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Prostaglandin I2 (PGI2) protects against RSV-induced illness in mice. A variable-number tandem repeat (VNTR) polymorphism has been detected in the promoter region of the PGI2 synthase (PGIS) gene. We sought to determine if PGI2 concentrations or polymorphisms of the PGIS gene correlate with severity of RSV lower respiratory tract infections (LRTI) in human infants. VNTR polymorphisms were studied in 81 previously healthy children between birth and 12 months of age who were hospitalized for LRTI due to RSV and 98 healthy adult control subjects. The severity of RSV infection was quantified using a clinical scoring system, and infant urine samples were collected during the acute illness for measurement of the urinary metabolite of PGI2. There were no significant differences in the overall distribution of alleles and genotypes between infants with RSV LRTI and the control subjects. The severity of RSV infection significantly inversely correlated with urinary PGI2 metabolite concentrations. The urinary PGI2 metabolite concentration correlated with the number of VNTR. The presence of a genotype with a low number VNTR repeats significantly correlated with the most severe RSV LRTI, and genotypes with the highest number of VNTR correlated with the least severe RSV LRTI. A functional polymorphism in the promoter region of the PGIS gene is associated with both significant differences in urinary PGI2 concentrations during RSV LRTI, and severity of RSV infection in previously healthy infants. J. Med. Virol. 80:2015–2022, 2008. © 2008 Wiley-Liss, Inc.

Genomic polymorphism of human cytomegalovirus (HCMV) leads to difficulties in the design of molecular diagnostic systems; therefore, a suitable target region was determined in the glycoprotein H (gH) gene, which has been reported to be the most conserved gene. A highly conserved region was identified from codon1282 to 1988 of the gH gene by alignment of 23 nucleotide sequences (14 registered in the DNA Data Bank of Japan and 9 sequenced in this laboratory). Diagnostic methods based on nested PCR, real-time PCR and loop-mediated isothermal temperature amplification (LAMP) were designed for this region. Primers and a probe for nested and real-time PCR were designed for the completely conserved sequences in all HCMV strains. However, a few mismatched nucleotides could not be excluded from the LAMP primers due to the need for eight primer-binding sites in a 200 bp-region. The sensitivities of the nested PCR, real-time PCR and LAMP reactions were 5, 10 and 100 copies/tube, respectively. An analysis of clinical specimens showed that both nested and real-time PCR detected HCMV with greater sensitivity than did a pp65 antigenemia assay and were expected to minimize the incidence of false-negative results, whereas the sensitivity of the LAMP reaction was comparable with that of the antigenemia assay.

Background Sensorineural hearing loss (SNHL) is the most common congenital disease. Longitudinal studies of infants with congenital cytomegalovirus (CMV) infection have demonstrated an association between CMV and SNHL. However, because of the lack of suitable neonatally collected specimens, the proportion of CMV-associated SNHL has not been defined, nor has the relationship between CMV and the major genetic causes of SNHL, such as mutations in the GJB2 gene. Methods Sixty-seven children with severe SNHL were analyzed for CMV and human herpesvirus 6 (HHV-6) infections and for GJB2 mutations. DNA specimens were prepared from dried umbilical cords, which are available for everyone born in Japan. Four children with typical symptomatic infection at birth served as positive control subjects. Results Congenital CMV infection and GJB2 mutations were identified in 15% and 24% of the patients, respectively. HHV-6 was not detected. All children with CMV-associated cases developed SNHL before they were 2 years old. Most children with CMV-associated SNHL had no obvious clinical abnormality at birth, and their viral loads were lower than those of symptomatic children. Conclusions Congenital CMV infection is an important cause of severe SNHL, and it has an incidence comparable to that of GJB2-associated SNHL.

A 46-year-old woman was referred to our hospital for a tumor in the anterior mediastinum. She had no symptoms of myasthenia gravis(MG). Acetylcholine receptor antibody(AchR-Ab) was within the normal range. The tumor was completely resected by thymectomy. Pathological examination of the tumor identified it as a type AB thymoma (Masaoka stage I). Five days after the surgery, she experienced post-thymectomy MG (raised AchR-Ab and positive tensilon test). Her symptoms improved with anti-cholinesterase and tacrolimus therapy.

オープンアクセス, We present a surgical case of a rare primary tracheal tumor. In a 44-year-old asymptomatic man, computed tomography (CT), performed as part of health check-up, revealed a tumor measuring 1.5 cm in diameter in the mediastinal trachea. Biopsy failed to yield a definitive diagnosis, but the tumor tended to grow rapidly; therefore, surgery was performed. Five tracheal rings were resected through median sternotomy, followed by interrupted suture with 3–0 absorbable thread. The postoperative course has been favorable with no evidence of recurrence. The pathological diagnosis was leiomyoma. We report this case with literature review.

INTRODUCTION AND OBJECTIVES: Although bladder compliance has previously been considered a “static” urodynamic property, recent pre clinical studies have established that repeated passive fills of the bladder can acutely increase compliance. Moreover, acute compliance changes can be reversed by active contraction, a process we call “dynamic compliance.” In addition, compliance may be decreased in animal models of detrusor overactivity due to greater changes in dynamic compliance. The goal of this study was to identify and quantify dynamic compliance during urodynamics in patients with OAB. METHODS: Individuals with OAB defined as ICIq OAB question 5a 3 were enrolled in an IRB approved extended urodynamics protocol. An initial fill was used for clinical purposes and to determine cystometric capacity (Ccap). Four repeat fills were then initiated at a rate 10%Ccap/min as follows: 1) fill to 30% Ccap and passively empty via syringe aspiration, 2) fill to 60%Ccap and passively empty, 3) fill to Ccap and void (voluntary or involuntary) and 4) fill to Ccap and void. Extracted data from the bladder pressure (Pves) were graphed for each fill and data were then normalized to Pves at 75ml in fill 1 for statistical analysis. RESULTS: Five patients completed the study and had results available for analysis. In comparison to repeat fill 1, dynamic compliance was increased (lower Pves throughout filling) in subsequent fills (fills 2 and 3) (Figure 1A). This was likely due to strain softening during filling not restored by passive emptying. Voiding then occurred at the end of fill 3, and the final fill (fill 4) showed the reversibility of this process (decreased dynamic compliance). Normalized data at 75 ml infused volume (Figure 1B) showed increased dynamic compliance (decreased pressure/volume) after passive emptying (Fill #3: 0.69 0.10 vs. Fill #1: 1.0, p

