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This study aimed to evaluate the feasibility and utility of an e-learning training program to improve healthcare professionals' knowledge about providing appearance care to patients with cancer. Healthcare professionals who provide appearance support were invited to participate voluntarily and complete a survey before and after the program. Participation request letters were distributed to 133 individuals, including 75 from four facilities invited via professional connections, and agreed to participate in the study and 58 participated in the National Cancer Center's appearance care training and indicated an interest in participating in the study. The 100 participants (75.2%) included 96 females, with an average age of 40.5 years. The participants reported high levels of satisfaction with the program, where more than 90% responded "satisfied" or "somewhat satisfied" and eager to use the content they learned in the program when they returned to their workplaces. However, the participants identified several barriers to applying their newly acquired knowledge including lack of knowledge (about 80%). Participant knowledge scores about appearance support were significantly higher after program participation. The survey results indicated the high feasibility of the e-learning program through improved knowledge about appearance care and high satisfaction with the program. The program needs further improvements for its practical utility., Competing Interests: Chikako Shimizu has received research grants from Eli Lilly, honoraria from Astra Zeneca, Pfizer, Chugai, Taiho, and Daiichi-Sankyo. The remaining authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

Hospitals that admit patients with COVID-19 face the challenge of not only dealing with these patients but also balancing normal medical care and hospital management to cope with the challenges posed by the new post-epidemic era. Over the past two years of responding to COVID-19 as a front-line clinical nurse, my colleagues and I have fully appreciated the need to establish a nursing system that is appropriate for the new post-epidemic era. The following four aspects should be emphasized: i ) the continuation of thorough infection control measures; ii ) exploring new approaches to training for new recruits; iii ) ensuring nursing workforce and improving the nursing capacity to cope with patients critically ill with COVID-19; and iv ) teamwork and team care to provide nurses with timely psychological assistance., Competing Interests: The author has no conflicts of interest to disclose., (2022, National Center for Global Health and Medicine.)

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin B-cell lymphoma which occurs mainly in capillaries and small blood vessels. Successful diagnosis of IVLBCL is challenging since it lacks tumor formation and presents various clinical manifestations. An 82-year-old Asian female patient presented to our emergency department with a history of general fatigue, weight loss, and fever for two weeks. The patient's random skin biopsy was negative, and her bone marrow biopsy revealed hemophagocytic syndrome with no obvious involvement of lymphoma cells. Gallium scintigraphy showed mild uptake in the uterus, pelvis, and spine. The repetitive bone marrow biopsy result and the endometrial cytology/biopsy were negative; however, the pelvic MRI was compatible with lymphoma, revealing lesions in the corpus uteri, pelvis, and vertebral body. After laparoscopic-assisted vaginal total hysterectomy and bilateral salpingo-oophorectomy, the diagnosis of the Asian variant of IVLBCL was made. Although total hysterectomy remains controversial for elderly patients with declining performance status, we could successfully diagnose the condition and initiate the treatment. The patient's general condition improved soon after starting rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen on day 26, and she was discharged on day 45.

Objective: The aim of this study was to compare the prognosis and time reduction between helicopter emergency medical services (HEMS) with a physician and ground emergency medical services (GEMS) in acute myocardial infarction (AMI) cases., Methods: This is a registry-based study of the Japan Helicopter Emergency Medical Service Registry from April 1, 2015, to March 31, 2018., Results: A total of 605 cases of AMI were registered in the HEMS group and 794 cases in the GEMS group. In the cases of non-cardiopulmonary arrest (CPA), the prognosis between HEMS and GEMS did not differ significantly. Regarding the road distance, for ranges of 20 to 40 km and > 40 km, the times from the call to the angiography room were significantly shorter with HEMS than GEMS (median 91 vs. 97 minutes, P = .036 and 101 vs. 132 minutes, P = .002, respectively). In cases of CPA, HEMS had a higher rate of return of spontaneous circulation than GEMS (55.3% vs. 36.8%, P = .038), but HEMS had a lower prognosis than GEMS (22.9% vs. 38.9%, P = .036)., Conclusion: The present study suggested that HEMS had an advantage in reducing the time to angiography in AMI cases of non-CPA. In cases of CPA, HEMS increased the return of spontaneous circulation without improving the prognosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions., (© 2021. The Author(s).)

