IL-15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis.

BACKGROUND: Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. OBJECTIVES: To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. METHODS: In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. RESULTS: The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. CONCLUSION: This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

The influence of viscosity-enhancing agents on oral absorption of drugs.

The objective of this study was to evaluate the influence of viscosity-enhancing agents on oral absorption of metoprolol (MPL) and bisoprolol (BPL). Although the viscosity values were similar for MPL and BPL in hydroxypropyl methylcellulose (HPMC, 1.2 % (w/w)) and polyvinyl alcohol (PVA, 8.8 % (w/w)) solutions, the order of diffusion rate constants of the drugs in media were phosphate buffer solution (reference) > HPMC solution > PVA solution. In in vivo rat intestinal absorption experiments showed that the Cmax and AUC values of the drugs were lowest when they were administered into the rat jejunum in a PVA solution. In vitro binding studies showed that this may have been due to adsorption of the drugs to PVA molecules, resulting in decreased free fractions of the drugs. Our results indicated that intestinal absorption of the drugs in PVA solution was influenced both by decreased diffusion of the drugs and by interaction with PVA. Since various viscosity-enhancing agents are widely used as pharmaceutical and food additives, these findings may be of significance for understanding therapeutic efficacy and safety of oral drug products.

Effects of low-dose oleuropein diet supplementation on the oxidative status of skeletal muscles and plasma hormonal concentration of growing broiler chickens.

1. Oleuropein (Ole) is a major phenolic compound in Olea europaea, with anti-oxidative, anti-obesity, and anti-inflammatory properties. To explore the effect of Ole on the physiology and metabolism of poultry, this study, evaluated the effects of feeding low-dose Ole on the growth performance, metabolic hormonal status, muscle oxidative status in growing broiler chickens.2. Thirty-two 8-day-old chickens were assigned to four different treatments, and fed either 0 (control), 0.1, 0.5, or 2.5 ppm Ole-supplemented diets for 2 weeks.3. There were no differences in the body weight gain, feed consumption, and feed efficiency during the feeding periods between the groups tested. Birds fed Ole 0.5- and 2.5 ppm-supplemented diets exhibited a significant decrease in muscle carbonyl content compared to the control group. In the group fed Ole 0.5 ppm, the mRNA expression levels of mitochondrial ROS-reducing factors: avian uncoupling protein and manganese superoxide dismutase, as well as peroxisome proliferator-activated receptor γ coactivator 1-α, sirtuin-1 and -3 (each of which co-ordinately induce the transcription of the previous two factors) were upregulated compared to the control group, and the changes were independent of plasma noradrenaline and thyroid hormone levels. The group fed Ole-2.5 ppm did not show such transcriptional changes, but exhibited a higher corticosterone concentration.4. This study demonstrates that ingesting a low dose of Ole can reduce muscle oxidative damage, and that the suppression machinery may differ depending on the amount of Ole ingested by growing broiler chickens.

Controllable vitamin K deficiency under high-dose oral menatetrenone administration - a case report.

Vitamin (V) K deficiency may cause severe bleeding tendencies, which necessitates extreme caution. We report a case of a 30-year-old man diagnosed with VK deficiency of unknown etiology. He was treated with intravenous menatetrenone three times a week in an outpatient setting for about 1 year and 9 months. Eventually, he developed an allergic reaction to intravenous menatetrenone and was under steroid therapy. In order to reduce his hospital visits and discontinue steroid use, the pharmacist proposed to change the method of menatetrenone administration from intravenous to oral (high dose). The change in treatment method has greatly improved the patient's quality of life.

Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18 F]THK-5351, which we have recently developed. METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3 H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18 F]THK-5351. To detect amyloid-ß deposition, PET imaging with Pittsburgh compound B was also performed. RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. CONCLUSIONS: We conclude that [18 F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.

Synthesis of DNA fragments containing 2'-deoxy-4'-selenonucleoside units using DNA polymerases: comparison of dNTPs with O, S and Se at the 4'-position in replication.

4'-SelenoDNA fragments were synthesized for the first time using 4'-selenothymidine triphosphate (SeTTP) by taking advantage of its bioequivalence against DNA polymerases. DNA fragments each with a homologous element (O, S or Se) at the 4'-position of the thymidine units were effectively amplified using KOD Dash DNA polymerase.

Risk factors for linezolid-associated thrombocytopenia in adult patients.

