The isolation rate of atypical mycobacteria (mycobacteria other than tubercle bacilli) and their kinds of species were studied in twelve participating hospitals located in various places of Japan ...during 5 years (1971 to 1975). The subject of the study was patients hospitalized in these hospitals during screening-months, June, September, December and March, of every year. The isolation rate (ratio of the number of atypical mycobacterial strains per the number of all mycobacterial strains) was significantly higher in four hospitals (Tokyo, Tenryuso, Chubu and Kinki) locating in Tokyo, Shizuoka, Aichi and Osaka Prefectures, respectively (refer to Fig.1), than the average (6.2%), and the rates in these hospitals were about 8%. Three hospitals, Kanagawa, Tochigi and Nagasaki, showed the rates of about 5%, three hospitals, Miyagi, Niigata and Fukuoka, showed the rates of 2 to 3%, and two hospitals, Sapporo and Ehime only 0.7 to 0.8% (Table 1). Distribution of the kind of species in various hospitals did not differ significantly from each other, except for a few cases. (1) The ratio of M. kansasii in Tokyo and Kanagawa Hospitals was significantly higher than the others. (2) The ratio of M. fortuitum in Fukuoka Hospital was significantly higher than the average. (3) The ratio of M. gordonae was significantly higher in Kanagawa Hospital than the average in all hospitals. The ratios of species of 950 strains of atypical mycobacteria are shown in Table 2.
Sake (Japanese rice wine) has been recognized as being low risk in terms of its microbiological safety. However, a confirmation of the food safety aspects of sake based on scientific evidence is ...important for establishing consumer confidence, in part because consumer concerns regarding food safety have increased. The presence of Bacillus cereus spores in refined rice wine has been reported, and in light of consumers' growing concern over food safety, the establishment of food and beverage safety is important for consumers' reassurance. Herein, to confirm the microbiological safety of sake, we investigated the content and growth of B. cereus. We conducted a spore addition test to determine whether B. cereus spores grow during sake production, and we observed no growth or germination of B. cereus spores during the manufacturing process. We also observed that processes such as solid-liquid separation and filtration help remove the risk posed by B. cereus. We then conducted a survey to assess the density of B. cereus in various commercial sake products. We analyzed 162 samples of commercial sake and observed that 11 of the products had ≥1 CFU of living cells in 1 mL of sake (detection rate, 6.8%). There was no product in which ≥100 CFU of living cells per 1 mL of sake was detected. Our findings confirmed that the density of these bacteria in sake is lower than that in other foods and that the probability of infection is very low. The emetic toxin produced by B. cereus was not detected in any of the sake samples. This is the first study based on experimental data demonstrating that B. cereus is not able to grow in sake or during the sake manufacturing process. We, thus, conclude that the safety risk of B. cereus in sake is negligible. Our findings indicating that B. cereus is not a significant hazard in the sake brewing process will contribute to food hygiene management based on scientific evidence in sake breweries.
In mammals, most immature oocytes remain dormant in the primordial follicles to ensure the longevity of female reproductive life. A precise understanding of mechanisms underlying the dormancy is ...important for reproductive biology and medicine. In this study, by comparing mouse oogenesis in vivo and in vitro, the latter of which bypasses the primordial follicle stage, we defined the gene-expression profile representing the dormant state of oocytes. Overexpression of constitutively active FOXO3 partially reproduced the dormant state in vitro. Based on further gene-expression analysis, we found that a hypoxic condition efficiently induced the dormant state in vitro. The effect of hypoxia was severely diminished by disruption of the Foxo3 gene and inhibition of hypoxia-inducible factors. Our findings provide insights into the importance of environmental conditions and their effectors for establishing the dormant state.
Background
Prediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention.
Methods and Results
We developed the prediction rules ...for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO‐Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus‐Eluting Versus Everolimus‐Eluting Stent Trial) and NEXT (Nobori Biolimus‐Eluting Versus Xience/Promus Everolimus‐Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3‐year incidence of thrombotic events than a score that was intermediate (2–3, n=1178) or low (0–1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P<0.0001). A high bleeding risk score (≥3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1–2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P<0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%).
Conclusions
CREDO‐Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.
Aquaporin-2 (AQP2) is a water channel protein that is trafficked between intracellular vesicles and the plasma membrane of kidney collecting duct cells upon vasopressin stimulation. Vasopressin ...changes the phosphorylation states of the AQP2 C-terminal serines (Sers), Ser256, Ser261, Ser264, and Ser269, in rats and mice, which is thought to play a role in controlling trafficking. Here, we focused on Ser269. We developed a specific antibody to Ser269-phosphorylated AQP2. Using immunofluorescence microscopy, we examined its localization in the rat kidney following injection of vasopressin and a vasopressin type 2 receptor-specific antagonist (OPC-31260). Ser269-phosphorylated AQP2 was almost undetectable in the water-loaded rat kidney, but was detected intracellularly soon after vasopressin injection, and then highly accumulated on the apical membrane of connecting tubule and collecting duct principal cells. In addition to the apical membrane, Ser269- phosphorylated AQP2 was also detected on the basolateral membrane of connecting tubule cells and inner medullary collecting duct principal cells. OPC-31260 injection following vasopressin stimulation caused internalization of AQP2, a pool of which was phosphorylated at Ser269. These results suggest that 1) AQP2 is phosphorylated at Ser269 intracellularly upon vasopressin stimulation and is rapidly trafficked to the plasma membrane, and 2) AQP2 can be internalized from the plasma membrane even if it remains phosphorylated at Ser269.