Substrate specificities of glycoside hydrolase families 8 (Rex), 39 (BhXyl39), and 52 (BhXyl52) β-xylosidases from Bacillus halodurans C-125 were investigated. BhXyl39 hydrolyzed xylotriose most efficiently among the linear xylooligosaccharides. The activity decreased in the order of xylohexaose > xylopentaose > xylotetraose and it had little effect on xylobiose. In contrast, BhXyl52 hydrolyzed xylobiose and xylotriose most efficiently, and its activity decreased when the main chain became longer as follows: xylotetraose > xylopentaose > xylohexaose. Rex produced O-β-D-xylopyranosyl-(1 → 4)-[O-α-L-arabinofuranosyl-(1 → 3)]-O-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (Ara 2 Xyl 3 ) and O-β-D-xylopyranosyl-(1 → 4)-[O-4-O-methyl-α-D-glucuronopyranosyl-(l → 2)]-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (MeGlcA 2 Xyl 3 ), which lost a xylose residue from the reducing end of O-β-D-xylopyranosyl-(1 → 4)-[O-α-L-arabinofuranosyl-(1 → 3)]-O-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (Ara 3 Xyl 4 ) and O-β-D-xylopyranosyl-(1 → 4)-[O-4-O-methyl-α-D-glucuronopyranosyl-(1 → 2)]-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (MeGlcA 3 Xyl 4 ). It was considered that there is no space to accommodate side chains at subsite -1. BhXyl39 rapidly hydrolyzes the non-reducing-end xylose linkages of MeGlcA 3 Xyl 4 , while the arabinose branch does not significantly affect the enzyme activity because it degrades Ara 3 Xyl 4 as rapidly as unmodified xylotetraose. The model structure suggested that BhXyl39 enhanced the activity for MeGlcA 3 Xyl 4 by forming a hydrogen bond between glucuronic acid and Lys265. BhXyl52 did not hydrolyze Ara 3 Xyl 4 and MeGlcA 3 Xyl 4 because it has a narrow substrate binding pocket and 2- and 3-hydroxyl groups of xylose at subsite +1 hydrogen bond to the enzyme.

Purpose: Plasminogen has been detected in the corneal stroma after tissue injury and interacts with corneal fibroblasts during wound healing. We examined the effect of plasminogen on phagocytic activity of corneal fibroblasts., Methods: Cultured human corneal fibroblasts were exposed to plasminogen and then incubated with fluorescent microparticles before measurement of phagocytic activity by confocal microscopy or flow cytometry. The binding of corneal fibroblasts to immobilized plasminogen was quantitated with a real-time biomolecular interaction assay. The production of urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), and IL-1β by corneal fibroblasts was measured by fibrin zymography, by immunoblot analysis or gelatin zymography, or with an enzyme-linked immunosorbent assay, respectively., Results: Plasminogen increased phagocytic activity of corneal fibroblasts in a concentration- and time-dependent manner, with the maximal effect apparent at 30 μg/mL and 24 hours. Corneal fibroblasts bound to immobilized plasminogen in a manner dependent on time and cell number, and the stimulatory effect of plasminogen on phagocytic activity was blocked in the presence of epsilon-aminocaproic acid, an inhibitor of plasminogen binding to cell surface receptors. Plasminogen-induced phagocytic activity was not associated with changes in the production of uPA, MMPs, or IL-1β by corneal fibroblasts., Conclusions: Plasminogen induced phagocytic activity in corneal fibroblasts in a manner dependent on its binding to the cell surface. This effect was not associated with increased production of proteases or IL-1β. Thus, plasminogen may promote the clearance of foreign particles or damaged tissue components by corneal fibroblasts early after tissue injury.