OBJECTIVES: Thrombocytopenia (TP) is a common adverse effect of linezolid (LZD). However, risk factors for LZD-associated TP have been reported in Western patients with relatively heavy body weight. The aim of this study was to determine the risk factors for LZD-associated TP in Asian population. MATERIALS AND METHODS: A retrospective cohort study was conducted among 101 consecutive patients who received LZD therapy (1,200 mg/day) between July 2003 and December 2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious other causes for TP were excluded. The information of target infectious disease, patients' age, gender, body weight, body mass index, baseline serum creatinine (SCr), baseline platelet count, and treatment duration was collected retrospectively. TP was defined as ≥ 50% decrease in platelet count from baseline. Bi- and multi-variate analyses were performed. RESULTS: A total of 101 patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median duration [range] of LZD therapy was 14 days [1-67]. LZD-associated TP was identified in 42 patients (42%). For TP, adjusted odds ratio (OR) [95% CI] of daily per kg dose (DPKD) and SCr was 1.14 [1.05-1.26] and 1.51 [1.01-2.50], respectively. CONCLUSIONS: Higher DPKD and elevated SCr are significantly associated with LZD-associated TP. These findings suggest that daily dose of LZD should be adjusted using body weight, as typically done in pediatrics, in adults as well. Renal function also should be considered for dose adjustment.

Difference in direct charge-parity violation between charged and neutral B meson decays.

Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter-dominated. One of the prerequisites for understanding this elimination of antimatter is the nonconservation of charge-parity (CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson (K(0)) and B meson (B(0)) systems: CP violation involving the mixing between K(0) and its antiparticle (and likewise for B(0) and ), and direct CP violation in the decay of each meson. The observed effects for both types of CP violation are substantially larger for the B(0) meson system. However, they are still consistent with the standard model of particle physics, which has a unique source of CP violation that is known to be too small to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B(+/-)-->K(+/-)pi(0) decay is different from that in the neutral B(0) counterpart. The direct CP-violating decay rate asymmetry, (that is, the difference between the number of observed B(-)-->K(-)pi(0) event versus B(+)-->K(+) pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement. However, the asymmetry for versus B(0)-->K(+)pi(-) is at the -10% level. Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation-which would help to explain the dominance of matter in the Universe.

The Japanese Esophageal Society classification for prediction of superficial esophageal squamous cell neoplasia invasion depth: Validation in a Western population.

BACKGROUND: The Japan Esophageal Society proposed the JES microvessel classification to assess eligibility of early esophageal squamous cell neoplasia (ESCN) for endoscopic resection based on intrapapillary capillary loop assessment. We aimed to assess its diagnostic reproducibility and accuracy in Western ESCN patients. METHODS: Intrapapillary capillary loops on endoscopic images of Western ESCN lesions (n = 113) collected between 2010 and 2022 were assessed by nine endoscopists, including three Japanese expert endoscopists, three Western expert endoscopists, and three residents-in-training, and graded according to the JES microvessel classification where microvessel type A corresponds with normality or low-grade intraepithelial neoplasia, and microvessel types B1, B2, and B3 correspond with high-grade intraepithelial neoplasia or invasion into the lamina propria, muscularis mucosae or superficial submucosa, and deep submucosa, respectively. Outcomes included overall accuracy in predicting ESCN invasion depth and interobserver agreement. RESULTS: Good interobserver agreement was observed among expert endoscopists (Krippendorf's alpha 0.64, 95% CI 0.57-0.70), while agreement was moderate among residents-in-training (Krippendorf's alpha 0.58, 95% CI 0.52-0.72). Overall accuracy of the JES microvessel classification was 53% (95% CI 42-63), 52% (95% CI 41-62), and 44% (95% CI 34-55) for Japanese endoscopists, Western endoscopists, and residents-in-training, respectively. Sensitivity and specificity for vessel type A, B1, B2, and B3 across assessors were 0%-50% and 89%-100%, 55%-64% and 66%-77%, 42%-71% and 60%-76%, and 10%-24% and 92%-97%, respectively. Negative predictive value ranged between 80% and 85% for B3 vessels. CONCLUSION: Overall accuracy of the JES microvessel classification in Western ESCN patients is low, though absence of B3 vessels as assessed by experienced endoscopists may predict superficial ESCN amenable to endoscopic resection. TRIAL REGISTRY: www.trialregister.nl; NL8897 (6-9-2020).

Chylous ascites after hepatopancreatobiliary surgery.

