Search

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in low-susceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC90 of 2 micrograms/ml against MRSA and prevented growth of all strains with 4 micrograms/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5 microgram/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC90: 4 to 8 micrograms/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml; IPM prevented growth of all strains with 0.25 microgram/ml. CZOP and CTM also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/ml; MIC80 and MIC90 of CTM were 0.25 and 0.5 microgram/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. 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 Pseudomonas aeruginosa, almost drugs were not so active. The MIC90 of carbapenems and gentamicin (GM) were 16 micrograms/ml and those of all other drugs were more than 32 micrograms/ml. Against Serratia marcescens, the MIC90 of IPM and GM were the lowest value being 2 micrograms/ml, and that of MEPM was 4 micrograms/ml.

Five-hundred eighty eight bacterial strains isolated from 435 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. The majority of female patients aged 40 years and over had complicated UTIs while uncomplicated UTIs was most frequent in the patients being twenties. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and pseudomonas aeruginosa increased when the infection became complicated. Enterococcus faecalis was isolated more frequently in complicated UTIs than in uncomplicated UTIs. Considering this result by age of patients, isolated frequency of E. coli was gradually decreased with aging in patients aged 20 years and over with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolated frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were high in the patients with complicated UTIs without indwelling catheter. In the patients aged 70 years and over with complicated UTIs with indwelling catheter, P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa increased after administration in the patients with all types of infections. As for type of causative organisms in UTIs and surgical procedures, E. coli was frequently isolated in the patients without surgery in all types of infections, while P. aeruginosa was frequently isolated in the patients who underwent surgery. In uncomplicated UTIs, Proteus spp. and E. faecalis were frequently isolated in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients without surgery and E. faecalis was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, most of organisms except P. aeruginosa and S. aureus were frequently isolated in the patients without surgery.

These studies were designed to determine the combined inhibitory effect of a human monoclonal antibody (MAb) and cefsulodin on Pseudomonas aeruginosa renal infection in a neutropenic condition.Protection against the infection of mice was estimated by survival rate and bacterial numbers in the kidney and blood. Opsonophagocytic assay by human polymorphonuclear neutrophils (PMNs) and fluorescence activated cell sorter (FACS) analysis were also examined.Treatment of infected mice with MAb combined with a suboptimal dose of cefsulodin prevented the mice from developing pyelonephritis and bacteremia and resulted in a significantly higher survival rate than treatment with either MAb or cefsulodin alone (p0.01). When bacteria were preexposed to cefsulodin, a significant enhancement in opsonophagocytic killing with MAb was observed. Fluorescence activated cell sorter analysis suggested that the bacteria incubated with 1/4 minimal inhibitory concentration (MIC) of cefsulodin showed greater binding of MAb to bacteria than the control.The combination therapy with human antilipopolysaccharide MAb and cefsulodin is useful for P. aeruginosa pyelonephritis in neutropenic hosts.

Background We evaluated the usefulness of in vitro tumor culture system using a specialized collagen gel matrix (CGM assay) as a chemosensitivity test. Patients and methods Chemosensitivity results of CGM assay were compared with other in vivo and in vitro assays on an implantable murine bladder tumor cell line (MBT-2). In addition we investigated the possibility of the clinical use of CGM assay using clinical specimens obtained from urogenital malignant tumor patients by comparing the result with that of the other chemosensitivity test, SDI testing using single cells (conventional SDI test). Methods of CGM assay were as follows. Tumor tissues on the collagen gel matrices were incubated under the existence of anticancer drugs following 4 days preculture. Drug sensitivities were evaluated by counting the number of viable cells adjusted to the tumor weight. Results Inhibition rates in MBT-2 were high in the order of mitomycin C, cisdiamminedichloroplatinum (II), (2"R)-4'-0-tetrahydropyranyl adriamycin. Four of 6 anticancer drugs were decided as chemosensitive drugs. These results corresponded to the results of the antitumor effects on subcutaneously transplanted MBT-2 in vivo, moreover was correlated well with those of the conventional SDI test. Twenty of 22 cases, including 11 of 13 bladder cancer cases, 1 of 3 renal cancer cases, 2 of 3 testicular cancer cases and 1 of 1 adrenal cortical cancer cases, were evaluable in the clinical study of the CGM assay. Corresponding rates between the results of the CGM assay and those of the conventional SDI test performed simultaneously in 12 cases were excellent for each anticancer drug. Conclusion This CGM assay can serve as an effective tool for chemosensitivity testing because of its convenience and high evaluable rate.