Purpose: Staphylococcus aureus is a common cause of corneal ulceration, and staphylokinase (SAK) produced by this bacterium is a plasminogen activator. To investigate the pathogenesis of corneal ulceration induced by S. aureus, we examined the effects of bacterial culture broth and SAK on collagen degradation in a culture model in which human corneal fibroblasts are embedded in a collagen gel., Methods: Corneal fibroblasts embedded in collagen were exposed to S. aureus culture broth or SAK. Collagen degradation was assessed by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Expression of pro-matrix metalloproteinase-1 (pro-MMP-1) was detected by immunoblot analysis as well as reverse transcription and real-time polymerase chain reaction analysis., Results: Both S. aureus culture broth and SAK markedly increased collagen degradation in the presence of corneal fibroblasts and plasminogen. This effect of the culture broth was dependent on cell number to a greater extent than was that of SAK. Whereas the culture broth also increased the expression of pro-MMP-1 in corneal fibroblasts at both mRNA and protein levels, SAK did not., Conclusions: Our results suggest that S. aureus may promote collagen degradation both by upregulating pro-MMP1 expression in corneal fibroblasts, with pro-MMP-1 then being converted to active MMP-1 by plasmin, and by directing plasmin activity toward collagen in a SAK-dependent manner.

Endoxylanases are important enzymes in bioenergy research because they specifically hydrolyze xylan, the predominant polysaccharide in the hemicellulose fraction of lignocellulosic biomass. For effective biomass utilization, it is important to understand the mechanism of substrate recognition by these enzymes. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases classified into glycoside hydrolase family 30 (GH30) were quite different. While the functional differences have been described, the mechanism of substrate recognition is still unknown. Therefore, a gene encoding a putative GH30 endoxylanase was cloned from Streptomyces turgidiscabies C56, and the recombinant enzyme was purified and characterized. GH30 glucuronoxylan-specific xylanase A of Streptomyces turgidiscabies ( St Xyn30A) showed hydrolytic activity with xylans containing both glucuronic acid and the more common 4- O -methyl-glucuronic acid side-chain substitutions but not on linear xylooligosaccharides, suggesting that this enzyme requires the recognition of glucuronic acid side chains for hydrolysis. The St Xyn30A limit product structure was analyzed following a secondary β-xylosidase treatment by thin-layer chromatography and mass spectrometry analysis. The hydrolysis products from both glucuronoxylan and 4- O -methylglucuronoxylan by St Xyn30A have these main-chain substitutions on the second xylopyranosyl residue from the reducing end. Because previous structural studies of bacterial GH30 enzymes and molecular modeling of St Xyn30A suggested that a conserved arginine residue (Arg296) interacts with the glucuronic acid side-chain carboxyl group, we focused on this residue, which is conserved at subsite -2 of bacterial but not fungal GH30 endoxylanases. To help gain an understanding of the mechanism of how St Xyn30A recognizes glucuronic acid substitutions, Arg296 mutant enzymes were studied. The glucuronoxylan hydrolytic activities of Arg296 mutants were significantly reduced in comparison to those of the wild-type enzyme. Furthermore, limit products other than aldotriouronic acid were observed for these Arg296 mutants upon secondary β-xylosidase treatment. These results indicate that a disruption of the highly conserved Arg296 interaction leads to a decrease of functional specificity in St Xyn30A, as indicated by the detection of alternative hydrolysis products. Our studies allow a better understanding of the mechanism of glucuronoxylan recognition and enzyme specificity by bacterial GH30 endoxylanases and provide further definition of these unique enzymes for their potential application in industry. IMPORTANCE Hemicellulases are important enzymes that hydrolyze hemicellulosic polysaccharides to smaller sugars for eventual microbial assimilation and metabolism. These hemicellulases include endoxylanases that cleave the β-1,4-xylose main chain of xylan, the predominant form of hemicellulose in lignocellulosic biomass. Endoxylanases play an important role in the utilization of plant biomass because in addition to their general utility in xylan degradation, they can also be used to create defined compositions of xylooligosaccharides. For this, it is important to understand the mechanism of substrate recognition. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases that are classified into glycoside hydrolase family 30 (GH30) were distinct, but the difference in the mechanisms of substrate recognition is still unknown. We performed characterization and mutagenesis analyses of a new bacterial GH30 endoxylanase for comparison with previously reported fungal GH30 endoxylanases. Our study results in a better understanding of the mechanism of substrate specificity and recognition for bacterial GH30 endoxylanases. The experimental approach and resulting data support the conclusions and provide further definition of the structure and function of GH30 endoxylanases for their application in bioenergy research., (Copyright © 2018 American Society for Microbiology.)