INTRODUCTION AND OBJECTIVES: Abnormal chromosome segregation during mitosis causes aneuploidy, a hallmark of cancers associated with high risk for tumorigenesis. Mitotic checkpoint, or spindle assembly checkpoint prevents missegregation of chromosomes by arresting cells in metaphase until all the chromosomes are properly aligned. Mps1 kinase activity is essential for spindle checkpoint signaling. High levels of Mps1 serine/threonine kinase are found in colon cancer tissues and several cancer cell line. We found that Mps1 is over-expressed in ccRCC. We have further shown that Mps1 requires the molecular chaperone Hsp90 for its activity. Hsp90 protects an array of mutated, over-expressed and/or chimeric kinases that are vital for tumor growth and survival. The Hsp90 inhibitors are currently undergoing evaluation in human trials. We have previously shown that Hsp90 is a post-translationally modified protein and this regulates its chaperone activity. We hypothesize that Mps1 kinase targets and phosphorylates Hsp90 and therefore regulates its chaperone activity. This in turn impacts the tumor selectivity of Hsp90 inhibitors. METHODS: Functional genomics and quantitative proteomic (stable isotope labeling by amino acids in cell culture) was used to identify the Mps1 kinase that targets and phosphorylates Hsp90. ccRCC and adjacent normal tissue was obtained with written informed consent through the Upstate Department of Urology. 8-mm core of tissue was dissected into 3mm pieces and cultured in 24-well plates containing 1 mL RPMI-1640 with 10% FBS, antibiotic/antimycotic solution. Tissues were cultured at 37 C for 24 hours with or without Mps1 inhibitor NMS-P715 and for further 24 hours in the presence of fluorescently labeled Hsp90 inhibitor ganetespib (FL-ganetespib), then formalin-fixed and paraffin embedded. The tissues were immunostained for Hsp90. RESULTS: Mps1 kinase is over-expressed in ccRCC compared to normal adjacent tissue. Mps1 targets and phosphorylates T115 in the molecular chaperone Hsp90 and this regulates the chaperone activity. Ex vivo data showed that FL-ganetespib selectively accumulates in ccRCC and not in the normal tissue. Pharmacologic inhibition of Mps1 reverts this drug uptake by ccRCC. CONCLUSIONS: Mps1 protein kinase is an Hsp90 client and it is involved in post-translational regulation of the chaperone function. Over-expression of Mps1 in the ccRCC hyperphosphorylates Hsp90 and this is the molecular basis of the tumor selectivity of Hsp90 inhibitors.

オープンアクセス, BACKGROUND: We have developed a new diagnostic method using the photosensitizer 5-aminolevulinic acid (5ALA) for diagnosing intrathoracic malignant lesions. When ingested exogenously, 5ALA is metabolized to a heme precursor, protoporphyrin IX, which stays in malignant cells and emits red to pink luminescence of about 630 nm. METHODS: We enrolled 40 patients who underwent respiratory surgery and consented to participate in this study. Twenty-eight patients had primary lung cancer, 8 metastatic lung tumors, 2 malignant pleural tumors, and 2 benign tumors. Localization of malignant lesions was attempted by observing such lesions with an autofluorescence imaging system and by comparing the color tone of the autofluorescence between malignant lesions and normal tissues after oral administration of 5ALA. Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues. RESULTS: When 28 patients with primary lung cancer were examined according to the degree of pleural infiltration (pl), red fluorescence was confirmed in 10 of 10 patients (100%) with p11-p13 and 5 of 18 patients (27.7%) with p10. The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively. CONCLUSION: This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

Aims In human urinary bladder, beta3-ARs play an important role in promoting detrusor relaxation during the storage phase of the micturition cycle. The present study investigated whether a Trp64Arg polymorphism of the gene encoding the beta3-AR is associated with overactive bladder (OAB) syndrome. Methods This study involved 100 women with OAB and 101 healthy control women without OAB. Hair root samples were obtained from all subjects and used for beta3-AR gene analysis. Polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) analysis was performed to analyze a polymorphism in the gene of Trp64Arg. Results The overall frequency of the 64Arg variant (heterozygous plus homozygous) in OAB patients was 47% and significantly higher than the frequency of 22.8% found in non-OAB control women. Within OAB patients, numbers of micturitions per day, urgency episodes per day, and urgency incontinence episodes per day in the 64Arg variant carriers were not significantly different from those in the normal gene carriers. Conclusions This study shows that the Trp64Arg polymorphism in the beta3-AR gene is weakly but significantly associated with OAB syndrome. Neurourol. Urodynam. 33:400–402, 2014. © 2013 Wiley Periodicals, Inc.

A total of 21 clones of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) and 23 clones of penciclovir (PCV)-resistant (PCVr) HSV-1, emerging during serial passages in the presence of ACV or PCV, were isolated under conditions excluding contamination of resistant mutants in the starting virus culture, and their mutations in the thymidine kinase (TK) and DNA polymerase (DNA Pol) genes were analyzed comparatively. Mutations in the TK genes from ACVrmutants consisted of 50% single nucleotide substitutions and 50% frameshift mutations, while the corresponding figures for the PCVrmutants were 4 and 96%, respectively (P< 0.001). Eight of the 21 ACVrclones, but none of the 23 PCVrclones, had mutations in DNA Pol. Only nucleotide substitution(s) could be detected in the DNA Pol gene, as the gene is essential for virus replication. Therefore, the results for the DNA Pol mutants are concordant with those for the TK mutants in that a single nucleotide substitution was commonly observed in the ACVr, but not in the PCVr, mutants. These results clearly point to differential mutation patterns between ACVrand PCVrHSV-1 clones.