BACKGROUND: Postoperative chylous ascites following abdominal surgery is uncommon. It potentially induces malnutrition and immunodeficiency, contributing to increased mortality. In the field of hepatopancreatobiliary (HPB) surgery, no large studies have been conducted that focused on postoperative chylous ascites. The aim of this study was to determine the incidence, risk factors and management of chylous ascites following HPB surgery, with particular emphasis on pancreatic resection. METHODS: Consecutive patients who had HPB surgery between 2000 and 2011 at a single institution were reviewed retrospectively. Chyle leak was defined as 100 ml/day or more of milky, amylase-free peritoneal fluid with a triglyceride concentration of 110 mg/dl or above. Risk factors for chylous ascites associated with pancreatic resection and the clinical efficacy of octreotide in treating chylous ascites were evaluated. RESULTS: Of 2002 consecutive patients who underwent HPB surgery during the study period, 21 (1·0 per cent) developed chylous ascites. Chylous ascites occurred relatively frequently in patients who had a pancreatic resection, such as pancreaticoduodenectomy (3·3 per cent) or distal pancreatectomy (3·8 per cent). Multivariable analysis revealed that manipulation of the para-aortic area (P < 0·001), retroperitoneal invasion (P = 0·031) and early enteral feeding after operation (P < 0·001) were independent risk factors for chylous ascites following pancreatic resection. Octreotide treatment decreased drainage output of chylous ascites on day 1 after initiation of treatment (P = 0·002). CONCLUSION: Chylous ascites is a rare complication following HPB surgery. It is more common after pancreatic resection. Treatment with octreotide combined with total parenteral nutrition is recommended.

Treatment of domestic sewage by a metal membrane bioreactor.

A submerged flat metal MBR (membrane bioreactor) was used to treat synthetic domestic sewage in this study. The experiment was continued for 270 days and ran under two modes as AMBR (aerobic membrane bioreactor) and A/O-MBR (anoxic/aerobic membrane bioreactor) at a permeate flux of 0.4-1 m³/(m² d). PVA (polyvinyl alcohol) gel beads were added to the aeration tank with a volume ratio of 10% at the end of the A/O-MBR mode. The mean COD and TN removal efficiencies achieved 96.69 and 32.12% under the AMBR mode, and those were 92.17 and 72.44% under the A/O-MBR mode, respectively. SND (simultaneous nitrification and denitrification) occurred at high MLSS (mixed liquor suspended solids) concentration. The metal membranes reduced effluent COD during filtration. The system ran stably for 115 days at a permeate flux of 0.8-1 m³/(m² d) without changing membranes under the AMBR mode, but the membrane filterability decreased gradually under high MLSS or A/O-MBR mode, and the addition of PVA worsened the membrane filterability on the contrary. PSD (particle size distribution) and sludge fractions had evident influence on membrane fouling. The main fouling mechanism was cake formation under the AMBR mode, and that was pore blocking under the A/O-MBR mode.

Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer's disease.

BACKGROUND AND PURPOSE: Life style-related disorders such as hypertension, diabetes, dyslipidemia, and obesity are reported to be a great risk of dementia. Adipocytokines released from adipose tissue are thought to modulate some brain functions including memory and cognition. We here analysed adiponectin, one of the most important adipocytokines, in plasma and cerebrospinal fluid (CSF) from cognitive normal controls (NC), mild cognitive impairment (MCI) subjects, and patients with Alzheimer's disease (AD) and discussed if/how adiponectin could relate to the pathogenesis of AD. METHODS: Normal controls (n = 28), MCI (n = 18), and AD (n = 27) subjects were recruited at Tohoku University Hospital. The diagnosis of AD was based on NINCDS-ADRDA criteria. All the blood and CSF samples were obtained from each fasted subject. Adiponectin was assayed using a sandwich ELISA system. RESULTS: The levels of adiponectin between in plasma and in CSF showed a positive correlation. Plasma adiponectin was significantly higher in MCI and AD compared to NC, whereas CSF adiponectin was significantly higher in MCI compared to NC. CONCLUSION: It is possible that the level of adiponectin in plasma reflects its level in CSF. The tendency to have higher adiponectin in plasma and CSF from MCI and AD suggests that this molecule plays a critical role in the onset of AD.

A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97.

Analysis of antibodies present in the serum of melanoma patient FD has shown that they detect a unique tumor epitope present only on the autologous melanoma cell line SK-MEL-131. Previous results had shown that the unique FD epitope is carried on a common glycoprotein of approximately 90 kD, widely expressed on melanoma and a few other cell types. We now show by sequential radioimmunoprecipitation and partial amino acid sequencing that this common molecule is a previously recognized melanoma antigen, originally identified by mouse mAbs, designated gp95 or p97 (and also known as melanotransferrin). Thus, FD is the first of the class I (unique) melanoma antigens that has been characterized and related to a known cell surface molecule.

T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy.

