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We present a novel application of cosmic-ray muon radiography to image the shallow density structure beneath Asama Volcano, Japan. We use a single detector (emulsion cloud chamber) set up in an underground vault at an elevation of 2250 m on the eastern flank of Asama, 310 m below the summit of the edifice and 1 km away from the crater. The results point to two high-density anomalies located between the original pre-2004 eruption crater floor and post-2004 eruption crater profile. A third low-density anomaly is imaged immediately below the pre-2004 eruption crater floor. The spatial extent of each density anomaly is about 100 to 200 m. To know if this method, applied to other volcanoes, would produce contrasting results, we performed the measurement in 1944 Usu lava dome. We confirmed a bulbous shape measuring approximately 300 m in diameter and narrowing downwards. The diameter of the uppermost part of the conduit is estimated at 100 ± 15 m at an elevation of 260 m a.s.l. and 50 ± 15 m at an elevation of 217 m a.s.l., demonstrating a resolution that is significantly better than that typically achieved with seismic tomography based on picks of first arrival times from earthquakes or artificial sources.

We have developed a novel radiographic imaging method to survey the inhomogeneous structure of the crust. As an example, we performed measurements at Mt. Asama volcano, and studied the feasibility of using an azimuthally isotropic flux of cosmicray muons in the energy range up to a few TeV. The principle of the technique is that by measuring muon absorption along different nearly horizontal paths through a solid body, one can deduce the density distribution in the interior of the object. A muon detector with an area of 4000 cm 2 was installed in a 1-m deep instrument vault located about 1 km from the summit crater of Mt. Asama. Muon tracks within emulsion layers in the detector were analyzed by 3d image processing to determine the level of energy absorption along different ray paths through the summit crater region. A typical angular resolution of the muon detector of 10 milliradians (mrad) corresponds to a spatial resolution of 10 m at a distance of 1 km. The measurements would be ideal for studying the shallow structure of the crust at sites which cannot be well resolved because of their strong structural heterogeneity and potential difficulty to be accessed, and which therefore cannot have their structure determined by conventional electromagnetic or seismic techniques. The present method can also provide three dimensional images of the subsurface by making measurements from two or more different points. In this work, we have radiographically imaged a few hundred meters below the crater floor of Mt. Asama, Japan, and have detected a dense region, which corresponds to the position and shape of a lava mound created during the last eruption (Urabe, B., Watanabe, N., Murakami, M., Topographic change of the summit crater of Asama Volcano during the 2004 eruption derived from Airborne Synthetic Aperture Radar (SAR) measurements, Bulletin of Geographical Survey Institute, 53, 1–6 (2006).). Right below the lava mound we found a low density region that suggests a drain-back-induced porous conduit (Urabe, B., Watanabe, N., Murakami, M., Topographic change of the summit crater of Asama Volcano during the 2004 eruption derived from Airborne Synthetic Aperture Radar (SAR) measurements, Bulletin of Geographical Survey Institute, 53, 1–6 (2006).). The density contrast was resolved with a precision of 1–3%. This method

The aims of this study were (1) to measure levels of cytokines and stress hormones in ulcerative colitis (UC) patients and determine whether there were any disturbances in the nervous, endocrine, or immune systems, and (2) to measure the ability of UC patients to cope with stress (using a sense of coherence, SOC, test) and their perceived self-efficacy, and to elucidate their response to a stress load.We administered questionnaires to and took blood samples from 42 outpatients and eight inpatients whose UC was in remission, and 21 healthy volunteers. In addition, we evaluated blood samples from the inpatients and healthy volunteers following a mental calculation stress test.The questionnaire results revealed that self-efficacy was significantly decreased in the patient groups. Levels of adrenocorticotropic hormone, beta-endorphin and interleukin (IL)-6 were significantly higher in the outpatient than in the control group. IL-6 levels significantly increased following the mental calculation stress test in UC patients compared with in the volunteers.These results indicate that UC patients (1) have hypersensitive nervous, endocrine, and immune systems, and (2) this hypersensitivity was augmented by the mental calculation stress test.

Temporal changes of seismic properties, such as velocity, attenuation, anisotropy, and scattering properties, have been inferred by active methods for decades and more recently by passive methods. In particular, passive methods are capable of monitoring seismic properties because they do not require earthquakes but rely on continuously excited signals in the ocean, for example. A collection of continuous monitoring of seismic velocities has revealed that the susceptibility of velocity changes to stress perturbations are highly variable. These variations can be translated to variability of third-order elastic moduli, elastic moduli arising by considering finite deformation. The third-order elastic moduli are shown by theoretical studies to be a good indicator of granular properties of rocks and, in general, as to how fluids interact with solid rocks. Advancement of theoretical and observational studies will gain more insights into the nature of third-order elastic moduli, which will eventually become yet another parameters to characterize the properties of rocks.