Background Interleukin 6 (IL-6), one of the proinflammatory cytokines, contributes to the onset and maintenance of various types of cancer. IL-6 signaling induces up-regulation of SOCS3, which leads to interferon (IFN) –α resistance in renal cell carcinoma (RCC) cells. To propose a new treatment for mRCC, we investigated the effect of combination therapy with IFN-α and humanized antihuman IL-6R antibody, tocilizumab. Material and methods Real time PCR (RT-PCR) was used to analyze gene expression of IL-6 and SOCS3 after IFN stimulation and ELISA were used for IL-6 secretion in RCC cell lines. These expression levels were compared among the RCC cell lines, i.e., ACHN, Caki-1, TUHR3TKB, TUHR4TKB and 786-O. Phosphorylation of STAT-1, STAT-3 and ERK were investigated by Western blotting (WB) analysis. We investigated alteration of IL-6 signaling by tocilizumab, and analyzed its impacts on the susceptibility to IFN-α in RCC cells by MTT assay. The effects of tocilizumab on in vivo growth on 786-O xenografts were determined by SOCS3 expression, morphological observation and tumor volume. Results Among the RCC cell lines, the expression levels of IL-6, SOCS3 in RT-PCR and the production level of IL-6 were highest in 786-O. These results revealed a correlation between the expression levels IL-6 and SOCS3 (P = 0.0001, r = 0.99974). Although the 786-O cells had IFN-α resistance, MTT assay showed that the tocilizumab induced a growth inhibitory effect of IFN-α. WB analysis showed that phosphorylation level of STAT-1 was increased and the levels of STAT-3 and ERK were decreased with the simultaneous use of tocilizumab in 786-O cells. An in vivo study demonstrated that tocilizumab promoted IFN-α-induced cell death and growth suppression in 786-O cell xenograft in nude mice. Conclusions IL-6 could be a key component in the resistance to IFN-α treatment of renal cell carcinoma. Antihuman IL-6R antibody can be an effective strategy to enhance the anti-tumor effect of IFN-α, and probably, the effect of angiogenic inhibitors, in human RCC cells. Disclosure All authors have declared no conflicts of interest.

2) investigated the time of appearance of auto-antibodies with respect to CMV antigenemia in liver transplant recipients. In this study, AECAs were detected in coincidence with or immediately after the CMV antigenemia peak in most cases and were observed for at least 15 days. It is speculated that the CMVinduced endothelial damage and the presence of circulating cytomegalic endothelial cells may be a potent antigenic stimulus that leads to the production of AECAs. CMV antigenemia is considered as a possible indirect marker of endothelial cell infection and can reflect the state of the endothelial barrier. We reported the differences in the clinical outcomes between the recipients with mismatched and matched combinations of CMV glycoprotein H (gH) antibodies 3) . In our study, most acute rejection was diagnosed within one month after transplantation (mean 25±32 days of rejection after transplantation), and initial positive antigenemia was detected thereafter. On the other hand, the mean weeks of the initial antigenemia detection was 7 weeks after transplantation and its range was varied from 1 to 20 weeks after transplantation. Although this might indicate that most acute rejection was diagnosed prior to AECAs production, association between auto-antibodies and acute rejection could not be ruled out. In addition to measurement of the AECAs titers and their comparison between gH match and mismatch recipients, longer follow up data would be interesting to evaluate the AECAs as a predictor of acute renal allograft vascular rejection.

Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues. We therefore investigated whether intratumoral injection of IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma cells and has additional antitumor effects when combined with anti-PD-L1 mAb treatment. IFN-β treatment enhanced CD8+ T-cell infiltration into tumors and CCL5 and CXCR3 ligand expression. In vivo studies using a mouse model showed that monotherapy with IFN-β, but not with anti-PD-L1 mAb, inhibited tumor growth in comparison to control. However, the therapeutic efficacy of IFN-β was significantly enhanced by the addition of anti-PD-L1 mAb. This antitumor response of combination therapy was abrogated by anti-CD8 mAb and IFN-β augmented the neoantigen-specific T-cell response of anti-PD-L1 mAb. Our findings suggest that IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma, which could play a role in T-cell recruitment, and enhances the efficacy of anti-PD-L1 mAb treatment in a CD8-dependent manner.

Background Radiation therapy (RT) is considered a risk factor for the development of sarcoma in patients with breast cancer. However, there are few reports regarding post-irradiation sarcoma (PIS). Case presentation The patient was a 59-year-old woman who presented with a chief complaint of induration in the lower outer quadrant of the left breast. She underwent breast-conserving surgery (BCS) for breast cancer located in the left upper inner region and received endocrine therapy following RT (50 Gy/25 fractions/5 weeks) for breast conservation 6 years previously. Core needle biopsy revealed leiomyosarcoma. There was no distant metastasis. Repeat BCS including part of the pectoralis major muscle was performed. Chest wall resection was not performed because of the lack of invasion. Based on the morphological and immunohistochemical features, a diagnosis of leiomyosarcoma was made. All of the resection margins in the specimen were tumor-free. She has been disease-free for over 20 months. Conclusions Post-irradiation leiomyosarcoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.