We report a case of bilateral synchronous testicular torsion in a newborn. A male neonate was referred one day after birth because his left testis was firm and enlarged. We found that the scrotum was firm bilaterally and suspected it to be bilateral testicular tumor. Surgical exploration which was performed at 2 days after birth revealed testicular torsion on both sides. Left orchiectomy, right detorsion biopsy and orchiopexy were performed. Histopathological examination confirmed hemorrhagic necrosis of bilateral testes.

Background Nodular fasciitis is a benign reactive proliferative lesion of fibroblast cells, which can occur throughout the body. However, it has rarely been reported in the breast of an elderly woman. Case presentation Our patient was an 88-year-old Asian woman who had noticed a mass in her right breast for 1 month before presentation to our hospital. The mass was elastic-hard and 20 mm in size. No qualitative diagnosis was made by core needle biopsy. Because of potentially malignant findings on mammography and ultrasonography, she underwent an excisional biopsy. Microscopically, spindle cell proliferation with abundant elastic fibers were observed. The tumor cells were positive for α-smooth muscle actin and negative for pancytokeratin, β-catenin, and cluster of differentiation 34. Based on these morphological and immunohistochemical features, a diagnosis of nodular fasciitis was made. All resection margins in the specimen were tumor-free. The patient has been disease-free for over 12 months. Conclusions Nodular fasciitis shows clinical features and imaging findings similar to those of breast cancer. To avoid unnecessary surgery, nodular fasciitis should be taken into consideration when there is spindle cell proliferation found by biopsy.

We investigated the effect of pelvic arterial occlusive disease on the RhoA/Rho-kinase pathway in a rat model of chronic bladder ischemia.Male adult Sprague Dawley® rats at age 16 weeks were divided into arterial endothelial injury and control groups. The injury group underwent balloon endothelial injury of the bilateral iliac arteries and received a 2% cholesterol diet to induce pelvic arterial occlusive disease. The control group received a regular diet. At 8 weeks cystometrograms were performed. Bladder tissue was harvested for pharmacological studies and Western blot.Cystometrograms showed significantly lower bladder capacity in the arterial endothelial injury group than in controls. Organ bath studies revealed significantly decreased phasic contractions induced by carbachol in bladder strips from the injury group than from controls. In controls bladder strip tonic contractions induced by carbachol were significantly decreased compared with phasic contractions. However, no significant difference was observed between phasic and tonic contractions in the injury group. The Rho-kinase inhibitor Y-27632 produced a concentration dependent decrease in tonic contractions, which was more pronounced in the injury group. Western blot showed significantly increased RhoA and Rho-kinase β expression in the injury group.Our results suggest that pelvic arterial occlusive disease can affect the RhoA/Rho-kinase pathway in the bladder. This pathway might possibly be involved in the maintenance of tonic contraction and contribute to the bladder hyperactivity caused by pelvic arterial occlusive disease.

To determine whether lysophosphatidic acid activates the mitogen-activated protein kinase and increases DNA synthesis in human bladder smooth muscle cells, and to examine the involvement of lysophosphatidic acid and lysophosphatidic acid receptor in mechanical stretch-induced mitogen-activated protein kinase activation in cultured human bladder smooth muscle cells.TaqMan reverse transcription polymerase chain reaction was used to determine the mRNA expression levels of six lysophosphatidic acid receptor subtypes. Mitogen-activated protein kinase activity enhanced by either lysophosphatidic acid or mechanical stretch was measured by western blotting. The effect of lysophosphatidic acid on DNA synthesis was assessed by 5-bromo-2'-deoxy-uridine incorporation assay.Lysophosphatidic acid 1 subtype mRNA was predominantly expressed (96%). Lysophosphatidic acid activated the mitogen-activated protein kinase in a concentration-dependent manner. C-jun NH2 -terminal kinase showed the highest activity among the three subsets of the mitogen-activated protein kinase family members (c-jun NH2 -terminal kinase, extracellular signal-regulated kinases, p38). Lysophosphatidic acid also increased incorporation of 5-bromo-2'-deoxy-uridine. These responses were suppressed by Ki16425 (lysophosphatidic acid receptor antagonist). Mechanical stretch mainly induced c-jun NH2 -terminal kinase activation. This activation was partially inhibited by Ki16425.Lysophosphatidic acid might activate the c-jun NH2 -terminal kinase component of the mitogen-activated protein kinase family and DNA synthesis through lysophosphatidic acid receptors (presumably, through lysophosphatidic acid 1) in human bladder smooth muscle cells. The present study also implicates the involvement of lysophosphatidic acid and lysophosphatidic acid receptors in mechanical stretch-induced c-jun NH2 -terminal kinase activation. Lysophosphatidic acid receptor can be partially activated by mechanical stretching through lysophosphatidic acid-dependent or independent mechanism.

Although open retropubic radical prostatectomy has been the most commonly used surgical technique for patients with localized prostate cancer for decades, robot-assisted radical prostatectomy (RARP) has recently become an alternative option and widely used in Japan as well as around the world. RARP has been shown to have higher postoperative continent rates than retropubic and laparoscopic radical prostatectomy; however, urinary incontinence has remained one of the most significant causes for concern among patients who seek surgical treatment for prostate cancer, even after the introduction of RARP. The literature has shown that certain technical modifications to improve urinary continence are advocated as potential aids to reduce the risk of urinary incontinence after RARP. These modifications might be divided into 3 categories to realize the improvement of early return of urinary continence after RARP: 1) preservation, 2) reconstruction, and 3) reinforcement of the anatomic structures in the pelvis, which will make a new supporting system after radical prostatectomy. In this review, we discuss the intraoperative techniques to improve outcomes for early return of urinary continence following RARP, and provide a critical summary of current knowledge on its outcome in the literature.

