was also investigated. Lastly, the effect of hypoxia upon the mRNA expression of AM, VEGF and hypoxia inducible factor-1 (HIF-1) by RCC cell lines was determined. Results: Immunohistochemistry indicated that AM and VEGF were primarily localized in the cytosol of RCC cells. AM and VEGF mRNA were detected in all RCC specimens and cultured RCC cell lines analyzed by RT-PCR. There was a positive correlation between AM mRNA expression and MVC (r = 0.516, P = 0.0062), and between VEGF mRNA expression and MVC (r = 0.485, P = 0.0111). We also observed a positive correlation between AM mRNA expression and VEGF mRNA expression (r = 0.552, P = 0.0029). Hypoxia significantly induced AM and VEGF mRNA expression, although the increase of the AM mRNA level (10.6–26.7 fold) was markedly greater than that of the VEGF mRNA level (1.5–1.9 fold). Conclusion: These results suggest that hypoxia-induced AM plays a part in tumor angiogenesis in conjunction with VEGF and facilitates human RCC growth under hypoxic conditions.

Bone adaptation to exercise relies on exposures to impact loading in sports, but the ability of skeletal change seems to be highly variable among individuals. The present study was designed to investigate the association between a poly-morphism in the vitamin D receptor (VDR) gene at the translation initiation site and impact loading on bone mineral density (BMD). Analysis of the VDR genotypes detected by endonuclease FokI (FF, Ff, and ff) and measurement of total body BMD (TBMD) were performed in 212 young males; 84 athletes were involved in weight-bearing sports, 48 in competitive swimming, and 80 non-athletic controls. The differences in TBMD between athletes and controls de-pended on the VDR genotypes; enhanced BMD in weight-bearing athletes was found in FF (7.7%, p

Summary. To investigate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups after remission induction therapy. The G-CSF group received G-CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1·5 × 109/l. The control group did not receive G-CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF and control groups respectively). The complete remission rate was similar in the G-CSF and control groups (80·8% versus 76·8%), as was the 5-year probability of disease-free survival (34·5% versus 33·6%) and overall survival (42·7% versus 35·6%). Neutrophil recovery was significantly faster in the G-CSF group than in the control group (12 d versus 18 d, P = 0·0001). The median duration of febrile neutropenia was significantly shorter in the G-CSF group than in the control group (3 d versus 4 d, P = 0·0001). In conclusion, prophylactic administration of G-CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.

Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.

Angiopoietin-like proteins (ANGPTLs), which comprise 7 members (ANGPTL1-ANGPTL7), structurally resemble angiopoietins. We investigated the roles of ANGPTLs in the acquisition of androgen independence and the malignant behavior of human prostate cancer cells. Expression of ANGPTL messenger RNA (mRNA) and proteins were ascertained using RT-qPCR and western blot analysis in human prostate cancer cell lines. Androgen-dependent LNCaP and androgen-independent LNCaP/AI cells, respectively, were cultured in fetal bovine and charcoal-stripped medium. Cell proliferation, androgen dependence, migration and invasion, respectively, were examined under the overexpression and knockdown of ANGPTL2 by transfection of ANGPTL2 cDNA and its small-interfering RNA (siRNA). The effects of exogenous ANGPTL2 and blocking of its receptor, integrin α5β1, were also investigated. Human prostate cancer cell lines predominantly expressed ANGPTL2 among the members. Interrupting ANGPTL2 expression with siRNA suppressed the proliferation, migration and invasion of LNCaP cells. LNCaP/AI cells showed a higher ANGPTL2 expression than that of LNCaP cells. Furthermore, siRNA led to apoptosis of LNCaP/AI cells. The ANGPTL2-overexpressing LNCaP cells markedly increased proliferation, epithelial-to-mesenchymal transition (EMT) and malignant behavior in androgen-deprived medium. The migration rates were increased depending on the concentration of ANGPTL2 recombinant protein and were inhibited by anti-integrin α5β1 antibodies. To the best of our knowledge, this is the first study to elucidate the expression of ANGPTL2 in human prostate cancer cells. ANGPTL2 may be important in the acquisition of androgen independency and tumor progression of prostate cancer in an autocrine and/or paracrine manner via the integrin α5β1 receptor. Targeting ANGPTL2 may therefore be an efficacious therapeutic modality for prostate cancer.