Background Excessive mechanical overload may be involved in bladder wall remodelling. Since the activity of Rho kinase is known to be upregulated in the obstructed bladder, we investigate the roles of the RhoA/Rho kinase pathway in mechanical overloaded bladder smooth muscle cells. Methods Human bladder smooth muscle cells were stimulated on silicon culture plates by 15 % elongated uni-axial cyclic stretch at 1 Hz. The activity of c-Jun NH2-terminal kinase was measured by western blotting and actin stress fibers were observed by stained with phallotoxin conjugated with Alexa-Fluor 594. Results The activity of c-Jun NH2-terminal kinase 1 peaked at 30 min (4.7-fold increase vs. before stretch) and this activity was partially abrogated by the RhoA inhibitor, C3 exoenzoyme or by the Rho kinase inhibitor, Y-27632. Stretch induced the strong formation of actin stress fibers and these fibers re-orientated in a direction that was perpendicular to the stretch direction. The average angle of the fibers from the perpendicular to the direction of stretch was significantly different between before, and 4 h after, stretch. Actin stress fibers reorganization was also suppressed by the C3 exoenzyme or Y-27632. Conclusions Bladder smooth muscle cells appear to have elaborate mechanisms for sensing mechanical stress and for adapting to mechanical stress overload by cytoskeletal remodeling and by activating cell growth signals such as c-Jun NH2-terminal kinase via RhoA/Rho kinase pathways.

This is an open access article distributed under the terms of the Creative Commons Attribution License, BACKGROUND: Non-islet cell tumor hypoglycemia (NICTH) is defined as a form of hypoglycemia caused by an extrapancreatic tumor. Solitary fibrous tumor (SFT) associated with hypoglycemia is rare. CASE PRESENTATION: A 76-year-old woman, who had frequently experienced hypoglycemic symptoms such as presyncope for the prior 6 months, visited our hospital to undergo detailed examinations. Her fasting glucose level was low at 49 mg/dl. The blood levels of IRI and C-peptide were also low at 0.2 μU/ml and 0.21 ng/ml, respectively. Chest computed tomography revealed a mass measuring 15 cm in the left thoracic cavity. Percutaneous needle biopsy yielded a diagnosis of intrathoracic SFT associated with NICTH. The tumor was removed by video-assisted thoracoscopic surgery. Histological examination showed a tumor composed of simple spindle-shaped cells with an irregular arrangement. Immunohistochemical staining was positive for CD34, bcl-2, and vimentin and negative for alpha SMA and mesothelin. These results confirmed the diagnosis of SFT. Her hypoglycemic symptoms resolved rapidly after surgery. The clinical course has since remained favorable with no signs of recurrence. CONCLUSION: We report a case of non-islet cell tumor hypoglycemia caused by intrathoracic SFT. The high-molecular-weight IGF-II produced by the tumor has been regarded as the cause of NICTH.

© 2011 Kitada et al; licensee BioMed Central Ltd., Mucoepidermoid carcinoma of the lung (MEC) is a tumor of low malignant potential of bronchial gland origin. MEC and adenoid cystic carcinoma are both considered to be salivary gland-type neoplasms. MECs are comparatively rare with an incidence of all lung cancers. We recently encountered a case of this type of lung cancer. A 60-year-old man was found to have an abnormal shadow in the left lower lung field on a regular check-up for lung cancer at his company. Chest radiography and CT revealed a mass shadow measuring 30 mm in diameter in the left lower lung field. Bronchoscopy revealed a protuberant tumor in the S9 bronchus, leading to a diagnosis of low-grade MEC by transbronchial lung biopsy. He underwent left lower lobe resection and mediastinal lymph node dissection using VATS. Tumor cells had a scattering of mucus-producing epithelial components in papillary growth of stratified squamous epithelia with anisokaryosis and minimal pleomorphism, indicating a diagnosis of MEC. Because the postoperative course was good and the tumor was low-grade, no adjuvant treatment was administered. The patient has had no signs of tumor recurrence for 9 months, to date, since resection of the tumor.

Publisher, Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with giant cell carcinoma is extremely rare. A 65-year-old man was found to have an abnormal shadow in his left lung field. Computed tomography revealed a solid, round mass measuring 2.8 × 2.2 cm that was located in the left S9. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Histopathological examination revealed an LCNEC, combined with giant cell carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine) chemotherapy, and he has been disease-free for over 8 months. Combined LCNEC with giant cell carcinoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.