[show abstract][hide abstract] ABSTRACT: The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: -15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.
European Journal of Clinical Microbiology 10/2012; · 3.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Oral administration of probiotics has been known to improve inflammatory responses against infectious diseases. Here, we describe the inhibitory effect of oral intake of heat-killed Lactobacillus pentosus strain b240 (b240) on pneumococcal pneumonia in a murine experimental model.
The mice treated with oral b240 for 21 days before Streptococcus pneumoniae infection exhibited prolonged survival time and less body weight loss, compared with saline-treated control mice. Mild pneumonia with significantly reduced secretion of inflammatory cytokines/chemokines according to related mitogen-activated protein kinase signalling molecules (phosphorylated c-Jun N-terminal kinase) was found in b240-treated mice, whereas severe pneumonia with hypercytokinemia was evident in control mice. Prominent reduction in the number of pneumococci and elevated expression of Toll-like receptor 2 and 4 in the lung tissues was concomitantly noted in b240-treated mice.
These findings indicate that b240 has inhibitory effects on pneumococcal pneumonia induced by Strep. pneumoniae infection and improves inflammatory tissue responses, resulting in reduced damages to the respiratory tissues.
These results demonstrate that oral administration of b240 might protect host animals from Strep. pneumoniae infection by augmentation of innate immune response.
Letters in Applied Microbiology 07/2011; 53(1):35-43. · 1.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report the case of a 31-year-old male with enlarged kidneys and glomerulocystic kidney disease (GCKD). The patient had no family history of renal disease or other diseases. On initial presentation he complained of poor eyesight, and hypertensive retinopathy and elevated serum creatinine (5.0 mg/dl) were found at that time. Renal biopsy showed cystic dilatation of Bowman's capsule and atrophy of the glomerular tuft. Thus, an adult case of sporadic GCKD was diagnosed. Based on previous reports, kidney size in patients with adult type GCKD varies from small to large. Our patient's kidneys are the largest ever reported (right kidney was 22 cm×10 cm, left kidney was 19 cm×10 cm). A review of the literature dealing with sporadic adult GCKD suggested that it is difficult to diagnose this disease early in its course.
[show abstract][hide abstract] ABSTRACT: The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there is little understanding of how inhaled fungi affect the host response to mite allergens.
To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma.
Murine bone marrow-derived DCs were pulsed with Derf and/or live or heat-inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naïve mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated.
Live Af significantly enhanced IL-10 production and the expression of Toll-like receptor (TLR) 2 and Dectin-1 in Derf-pulsed DCs. Live Af infection significantly attenuated Derf-pulsed DC-induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin-1 significantly reversed the inhibitory effects of live Af in the development of Derf-pulsed DC-induced allergic airway inflammation.
Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen-induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen-induced allergic airway inflammation via regulation of their PRRs. Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen-induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.
[show abstract][hide abstract] ABSTRACT: Endoscopic submucosal dissection (ESD) permits removal of colorectal epithelial neoplasms en bloc, but a substantial risk of procedure-related perforation has been reported. We sought to unravel the clinicopathological factors associated with the clinical outcomes of ESD for colorectal epithelial neoplasms in a large series.
ESD was done in 278 patients with 292 colorectal tumors that fulfilled the inclusion criteria. The criteria for ESD were: lesion greater than 20 mm in size, lesion with fibrotic scarring, locally residual colorectal lesion, or invasive carcinoma with slight submucosal penetration. Resection was assessed as en bloc or piecemeal, complete (en bloc with tumor-free lateral and basal margins) or incomplete. Complications including perforation and bleeding were assessed, and factors related to each were analyzed using logistic regression. Patients underwent multiple follow-up endoscopic examinations (mean 4.6; median 4; range 2 - 9; total number 1010).
En bloc resection was achieved in 90.1 % of lesions (263/292) and resection was deemed to be complete in 233 (79.8 %). Right-side colonic location and the finding of fibrosis were the significant contributors to incomplete resection. Perforation was seen in 24 cases (8.2 %), and was associated with large tumor size and the presence of fibrosis. When the contributive factors for each were combined, the risks of incomplete resection and perforation were substantially increased.
The present study provides useful information for predicting risks for incomplete resection and complication in colorectal ESD.