growth rates, protein, and gene expression were analyzed. Effects of combination AR-ASO and OGX-011 on ENZ-R LNCaP progression rates were assessed in castrated male athymic mice. RESULTS: ENZ-R LNCaP-derived sub-lines expressed high levels of CLU and AR compared to CRPC LNCaP cell lines. LNCaP cells overexpressing CLU acquire resistance to AR-ASO induced apoptosis as shown by decreased cell growth inhibition rates and apoptosis induction. AR-ASO induced timeand dose-dependent increases in CLU levels in parental and ENZ-R LNCaP cells. Co-targeted suppression of CLU and AR synergistically inhibited ENZ-R cell growth rates compared to monotherapy. Increased apoptosis (PARP and caspase-3 cleavage, sub G0/G1 fraction) together with reduced AKT phosphorylation was most enhanced with combined therapy. In vivo, combined OGX-011 + AR-ASO significantly delayed ENZ-R LNCaP tumor progression compared to scramble ASO + AR-ASO. CONCLUSIONS: Suppression of CLU combined with AR knockdown inhibited ENZ-R LNCaP cell growth, providing pre-clinical proof-ofprinciple as a promising AR co-targeting approach in ENZ-R CRPC.

OBJECTIVE We examined laparoendoscopic single-site surgery (LESS) for urachal remnants and evaluated its usefulness and efficacy. PATIENTS AND METHODS From August 2011 to July 2012, we underwent this surgery for 5 patients (3 males, 2 females). The mean age was 30.8 (25-36) years old. A 2 cm incision was made around the umbilicus and Access Platform was placed. The entire urachal tissues were excised, and this 2 cm incison was reshaped as the umbilicus. RESULTS The median operative time was 220 (156-460) minutes, and the median operative blood loss was 10 (10-70) ml. They had no operative complications, and were discharged 6 (5-14) days after surgery. CONCLUSIONS Our surgical procedures have very excellent cosmesis and advantages in particular for young because we reshape as the umbilicus the surgical wound. We think that this surgery can be performed safe and effectively for surgeons trained in the conventional laparoscopic procedures.

Physical exercise has been reported to be the most effective method to improve cognitive function and brain health, but there is as yet no research on the effect of water-based exercise. The aim of the present study was to compare the effects of water-based exercise with and without cognitive stimuli on cognitive and physical functions. The design is a single-blind randomized controlled study. Twenty-one participants were randomly assigned to a normal water-based exercise (Nor-WE) group or a cognitive water-based exercise (Cog-WE) group. The exercise sessions were divided into two exercise series: a 10-min series of land-based warm-up, consisting of flexibility exercises, and a 50-min series of exercises in water. The Nor-WE consisted of 10 min of walking, 30 min of strength and stepping exercise, including stride over, and 10 min of stretching and relaxation in water. The Cog-WE consisted of 10 min of walking, 30 min of water-cognitive exercises, and 10 min of stretching and relaxation in water. Cognitive function, physical function, and ADL were measured before the exercise intervention (pre-intervention) and 10 weeks after the intervention (post-intervention). Participation in the Cog-WE performed significantly better on the pegboard test and the choice stepping reaction test and showed a significantly improved attention, memory, and learning, and in the general cognitive function (measured as the total score in the 5-Cog test). Participation in the Nor-WE dramatically improved walking ability and lower limb muscle strength. Our results reveal that the benefits elderly adults may obtain from water-based exercise depend on the characteristics of each specific exercise program. These findings highlight the importance of prescription for personalized water-based exercises to elderly adults to improve cognitive function.

Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down-regulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Background: We determined the tumor-associated macrophage (TAM) count to investigate its importance in predicting clinical outcome or prognosis in patients with bladder cancer. Methods: The TAM count and microvessel count (MVC) were determined immunohistochemically in 63 patients with bladder cancer, including 40 superficial bladder cancers and 23 invasive bladder cancers. To examine the relationship between TAM count and clinical outcome or prognosis in bladder cancer, cystectomy rates, distant metastasis rates, vascular invasion rates and 5 year survival rates were compared between patients with low (< 67) and high (≥ 67) TAM counts. Results: The TAM count in invasive bladder cancers (154.22 ± 11.98) was significantly higher than in superficial bladder cancers (49.05 ± 7.76; P < 0.0001). The MVC in invasive bladder cancers (71.55 ± 10.44) was also significantly higher than in superficial bladder cancers (47.02 ± 5.57; P < 0.05). There was a positive correlation between TAM count and MVC (r = 0.30; P = 0.02). Immunohistochemical staining using CD68/horseradish peroxidase monoclonal antibody showed more infiltrating cells in invasive than superficial bladder cancers. Patients with a high TAM count (≥ 67) showed significantly higher rates of cystectomy, distant metastasis and vascular invasion than those with a lower TAM count (< 67). The 5 year survival rate estimated using the Kaplan– Meier method was significantly lower in patients with a high TAM count than in those with a low TAM count (P < 0.0001). Conclusions: Our results suggest that determination of TAM count in bladder cancer tissues is of value to predict the clinical outcome or prognosis and to select appropriate treatment strategies in patients with bladder cancer.

Land stretching exercises are common exercise therapy for low back pain (LBP) patients. However, recently, water exercise became a popular rehabilitation for LBP patients, and many studies have reported the physical benefits of water exercise. This study compared the psychological and endocrinological effects of water exercise and land stretching by measuring salivary cortisol concentration and anxiety in chronic LBP patients. Seven volunteers (4 female and 3 male, mean age: 61.9 +/- 11.8 yrs) who suffered from chronic LBP (pain duration: 4.5 +/- 1.3 yrs) participated in the sessions of water exercise and land stretching programs (90 minutes) on different days. The land stretching program consisted mainly of stretching, and the water exercise program contained not only stretching, but also walking, jogging, muscle strengthening, swimming and relaxation. After both exercise programs, the subjective pain scores of the patients showed a significant decrease. Salivary cortisol concentrations were also significantly decreased during pre- to post-90 minute water exercise. (P < 0.05). With land stretching, salivary cortisol concentrations also decreased significantly (P < 0.05). State anxiety decreased significantly (P < 0.05) after both water exercise and land stretching compared with pre-exercise scores (P < 0.05), though no significant changes were found in the patients' trait anxiety scores. No significant correlation was found between salivary cortisol concentrations and state anxiety with water exercise and land stretching. The findings of the present study suggested both exercises showed similar tendencies, and had decreased salivary cortisol level and state anxiety.

症例は55歳男性. 主訴は肉眼的血尿. 1991年糖尿病性腎症のため血液透析導入され, 週3回の維持透析が施行されていた. 1995年11月27日肉眼的血尿出現し当院入院, 膀胱鏡検査で乳頭状腫瘍を認め同12月19日経尿道的膀胱腫瘍切除術 (TUR-Bt) を施行した. 病理組織診断はTCC, G3, pTaであった. 以後経過観察していたが, 1996年8月肉眼的血尿, 尿細胞診class Vのため再度膀胱鏡検査施行したところ多発性膀胱腫瘍再発を認めたため, 同9月4日全身状態を考慮し, 単純性膀胱摘除術を施行した. 病理組織診断はTCC, G 2, pT 2であった. 2か月後, 症候性右水腎症を発症し, 同11月27日右腎摘除術を施行した. 病理組織診断にて腎孟, 尿管断端にTCC, CISを認めたため1997年1月22日残遺尿管摘除術を施行した.さらに同6月, 左膿腎症を発症したため, 左腎摘除術を試みたが高度癒着のため摘出できず, 腎瘻術のみに止めた. 同時に採取した腎盂尿細胞診はclass Vであった. その後全身状態は徐々に悪化し1998年2月11日死亡した. 本症例は血液透析患者に合併した多発性尿路上皮癌と考えられ, 診断および治療に難渋した症例であった.