then tumor infiltrating lymphocyte was analyzed by immunohistochemistry. RESULTS: All three treatment groups ((1), (2) and (3)) showed significant decrease in tumor size compared with vehicle group. In particular, combination of PD-1 Ab and CTLA-4 Ab exhibited the most significant anti-tumor effect. The percentage of PCNA+ tumor cells were very similar amongst all therapies, but the percentage of Ki-67+ tumor cells were significantly decreased with combination of PD-1 Ab and CTLA-4 Ab. Combination of PD-1 Ab and CTLA-4 Ab demonstrated the most potent effect to trigger the infiltration of both CD4+ lymphocyte and CD8+ lymphocytes. These in vivo results indicate that combination of PD-1 Ab and CTLA-4 Ab may have a significant immunostimulatory effect to exert the anti-tumor effect to renal cell carcinoma. CONCLUSIONS: Combination therapy of anti-CTLA-4 antibody and anti-PD-1 antibody can be a potential therapeutic option for advanced kidney cancer patients.

Objective To elucidate the etiology of lower urinary tract symptoms (LUTS) after radical prostatectomy, the present study investigated associations between postoperative urethral and vesical anatomic features on magnetic resonance imaging (MRI) and LUTS. Patients and Methods Fifty consecutive patients undergoing radical prostatectomy also underwent preoperative and postoperative MRI. Preoperative MRI only evaluated preoperative membranous urethral length (MUL). Postoperative MRI evaluated postoperative MUL, posterior-urethral vesical angle, depth of the urethrovesical junction (UVJ), and urinary pooling inside the urethra and bladder neck configuration. At the same time as postoperative MRI, International Prostate Symptom Score (IPSS), quality of life index, continence grade, and uroflowmetry parameters were investigated. Associations between preoperative or postoperative MRI variables and questionnaire results or uroflowmetry were analyzed to examine the relationships between the morphology of urethral and vesical anatomic features and LUTS. Results Preoperative and postoperative MRI variables were not significantly associated with IPSS total score or uroflowmetry results. Urinary pooling inside the urethra was significantly associated with urgency score in the IPSS ( P = .005). Postoperative MUL ( P P = .002), and urinary pooling inside the urethra ( P = .04) were significantly associated with continence grade. Conclusion Urinary pooling inside the urethra might induce urgency, and postoperative MUL and depth of UVJ were related to urinary incontinence. Avoiding damage to the nerves involved in continence to prevent inflow of urine into the urethra, preservation of MUL, and development of procedures to prevent descent of the bladder neck during surgery are therefore recommended.

We report a case of Mycobacterium bovis BCG vertebral osteomyelitis 1.8 years after intravesical BCG therapy for bladder cancer. We differentiated BCG from other Mycobacterium tuberculosis complex members by PCR analysis of deletion regions and started an appropriate chemotherapy regimen resulting in the remission of symptoms within 1 month.

Polyorchidism is a rare anomaly with approximately 70 cases reported in the literature. We reported a case of polyorchidism with embryonal carcinoma, the first case, in one of 4 testes. Polyorchidism with malignancy had been reported in 5 cases and bilateral polyorchidism in 3 cases. Authors have not been clarified whether the incidence of malignancy in polyorchidism is high or low. But we have to treat the patients with polyorchidism carefully, because polyorchidism is highly associated with cryptorchidism.

Background The aim of the present study was to investigate the impact of the Great East Japan Earthquake on laboratory findings in chronic hemodialysis (HD) patients in Fukushima. Methods Changes in laboratory findings and cardiothoracic ratio (CTR) between before and after the earthquake were retrospectively analyzed in 90 adult HD patients with end-stage renal disease (ESRD). Two hospitals located within 80 km from the Fukushima Daiichi Nuclear Power Plant, where American government recommended to evacuate from the area, participated in the study. HD duration was shortened by 0.5-1 hour for 1 month after the earthquake. Multivariate analyses were performed to identify the factors contributing to change of measurement values. Results Blood urea nitrogen (BUN) value was significantly transiently decreased for 1-2 weeks after the earthquake (P=0.002). In multivariate analysis, age showed a tendency to be related to the decrease of BUN level (P=0.05). Hematocrit value was significantly elevated after two months compared with that at baseline (P=0.02), although the elevation was small. The other measured values and CTR were not significantly changed compared with those before the earthquake. Conclusions Laboratory findings and CTR did not worsen despite the shortening of HD duration. Hence, in this disaster, as far as chronic HD patients with ESRD were concerned, it was possible for the duration of HD treatment to be safely decreased.

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.

Publisher, Immunoglobulin G4 (IgG4)-related lung disease is a disease in which IgG4-positive plasma cells and lymphocytes infiltrate lung tissues along with immunohistochemically evident fibrous interstitial proliferation in the background, in addition to hyper-IgG4 disease. The diagnosis of this disease can be difficult. Here, we report 2 cases with IgG4-related lung disease that was difficult to differentiate from malignant tumors because both cases had pulmonary lesions showing high standardized uptake values (SUV) on positron emission tomography (PET). Case 1: A 75-year-old man under treatment for autoimmune pancreatitis and diabetes mellitus was noted to have multiple nodular opacities in both lungs and a mass density in the right paravertebral region on computed tomography (CT). As high SUVmax was noted for both lesions on exploration by fluorodeoxyglucose (FDG)-PET/CT, an advanced malignant tumor was diagnosed and a video-assisted thoracoscopic (VATS) biopsy was performed and diagnosed IgG4-related lung disease. Case 2: A 48-year-old woman consulted our clinic with a chief complaint of bloody sputum. Chest CT revealed a mass density with 12-, 13-, and 16-mm spiculations in the S2 segment of the right upper lobe and irregular thickening of the pleura including the paravertebral region. The lesion was a mass showing high SUV in the S2 segment on FDG-PET. Malignancy was suspected from the imaging findings, and a VATS biopsy was performed and diagnosed IgG4-related lung disease. Actively undertaking VATS biopsy in cases with this disease is valuable for making the differential diagnosis between malignant tumors and IgG4-related lung disease, since the diagnosis can be difficult in some patients showing high SUV.