Taste disorders are one of the most common complications in patients undergoing allogeneic hematopoietic cell transplantation (HCT). They persist in some patients as a late complication 3 months or more after HCT. Therefore, we conducted a cross-sectional study to evaluate the prevalence and predictive factors of late taste disorders, with the help of a self-reporting and closed-ended questionnaire, which was distributed among 91 patients in our institute. The median age at this study was 50 (range, 25-69) years. The median follow-up period was 54 (range, 3-234) months after HCT. Taste disorders were observed in 43 patients (47%). The most frequent form of late taste disorders was reduced appetite in 18 patients (20%). The most frequent form of decline of basic taste was umami, which was observed in 12 patients (13%). Almost all taste disorders were mild in their severity. Multivariate logistic regression analyses showed that the duration of less than 1 year post HCT and the presence of oral chronic graft-versus-host disease are important risk factors for late taste disorders in survivors of HCT. These data suggested that taste disorders usually return to normal levels more than a year after HCT in most recipients.

Objectives: Falls and fall-related injuries are major problems in hospitals. In hematologic patients, both disease and its treatment, including chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT), can cause anemia, febrile neutropenia, and bleeding tendency, which may result in falls and fall-related injuries., Materials and Methods: We retrospectively analyzed 397 consecutive admissions to the hematology unit at our institute which included 201 adult patients with hematologic disease., Results and Conclusions: A total of 56 fall events were observed in 43 patients, and the incidence of falls was 2.49 per 1000 person-days. The median hemoglobin, platelet, and serum albumin levels prior to fall events were 8.65g/dl (range, 6.3-12.7), 38×10 9 /l (range, 7-454), and 2.85g/dl (range, 1.6-4.3), respectively. Despite the presence of thrombocytopenia among the majority of patients who fell, no serious injury was observed. Multiple variable logistic regression analysis demonstrated that age older than 65years (hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.17-6.99, P=0.02), admission for allo-HCT (HR, 9.48; 95% CI, 3.35-26.80, P<0.001), hypnotic medication (HR, 3.57; 95% CI, 1.56-8.20, P=0.002), urinary or intravenous catheter placement (HR, 2.34; 95% CI, 1.08-5.09, P=0.03), and hypoalbuminemia (HR, 2.30; 95% CI, 1.07-4.96, P=0.03) were significantly associated with increased fall risk. These findings indicated that special attention should be paid to patients with such risk factors during their treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The understanding of fracture phenomena of a material at extremely high strain rates is a key issue for a wide variety of scientific research ranging from applied science and technological developments to fundamental science such as laser-matter interaction and geology. Despite its interest, its study relies on a fine multiscale description, in between the atomic scale and macroscopic processes, so far only achievable by large-scale atomic simulations. Direct ultrafast real-time monitoring of dynamic fracture (spallation) at the atomic lattice scale with picosecond time resolution was beyond the reach of experimental techniques. We show that the coupling between a high-power optical laser pump pulse and a femtosecond x-ray probe pulse generated by an x-ray free electron laser allows detection of the lattice dynamics in a tantalum foil at an ultrahigh strain rate of [Formula: see text] ~2 × 10 8 to 3.5 × 10 8 s -1 . A maximal density drop of 8 to 10%, associated with the onset of spallation at a spall strength of ~17 GPa, was directly measured using x-ray diffraction. The experimental results of density evolution agree well with large-scale atomistic simulations of shock wave propagation and fracture of the sample. Our experimental technique opens a new pathway to the investigation of ultrahigh strain-rate phenomena in materials at the atomic scale, including high-speed crack dynamics and stress-induced solid-solid phase transitions.