In acute leukemia (AL) with a late-appearing Philadelphia (la-Ph) translocation, it is unclear whether these translocations arise from the same molecular event as classical Ph translocations. In order to elucidate the molecular events of la-Ph and subsequent translocations of la-Ph leukemia, we performed molecular analysis on the complex rearrangements, in a cell line, MY, which was established from bone marrow mononuclear cells of a patient with a la-Ph acute biphenotypic leukemia. This la-Ph, expressing an acute lymphoblastic leukemia (ALL)-type BCR/ABL transcript, produces a novel P180BCR/ABL fusion protein reflecting deletion of 174 bases (58 amino acids) encoded by the a2 exon of the ABL gene. An immune complex kinase assay showed that this protein had autophosphorylation activity. Fluorescence in situ hybridization (FISH) in conjunction with G-banding analysis revealed that the initial der(9)t(9;22)(q34;q11) progressed to a der(9)(9pter-->9q34::22q11-->22q13::5q11.2 -->5q15:: 10q23-->10qter) by, first, a three-way translocation among the der(9)t(9;22)(q34;q11), chromosome 5, and the normal chromosome 22, and then a subsequent translocation with chromosome 10. Moreover, both the end-stage leukemic cells of the patient and the MY cell line had another translocation, t(X;12)(p11.2;p13). The 12p breakpoint was located near the ETV6 gene by analysis of pulsed-field gel electrophoresis, but transcription of ETV6 was unaffected. Tumorigenicity analysis indicated that an additional translocation, t(2;3)(p16;q29), may have caused a more malignant clone, because only MY cells with the t(2;3)(p16;q29) were capable of growing subcutaneously in nude mice within 40 days. The molecular events of leukemogenesis and leukemic progression in the present la-Ph AL occurred by accumulation of unique translocations. This cell line, MY, expressing a novel variant P180BCR/ABL protein with a deletion of the a2 exon of the ABL gene, may be useful for elucidating the pathophysiology of this fusion protein and for studying ETV6-related leukemogenesis and t(2;3), as well as the molecular mechanisms of the complex translocations.

The cure rate of acute myeloid leukemia might increase if G-CSF were given concurrently with repeated postremission chemotherapy. However, this therapy might cause severe complications, including depletion of normal hematopoietic progenitors as a long-term toxicity. Thus, we conducted a pilot study of this strategy. Twenty-six acute myeloid leukemia patients in a first complete remission (CR) were treated with two courses of consolidation chemotherapy (10-day BHAC-DMP, consisting of behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone) and repeated maintenance-intensification therapy including eight cycles of six-day BHAC-DMP. G-CSF (filgrastim) was administered concurrently with these BHAC-DMP therapies. Toxicity during the therapeutic period was not significant in the study group compared with the historical control, treated with the same regimen without G-CSF. Neutrophil recovery after the consolidation therapy was more rapid in the study group than in the historical control (p = 0.066 and 0.024 for the first and second consolidation courses, respectively). Long-term toxicity, such as cytopenia, has not been seen in eight patients who have remained in CR for a long period (range: 39-58 months). At a median follow-up of 39 months, the predicted rate of 42-month CR duration for these 26 patients was 50% (95% confidence limits: 30% to 71%). We conclude that G-CSF-combined repeated BHAC-DMP postremission therapy is feasible. Full elucidation of the clinical benefit of this strategy will require further study.

Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and granulocyte colony-stimulating factor (G-CSF). However, because such cases received chemotherapy that alone frequently causes pulmonary toxicity, the role of G-CSF in this toxicity has been unclear. CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) only slightly induces pulmonary toxicity. However, we observed a considerable incidence of this toxicity in non-Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF (6 out of 52 subjects, 11.5%). In this cohort, among various characteristics, including the dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with each therapy cycle was associated with development of this toxicity (MPLC > or = 23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23 cases; P = 0.020). These findings suggest that the effect of G-CSF is the main determinant of the pulmonary toxicity in these cases. Because the toxicity was associated with a large MPLC and did not recur in cases readministered G-CSF, an idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of this toxicity. In all six cases, the time course of manifestation of the toxicity was the same, and early application of high-dose corticosteroid led to cure. This knowledge will be helpful in the care of similar cases. Images Figure 2

症例: 66歳女性. 1967年子宮全摘除. 1987年血液透析導入. 1996年7月下旬頃より右腰部痛, 下腹部痛, 発熱を認め, 腹部CTで右腎に腫瘤性病変を指摘され7月30日当科入院となった. 尿閉, 尿路感染を認め, 抗生物質投与および間歇導尿・膀胱洗浄を続け全身状態の改善を待って右腎摘出術を予定していたが, 8月8日38℃を超える発熱を認めたため膿腎症の診断で経皮的腎瘻術施行. 腎瘻術後は解熱傾向となり全身状態も改善した. 本症例は子宮全摘除術の合併症として神経因性膀胱を生じ, 尿閉, 尿路感染症を合併し, 腎盂腎炎, 膿腎症へと進展したと考えられた.長期透析患者での発熱の原因として尿路感染症を見逃してはならず, また膿腎症を発症した場合には, 経皮的腎瘻術による尿ドレナージを完全に行えば保存的に治療可能と考えられた.

Chronological changes in hematological findings were analyzed in 225 patients with myelodysplastic syndromes (MDS). They were diagnosed between 1990 and 1992. Their hematological findings, i.e. hemoglobin levels, leukocyte and platelet counts, proportions of peripheral blood (PB) blasts and monocytes, and proportion of blasts in bone marrow (BM), were recorded for up to 42 months after diagnosis, when available. BM was examined regularly in only a few patients. Therefore, it was impractical to use the French-American-British Cooperative Group criteria for subtype classification during the disease course. Thus, we used the percentage of PB blasts as the only indicator of stage evolution. We classified the disease into four stages: stage 1, less than 1% PB blasts; stage 2, 1-5% PB blasts; stage 3, 5-30% PB blasts; and stage 4, 30% or more PB blasts. There were 171 patients initially in stage 1, 37 initially in stage 2, and 17 initially in stage 3. Less than half (45%) of the patients initially in stage 1 progressed to stage 2, while 91% of the patients initially in stage 2 and all of the patients initially in stage 3 showed stage evolution. Eight variables, i.e. BM blasts 5% or more, male sex, karyotypic abnormalities, micromegakaryocytes, mononuclear large megakaryocytes, platelet counts 50 x 10(9)/l or higher, abnormal nucleus of granulocytes, and abnormal granules of granulocytes, were found to be significant risk factors for evolution from stage 1 to 2. Evolution from stage 1 to a higher stage within 15 months of diagnosis was associated with impending poor prognosis in most patients. However, of the 67 patients initially in stage 1 who died, 30 did not show stage evolution. Evolution from stage 2 to a higher stage and from stage 3 to stage 4 was also associated with impending poor prognosis. Higher levels of cytopenia were not associated with poorer prognosis in the stage 1 patients. In conclusion, our grading system proved to be useful in evaluating the chronological changes in MDS patients.