Addition of azurocidin, a protein in granulocytes similar to serine proteases but has no protease activity because of replacement of the active serine residue by glycine, to the incubation mixture containing medullasin induced elastinolytic activity of medullasin. Both medullasin and human leukocyte elastase were already shown to have negligible elastinolytic activity (Aoki, Y. et al. J. Biochem. 114, 122, 1993). Elastinolytic activity of medullasin was induced dose-dependently by the addition of azurocidin. Medullasin activity determined by using apo-ornithine transaminase or casein as substrates or that by N-methoxy-succinyl-(Ala)2-Pro-Val-p-nitroanilide as substrate remained unchanged when azurocidin was added to the tube containing medullasin. Therefore, azurocidin is considered to cause an appearance of elastinolytic activity of medullasin without affecting the protease activity of it.

We already showed that injection of Shiga toxin (Stx) 2 into mice caused severe granulocytosis in the peripheral blood. In this study we further clarified changes of granulocyte function by Stx 2. The activity of medullasin, a neutral serine protease in granulocytes that injures endothelial cells in vessels, significantly increased when Stx 2 was injected into mice intraperitoneally. Since granulocyte count in the peripheral blood of mice was markedly increased after intraperitoneal injection of Stx 2, medullasin activity in the peripheral blood was remarkably elevated. In contrast to Stx 2, injection of Stx 1 into mice caused no elevation of medullasin activity in granulocytes nor increase in granulocyte count in the peripheral blood. Cathepsin G levels in granulocytes increased only slightly after Stx 2 injection. Granulocytes obtained from mice injected with Stx 2 showed reduced superoxide-producing activity compared with those from controls. Addition of Stx 2 or Stx 1 to human mature granulocytes in vitro decreased their superoxide-producing activity when stimulated with agonists. Therefore, these toxins produced from Escherichia coli augment toxic effect of the bacteria by reducing bactericidal activity of granulocytes. Tissue injury in organisms infected with Shiga toxin-producing E. coli is mainly derived from elevated neutral proteases, such as medullasin, in granulocytes rather than direct toxic effect of superoxide from granulocytes. Hemolytic uremic syndrome caused by Shiga toxin-producing E. coli infection is due, at least in part, to the elevation of medullasin levels produced by granulocytes.

A 20-year-old male was admitted to our hospital with the chief complaints of high fever and pain around his right hip joint. He had his right knee injured with a slight abrasion three weeks before. The diagnosis of suppurative lymphadenitis of inguen was made, and intravenous cefotiam was started. Despite these treatments his fever continued, general edema and dry cough appeared. Arterial blood gas showed severe hypoxia and chest X ray revealed marked cardiomegaly associated with ground-glass opacity over bilateral lower pulmonary fields. Slight renal insufficiency was also observed. On the fifth hospital day, the culture specimens of both blood and pus from the abrasion on admission yielded Streptococcus pyogenes. His condition was diagnosed as severe group A Streptococcus infection, then antibiotics were switched to intravenous administration of high dose aminobenzyl penicillin and clindamycin in combination with protease inhibitor, urinastatin. After these treatments, his condition improved and he was discharged from the hospital after one month. Group A Streptococcus may cause uncommon but life-threatening infection such as septicemia. Early recognition of the disease and prompt initiation of appropriate treatment may lead to successful outcome.

To investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immunohistochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.

Chemically synthesized polyaniline (PANI) can be used as a functional binder in the manufacture of the LiFePO4 cathode of lithium batteries, and it provides LiFePO4 particles with effective conduct...

The decomposition of a poly(amide-imide) thin film coated on a solid copper wire was attempted using atmospheric pressure non-equilibrium plasma. The plasma was produced by applying microwave power to an electrically conductive material in a gas mixture of argon, oxygen, and hydrogen. The poly(amide-imide) thin film was easily decomposed by argon-oxygen mixed gas plasma and an oxidized copper surface was obtained. The reduction of the oxidized surface with argon-hydrogen mixed gas plasma rapidly yielded a metallic copper surface. A continuous plasma heat-treatment process using a combination of both the argon-oxygen plasma and argon-hydrogen plasma was found to be suitable for the decomposition of the poly(amide-imide) thin film coated on the solid copper wire.