Importance: Ocular inflammation is occasionally observed after vaccinations, and most of them resolve without permanent visual disturbances. However, there are some rare cases of severe ocular complications following vaccinations., Objective: To report the findings in an infant boy who developed an acute loss of vision bilaterally after Haemophilus influenzae type b, Pneumococcal conjugate vaccination, and measles and rubella vaccination. His vision did not recover., Design, Setting, and Participant: A retrospective review of the medical records of a 13-month-old Japanese boy., Main Outcomes and Measures: Fundus and fluorescein angiographic findings, ultrasonographic and optical coherence tomographic images, and electroretinographic findings., Results: A healthy 13-month-old boy had an acute loss of vision in both eyes 31 days after Haemophilus influenzae type b and Pneumococcal conjugate vaccinations and 24 days after a measles and rubella vaccination. He also developed a common cold 10 days before the vision loss. Ultrasonography showed an exudative retinal detachment 1 day after the onset of the visual reduction; however, his fundi appeared normal 4 days later. His eyes did not pursue objects, and pupillary light reflexes were not present. No signs of anterior uveitis were noted. He was treated with corticosteroids, but his vision did not improve. The retinal vessels gradually attenuated, and diffuse small white punctate lesions appeared in the deep retina. Optical coherence tomography showed a thinner outer nuclear layer and an absent ellipsoid zone. The electroretinograms were nonrecordable. These findings suggested a severe impairment of the photoreceptors, especially their outer segments. Western blot analysis of the patient's sera detected an antibody against recoverin, a calcium-binding protein of photoreceptors., Conclusions and Relevance: We hypothesize that an infection induced severe chorioretinitis with an exudative retinal detachment, which then produced an autoantibody against recoverin. The autoantibody then altered the function of the photoreceptors very rapidly. The initial infection may have been caused by the measles and rubella vaccination. However, because to our knowledge this has not been reported previously, the visual loss after the vaccinations may have been an extremely rare event that was coincidental or may have been related to the vaccination.

Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis worldwide.　In Japan, the treatment for use as an initial therapy was established in Guidelines for the Treatment of Childhood IgA nephropathy; however, no rescue therapy for recurrent or steroid-resistant pediatric IgAN was established.　We report here a 15-year-old boy with severe IgAN, who was treated with combination therapy involving prednisolone, mizoribine, warfarin, and dilazep dihydrochloride for 2 years.　The response to the combination therapy was good and both proteinuria and hematuria disappeared.　The pathological findings at the second renal biopsy were improved and PSL was discontinued.　However, due to nonadherence to the treatment regimen and tonsillitis, macrohematuria and an increase of proteinuria were again observed and the pathological findings at the third renal biopsy showed clear deterioration.　The patient was, therefore, diagnosed with recurrent IgAN.　Tonsillectomy plus methylprednisolone pulse therapy (TMP) was performed as a rescue therapy for the recurrence of severe IgAN.　Both the proteinuria or hematuria subsequently disappeared, and no proteinuria or hematuria has been observed and kidney function has remained normal during a 5-year follow-up.　The patient experienced no severe side effects associated with the drug regimens.　In conclusion, our case suggests that TMP may be an effective and useful rescue therapy for recurrent IgAN after multi-drug combination therapy.

Introduction: Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda., Methods: We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation., Results: The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans' caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers., Conclusions: Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.

We should take care of the occurrences of apnea and hypopnea after emergence from general anesthesia in the children with sleep apnea syndrome (SAS) due to an increase in sensitivity to opioid agonists given for previous recurrent hypoxia. Preoperative assessment for SAS with apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum artery oxygen saturation by pulse oxymetry (lowest SpO2) obtained from polysomnography (PSG) test could help to predict the postoperative respiratory depression. In perioperative management in the children with SAS who are candidates for adenotonsillectomy, the dose of opioid agonists during anesthesia maintenance for purpose of postoperative analgesia and sedation should be reduced; postoperative respiratory and circulatory management with monitoring of respiratory movement of the thoracoabdominal part, and electrographic (ECG) and SpO2 monitoring should be continued intensively under long-term oxygen administration; and airway management, nasal continuous positive airway pressure (nCPAP), and artificial ventilation should be prepared for the occurrence of postoperative respiratory depression.

