O-glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer. The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations. The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA. METHODS: We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases. Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling. Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans. RESULTS: Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer. Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry. It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases. Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin. When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease. CONCLUSION: For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.

Glycosylation status of serum immunoglobulin G in patients with prostate diseases.

Occurrences of high values in patients with benign prostate disease and low values in patients with highly suspicious cancer have diminished the trustworthiness of prostate-specific antigen as an early diagnostic marker of prostate cancer. In the search for other complimentary markers, we focused on serum IgG from patients with prostate diseases as well as normal subjects. IgG purified from the sera of normal control subjects and patients with prostate diseases, was digested with peptide N-glycanase. Released glycans were quantified using MALDI-time of flight mass spectrometry. We report that N-linked (N-acetylhexosamine)2 (deoxyhexose)(mannose)3 (N-acetylglucosamine)2 was significantly increased in the IgG heavy chains of patients with prostate cancer compared with that of either benign prostatic disease patients or healthy subjects, whereas (hexose)(N-acetylhexosamine)2 (deoxyhexose)(mannose)3 (N-acetylglucosamine)2 was more abundant in the heavy chains of healthy subjects and benign prostatic disease patients. Thus, an absence of the terminal hexose of N-linked glycans has been closely connected to the progression of prostate cancer. Furthermore, surface plasmon resonance analyses have revealed that IgG from patients with prostate cancer has a decreased binding for Sambucus nigra lectin, compared with that from the benign prostatic disease patients or from normal subjects, suggesting lower levels of (N-acetylneuraminic acid)(α2-6)galactose/N-acetylgalactosamine groups in the N-linked glycans of patient IgG. Meanwhile, wheat germ agglutinin binding to IgG of the cancer group was significantly larger than that for the benign prostatic disease group but smaller than that for normal subjects. Our study indicates that the glycosylation changes in IgG can become useful diagnostic parameters for prostate cancer.

Metastatic seminoma in the duodenum: diagnosis with endoscopy followed by successful treatment.

Seminomas rarely metastasize to the gastrointestinal tract. In general, these lesions metastasize to the lungs or retroperitoneal lymph nodes. A 34-year-old Japanese man who had undergone orchiectomy for seminoma two years earlier experienced shortness of breath and tarry stools. The patient presented at our hospital and was diagnosed with metastatic seminoma to the third portion of the duodenum on double balloon endoscopy. He was effectively treated with chemotherapy and continues to progress well, with no episodes of recurrence.

Stone attenuation value and cross-sectional area on computed tomography predict the success of shock wave lithotripsy.

PURPOSE: To identify the parameters on noncontrast computed tomography (NCCT) that best predict the success of shock wave lithotripsy (SWL). MATERIALS AND METHODS: We reviewed the records of 75 patients who underwent SWL for urinary calculi measuring 5 to 20 mm. Using NCCT images, we estimated the largest stone cross-sectional area and contoured the inner edge of the stone. Clinical outcome was classified as successful (stone-free or <4 mm in diameter) or failed (stone fragments, ≥4 mm). The impact of preoperative parameters was evaluated by univariate and multivariate analysis. RESULTS: The overall success rate was 73.3%. Average stone attenuation value, stone length, and stone cross-sectional area in the success and failure groups were 627.4±166.5 HU (Hounsfield unit) vs. 788.1±233.9 HU (p=0.002), 11.7±3.8 mm vs. 14.2±3.6 mm (p=0.015), and 0.31±0.17 cm(2) vs. 0.57±0.41 cm(2) (p<0.001), respectively. In the multivariate analysis, stone attenuation value was the only independent predictor of SWL success (p=0.023), although stone cross-sectional area had a tendency to be associated with SWL success (p=0.053). Patients were then classified into four groups by using cutoff values of 780 HU for stone attenuation value and 0.4 cm(2) for cross-sectional area. By use of these cutoff values, the group with a low stone attenuation value and a low cross-sectional area was more than 11.6 times as likely to have a successful result on SWL as were all other groups (odds ratio, 11.6; 95% confidence interval, 3.9 to 54.7; p<0.001). CONCLUSIONS: Stone attenuation value and stone cross-sectional area are good predictors of extracorporeal SWL outcome.

[Diagnostic study of the usefulness of virtual endoscopic images and 3-D modeling for lower urinary tract obstruction].