A 74-year-old man presented with sudden onset of aphasia and apraxia. Magnetic resonance image (MRI) of the brain disclosed a left frontal hemorrhage. The concomitant low grade fever suggestive of infection was unresponsive to cefazolin 1 g q12h, and refractory to piperacillin (PIPC) 2 g q8h. Blood culture grew enterococci, establishing together with echocardiography the diagnosis of infective endocarditis. The angiography revealed cerebral hemorrhage to have resulted from the rupture of the infected intracranial aneurysm. The antimicrobial therapy was switched to ampicillin (ABPC) 2 g q4h plus gentamicin (GM) 60 mg q8h. The positive blood culture was subsequently identified Enterococcus faecium to which the minimum inhibitory concentration (MIC) of PIPC, and ABPC was 16 mcg/mL, and 4 mcg/mL, respectively. The peak concentration of serum ABPC was 83.1, median 50.8, and trough 25.8 mcg/mL. Thus, the percent time > MIC for ABPC was 100%, and the time > minimum bactericidal concentration (MBC) as well. On the other hand, time > MIC for PIPC, was found nearly 30% in retrospective analysis using population pharmacokinetics. The neurological deficit of the patient was completely restored to the normal status after 4-weeks' antimicrobial therapy with ABPC plus GM, then he underwent cardiac surgery for valvular replacement, where microbiological culture of the resected valve was negative. The constellation of the clinical, pharmacological and microbiological outcome in our case provides scientific evidence that the antibiotic therapy given to our case is the best available strategy as an antimicrobial treatment of severe enterococcal endocarditis complicated by disseminated lesion as infected intracranial aneurysm.

In general, a search engine is used to obtain information about specified keywords of interest. However, users must go through the list of web pages presented by the search engine in order to find the page that meets the purpose. In order to reduce this burden, we propose Web Index (WIX), a hyperlink generation system that achieves joining information resources on the web. The WIX system replaces keywords that appear in Web documents on browser into hyperlinks to a specific web page group of the user's choice. However, when there are multiple URLs paired up with a keyword, there is a need to choose the web page that meets the user's purpose. In this paper, we propose WIX System and an architecture that decides and presents likely candidates for hyperlink destination based on similarity of URLs and the content of each candidate.

A 57-year-old man presented with pneumonia, respiratory distress, and myelodysplastic syndrome. A diagnosis of Legionnaires' disease due to Legionella pneumophila (L. pneumophila) was established. The patient had long been drinking tap water via a conduit from a hot spring resource, from which L. pneumophila was also isolated. Both the patient's strain and the water strain of L. pneumophila were identified as serogroup 1, and the genetic relatedness between the two strains as seen by pulsed-field gel electrophoresis was 87%. The patient was successfully treated with erythromycin, fluoroquinolone, and rifampicin. This case raises an important issue on public health represented by legionellosis in Japan.(Internal Medicine 40:1064-1067, 2001)

To better define clinically relevant non-classic radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with small hepatocellular carcinoma (HCC).We retrospectively evaluated the influence of acute liver toxicities on fatal hepatic failure in HCC patients treated with SBRT. Between April 2006 and February 2012, 194 HCC were treated with SBRT. Among them, patients followed up for more than 6 months were eligible. Laboratory results and Child-Pugh (CP) scores were obtained before treatment and at monthly follow-up visits. Toxicities were evaluated by the Common Terminology Criteria for Adverse Events version 4.0. Possible definitions of RILD were evaluated with respect to fatal hepatic failure within 12 months.One hundred and eighty HCC were evaluated with a median follow-up of 28.2 months. Fatal hepatic failure within 12 months occurred in eight patients (4%). On univariate analysis, grade 3 or more elevated transaminases, CP score of 8 or more, and/or grade 3 or more decreased platelet count significantly predicted fatal hepatic failure within 12 months. Combinations of these factors (i.e. having at least one criterion) also predicted fatal hepatic failure within 12 months (16% with criteria vs 1% without criteria). Two-year overall survival rates for patients with and without RILD was 64.9% and 83.8% (P 0.001), respectively.We identified three criteria that affected overall survival in HCC patients treated with SBRT. Further prospective studies are warranted to validate the safety and effect of SBRT for HCC.

Objectives - To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. Patients and methods - Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. Results - A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals+2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. Conclusion - This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis.

In this report, we describe three patients with pulmonary tuberculosis with acute respiratory failure with an extensive tuberculous consolidation in bilateral lung fields. Disseminated intravascular coagulation (DIC) was present in one patient and miliary tuberculosis in two patients. They all developed acute respiratory distress syndrome (ARDS), nessecitating management by mechanical ventilation with a combination therapy of antituberculous agents and methylprednisolone (m-PSL) pulse therapy. Only one patient survived in whom the PaO2/FiO2 ratio recovered rapidly after the initiation of therapy. Two patients whose systemic condition upon admission was critically ill eventually died of hepatic failure and bacterial pneumonia, even though ARDS and pulmonary tuberculosis were successfully treated. Prognosis of pulmonary tuberculosis complicating ARDS and DIC is poor, and these patients need systemic intensive treatment, in which m-PSL therapy may be beneficial.