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.

An anti-hepatitis A virus (HAV)-specific immunoglobulin M capture enzyme-linked immunosorbent assay (anti-HAV IgM ELISA) kit was re-designed for laboratory use and compared with a commercial anti-HAV IgM detection system using 58 serum samples collected from patients, vaccines, and healthy individuals. Because concordance between the two systems was high (r = 0.93, P < 0.05), 19 sets of serum and fecal samples obtained from individuals exposed to an HAV outbreak were also examined. Serum levels of anti-HAV IgM were determined using the in-house ELISA kit and the HAV genome in fecal samples was detected using the polymerase chain reaction (PCR). Among the 19 sets of sample, 14 were positive for both anti-HAV IgM and the HAV genome. All of those whose serum samples were anti-HAV IgM negative were also negative for the HAV genome in fecal samples. The results of the in-house IgM ELISA were consistent with those of the HAV genome detected by PCR and with the commercial IgM ELISA. The in-house anti-HAV IgM ELISA kit was therefore proven suitable for laboratory use and applicable to epidemiological studies of HAV infection.

We have developed synchrotron x-ray absorption and diffraction techniques for measuring the density and structure of noncrystalline materials at high pressures and have applied them to studying the behavior of SiO2 glass. The density, coordination number, and Si-O bond length at a pressure of 50 GPa were measured to be 4.63 g/cm;{3}, 6.3, and 1.71 A, respectively. Based on the density data measured in this study and the sound velocity data available in the literature, the bulk modulus at 50 GPa was estimated to be 390 GPa, which is consistent with the pressure dependence of the density in the vicinity of 50 GPa. These results, together with the knowledge from our exploratory study, suggest that SiO2 glass behaves as a single amorphous polymorph having a sixfold-coordinated structure at pressures above 40-45 GPa up to at least 100 GPa.

CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein whose expression is up-regulated in squamous cell carcinomas (SCCs) of the lung, esophagus, and uterus. The purpose of this study was to evaluate CD109 expression in oral tumors, including premalignant lesions, and to assess the clinical application of CD109 in oral cancer. CD109 expression in oral normal and tumor tissues from 124 patients was examined by immunohistochemical staining with anti-CD109 antibody, and significant relations between clinical features and CD109 expression were statistically assessed. We found that high levels of CD109 expression were frequently detected in SCCs and premalignant lesions of the oral cavity, but not in normal squamous epithelia. The CD109 expression level was higher in well-differentiated SCCs than in poorly differentiated SCCs. Furthermore, premalignant lesions highly expressing CD109 showed higher risk to progress to SCCs. Oral SCC cell lines overexpressing CD109 exhibited accelerated cell growth in vitro compared with control cell lines. In addition, overexpression of CD109 impaired the transforming growth factor (TGF)-beta1-mediated suppression of cell growth. These findings suggest that CD109 plays a role in the development of oral cancers, and is a useful prognostic marker to predict malignant transformation of premalignant lesions.