Induction of a T-cell mediated antitumor response is the ultimate goal for tumor immunotherapy. We demonstrate here that antibody-targeted IL2 therapy is effective against established pulmonary and hepatic melanoma metastases in a syngeneic murine tumor model. The effector mechanisms involved in this tumor eradication are not dependent on NK cells, since the therapeutic effect of antibody-IL2 fusion protein was not altered in NK cell-deficient mice. In contrast, T cells are essential for the observed antitumor effect, since therapy with antibody IL2 fusion proteins is unable to induce tumor eradication in T cell-deficient SCID mice. In vivo depletion studies characterized the essential effector cell population further as CD8 + T cells. Such CD8 + T cells, isolated from tumor bearing mice after antibody-directed IL2 therapy, exerted a MHC class I-restricted cytotoxicity against the same tumor in vitro. These data demonstrate the ability of antibody-targeted IL2 delivery to induce a T cell-dependent host immune response that is capable of eradicating established melanoma metastases in clinically relevant organs.

Risk factors of mid-term mortality of patients with infective endocarditis.

In-hospital and long-term mortality of infective endocarditis (IE) are well noted, but the studies for mid-term (90-day) mortality of IE is still limited. We determine the mid-term mortality rate of IE and its significant predictors. Seventy patients with IE were hospitalised at St. Luke's International Hospital between January 1996 and March 2009, of whom 62 consecutive patients could be followed up for 90 days after diagnosis. We then calculated Kaplan-Meier (KM) estimates and performed time-to-event analysis. The mean (standard deviation, SD) age was 66.6 (15.3) years. Thirty-five patients (56%) were male. Blood cultures were positive in 87%. Causative microorganisms were: viridans group streptococci (23%), ß-streptococci (16%), Staphylococcus aureus (15%), including methicillin-resistant S. aureus (MRSA) (5%). Thirty-three cases (53%) had at least one complication such as heart failure (34%), central nervous system (CNS) complication (29%) or emboli peripheral to CNS (6%). KM estimates (95% CI) of the 90-day mortality was 14.5% (7.8-25%). In multiple regression analysis using the Cox proportional hazards model, hazard ratios of at least one complication for the 90-day mortality was 8.2 (1.4-155). Mid-term mortality of IE continues to be high and the presence of at least one complication may be considered as an independent risk factor of mid-term mortality.

Enrichment of marine anammox bacteria from seawater-related samples and bacterial community study.

Anaerobic ammonium oxidation (anammox) is a novel nitrogen pathway catalyzed by anammox bacteria which are obligate anaerobic chemoautotrophs. In this study, enrichment culture of marine anammox bacteria (MAAOB) from the samples related to seawater was conducted. Simultaneous removal of ammonium and nitrite was confirmed in continuous culture inoculated with sediment of a sea-based waste disposal site within 50 days. However, no simultaneous nitrogen removal was observed in cultures inoculated with seawater-acclimated denitrifying sludge or with muddy sediment of tideland even during 200 days. Nitrogen removal rate of 0.13 kg/m(3)/day was achieved at nitrogen loading rate of 0.16 kg/m(3)/day after 320th days in the culture inoculated with the sediment of waste disposal site. The nitrogen removal ratio between ammonium nitrogen and nitrite nitrogen was 1:1.07. Denaturing gradient gel electrophoresis (DGGE) analysis indicated that an abundance of the bacteria close to MAAOB and coexistence of ammonium oxidizing bacteria and denitrifying bacteria in the culture.

Recent trends in the incidence and lifetime risk of hip fracture in Tottori, Japan.

SUMMARY: Hip fracture incidence from 2004 to 2006 in the Tottori prefecture of Japan was investigated and compared with previously reported rates. The age- and gender-specific incidence of hip fracture in the Tottori prefecture has not plateaued, as has been reported for populations in Northern Europe or North America. INTRODUCTION: Recent data from Northern Europe and North America indicate that the incidence of hip fracture has plateaued, whereas most reports from Asia indicate that the incidence is increasing. The aims of this study were to investigate the recent incidence of hip fracture in the Tottori prefecture, Japan, and to compare it with previous reports. METHODS: All hip fractures in patients aged 35 years and older occurring between 2004 and 2006 were surveyed in all of the hospitals from the Tottori prefecture. The age- and gender-specific incidence rates were then calculated. Using these and previously reported data, the estimated number of hip fracture patients was determined using the age- and gender-specific incidence rates in each year from 1986 to 2006. RESULTS: The survey identified 851, 906, and 1,059 patients aged 35 years and older, in 2004, 2005, and 2006 respectively. The residual lifetime risk of hip fracture for individuals at 50 years of age was estimated to be 5.6% for men and 20.0% for women. The estimated number of patients from 1986 to 2006 showed a significant increase over time for both genders. CONCLUSIONS: The age- and gender-specific incidence of hip fracture in the Tottori prefecture, Japan has not plateaued for either gender.