Objective To investigate how patients with bacteremic sepsis are managed in a tertiary care teaching hospital. Patients and Methods Prospective observational study on patients with bacteremic sepsis. Clinical and microbio-logical characteristics of bacteremic sepsis were analyzed in relation to prognosis. Severity of the illness was quantitatively analyzed by the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III scoring system. Also investigated was how closely physicians paid attention to acute physiological alterations in patients. Results The 28-day mortalities in fifty hemodynamically stable patients and in twenty-three septic shock patients were 26% and 52%, respectively (p=0.028). Gram-positive organisms accounted for 54% of all organisms, with the mortality and incidence of septic shock being the same as with Gram-negative infections. The mean APACHE III score was 42.9 in survivors, and 76.5 in non-survivors (p < 0.001). Although serum levels of C-reactive protein and acute physiology score (APS) was significantly higher in non-survivors than in survivors, the correlation with APACHE III score was more prominent in APS. The number of vital signs recorded was 1.67 in physicians and 3.6 in nurses (p < 0.001). Conclusions The present study proved that the APACHE HI score accurately discriminates between survivors and non-survivors of patients with sepsis. By addressing the need for an objective evaluation of severity of illness, it strongly recommends that physicians should be made aware of physiologically defined sepsis and that they should pay closer attention to patients' physiological alterations to identify the development of sepsis in critically ill patients.(Internal Medicine 39: 901-909, 2000)

In 1998, we developed a Total Infection Control System in Saga Medical School Hospital, and would like to introduce it for the practical use. This system was named "Dr. FLEMING" (Flexible Microbiological Test & Information System for the New Generation) and is expected to help physicians by providing highly valuable test results and useful information. For example, bacterial identification and drug susceptibility test can be completed within 4-6 hrs after bacterial colony is isolated, and the test report the contains full-colored pictures to enhance understanding. In addition, we have made an information center for infectious disease, where physicians can have access to various data bases outside our hospital. Furthermore, we offer many kinds of useful information to physicians working at other medical facilities to assist their clinical practice of infectious diseases.

The spatio-temporal evolution of a propagating magma-filled crack was estimated from inversion of Global Positioning System (GPS) data, tiltmeters, and leveling. The dike opened at a maximum rate of 50 millimeters per day and had a peak magma flux of 2 × 10 6 cubic meters per day. Although the spatial resolution was limited, slow upward propagation was resolved during the 9-day-long intrusion. In contrast, the earthquakes migrated rapidly upward during the first 12 hours of the swarm, and nearly all of the seismic energy was released in the first 2 days. Comparison of inversion results with accurate hypocenter locations will lead to improved understanding of magma transport through the brittle crust and of the causes of volcanic seismicity.

In 16HBE transformed human bronchial epithelial cells, histamine stimulated interleukin (IL)-8 mRNA and protein secretion, and this histamine stimulation was inhibited by the H1-receptor antagonist diphenhydramine (DPH), by the inhibitor of 5-lipoxygenase-activating protein (FLAP) MK-886, by the 5-lipoxygenase inhibitor Zileuton, and by dexamethasone. Histamine stimulated bronchial epithelial cell production of leukotriene B4(LTB4), and this production was inhibited by FLAP inhibitors MK-886 and L-655,238 and Zileuton. Histamine stimulated IL-8 luciferase reporter gene activity that was inhibited with DPH, dexamethasone, MK-886 and L-655,238, and Zileuton. The inhibition of IL-8 transcription and protein secretion by FLAP inhibitors and Zileuton was reversed with exogenous LTB4. There was increased IL-8 nuclear factor-κB (NF-κB) DNA-binding activity after histamine stimulation, and this was inhibited by DPH and MK-886. Cytoplasmic phospholipase A2mRNA levels were also potently induced by histamine. Thus histamine stimulation of bronchial epithelial cells involves binding at H1receptors, production of LTB4, activation of NF-κB and increased expression of IL-8.

Since 2005, we have treated hepatocellular carcinoma (HCC) with stereotactic body radiotherapy (SBRT) uniformly at two dose levels, according to baseline liver function and normal liver dose. We retrospectively examined the outcomes for these patients.Between 2005 and 2012, 221 HCC patients were treated with SBRT. Eligibility criteria for SBRT included a single (either solitary or recurrent) HCC lesion; unfeasible, difficult or refusal to undergo other surgery or percutaneous ablative therapies; Child-Pugh Classification (CPC) A or B; tumors ≤ 5 cm; dose to the bowels25 Gy/5 fractions; curative intent. Patients followed up ≥ 6 months were eligible. The prescribed dose depended on liver function and liver dose: 40 Gy for CPC-A and 35 Gy for CPC-B, in 5 fractions, requiring a 5-Gy dose reduction if the proportion of the liver receiving ≥ 20 Gy exceeded 20%. Treatment outcomes and safety were analyzed.A total of 185 patients (n = 48 in the 35-Gy group; n = 137 in the 40-Gy group) were eligible, with a median follow-up duration of 24 months (range 3-80). The three-year local control and overall survival rates were 91% and 70%, respectively. There were no significant differences in outcomes between dose levels: the three-year local control and overall survival rates in the 35-Gy and 40-Gy groups were 91% and 89% (log-rank p = 0.99) and 66% and 72% (p = 0.54), respectively. Acute toxicities ≥ grade 3 were observed in 24 (13.0%) patients, and 19 (10.3%) patients had worsening of CPC score by two points. All but three (1.6%) patients promptly recovered to grade 1-2. Grade 5 liver failure occurred in two patients in the 35-Gy group.SBRT for HCC was safe and provided equivalent outcomes when administered either in 35 or 40 Gy/5 fractions.