INTRODUCTION AND OBJECTIVES: Urodynamic studies have shown that detrusor underactivity (DU) in women increases with age. One cause of this impaired bladder function that has recently attracted attention is estrogen deficiency. However, mechanisms underlying the association between estrogen deficiency and DU are still not understood. On the other hand, it is known that estrogen modulates the expression of myosin heavy chain (MHC) isoforms in smooth muscle. Thus, using a rat animal model, we investigated the effect of estrogen withdrawal and replacement on the expression of MHC isoforms and contractile power in bladder. METHODS: Thirty female SD rats were divided into sham (Sham), bilateral ovariectomy (OVX), and OVX plus estrogen replacement (OVX E) groups. The OVX E group was given estradiol subcutaneously at 5 g/kg/day for 4 weeks. At 4 weeks after surgery, each bladder was used for analysis of histology, MHC isoform (SM1, SM2) mRNA expression, and contractile power. Using bladder strips, the shortening responses to electrical field stimulation under various loads (4.9 mN to 19.6 mN) were recorded. The applied load was regarded as force generated (F), and velocity of shortening (V) was calculated from the shortening curve. Contractile power was defined as the total mechanical power (P), which is given by the following Hill equation: P FV aV bF, where a and b are constants of each bladder strip. RESULTS: Bladder weight and histological findings were not different between groups. The force/velocity plots obtained from the isotonic contraction study were well fitted to the Hill equation. Thus, contractile power for each strip could be determined. The contractile power significantly decreased in OVX, and estrogen replacement suppressed this decrease (Fig. 1a). The SM2/SM1 ratio significantly increased in OVX, and estrogen replacement suppressed this increase (Fig. 1b). CONCLUSIONS: Our results suggest that estrogen maintains bladder contractile power via modulation of the expression of MHC isoforms. Clinical application of estrogen replacement may be beneficial for treating postmenopausal DU.

Background Congenital cytomegalovirus (CMV) infection is caused by maternal primary infection as well as CMV reinfection or reactivation during pregnancy, although differences in the clinical impact between these modes of infection remain to be clarified. Objectives To investigate the latest prevalence and risk of multiple CMV infection in healthy pregnant women, as well as the types of maternal CMV infection associated with congenital CMV infection. Study design Seroprevalence against CMV and IgG subclasses were determined in 344 serum samples from healthy pregnant women in Japan. CMV genotype and serotype were also determined in 18 pairs of mothers and neonates with congenital CMV infection identified in our CMV screening program. Results Thirty-two percent of the pregnant women were seronegative, while 66% of CMV seropositive women had IgG3 antibodies against one epitope on glycoprotein H (gH) as the major subclass, and 52% had IgG1 antibodies against one epitope on glycoprotein B (gB). Only a single genotype determined by CMV gH neutralizing epitope was found in the urine from the 18 neonates with congenital CMV infection, even though one case possessed antibodies against multiple CMV strains. In that case, the antibodies against the strain not detected in the urine from the infant disappeared within one month after birth, whereas the antibodies against the infecting CMV strain continued to be detected at 12 months after birth. Conclusions Two (11%) of 18 cases of congenital CMV infection occurred via maternal CMV reinfection. Maternal humoral immunity did not prevent congenital CMV infection with another gH subtype.

In human urinary bladder, beta3-ARs play an important role in promoting detrusor relaxation during the storage phase of the micturition cycle. The present study investigated whether a Trp64Arg polymorphism of the gene encoding the beta3-AR is associated with overactive bladder (OAB) syndrome.This study involved 100 women with OAB and 101 healthy control women without OAB. Hair root samples were obtained from all subjects and used for beta3-AR gene analysis. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis was performed to analyze a polymorphism in the gene of Trp64Arg.The overall frequency of the 64Arg variant (heterozygous plus homozygous) in OAB patients was 47% and significantly higher than the frequency of 22.8% found in non-OAB control women. Within OAB patients, numbers of micturitions per day, urgency episodes per day, and urgency incontinence episodes per day in the 64Arg variant carriers were not significantly different from those in the normal gene carriers.This study shows that the Trp64Arg polymorphism in the beta3-AR gene is weakly but significantly associated with OAB syndrome.

Robot-assisted radical prostatectomy has been shown to have comparable and possibly improved postoperative continent rates compared with retropubic and laparoscopic radical prostatectomy. However, postoperative urinary incontinence has remained one of the most bothersome postoperative complications. The basic concept of the intraoperative technique to improve postoperative urinary continence is to maintain as normal anatomical and functional structure in the pelvis as possible. Therefore, improved knowledge of the normal structure in the pelvis should lead to a greater understanding of the pathophysiology of urinary incontinence, and further development of intraoperative techniques to improve the outcomes of urinary continence. It might be necessary to carry out three steps to realize improvement of the early return of urinary continence after robot-assisted radical prostatectomy: (i) preservation (bladder neck, neurovascular bundle, puboprostatic ligament, pubovesical complex, and/or urethral length, etc.); (ii) reconstruction (posterior and/or anterior reconstruction, and/or reattachment of the arcus tendineus to the bladder neck, etc.); and (iii) reinforcement (bladder neck plication and/or sling suspension, etc.). On the basis of these steps, further modifications during robot-assisted radical prostatectomy should be developed to improve urinary continence and quality of life after robot-assisted radical prostatectomy.