PURPOSE: I observed bladder and urethral morphology and lumen by making a virtual endoscopy (VE) of the bladder and a urethra for patients with lower urinary tract symptoms. I have herein reported the procedures to use this model to evaluate the condition of patients more precisely. PATIENTS AND METHODS: Of those referred for investigation of lower urinary tract symptoms, subjects were 22 boys (5-13 years old, mean 9) in whom voiding cystourethrography (VCUG) was suspected for urethral obstruction between March, 2009 and October, 2010. Eleven of these 22 cases were extracted at random and underwent voiding computed tomography (VCT). Except one dropped out, the 21 cases were assigned to a VCT/VCUG combination group or a VCUG-single group. We confirmed the two groups, the rate of agreement of imaging views and cystourethroscopy (CS) views, and the effectiveness of endoscopic operation. RESULT: I made the following imaging diagnoses in the VCT/VCUG combination group: congenital obstructive posterior urethral membrane (COPUM), n = 7; Cobb's collar, n = 1; and COPUM and Cobb's collar combined, n = 3. In contrast, in the VCUG-single group, I diagnosed COPUM, n = 5; bulbar region urethral stricture, n = 2; posterior urethral expansion, n = 2; and bladder form abnormality, n = 1. The rate of agreement between preoperative diagnosis and CS views on imaging was 72.7% in the VCT/VCUG combination group, and 33.3% in the VCUG-single group. All patients underwent transurethral incision (TUI) of the urethral obstruction. In the VCT/VCUG combination group, effectiveness of the TUI was assessed as good in 2 cases and moderate in 6 cases giving an overall effectiveness rate (good + moderate) of 72.7%. In the VCUG-single group, effectiveness was rated as moderate in 5 cases (overall effectiveness rate = 50%). CONCLUSION: I developed a method of VE for lower urinary tract obstruction of children and examined the effectiveness. This method was found to be more effective than conventional urinary tract imaging. With the developments in the equipment, this method may in future be useful as an adjunct to CS and urodynamic studies.

Multi-sequential surface plasmon resonance analysis of haptoglobin-lectin complex in sera of patients with malignant and benign prostate diseases.

Screening for prostate cancer remains unsatisfactory. Recent studies have examined the cancer diagnostic/prognostic values of various acute phase proteins, such as haptoglobin. We describe here a novel method of surface plasmon resonance (SPR) based on multi-sequential analysis with SNA-1, AAL, and PHA-L(4) lectin, to estimate the glycosylation status of haptoglobin in sera of patients with prostate cancer (n=15), benign prostate disease (BPD) including benign prostatic hypertrophy (n=20), and normal subjects (n=11). The SPR-based analysis involves the use of anti-haptoglobin as ligand and dilution of the analyte to 1400-fold and filtration, followed by detection of the sugar chain by lectin solution. The normalized RU of lectin to haptoglobin represents the binding amount of lectin divided by that of haptoglobin. The normalized RU by SNA-1 of the prostate cancer group was significantly higher than those of the control and BPD group. SNA-1 detected NeuAcα2,6 in a biantennary sugar chain, whose content was the highest among the major glycoproteins in serum. Serum samples diluted about 7000-fold were subjected to microanalysis at 10 ng/µl and 10 µl/min for 4 min. The combination of SNA-1 and haptoglobin by SPR multi-sequential analysis offered the most accurate diagnosis of prostate cancer without any modification of serum glycoproteins.

Impact of dry ejaculation caused by highly selective alpha1A-blocker: randomized, double-blind, placebo-controlled crossover pilot study in healthy volunteer men.

INTRODUCTION: Dry ejaculation with loss of seminal emission is reported in patients who have been administered silodosin, an alpha1A-adrenoceptor antagonist. AIM: We investigated the impact of dry ejaculation caused by orally administered silodosin on orgasmic function. METHODS: In a double-blind crossover study, 50 healthy volunteer men were randomly assigned to receive either a single dose of 4-mg silodosin or placebo with 3 days of washout before crossover. Subjects masturbated 4 hours after administering agents. MAIN OUTCOME MEASURES: Numerical rating scale (NRS) score from 0 (highest) to 10 (lowest) for subjective quality of orgasm, the subjective number of contractions of the bulbocavernosus/pelvic floor muscles, and the amount of semen were examined. Results. After the administration of silodosin, the NRS score worsened by 1.3 points (P = 0.003), the number of contractions of the bulbocavernosus/pelvic floor muscles decreased by about 1 (P = 0.003), and there was a decrease of 1.8 mL in the amount of semen produced (P < 0.0001). Eleven men overall (22%) on silodosin administration had less than a 50% decrease from baseline in the amount of semen. CONCLUSIONS: Silodosin may adversely affect the subjective orgasmic function by causing an abnormal ejaculation with decreased (or no) semen discharge and a decrease in the number of bulbocavernosus/pelvic floor muscle contractions. Semen passing through the urethra and sufficient rhythmic contraction of the muscle of the pelvic floor may contribute to the subjective pleasure of orgasm.