[show abstract][hide abstract] ABSTRACT: To determine the association of distinct clinical subsets with myositis-specific autoantibodies (MSAs) towards anti-155/140-kDa polypeptides [anti-155/140 antibodies (Abs)], anti-140-kDa polypeptides (anti-140 Abs), and anti-aminoacyl tRNA synthetases (ARS Abs) in Japanese patients with dermatomyositis (DM).
We compared the clinical features and short-term prognoses of 30 DM patients whose serological status included these MSAs. The MSAs were determined by immunoprecipitation.
Anti-155/140 Abs (n = 5), anti-140 Abs (n = 8), and anti-ARS Abs (n = 7) did not overlap each other. All of the anti-155/140 Ab-positive patients (n = 5) were complicated by malignancies, as were all of the anti-140 Ab-positive patients (n = 8), who showed rapidly progressive interstitial lung disease (ILD). The survival rate at 6 months from the diagnosis of DM was significantly lower in the anti-140 Ab-positive patients than in the other patients.
This is the first study to report, in a single cohort of DM patients, that distinct clinical subsets are distributed in an anti-155/140 Ab-positive group, an anti-140 Ab-positive group, or an anti-ARS Ab-positive group. Our data also confirm previous evidence that anti-155/140 Abs are involved in malignancies and that anti-140 Abs are involved in rapidly progressive ILD.
Scandinavian journal of rheumatology 06/2009; 38(4):263-7. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Impaired production/release of defensins, representative endogenous antimicrobial peptides, is associated with the pathogenesis of inflammatory bowel disease (IBD).
Employing in house radioimmunoassay, we examined concentrations of the major forms alpha-defensins, human neutrophil peptides (HNP) 1-3 and human beta-defensin (HBD)-2 in plasma of 55 IBD patients consisting of 29 patients with ulcerative colitis (UC) and 26 with Crohn's disease (CD) and 57 controls.
The circulating HNP 1-3, but not HBD-2, levels in IBD patients were significantly higher than those in controls. Plasma HNP 1-3 concentrations in CD patients significantly correlated with Crohn's disease activity index, peripheral white blood cell counts, serum CRP values and TNF-alpha levels.
Elevation of circulating alpha-defensins levels is suggestive of their physiopathological roles in IBD. Plasma HNP 1-3 concentrations may be an indicator for CD activity and their association with CRP and TNF-alpha supports a possible association with the inflammatory process.
Agents and Actions 03/2009; 58(4):192-7. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: The prevalence of chronic obstructive pulmonary disease (COPD) continues to increase all over the world. Nonetheless, COPD is often misdiagnosed in general clinics because of insufficient use of spirometry.
To estimate the prevalence of COPD in general clinics in Japan, we performed spirometry to screen patients who consulted general clinics.
Patients 40 years of age and older who consulted clinics in Nagasaki Prefecture, Japan, for non-respiratory diseases and who met certain inclusion criteria had their airflow limitation measured by spirometry. We defined COPD as forced expiratory volume in the first second (FEV(1)) over forced vital capacity (FVC) (FEV(1)/FVC) of < 70% in patients without active pulmonary disease, including physician-diagnosed asthma.
Of the 1424 patients included in the study, 193 (13.6%) showed airflow limitation. Airflow limitation was significantly related to older age, male gender and cumulative pack-years. FEV(1)/FVC in patients with hypertension and chronic hepatitis were significantly lower than in patients without these diseases when adjusted for age, gender and pack-years.
We showed that there are potentially a number of cases with COPD that are undiagnosed by general physicians in Japan. Measuring airflow limitation by spirometry in smokers with coexisting diseases, such as hypertension and chronic hepatitis, may be very beneficial because COPD is thought to be a systemic disease. The distribution of spirometers to general clinics is definitely needed to detect undiagnosed COPD.
International Journal of Clinical Practice 02/2009; 63(2):269-74. · 2.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endoscopic submucosal dissection (ESD) has the advantage over conventional endoscopic mucosa resection, permitting removal of early gastric cancer (EGC) en bloc, but long-term clinical outcomes remain unknown. A follow-up study on tumour recurrence and survival after ESD was conducted. Method: ESD was performed for patients with EGC that fulfilled the expanded criteria: mucosal cancer without ulcer findings irrespective of tumour size; mucosal cancer with ulcer findings <or=3 cm in diameter; and minute submucosal invasive cancer <or=3 cm in size. 551 patients with 589 EGC lesions were enrolled. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6-89 months (median, 30 months). The main outcome measures were resectability (en bloc or piecemeal resection), and curability (curative or non-curative). Complications were assessed, and factors related to each were analysed statistically. The overall and disease-free survival rates were estimated.