Background When urine output increases, voided volume at each voiding also increases in normal subjects. This is generally understood as a vesical adaptation response to diuresis (VARD). Because lower urinary tract symptoms (LUTS) are supposed to be improved by the change in bladder function after robot-assisted laparoscopic radical prostatectomy (RARP), the aim of the present study was to investigate whether VARD is involved in the improvement of LUTS after RARP. Methods 100 consecutive patients who underwent RARP and had the International Prostate Symptom Score (IPSS), quality of life (QOL) index, a frequency-volume chart (FVC), uroflowmetry, and post-voided residual urine (PVR) available were evaluated before and after RARP. This cohort was divided into patients with and without preoperative LUTS according to the preoperative IPSS total score. VARD was defined as the presence of a significant correlation between the urine output rate and voided volume at each voiding (R2>0.2). Results In patients with preoperative LUTS, the IPSS total, storage, and voiding symptom scores were significantly improved after RARP (all P

The present study investigated the role of the Rho-kinase (ROK) pathway in the maintenance of bladder tone during the storage phase, and its effects on bladder compliance.Muscle strips from isolated rat bladder (detrusor strips) were used to evaluate the effects of the ROK inhibitors Y-27632 and HA-1077 on resting tension, which is independent of G-protein coupled pathways. Stretch-induced ROK activation was assessed by measuring phosphorylation of MYPT1 (myosin phosphatase targeting subunit) using Western blotting. The effect of ROK inhibitors on bladder compliance during bladder filling was assessed in an in vitro whole bladder model.Y-27632 and HA-1077 caused concentration-dependent relaxation of detrusor strips. Stretch increased MYPT1-p[Thr853] levels by approximately 1.5-fold in normal Krebs buffer. The ROK inhibitor Y-27632 abolished the stretch-induced increase and reduced the level of MYPT1-p[Thr853] to50% of the basal values in normal Krebs buffer. Stretch-induced phosphorylation of MYPT1 was independent of Ca(2+) originating from either extracellular or intracellular stores. When tested in the isolated whole rat bladder model, HA-1077 significantly increased bladder compliance at both 3 and 10 µM.This study demonstrates that the ROK pathway is constitutively active and stretch further activates the ROK pathway, which contributes to the generation of bladder tone, thereby affecting bladder compliance.

The 2011 St. Gallen Consensus Statement advocated using histological grade (HG) as a proliferation marker of breast cancer (BC) if reliable Ki67 labeling index (Ki67-LI) assessment is not available. However, it has been difficult to evaluate tumor aggressiveness in case of HG2. A total of 259 cases of BC were assessed for HG, Ki67-LI and other clinicopathological features. The cut point for Ki67-LI was interpreted as low and high using a 14 % threshold. The average age at diagnosis was 58.2 years (range 28–86); 64.9 % of the patients were postmenopausal. Of the 259 cases, 151 were stage I, 78 were stage II, 29 were stage III, and 1 was stage IV. The subtypes based on immunohistochemical staining were 60 cases of luminal A (LA) type (23.2 %), 37 cases of luminal B (LB) (HER2−) type (14.3 %), 91 cases of LB (HER2+) type (35.1 %), 40 cases of human epidermal growth factor receptor 2 (HER2) type (15.4 %) and 31 cases of triple negative (TN) type (12 %). HG was 1 (89 cases, 34.4 %), 2 (117 cases, 45.2 %) and 3 (53 cases, 20.5 %). High Ki67-LI cases were observed in HG1 (37.1 %), HG2 (56.4 %) and HG3 (96.2 %). Especially in cases of HG2, high Ki67-LI cases were observed in 0 % of LA type, 100 % of LB (HER2−) type, 71.2 % of LB (HER2+) type, 68.8 % of HER2 type and 40.0 % of TN type. The average Ki67-LI was 6.0 ± 3.8 (LA type), 31.4 ± 15.7 [LB (HER2−) type], 20.2 ± 14.8 [LB (HER2+) type], 32.7 ± 21.9 (HER2 type) and 55.7 ± 32.2 (TN type). All LA-type cases and 66.7 % of LB (HER2+)-type cases were low Ki67-LI. Our study demonstrates that all LA-type cases and most HG1 of LB (HER2+)-type cases are low proliferative. However, HG was not informative enough for estimating tumor proliferation in cases of LB (HER2−), HER2 and TN types. It is necessary to add other proliferation tools such as the gene expression profiling tool and Ki67-LI except in LA and HG1 of LB (HER2+)-type cases.

A 22-year-old woman had a well differentiated nephroblastic tumor. The tumor was composed of mesenchymal elements with mature tubules and occasionally smooth muscle elements. None of the cellular elements showed any feature indicative of malignancy. Histologically this was similar to congenital mesoblastic nephroma, but the tumor showed an evidence of a uniform expansile growth. It was considered to be a form of mature nephroblastoma.

• Secondary analysis of anonymous data from 10,434 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan was performed. Data were prospectively collected through the central register from men diagnosed with LUTS in 1100 medical institutions between October 2004 and March 2005. • Those who had received an α1-adrenoceptor antagonist within 1 week before the initial visit were excluded. • The survey items were International Prostate Symptom Score (IPSS), quality of life (QOL) score, and patient characteristics including age, bodyweight, body mass index, and LUTS-related comorbid conditions. • Data on IPSS items were used in a hierarchical cluster analysis (Ward's method).• Of 10,434 men with LUTS, 9910 were included in the analysis after 5% data trimming (524 patients). Five symptom clusters were identified and the symptom types of each cluster were examined. • The largest cluster (27%) consisted of patients with multiple severe symptoms, i.e. complaining of six or more symptoms with a mean score ≥2.8. In contrast, the second smallest cluster (13%) consisted of patients with minimal symptoms, i.e. complaining of essentially one or two symptom with a mean score ≤2.1. • The other three clusters were labelled based on their dominant symptoms. The clusters were weak stream (27%), storage symptoms (21%) and voiding symptoms (12%). • The storage symptoms group was older, and had more comorbidities. • The distribution of the QOL score was different among the clusters, and the percentage of patients who were very dissatisfied was highest in the multiple severe symptoms group and lowest in the minimal symptoms group.• Cluster analysis using the IPSS showed that men with LUTS can be classified into five characteristic symptom groups. • A new approach to symptom-based classification may be useful to elucidate the pathology of male LUTS and individualize the therapeutic strategy for affected patients, but further studies are needed.