スーパー・オレフィンポリマー (SOP) は高性能バンパー材として, 現在広く使用されている. この材料の特徴はエラストマー相のミクロ結晶制御によりマトリックスを強化し, さらにPP樹脂相の超高結晶化とミクロドメイン化を図ることで, 従来材に比べ大幅な性能の向上が行われている. 今回, 一軸引張試験, Uノッチ曲げ試験, 体積ひずみ測定, ポアソン比測定, TEM観察により, SOPのタフネスの発現機構を解析した. その結果, SOPは高次構造を制御することにより, 高剛性, 高流動にもかかわらず高いタフネスを示し, さらに従来材 (EMT) のクレイズによる変形とは異なるせん断変形様式を示した.

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.

There is a paucity of definitive evidence that supports the use of enoxaparin to prevent venous thromboembolism (VTE) after urologic laparoscopic surgery. The purpose of this study was to evaluate the efficacy and safety of postoperative subcutaneous enoxaparin injection in patients who underwent urologic laparoscopic surgery. A total of 63 patients were evaluated from June 2010 to December 2012. All patients received postoperative prophylaxis with enoxaparin (2000 IU twice daily for 5 days). None of the patients treated with enoxaparin developed symptomatic VTE, but two cases (3.2%) of pulmonary embolism were noted before initial enoxaparin administration. Statistically significant differences were observed between the prothrombin time (PT) and activated partial thromboplastin time (APTT) values and D-dimer levels obtained at baseline and on day 7 after surgery; however, the PT and APTT values did not exceed the normal range. In addition, signs of any adverse events were not encountered in any of the patients treated with enoxaparin. The use of enoxaparin immediately after a surgery may confer valuable thromboprophylaxis benefits for urologic laparoscopic surgery.

INTRODUCTION AND OBJECTIVES: Although it is well known that deregulation of VHL-HIF1 pathway is responsible for the carcinogenesis of clear cell renal cell carcinoma (ccRCC), molecular mechanisms responsible for the development of metastasis are still poorly investigated. The first aim of this study is to identify copy number alteration (CNA) that is specifically detected in metastasis but not in primary lesion. The second aim is to identify a gene whose deregulation is responsible for the development of metastasis. METHODS: For the array comparative genomic hybridization (CGH) analysis, genomic DNAs were extracted from the formalin-fixed, paraffin-embedded tissues. Twenty cases of primary ccRCCs and their corresponding metastases were analyzed using 4x44K oligonucleotide CGH array (Agilent Inc.). For the gene expression analysis, total RNA was extracted from frozen samples of 30 primary ccRCCs. Expression levels of the 58 genes were analyzed by qRT-PCR. To investigate the biologic function of candidate genes, RCC cell lines, 786-O and 769-P were used. Cell proliferation, invasiveness and apoptosis were analyzed before and after the infection of lenti-virus encoding candidate genes to the RCC cell lines. RESULTS: By comparing CNAs of primary ccRCCs with their corresponding metastases, we found that gene copy number loss at 9p24.1-p13.3 was more frequently found in metastases than in primary lesions. Out of 58 genes located at 9p24.1-p13.3, we identified 2 genes, NDUFB6 and LRRC19, both of which were down-regulated due to copy number loss. Next, using lenti-virus encoding each gene, we introduced the two genes into 786-O and 769-P cells in which both the 2 genes were down-regulated. We found that, when NDUFB6 was overexpressed in both cell lines, cell proliferation was significantly suppressed (figure shown below), although apoptotic activity and invasion activity were unchanged. CONCLUSIONS: Down-regulation of NDUFB6 caused by gene copy number loss at 9p24.1-p13.3 may bring about growth advantage to metastatic ccRCC cells. We propose that NDUFB6 is a new candidate for a tumor suppressor and that its down-regulation may play an important role in the development of metastasis of ccRCC.

TJ-137 administered to patients with chronic ITP increased the platelet count "slightly" or more in 31.7% of the patients and showed a clinical effect in 40.9% with a rating of "modestly effective" or better. With a low incidence of adverse reactions, TJ-137 is ex pected to be a new drug for the treatment of ITP.