Gastrointestinal hemorrhage as the first manifestation of metastatic extragonadal choriocarcinoma.

Although germ cell tumors are the most common malignancy in young men, extragonadal germ cell tumors are rare. Gastric metastasis presenting initially as upper gastrointestinal hemorrhage is also exceedingly rare. A 27-year-old man presented at our hospital with tarry stool. Gastric fiberscopy images revealed a bleeding gastric polypoid lesion in the anterior wall of the gastric body, from which a biopsy specimen was obtained. Histopathological analysis of the biopsy showed syncytiotrophoblast-like cells with multiple, large nuclei, consistent with choriocarcinoma. Based on these results, our diagnosis was extragonadal retroperitoneal germ cell tumor with gastric metastasis.

Factors associated with variation in utility scores among patients with prostate cancer.

OBJECTIVE: We aimed to assess the effects of age, comorbidity, and disease-specific functions on utility scores derived from three methods on prostate cancer. METHODS: A total of 330 Japanese prostate cancer patients were asked to answer self-administered questionnaires. Community-weighted utility scores were derived from the EuroQoL-5D (EQ-5D) and the Short Form-36 (SF-36), while the patient's directly elicited utility score was derived from time trade-off technique. Univariate and multivariate analyses were performed to examine the relation between covariates and utility scores. We assigned age, the Index of Co-existent Disease, and disease-specific functions including sexual, urinary, bowel, and hormonal function as covariates. RESULTS: Bowel and hormonal function were related to utility scores, while age and sexual function were not. Comorbidities were more closely related to utility scores derived from EQ-5D and SF-36. CONCLUSIONS: These results contribute to an understanding of which factor has an impact on utility scores in patients with prostate cancer.

Evaluation using a combination of lymphatic invasion on D2-40 immunostain and depth of dermal invasion is a strong predictor for nodal metastasis in extramammary Paget's disease.

In extramammary Paget's disease (EPD), lymph node metastasis occasionally occurs and nodal metastasis influences prognosis. Therefore, in the present study a predictor of nodal metastasis in EPD was examined. Surgical specimens from 54 cases of EPD in the external genitalia were examined on D2-40 immunostain. In 23 cases, dissection of the inguinal lymph nodes was performed. Dermal invasion occurred in 24 patients (44.4%). Nodal metastasis was found in seven patients who had dermal invasion >1 mm. In non-metastatic patients, three had dermal invasion <0.5 mm in depth. Lymphatic invasion was well detected on D2-40 immunostain, and invasion was found in five patients. All four patients with lymphatic invasion, in whom lymph node dissection was performed, had nodal metastasis. However, three patients with dermal invasion, who did not have lymphatic invasion, did have nodal metastasis, and the depth of invasion was >1 mm. Dermal invasion (P < 0.001) and lymphatic invasion according to D2-40 immunostain (P = 0.001) had a positive correlation with nodal metastasis. In conclusion, evaluation using a combination of lymphatic invasion according to D2-40 immunostain and depth of dermal invasion is a strong predictor of nodal metastasis in EPD.

[Clinical study on renal trauma].

We analyzed 26 cases of renal trauma, which occurred during the last 7 years and 6 months. Computed tomography was performed in all cases. Four cases were of type Ib, 13 cases of type II, 3 cases of type IIIa, 5 cases of type IIIb and 1 case of type IVa, according to the classification of renal injury by the Japanese association for the surgery of trauma. Conservative treatment was done in 21 cases, selective transcatheter arterial embolization (TAE) in 4 cases, and surgical treatment in 1 case. Conservative treatment was effective for type I and II renal trauma. In the cases of type IIIa and IIIb renal trauma, open surgery could be avoided and the affected kidney preserved by early TAE.

Inadequacy of prostate-specific antigen doubling time estimates calculated using an ultrasensitive assay of prostate-specific antigen for biochemical failure after radical prostatectomy.