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of β-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

In beta-lactam therapy, investigation of the pharmacokinetic-pharmacodynamic (PK-PD) relationship has provided surrogate makers to predict clinical outcome. This study was designed to verify the therapeutic efficacy and clinical utility of beta-lactam therapeutic drug monitoring (TDM) in critically ill patients using high-performance liquid chromatography (HPLC). This cohort study included 13 patients who were intravenously administered ceftazidime (n = 6), cefepime (n = 1), imipenem (n = 1), meropenem (n = 1), or piperacillin (n = 4). Blood samples were collected at 3 time points fitted to a 1-compartment model, and concentrations were determined using HPLC. The PK-PD target was the percentage of the dosing interval during which the antibiotic concentration exceeded the minimum inhibitory concentration for the pathogens (%T > MIC), which is 50% for penicillins (piperacillin), 60% for cephalosporins (ceftazidime and cefepime), and 40% for carbapenems (imipenem and meropenem). Our process using HPLC enables the analytical results of TDM to be available within half a day. The results revealed significant inter-patient pharmacokinetic variability. During the initial regimen, beta-lactam concentrations reached the target %T > MIC in all patients, and dosage reduction was required for 5 patients (38%). Of the 13 evaluable patients, clinical improvement was observed in 11 (85%), and microbiological success was observed in 10 (77%). In summary, beta-lactam TDM achieved the treatment goals and might also allow for the personalization to prevent overdosing for variable pharmacokinetic changes in critically ill patients. These findings indicate that beta-lactam TDM using HPLC can be used in the standard pharmacy clinical practice for critically ill patients.

Objective This study aimed to establish the clinical significance of positive blood cultures during the past 10 years in Saga University Hospital. Methods All hospitalized patients with positive blood cultures in the gastroenterology, hepatology and respiratory wards in the Department of Internal Medicine, Saga University Hospital were evaluated by retrospective chart review between January 1999 and December 2008. The results were compared between period I (1999-2003) and period II (2004-2008). Results During the study, 2,680 isolates from 22,694 samples (11.8%) were detected in Saga University Hospital: 106 (13.1%) isolates from 812 samples were detected in the gastroenterology ward; 71 (7.8%) from 914 in the hepatology ward; and 160 (6.0%) from 2,671 in the respiratory ward. The number of positive blood cultures increased during period II compared with period I in all three wards. The ratio of Gram-negative rods increased in the gastroenterology ward during period II (p

Addition of Shiga toxin 2 to human bone marrow or cord blood cell culture induced macrophage-granulocyte colonies. Although Shiga toxin 2 alone induced colonies mainly composed of macrophages, it induced colonies mainly consisting of granulocytes when combined with physiological doses of interleukin-1β, granulocyte colony-stimulating factor, or stem cell factor with interleukin-3.

We describe a case of vertebral osteomyelitis caused by Prevotella intermedia, which is an extremely unusual cause of vertebral osteomyelitis. The organism was isolated from vertebral biopsies and the patient was treated successfully with intravenous ampicillin-sulbactam and clindamycin. Diagnosis and management of this condition are described, and the importance of anaerobic bacteria in the pathogenesis of vertebral osteomyelitis is discussed.

The main purpose of the present study was to develop a novel respirable powder (RP) formulation of cyclosporine A (CsA) using a spray-dried O/W-emulsion (DE) system. DE formulation of CsA (DE/CsA) was prepared by spray-drying a mixture of erythritol and liquid O/W emulsion containing CsA, polyvinylpyrrolidone, and glyceryl monooleate as emulsifying agent. The DE/CsA powders were mixed with lactose carriers to obtain an RP formulation of DE/CsA (DE/CsA-RP), and its physicochemical, pharmacological, and pharmacokinetic properties were evaluated. Spray-dried DE/CsA exhibited significant improvement in dissolution behavior with ca. 4500-fold increase of dissolution rate, and then, nanoemulsified particles were reconstituted with a mean diameter of 317 nm. Laser diffraction analysis on the DE/CsA-RP suggested high dispersion of DE/CsA on the surface of the lactose carrier. Anti-inflammatory properties of the inhaled DE/CsA-RP were characterized in antigen-sensitized asthma/COPD-model rats, in which the DE/CsA-RP was more potent than the RP formulation of physical mixture containing CsA and erythritol in inhibiting inflammatory responses, possibly due to the improved dissolution behavior. Pharmacokinetic studies demonstrated that systemic exposure of CsA after intratracheal administration of the DE/CsA-RP at a pharmacologically effective dose (100 μg-CsA/rat) was 50-fold less than that of the oral CsA dosage form at a toxic dose (10 mg/kg). From these findings, use of inhalable DE formulation of CsA might be a promising approach for the treatment of airway inflammatory diseases with improved pharmacodynamics and lower systemic exposure.