To clarify the transcellular transport of organic cations via basolateral and apical transporters, we established double-transfected Madin-Darby canine kidney (MDCK) cells expressing both human organic cation transporter hOCT1 and hMATE1 (MDCK-hOCT1/hMATE1), and hOCT2 and hMATE1 (MDCK-hOCT2/hMATE1) as models of human hepatocytes and renal epithelial cells, respectively. Using the specific antibodies, hOCT1 and hMATE1 or hOCT2 and hMATE1 were found to be localized in the basolateral and apical membranes of MDCK-hOCT1/hMATE1 or MDCK-hOCT2/hMATE1 cells, respectively. A representative substrate, [14C]tetraethylammonium, was transported unidirectionally from the basolateral to apical side in these double transfectants. The optimal pH was showed to be 6.5 for the transcellular transport of [14C]tetraethylammonium, when the pH of the incubation medium on the apical side was varied from 5.5 to 8.5. The basolateral-to-apical transport also decreased in the presence of 10 mM 1-methyl-4-phenylpyridinium or 1 mM levofloxacin on the basolateral side of both double transfectants. In MDCK-hOCT2/hMATE1 cell monolayers, but not in MDCK-hOCT1/hMATE1 cell monolayers, the accumulation of [14C]tetraethylammonium was decreased in the presence of 10 mM 1-methyl-4-phenylpyridinium, but significantly increased in the presence of 1 mM levofloxacin. The uptake of [14C]tetraethylammonium, [3H]1-methyl-4-phenylpyridinium, [14C]metformin and [3H]cimetidine, but not of [14C]procainamide and [3H]quinidine, by HEK293 cells was stimulated by expression of the hOCT1, hOCT2 or hMATE1 compared to control cells. However, transcellular transport of [14C]procainamide and [3H]quinidine was clearly observed in both double-transfectants. These cells could be useful for examining the routes by which compounds are eliminated, or predicting transporter-mediated drug interaction.

CD109 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, which is a member of the alpha2-macroglobulin/C3, C4, C5 family of thioester-containing proteins. It has been reported that CD109 is expressed in a subset of hematopoietic cells, endothelial cells and several kinds of human tumors. Herein it is reported that the CD109 protein is preferentially expressed in lung squamous cell carcinomas compared with other types of lung carcinoma including adenocarcinomas, large cell carcinomas and small cell carcinomas. Immunohistochemical staining of surgically resected lung specimens using an anti-CD109 antibody detected CD109 expression in basal cells of bronchial and bronchiolar epithelia and myoepithelial cells of bronchial secretary glands, but not in bronchial and bronchiolar apical epithelial cells and alveolar epithelial cells. Furthermore, the CD109 immunoreactivity was observed in squamous cell carcinomas at a high frequency compared with other types of lung carcinoma. Although the detailed function of CD109 protein is unclear, these results suggest that CD109 expression may play a role in the development of lung squamous cell carcinoma.

The substrate specificities of human (h) multidrug and toxin extrusion (MATE) 1 and hMATE2-K were examined to find functional differences between these two transporters by the transfection of the cDNA of hMATE1 and hMATE2-K into HEK293 cells. Western blotting revealed specific signals for hMATE1 and hMATE2-K consistent with a size of 50 and 40kDa, respectively, in the transfectants as well as human renal brush-border membranes under reducing conditions. In the presence of oppositely directed H(+)-gradient, the transport activities of various compounds such as tetraethylammonium, 1-methyl-4-phenylpyridinium, cimetidine, metformin, creatinine, guanidine, procainamide, and topotecan were stimulated in hMATE1- and hMATE2-K-expressing cells. In addition to cationic compounds, anionic estrone sulfate, acyclovir, and ganciclovir were also recognized as substrates of these transporters. Kinetic analyses demonstrated the Michaelis-Menten constants for the hMATE1-mediated transport of tetraethylammonium, 1-methyl-4-phenylpyridinium, cimetidine, metformin, guanidine, procainamide, topotecan, estrone sulfate, acycrovir, and ganciclovir to be (in mM) 0.38, 0.10, 0.17, 0.78, 2.10, 1.23, 0.07, 0.47, 2.64, and 5.12, respectively. Those for hMATE2-K were 0.76, 0.11, 0.12, 1.98, 4.20, 1.58, 0.06, 0.85, 4.32, and 4.28, respectively. Although their affinity for hMATE1 and hMATE2-K was similar, the zwitterionic cephalexin and cephradine were revealed to be specific substrates of hMATE1, but not of hMATE2-K. Levofloxacin and ciprofloxacin were not transported, but were demonstrated to be potent inhibitors of these transporters. These results suggest that hMATE1 and hMATE2-K function together as a detoxication system, by mediating the tubular secretion of intracellular ionic compounds across the brush-border membranes of the kidney.