BACKGROUND: The objective of this study was to evaluate the adequacy in calculating prostate-specific antigen doubling time (PSADT) using an ultrasensitive assay of prostate-specific antigen (PSA) for biochemical failure after radical prostatectomy (RP). METHODS: In this research, we included 52 consecutive patients who experienced more than or equal to three consecutive increases in ultrasensitive PSA values after RP at two institutions. PSADT is to be calculated by fitting a linear model to post-nadir longitudinal logarithm ultrasensitive PSA (lnPSA) values. The goodness of fit of linear model for longitudinal lnPSA values was evaluated by applying a mixed effect model for all patients or two groups divided by median PSADT. RESULTS: Median PSADT was 4.7 months. A mixed effect model showed that the fit of linear model for longitudinal lnPSA values was not good in lower ultrasensitive PSA values for all patients (p < 0.0001) or the group with a value longer than the median PSADT (p < 0.0001), while it was not worse for the group with a value shorter than the median PSADT (p = 0.079). CONCLUSIONS: These findings suggest that calculating PSADT using an ultrasensitive assay for biochemical failure after RP may still be open for discussion.

Transforming growth factor-beta promotes survival of mammary carcinoma cells through induction of antiapoptotic transcription factor DEC1.

Transforming growth factor-beta (TGF-beta) signaling facilitates tumor growth and metastasis in advanced cancer. In the present study, we identified differentially expressed in chondrocytes 1 (DEC1, also known as SHARP2 and Stra13) as a downstream target of TGF-beta signaling, which promotes the survival of breast cancer cells. In the mouse mammary carcinoma cell lines JygMC(A) and 4T1, the TGF-beta type I receptor kinase inhibitors A-44-03 and SB431542 induced apoptosis of cells under serum-free conditions. Oligonucleotide microarray and real-time reverse transcription-PCR analyses revealed that TGF-beta induced DEC1 in these cells, and the increase of DEC1 was suppressed by the TGF-beta type I receptor kinase inhibitors as well as by expression of dominant-negative TGF-beta type II receptor. Overexpression of DEC1 prevented the apoptosis of JygMC(A) cells induced by A-44-03, and knockdown of endogenous DEC1 abrogated TGF-beta-promoted cell survival. Moreover, a dominant-negative mutant of DEC1 prevented lung and liver metastasis of JygMC(A) cells in vivo. Our observations thus provide new insights into the molecular mechanisms governing TGF-beta-mediated cell survival and metastasis of cancer.

Decision analyses in consideration of treatment strategies for patients with biochemical failure after curative therapy on clinically localized prostate cancer in the prostate-specific antigen era.

BACKGROUND: The introduction of prostate-specific antigen (PSA) testing has not only shortened the time required to make diagnosis but changed the treatment strategies of localized prostate cancer. We conducted the decision analysis on its treatment focusing on patients with biochemical failure. METHODS: We developed a Markov model to calculate life expectancy (LE) and quality-adjusted life expectancy (QALE) stratified by age, comorbidity and tumor characteristics in patients with newly diagnosed prostate cancer or biochemical failure after curative therapy. For newly diagnosed patients, three treatment strategies were considered as primary managements: radial prostatectomy (RP), external beam radiotherapy (EBRT) and watchful waiting (WW). Managements considered for biochemical failure were: after RP, salvage radiotherapy (SRT), salvage hormonal therapy (SHT) and WW; and after EBRT, SHT and WW. Transition probabilities in the Markov model were derived from published studies. Quality of life (QOL) data to estimate QALE score were derived from 323 patients with prostate cancer. RESULTS: For patients with Gleason 2-6 cancer at diagnosis, WW yielded the greatest number of QALE. For patients with Gleason 7 cancer, it was controversial whether curative therapy was the preferred strategy. For patients with Gleason 8-10 cancer, curative therapy yielded the greatest number of QALE in younger patients without severe comorbidity. Patients' benefit from salvage therapy for biochemical failure after curative therapy depended on age, comorbidities, tumor characteristics and QOL effect. CONCLUSIONS: Our findings support the need for various treatment options, taking into consideration the patient's age, comorbidity and the QOL effect in the aging society.

Evaluation of urinary CA19-9 levels in bladder cancer patients classified according to the combinations of Lewis and Secretor blood group genotypes.