[1] In the paper “Three‐dimensional computational axial tomography scan of a volcano with cosmic ray muon radiography” by Hiroyuki K. M. Tanaka, Hideaki Taira, Tomihisa Uchida, Manobu Tanaka, Minoru Takeo, Takao Ohminato, Yosuke Aoki, Ryuichi Nishiyama, Daigo Shoji, and Hiroshi Tsuiji (Journal of Geophysical Research, 115, B12332, doi:10.1029/2010JB007677, 2010), the spelling of Ryuichi Nishiyama’s surname was incorrect. The correct spelling is given here.

Vasoactive intestinal peptide (VIP) has been considered as a promising drug candidate for asthma and COPD because of its potent immunomodulating and anti-inflammatory activities. Recently, our group developed a new VIP derivative, [R(15, 20, 21), L(17), A(24,25), des-N(28)]-VIP-GRR (IK312548), with improved chemical and metabolic stability. In the present study, a dry powder inhaler system of IK312548 was designed for inhalation therapy with minimal systemic side effects, the physicochemical properties of which were also evaluated with a focus on morphology, particle size distribution, inhalation performance, and peptide stability. Laser diffraction and cascade impactor analysis suggested high dispersion and deposition in the respiratory organs with a fine particle fraction of 31.2%. According to UPLC/ESI-MS and circular dichroic spectral analyses, no significant changes in the purity and structure of VIP derivative were observed during preparation of respirable formulation. Anti-inflammatory properties of IK312548 respirable powder (RP) were characterized in antigen-sensitized asthma/COPD-model rats. There were marked inflammatory cells infiltrated into the lung tissues of experimental asthma/COPD-model rats; however, intratracheal administration of IK312548-RP led to significant reductions of recruited inflammatory cells in lung tissues and BALF by 72 and 78%, respectively. Thus, respirable powder formulation of IK312548 might be a promising medication for asthma, COPD, and other airway inflammatory diseases.

Elastinolytic activity of medullasin was investigated precisely and compared with that of human leukocyte elastase, because the structure of medullasin is quite similar to that of human neutrophil elastase, which was reported to have elastinolytic activity. When elastinolytic activity of medullasin and human leukocyte elastase was determined by employing unstained elastin fibers and measuring the increase in 280-nm absorbance of the supernatant, elastinolytic activity amounting to several percent of that of porcine pancreas elastase was apparently observed. However, the susceptibility of elastin preparations to these proteases was proportional to their hydroxyproline content. Both medullasin and human leukocyte elastase digested collagen fibers obtained from bovine Achilles tendon to the same extent as collagenase from Clostridium histolyticum. When elastinolytic activity was determined by employing elastin fibers stained with orcein, both proteases showed negligible elastinolytic activity. The activity remained negligible even when the pH or ionic strength of the reaction mixture was altered. These results indicate that medullasin and human leukocyte elastase are essentially devoid of elastinolytic activity, and that apparent elastinolytic activity observed when unstained elastin fibers were employed as the substrate is due to the digestion of collagen fibers mingled with elastin preparations.

症例は75歳の男性で乾性咳嗽を主訴とし, 胸部X線写真で左下肺野に浸潤影を認めた. 気管支鏡で左B9入口部を閉塞するポリープ状腫瘤が認められ, 表面には一部壊死物質が付着していた. また, 対側の右B9入口部にも同様のポリープ状腫瘤を認め, 共に低分化型腺癌と診断された. 他臓器悪性腫瘍からの気管支内腔転移を疑い全身的検索を施行したが, 肺外諸臓器には異常を認めなかった. 胸部CTでは左B9ポリープ状腫瘤に隣接する原発巣と考えられる径3cmの充実性腫瘤と, 両側に肺内転移巣を示唆する複数の小結節影が認められた. 右B9入口部の腫瘤は, CT所見では気管支内腔病変のみであり, 気管支壁外には異常を指摘できなかった. 以上の結果より, 本症例は左B9原発の低分化型腺癌で一部がポリープ状発育を呈し, さらに対側肺に気管支内腔転移を来たしたものと考えられた.

[1] Cosmic ray muon radiography can measure the density distribution within a volcano. Unidirectional radiography shows a precise cross-sectional view of a conduit and a magma body through a volcano parallel to the plane of the detector. However, it only resolves the average density distribution along individual muon paths. Precise size and shape of underground structure, such as a conduit or a magma body, provide clear and pervasive information on understanding dynamics of volcanic eruption. Here we show a highly resolved three-dimensional tomographic image of an active volcano Asama in Japan. Specifically, we developed a portable power-effective muon radiography telescope that can be operated stable with a realistically sized solar panel so as to place it around an active volcano where commercial electric power is not available. The resulting image below the crater floor shows that a local low-density region accumulates sufficient gas pressure to cause Vulcanian eruption. The present muon computational axial tomography scan has a resolving power with a resolution of 100 m, allowing it to see great detail in volcanoes.