En bloc resection was achieved in 94.9% (559/589), and larger lesions were at higher risk of piecemeal resection. 550 of 581 lesions (94.7%) were deemed to have undergone curative resection. En bloc resection was the only significant contributor to curative ESD. Patients with non-curative resection developed local recurrence more frequently. The 5-year overall and disease-specific survival rates were 97.1% and 100%, respectively.
Precise assessment of curability with successful one-piece resection may reduce tumour recurrence after ESD. The prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted.
[show abstract][hide abstract] ABSTRACT: It is well known that the size of the condyle is different between males and females in humans. It has also been documented that ovariectomy (OVX) and orchiectomy (ORX) influence the remodeling of the condylar head in experimental animals. However, influences of sex hormones on the condyle in terms of its breadth have not been examined. With these considerations, this study was designed to examine the breadth of the mandibular condyle in OVX and ORX mice by histomorphometry 8 weeks after surgery. In the OVX mice, the condylar breadth was significantly larger than in the controls, while no significant differences in the breadth were found between the ORX mice and the controls. The thickness of the condylar cartilage layers exhibited similar findings to the breadth of the condyle. On the contrary, the trabecular bone volume was significantly smaller in the OVX and ORX mice than in the corresponding controls, and the difference was more substantial in female mice than in the males. These findings emphasize that a reduction of sex hormone levels, induced by OVX and ORX, significantly influences condylar morphogenesis.
Clinical Orthodontics and Research 10/2008; 4(3):172 - 176.
[show abstract][hide abstract] ABSTRACT: The load dependence of Tei-index, an index to estimate combined systolic and diastolic ventricular functions, remains controversial. Moreover, its significance in the setting of acute preload reduction including hemodialysis (HD) remains unknown. Therefore, we examined the significance of the Tei-index in HD patients.
Doppler echocardiographic parameters of 42 patients with normal left ventricular ejection fraction (LVEF) were evaluated before and after HD. Based on the index of body water excess calculated using a Crit-Line monitor, the patients were assigned to Group A (normal hydration approximately overhydration) and Group B (risk of pulmonary congestion).
Group A was younger and had a shorter isovolumic relaxation time (IRT) than Group B before HD. Hemodialysis significantly increased the Tei-index of Group A, which was derived from prolonging IRT and isovolumic contraction time and shortening the ejection time without changing LVEF. Changes in the Tei-index (DeltaTei-index) significantly correlated with the rate at which blood volume decreased. They were derived from graphs generated using the Crit-Line monitor. Furthermore, the DeltaTei-index inversely correlated with the Tei-index before HD.
These findings suggest that the Tei-index is preload-dependent, which is related to changes in volume and speed. Thus, the Tei-index should be cautiously interpreted according to various hemodynamic situations. However, the correlation between the DeltaTei-index and the Tei-index before HD implies that the latter could be a good indicator of effective fluid removal by HD.
[show abstract][hide abstract] ABSTRACT: Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. The spots were analysed by mass spectrometry, and identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a greater degree of lung damage and cell death. A1AT expression was increased significantly, and proteolytic enzymes from neutrophils, such as neutrophil elastase, myeloperoxidase and lysozyme, were also secreted abundantly in influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae or influenza virus singly infected lungs. These data suggest that A1AT may play a central role as a molecule with broad anti-inflammatory properties, and regulation of the neutrophil-mediated severe lung inflammation is important in the pathogenesis of co-infection with influenza virus and bacteria.
[show abstract][hide abstract] ABSTRACT: Gabexate mesilate is a synthetic protease inhibitor that is effective for acute pancreatitis. The effect of gabexate mesilate in influenza pneumonia in mice was investigated by examining the changes in pulmonary inflammatory cytokines and chemokines. Pathological changes in the lungs of treated mice were extremely mild, compared with changes in infected, untreated mice. Intrapulmonary levels of interleukin-6 and macrophage inflammatory protein-2 decreased in treated mice compared with untreated mice, despite similar viral titres in the lungs. Survival terms for treated and untreated groups were similar. These data indicate that gabexate mesilate has beneficial effects on influenza pneumonia, which may be due to the modulation of inflammatory cytokine/chemokine responses.
The Journal of international medical research 03/2008; 36(2):322-8. · 0.96 Impact Factor