To investigate the effects of long-term administration of the α(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT).Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry.The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle.Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.

Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. Reinfection of CMV can occur in CMV-seropositive donors and CMV seropositive recipients (D+/R+) settings because the protection against CMV conferred by preexisting immunity is limited due to its strain-dependent immune responses. To analyze the influence of CMV reinfection in renal transplantation, ELISA using fusion proteins encompassing epitope of glycoprotein H(gH) from both AD169 and Towne strains was employed before transplantation. The CMV-gH seropositive rate increased with increases in age and the rate of samples which contained antibodies against both AD169 and Towne were significantly high in the age of 50 years or over. Antibodies from HLA-DR10 and DR11 were associated with a significantly lower response rate against CMV-gH. In renal transplantation, the high degrees of antigenemia and high incidences of CMV disease are more prevalent in the CMV gH antibody-mismatched group in D+/R+ setting. The nucleotide sequence of the region of the gH epitope in the CMV-DNA extracted from the transplant recipients who showed high degree of antigenemia revealed the CMV reinfection from the donors. As a CMV indirect effect, the incidence of acute rejection in the mismatched gH antibody group was higher than that observed in the matched and D+/R- groups. The adverse events were more likely to occur in cases of D+/R+ renal transplantation with mismatched strain-specific antibodies which would indicates the risk of CMV reinfection after transplantation.

Respiratory syncytial virus (RSV) is one of the pathogens generally associated with the common cold, lower respiratory infection, and exacerbation of asthma. Disodium cromoglycate (DSCG) is a safe and widely used drug for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infections remains controversial. The purpose of the study was to investigate the effects of DSCG on parameters of RSV induced-illness. Using a well-characterized murine model of RSV infection, the effect of DSCG on RSV-induced illness was evaluated by body weight, respiratory function, viral replication, level of IFN-gamma in lungs, serology, and histopathology. Mice treated with DSCG were protected against RSV-induced weight loss. The baseline Penh in RSV-infected mice treated with DSCG was less than that in mice treated with saline. In methacholine challenge, the increase in Penh in RSV-infected mice treated with DSCG was suppressed to the same level as that in the mock-infected group. Further, there were no differences in viral replication between the mice treated with DSCG and those treated with saline, and the level of inflammation observed in the lungs in RSV-infected mice treated with DSCG was not as severe as that in mice treated with saline. These findings indicate that DSCG may be an effective agent for the prevention of RSV induced disease and the relief of symptoms of RSV infection.

Although there have been some reports describing the serostatus of cytomegalovirus, strain-specific antibody responses and their distribution remain unknown. In this study, ELISA using fusion proteins encompassing epitope of glycoprotein H from both AD169 and Towne strains was used to test 352 blood donors. Of these 352 donors, 207 were analyzed for strain-specific glycoprotein H antibodies. Of the 44 donors whose serum contained antibodies against both AD169 and Towne, 27 (60%) were aged 50 years or over (p = 0.0003). This may indicate serological evidence of reinfection with cytomegalovirus in the elder population. The nucleotide sequence analysis of cytomegalovirus glycoprotein H from the peripheral blood of the cytomegalovirus-positive renal transplant recipients showed that our strain-specific ELISA can reveal cytomegalovirus reinfection after transplantation.

Background. Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. The combination of CMV-seronegative transplant recipients with CMV-seropositive transplant donors places recipients at the highest risk of CMV disease. In cases of congenital CMV infection, existing immunity only partially protected mothers from reinfection with a different genotypic strain. The effect of differences in infected CMV strains between CMV-seropositive transplant donors and CMV seropositive transplant recipients on the outcome of transplantation remains unclear. Methods. In this prospective multicenter study, the presence of antibodies against strain-specific glycoprotein H epitopes in 84 CMV-seropositive transplant donor/CMV-seropositive transplant recipient renal transplantation cases were determined, and their relationships to acute transplant rejection, CMV infection, degree of antigenemia, and CMV disease were evaluated. Results. Among the 84 donor/recipient pairs, 45 and 32 had matched and mismatched strain-specific glycoprotein H antibodies, respectively. Acute transplant rejection in the mismatched group was more frequent than it was in the matched group (63% vs. 22%; P = .005). CMV disease was also more frequently observed in the mismatched group (28% vs. 9%; P = .026). The mismatched group had a higher level of antigenemia (P = .019). Conclusions. Our results illustrate more adverse events in the cases with a CMV-seropositive transplant donor and a CMV-seropositive transplant recipient in which the glycoprotein H antibodies are mismatched, suggesting that reinfection with a different CMV strain results in more complications.

Background: The expression of c-Met and its ligand HGF plays a critical role in cell proliferation and is involved in numerous malignancies. Because c-Met expression and its role in NK/T-cell lymphoma remain unclear, we studied the expression and function of c-Met in NK/T-cell lymphoma cells. In addition, we investigated the possibility that c-Met could function as a tumor-associated antigen for helper T lymphocytes (HTLs). Methods: We evaluated whether HGF and c-Met were expressed in NK/T-cell lymphoma and the capacity of predicted c-Met HTL epitopes to induce antitumor responses in vitro. In addition, c-Met inhibitor was evaluated for the ability to inhibit TGF-β production in tumor and subsequently increase HTL recognition. Results: c-Met and HGF were expressed in NK/T-cell lymphoma cell lines, nasal NK/T-cell lymphoma specimens and patient serum samples. Moreover, HGF was shown to promote NK/T cell lymphoma (NKTCL) proliferation in an autocrine manner. Furthermore, we have identified three novel c-Met HTL epitopes that were restricted by several HLA-DR molecules. Notably, peptide-induced HTL lines directly recognized and killed c-Met expressing NK/T-cell lymphomas and various epithelial solid tumors. The c-Met specific HTLs could also recognize dendritic cells (DCs) pulsed with c-Met expressing tumor cell lysates. In addition, we observed that c-Met inhibition augmented HTL recognition by decreasing TGF-β production by tumor cells. Lastly, autophagy partly regulated the HTL responses against tumors. Conclusions: We identified novel c-Met HTL epitopes that can elicit effective antitumor responses against tumors expressing c-Met. Our results provide the rationale of combining c-Met targeting therapy and immunotherapy for NKTCLs and epithelial tumors.