[1] We estimated the temporal changes of phase velocity of Rayleigh waves extracted from cross correlations of S-coda waves recorded at 12 stations around Mt. Asama, Japan. First, we extracted a Rayleigh wave by taking cross correlations of S-coda waves for 315 regional earthquakes between October 2005 and February 2009. The dispersion curve of the Rayleigh wave was measured and compared with the one extracted from 18 days of ambient seismic noise. We found that both dispersion curves are consistent with each other, demonstrating the dominance of the fundamental Rayleigh waves. We then divided the entire time period into sub-periods, each of which consists of 80 earthquakes, to measure the temporal changes at frequencies between 0.3 and 0.6 Hz. The result shows the reduction of phase velocity by 1.5 % and the subsequent recovery before the eruption of Mt. Asama in 2008.

Point-of-care diagnosis of influenza requires sound recognition of the prevalence of the signs and symptoms of the patients, which would help to define the pattern of clinical presentation of this infection. In severely ill patients, however, clinical features of influenza could be erroneously modified by the exacerbation of co-morbid conditions, resulting in a delay of the diagnosis. Enzymatic rapid diagnostic tests, although establishing the diagnosis with positive result especially when the virus is in high circulation, has relatively poor sensitivity for the 2009 A/H1N1 virus and it varies among the different age groups. Given the likelihood of long-term circulation of the novel H1N1 virus, patients' clinical features and the performance of the rapid tests should continuously be monitored.

Superfluidity of liquid $^{4}\text{H}\text{e}$ confined in one-dimensional (1D) nanometer-size channels has been studied by means of a torsional oscillator. When the channel is larger than 2.8 nm in diameter, liquid $^{4}\text{H}\text{e}$ becomes superfluid at low temperatures and a dissipation due to quantized vortex is observed. The superfluid onset temperature is 1.8 K at 0.14 MPa for the 4.7 nm channel and 0.89 K at 0.01 MPa for the 2.8 nm channel. For the latter, it is suppressed strongly under the application of pressure, and continuously approaches zero at around 2.1 MPa at absolute zero, which suggests a quantum phase transition between the superfluid and nonsuperfluid states in the 1D channel.

Vasoactive intestinal peptide (VIP) has been thought to be a promising candidate for asthma/chronic obstructive pulmonary disease (COPD), and our group previously developed several long-lasting VIP derivatives. The objective of the present study was to clarify the therapeutic potential of new VIP derivatives with improved chemical and metabolic stability. Exposure of rat alveolar L2 cells to cigarette smoke extract (CSE) for 1h led to release of lactate dehydrogenase (LDH) and decreased viability in a CSE concentration-dependent manner. There appeared to be marked induction of apoptosis after CSE exposure, as demonstrated by 59% elevation of caspase-3 activity and TUNEL staining. In contrast, a stabilized VIP derivative, [R(15,20,21), L(17)]-VIP-GRR (IK312532), at a concentration of 10(-7)M, exhibited 71% attenuation of LDH release and 85% decrease of the number of apoptotic cells. In addition to IK312532, new VIP derivatives also showed anti-apoptotic effects against CSE toxicity and marked reduction of nitric oxide production. In terms of cytoprotective effects, [R(15,20,21), L(17), A(24,25), des-N(28)]-VIP-GRR was more effective than VIP and IK312532, possibly due to the improved stability. Thus, the present study is the first to demonstrate that novel stabilized VIP derivatives exert anti-apoptotic and cytoprotective effects on CSE-induced cytotoxicity.

Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder (RP) of TL for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). In the CSD/TL, wet-milled crystalline TL particles with a mean diameter of 122 nm were dispersed, and there was a marked improvement in dissolution behavior of the CSD/TL-RP compared with that of a physical mixture of TL and carrier. Laser diffraction and cascade impactor analyses on the CSD/TL-RP demonstrated high dispersibility and deposition in the respiratory organs with emitted dose and fine particle fraction of ca. 98 and 60%, respectively. Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by histochemical analyses and inflammatory biomarkers such as lactate dehydrogenase, eosinophil peroxidase, and myeloperoxidase. The CSD/TL-RP seemed to be more potent than the physical mixture in inhibiting inflammatory responses, possibly due to the improved dissolution behavior. Systemic exposure of TL after intratracheal administration of CSD/TL-RP at a pharmacologically effective dose (100 μg of TL/rat) was found to be fivefold less than that of the oral TL dosage form at clinical dose (1.67 mg/kg). Given the improved pharmacodynamics and lower systemic TL concentration, the inhalable TL formulation might provide an interesting alternative to oral therapy with a better safety margin for the treatment of asthma and other airway inflammatory diseases.

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.