Most people generally ingest cadmium in their food. Cadmium that has accumulated in tissues induces the synthesis of metallothioneins (MTs) which are metal-binding proteins that bind tightly to ...cadmium to inhibit its renal toxicity. Individuals whose ability to induce the synthesis of MTs is low seem likely to be particularly susceptible to the toxic effects of cadmium. In this study, we analyzed the polymorphism of the promoter region of the gene for MT-IIA, the major species of MT in humans, in 119 adult Japanese subjects. We found that about 18% of the subjects had an A --> G single-nucleotide polymorphism in the core region of the promoter near the TATA box. A reporter-gene assay using HEK293 cells showed that replacement of A by G at position -5 reduced the efficiency of the cadmium-induced transcription of the gene for MT-IIA. This single-nucleotide polymorphism inhibited the binding of nuclear proteins to the core promoter region of the gene for MT-IIA. When the promoter region upstream of the TATA box was replaced by a sequence that contained three dioxin-responsive elements, the reporter-gene assay demonstrated that the A --> G single-nucleotide polymorphism resulted in a marked reduction in the rate of dioxin-induced transcription. These results suggest that the A --> G single-nucleotide polymorphism reduces the efficiency of those aspects of the transcription of the gene for MT-IIA that are controlled by general transcription factors.
Background Ischemic liver injury is often the result of surgical procedures such as liver transplantation and hepatic resection. Liver damage occurs after reperfusion, leading to increased systemic ...inflammation. Recent studies have reported that vitamin E and glutathione can ameliorate ischemia-reperfusion (I/R) injury. In the present study, we evaluated the ability of a new vitamin E derivative, ETS-GS, to improve liver I/R injury. Materials and Methods Male Wistar received a subcutaneous injection of ETS-GS (10 mg/kg) or saline before experimentally-induced liver I/R injury or sham treatment. The rats were sacrificed after the 60-min ischemia and 24-h reperfusion. Histology and serum levels of cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein and liver enzymes were determined to evaluate the protective effects of ETS-GS. Results We found that ETS-GS treatment attenuated I/R-induced histologic alterations, reduced levels of liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). In addition, ETS-GS treatment decreased serum cytokine levels. Conclusions Taken together, our results demonstrate that ETS-GS attenuates I/R injury in a rat model and suggests that ETS-GS may exert anti-inflammatory effects. Accordingly, ETS-GS may have therapeutic potential to treat various clinical conditions involving I/R injury.
Background Prior stroke is regarded as risk factor for bleeding after percutaneous coronary intervention (PCI). However, there is a paucity of data on detailed bleeding risk of patients with prior ...hemorrhagic and ischemic strokes after PCI. Methods and Results In a pooled cohort of 19 475 patients from 3 Japanese PCI studies, we assessed the influence of prior hemorrhagic (n=285) or ischemic stroke (n=1773) relative to no-prior stroke (n=17 417) on ischemic and bleeding outcomes after PCI. Cumulative 3-year incidences of the co-primary bleeding end points of intracranial hemorrhage, non-intracranial global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) moderate/severe bleeding, and the primary ischemic end point of ischemic stroke/myocardial infarction were higher in the prior hemorrhagic and ischemic stroke groups than in the no-prior stroke group (6.8%, 2.5%, and 1.3%,
<0.0001, 8.8%, 8.0%, and 6.0%,
=0.001, and 12.7%, 13.4%, and 7.5%,
<0.0001). After adjusting confounders, the excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for intracranial hemorrhage (hazard ratio (HR) 4.44, 95% CI 2.64-7.01,
<0.0001, and HR 1.52, 95% CI 1.06-2.12,
=0.02), but not for non-intracranial bleeding (HR 1.18, 95% CI 0.76-1.73,
=0.44, and HR 0.94, 95% CI 0.78-1.13,
=0.53). The excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for ischemic events mainly driven by the higher risk for ischemic stroke (HR 1.46, 95% CI 1.02-2.01,
=0.04, and HR 1.49, 95% CI 1.29-1.72,
<0.0001). Conclusions Patients with prior hemorrhagic or ischemic stroke as compared with those with no-prior stroke had higher risk for intracranial hemorrhage and ischemic events, but not for non-intracranial bleeding after PCI.
The use of a new end-fire type laparoscopic US probe with a forward-viewing convex-array transducer allows the caudate lobe of the liver to be accessed. This study evaluated the preliminary results ...of treatment of hepatocellular carcinoma in the caudate lobe by using this new instrument.
Three patients with hepatocellular carcinoma in the caudate lobe were selected. A laparoscopic US probe, with a forward-viewing convex-array transducer at the tip and a guide groove for puncture on the back, was used to monitor the position of the radiofrequency ablation needle during the treatment.
Ablation was performed without complication in all cases. Complete necrosis of the tumor was confirmed by postoperative CT. At a mean follow-up of 30.3 months, no local recurrence was observed in any patient.
Radiofrequency ablation of hepatocellular carcinoma in the caudate lobe of the liver by using a new laparoscopic US probe with a forward-viewing convex-array transducer at the tip was safe and effective.
Metallothionein gene is transcriptionally regulated by heavy metals through cis-acting metal responsive elements (MREs). Two proteins, metal-regulatory transcription factor-1 (MTF-1) and zinc ...regulatory factor (ZRF), have been isolated and cloned from human cells as MRE-binding transcriptional factor (MREBT). These proteins are almost identical to each other, except for only one base substitution at codon 185 that causes an amino acid change from histidine to tyrosine. This single amino acid difference has been reported to influence zinc-responsive transcriptional activities. In this study, we determined the nucleotide sequence of the region containing codon 185 in DNA samples obtained from normal Japanese (n = 30) and three human-derived cultured cell lines. The findings indicate that all subjects have the same sequence identical to ZRF, suggesting that ZRF is the original MREBT gene in normal humans, and MTF-1 is its minor variant.
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