OBJECTIVES: This study evaluated the clinical significance of urinary CA19-9 levels in bladder cancer patients classified according to various combinations of Lewis (Le) and Secretor (Se) genotypes. METHODS: Urinary CA19-9 and DU-PAN-2 levels were measured as units per mg creatinine (U/mg Cr) in 121 patients with bladder cancer and in 31 patients with other urologic diseases. Genotyping was carried out using polymerase chain reaction-based methods. RESULTS: Urinary CA19-9-values in patients with both Le and Se alleles (Le/Le, Se/Se; Le/Le, Se/se; Le/le, Se/Se; Le/le, Se/se) were significantly higher (P < 0.0001) in bladder cancer cases compared to the other urologic diseases. The cut-off value determined using receiver operating characteristics analyses was 37.6 U/mg Cr. Approximately 70% (57/87) of bladder cancer patients with both Le and Se alleles demonstrated urinary CA19-9 levels over the cut-off value. In contrast, only 16% (4/24) of patients with other urologic diseases were over the cut-off value. CONCLUSIONS: The urinary CA19-9 level can be a new effective diagnostic tool in bladder cancer patients with both Le and Se alleles.

Efficiency of ultrasensitive prostate-specific antigen assay in diagnosing biochemical failure after radical prostatectomy.

BACKGROUND: Ultrasensitive prostate-specific antigen (PSA) is a significant serum biomarker for identifying the PSA nadir and early biochemical failure after radical prostatectomy (RP). We assessed the efficiency of ultrasensitive PSA assay in the follow-up after RP. METHODS: We generated longitudinal ultrasensitive PSA data using a computer program assuming that patients experienced biochemical failure after RP. The simulation experiments, based on several different scenarios, were performed to assess the sensitivity and specificity in the diagnosis of biochemical failure using ultrasensitive PSA values and to estimate the lead time, which is the time advantage of detecting positivity for biochemical failure using the ultrasensitive PSA values compared with conventional PSA assay. We validated the sensitivity, specificity and lead time using actual follow-up data of 182 patients receiving RP. RESULTS: It was suggested that the sensitivity obtained from the actual data was more similar to that obtained using ultrasensitive PSA with an exponential increase than with a linear increase in the simulation experiments. Diagnosing biochemical failure based on two consecutive increases in the ultrasensitive PSA values was not recommended. Of non-biochemical failure patients, 9.4% showed four consecutive increases in their ultrasensitive PSA values. Average lead time in the actual data was 11.2 months (SD: 10.1). CONCLUSIONS: For an accurate diagnosis of biochemical failure, our findings suggest the importance of a certain duration of follow-up and exclusion of false-positive results afterwards.

Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line.

Transforming growth factor (TGF)-beta signaling has been shown to promote tumor growth and metastasis in advanced cancer. Use of inhibitors of TGF-beta signaling may thus be a novel strategy for treatment of patients with such cancers. In this study, we investigated the effects of a novel TGF-beta type I receptor (TbetaR-I) kinase inhibitor, Ki26894, on bone metastasis of a highly bone-metastatic variant of human breast cancer MDA-MB-231 cells, termed MDA-MB-231-5a-D (MDA-231-D). Ki26894 blocked TGF-beta signaling in MDA-231-D cells, as detected by suppression of phosphorylation of Smad2 and inhibition of TGF-beta-responsive reporter activity. Moreover, Ki26894 decreased the motility and the invasion of MDA-231-D cells induced by TGF-beta in vitro. Ki26894 also suppressed transcription of plasminogen activator inhibitor-1 (PAI-1), parathyroid hormone-related protein (PTHrP), and interleukin-11 (IL-11) mRNA of MDA-231-D cells, which were stimulated by TGF-beta. X-ray radiography revealed that systemic Ki26894 treatment initiated 1 day before the inoculation of MDA-231-D cells into the left ventricle of BALB/cnu/nu female mice resulted in decreased bone metastasis of breast cancer cells. Moreover, Ki26894 prolonged the survival of mice inoculated with MDA-231-D cells compared to vehicle-treated mice. These findings suggest that TbetaR-I kinase inhibitors such as Ki26894 may be useful for blocking the progression of advanced cancers.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). III. Secular changes in susceptibility].

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).

Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma.

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. We identified 257 genes that were commonly up-regulated and 721 genes that were down-regulated in RCCs. None of top 24 up-regulated genes that showed most significant differences in informative RCC-cases were included in previous reports describing expression profiles of RCC using RNAs isolated from bulk tissues. These findings suggest that it is important to purify as much as possible the populations of cancerous and normal epithelial cells obtained from surgical specimens. Among the significantly-transactivated genes, we focused on Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small-interfering RNA (siRNA). Effective down-regulation of its expression levels in RCC cells significantly attenuated RCC cell viability. In conclusion, our data should be helpful for a better understanding of the tumorigenesis of RCC and should contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with RCC.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). I. Susceptibility distribution].

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 to > 128 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).