Using quantitative Bayesian analysis as a clinical epidemiological approach, we developed a diagnosis for lower respiratory tract infection (LRTI) due to Methicillin-resistant Staphylococcus aureus (MRSA). We retrospectively reviewed the charts of 181 subjects--a derivation cohort-with MRSA retrieved from lower respiratory specimens June 2006 to March 2008. Dividing them into infection or colonization (no infection) groups, we compared them for the presence or absence of clinical parameters, including fever38 degrees C, MRSA106 CFU (colony-forming units)/mL, phagocytosis on Gram staining, serum albumin3.0 g/dL, and peripheral WBC count15,000/mL. We them determined positive and negative likelihood ratios (LR +, LR -) for these parameters to quantify MRSA-LRTI diagnostic probability based on combined likelihood ratios (Bayesian analysis). We then determined Bayesian MRSA-LRTI diagnostic probabilities (BDPs) in 40 subjects with respiratory MRSA--a validation cohort-from May 2008 to October 2008 clinically judged with either infection (n = 14) or colonization (n = 26) by infection control personnel (ICP) blinded to the test (parameter LR+ and LR -). BDPs (mean +/- SD) quantified by combining the four parameters-fever, MRSA CFU, phagocytosis, and serum albumin-were 62.3 +/- 25.4% for 14 judged with infection, and 40.2% +/- 20.4% for 26 patients judged with colonization (p = 0.005). Using a diagnostic probability of 51% as the cut off, we compared positive and negative predictive Bayesian diagnoses ICP judgment, i.c., 77% vs. 85%. The Bayesian approach proved useful in quantitatively diagnosing infectious disease such as MRSA-LRTI that lack established diagnostic, and may aid physicians in deciding the need for specific antimicrobial therapy.

Positive blood culture represents either true bacteremia or contaminants of the normal skin flora. The number of positive bottles, rapidity with which blood culture turns positive, and appropriate interpretation of Gram-stain findings usually assist physicians or technologists in deciding whether it reflects true-positive results or contamination. In the case of true bacteremia, two aspects of the Gram-stain findings, Gram-positive or negative, cocci or rod, are important initial findings that safely guide physicians to select appropriate antimicrobial agents. Gram-positive cocci in clusters strongly suggest Staphylococci, and "in-chains" indicates Streptococci or Enterococci. Although distinction between the latter two organisms is occasionally difficult, glycopeptide should be the first choice, especially in critically ill patients. Gram-positive rods, when first reported, also require the empiric administration of glycopeptides, and sometimes their false Gram-negative staining could result in errors of pathogen identification, resulting in the inappropriate choice of antibiotics. The detection of gas production by Gram-negative rods, which indicates Enterobacteriaceae, is helpful initial information to start cephalosporin antibiotics, whereas the absence of gas would suggest nonfirmentative rod bacteremia, for which the administration of anti-pseudomonal agents is strongly warranted. Gram-negative cocci, such as Moraxella or Acinetobacter sp., may initially be reported as Gram-positive, so empiric antimicrobial drugs should be carefully selected taking into account these pitfalls and patients' conditions, and the situation regarding the development of diseases (community-acquired vs. nosocomial). The rapid and appropriate treatment of bacteremia thus requires careful interepretation of Gram-stain findings as described above, and should always be integrated with pathognomonic features of individual patients.

A 67-year-old man clinically diagnosed a year earlier with sarcoidosis based on low-grade fever, lymphadenopathy, trunk skin rash, and histopathological skin tests was admitted for newly developing subcutaneous nodules on the trunk and arms and fever of 38 degrees C. Although initially suspected of recurrent sarcoidosis, he was diagnosed with Mycobacterium chromogenicum infection isolated from skin lesion culture. Combined clarithromycin of 800 mg/day, ethambutol of 750 mg/day, and embiomycin of 0.5 g/day was started, after which fever declined and WBC count and CRP decreased to normal in a week. One month later, skin lesions had disappeared. This case is interesting considering the association of nontuberculous mycobacterial infection with sarcoidosis.

On June 16 2007 (AM 10:13 in Japan Standard Time), an earthquake of magnitude 6.8 took place about 10 km offshore of Chuetsu area in Niigata, Japan.

Medullasin is a serine protease found in human bone marrow cells. It resembles elastase, but has no elastinolytic activity. It consists of 238 amino acid residues with Tie as the amino terminal and His as the carboxyl terminal. Medullasin causes inflammation characterized by the infiltration of a large number of macrophages when injected into animal skin. Protease inhibitors in plasma such as α2-macroglobulin and α1-antitrypsin inhibited the protease by equimolar ratio. Injection of the mixture of medullasin and α2-macroglobulin or α1-antitrypsin into animal skin caused no inflammation. When these inhibitors were injected 5 sec after the injection of medullasin, phlogistic activity of the protease was not prevented by them.These results indicate that medullasin released into the tissues directly from granulocytes attaches to them immediately in such a manner that plasma inhibitors are not able to inhibit it. Therefore, medullasin released from granulocytes directly to the tissues is considered to be able to act on them in spite of the presence of a large amount of plasma protease inhibitors.