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of these bacteria to various antimicrobial agents were measured. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1995 and 2003. The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin (VCM) and arbekacin (ABK). The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The susceptibility of E. coli to cephems in this year was generally good and was similar to those in up to the previous year. MIC90 of cefozopran (CZOP) was the most stable and 0.125 microg/mL or less since 1995. The susceptibility of E. coli to cefpirome (CPR) and cefotiam (CTM) also was good but to cefaclor (CCL), cefixime (CFIX), and cefpodoxime (CPDX) was largely decreased in complicated UTI groups. The sensitivity of E. coli to carbapenems also was good but to carumonam (CRMN) tended to decrease. The susceptibility of E. coli to quinolones, however, has largely changed and has decreased since 2003 in uncomplicated UTIs and 2000 in complicated UTIs. That was suggested the development of the resistance to the drug. The susceptibility of Klebsiella spp. to cefazolin (CEZ), CTM, CCL, CPDX, and cefditoren (CDTR) decreased in the previous year and recovered to the year before the previous year in this year. The susceptibility of Klebsiella spp. to other cephems was stable since 1995, especially against CZOP, the highest sensitivity (MIC90:or = 0.125 microg/mL) was maintained. The susceptibility of Klebsiella spp. to carbapenems and CRMN also was good. The susceptibility of Klebsiella spp. to aminoglycosides was lower than to CZOP but was stable since 1995. The susceptibility of P. aeruginosa was generally low and has largely changed against the majority of the agents since 1995. The susceptibility of P. aeruginosa isolated from uncomplicated UTIs has largely changed against ceftazidime (CAZ), cefsulodin (CFS), CZOP, imipenem (IPM), meropenem (MEPM), aztreonam (AZT), CRMN, gentamicin (GM), and tobramycin (TOB). The susceptibility of P. aeruginosa isolated from complicated UTIs has largely changed against CSF, CZOP, MEPM, GM, and ciprofloxacin (CPFX). The susceptibility of P. aeruginosa isolated from complicated UTIs has been stable against amikacin (AMK). For annual changes in MIC50, TOB and IPM had a relatively stable and high activity (MIC50: 0.5-2 microg/mL).

The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90:or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX):or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).

Six hundred six bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The frequency of bacteria isolation stratified with patient clinical background was compared. The clinical background investigated included sex, age, type of infections, timing of antibiotics administration, and presence or absence of surgery affecting a decrease in defense against infection. The bacterial strains were stratified with the age and sex of the patients and the types of infections. In males, the number of patients aged less than 60 years was few and the complicated UTIs without indwelling catheter was observed most frequently. In females, the number of patients aged less than 60 years was comparatively more than in males. In all of ages except 0-19 andor = 80 years, the ratio of the uncomplicated UTIs was high, accounting for 44.1-90.0% of all types of infections. In the present time, the bacteria most frequently isolated were Escherichia coli. Pseudomonas aeruginosa and Enterococcus faecalis also were relatively frequently isolated. E. coli most frequently isolated with the uncomplicated UTIs and P. aeruginosa and E. faecalis most frequently isolated with the complicated UTIs. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups except 0-19 years, accounting for 50% or higher. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli tended to be high in all age groups. In the complicated UTIs with indwelling catheter, P. aeruginosa were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, P. aeruginosa increased after the administration in any types of UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coli was more frequently isolated in the patients without surgery, while P. aeruginosa and E. faecalis were more frequently isolated in the patients with surgery in any UTIs.

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of September and December 2001. Then, the susceptibilities of them to a variety of antimicrobial agents were investigated. The number of them were 496 strains. The breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong activity, and this drug also had a strong activity against MRSA in preventing growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented growth of all strains at 4 micrograms/mL. ABK also showed a strong activity against Staphylococcus epidermidis in preventing growth of all strains at 0.5 microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM), and VCM showed strong activities against Enterococcus faecalis. No increase of low-susceptible strains in E. faecalis was observed against these antimicrobial agents. Against Escherichia coli, carbapenems showed the highest activities: meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E. coli was detected at frequency of 9.3%, which was lower than that in the last year, and was higher level than those in up to 1999. MEPM showed the strongest activity against Citrobacter freundii in preventing growth of all strains at 0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and 16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and amikacin were 16 micrograms/mL, and those of all other drugs were over than 32 micrograms/mL.

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 1999. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). E. faecalis showed good susceptibility to ampicillin (ABPC) and imipenem (IPM), and the MIC90s were 2 micrograms/ml. Also, E. faecalis showed good susceptibility to vancomycin (VCM). However, the MIC90, which was 2 micrograms/ml between 1992 and 1999, rose to 4 micrograms/ml in patients with complicated UTIs because the strains inhibited at 4 micrograms/ml increased more than before. The low susceptibility of S. aureus to arbekacin (ABK) in complicated UTIs, as shown in 1998 and 1999, recovered in 2000, and no strains inhibited ator = 4 micrograms/ml were detected. E. coli showed good susceptibility to CTM (MIC90: 0.25-0.5 microgram/ml) and CZOP (MIC90:or = 0.125 microgram/ml) and was not resistant to those. E. coli also showed good susceptibility to the other drugs except to penicillins. Decreases in susceptibility of E. coli to quinolones, ciprofloxacin (CPFX), and sparfloxacin (SPFX) were observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all drugs did not significantly change in 2000 and was generally good except to penicillins. Although the susceptibility of P. aeruginosa to carbapenems was notable, the MIC90 went up from 4 micrograms/ml to 16 micrograms/ml in complicated UTIs compared with those observed in the previous year.