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The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate (FS) cells are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands. They form follicular lumens, which are sealed by tight junctions (TJs). Although FS cells are hypothesized to contribute to fine-tuning of endocrine cells, little is known about the exact roles of FS cells. Here, we investigated the molecular composition of TJs in FS cells. We demonstrated that occludin is a good marker for TJs in the pituitary gland and examined the structure of the lumens surrounded by FS cells. We also found that claudin-9 is a major component of TJs in the FS cells. In immunoelectron microscopy, claudin-9 was specifically localized at TJs of the FS cells. The expression of claudin-9 was gradually increased in the pituitary gland after birth, suggesting that claudin-9 is developmentally regulated and performs some specific functions on the paracellular barrier of follicles in the pituitary gland. Furthermore, we found that angulin-1, angulin-2, and tricellulin are localized at the tricellular contacts of the FS cells. Our findings provide a first comprehensive molecular profile of TJs in the FS cells, and may lead us towards unveiling the FS cell functions.

Aims This study aimed to investigate the effect of Bacillus subtilis var. natto on the susceptibility of the model host, Caenorhabditis elegans, to bacterial infection. Methods and results Caenorhabditis elegans worms were fed with a standard food consisting of Escherichia coli OP50 strain (control) or B. subtilis (natto) during their larval stage. The worms were then infected with pathogenic bacteria. We analyzed their survival time and RNA sequencing-based transcriptome. Upon infection with Staphylococcus aureus and Enterococcus faecalis, the survival time of B. subtilis (natto)-fed worms was longer than that of the control. Transcriptome analyses showed upregulation of genes associated with innate immunity and defense response to gram-positive bacteria in B. subtilis (natto)-fed worms. Conclusions Bacillus subtilis (natto) conferred an increased resistance of C. elegans to gram-positive bacteria. Our findings provided insights into the molecular mechanisms underlying B. subtilis (natto)-regulated host immunity and emphasized its probiotic properties for preventing and alleviating infections caused by gram-positive bacteria. Significance and impact of the study To the best of our knowledge, this is the first study to show that B. subtilis (natto) confers specific resistance against gram-positive bacteria.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and in the outer and inner medulla. Proliferating stem cells expressing the nuclear transcription factor Pax2 give rise to renal epithelial cells. Pax2 expression ends once the epithelial cells differentiate into mature proximal and distal tubules, whereas expression of the related Pax8 protein continues. The collecting tubules and renal medulla are derived from Pax2-positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the crucial role of Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established. Methods To examine the roles of Pax2 and Pax8 in the adult mouse kidney, we deleted either Pax2, Pax8, or both genes in adult mice and examined the resulting phenotypes and changes in gene expression patterns. We also explored the mechanism of Pax8-mediated activation of potential target genes in inner medullary collecting duct cells. Results Mice with induced deletions of both Pax2 and Pax8 exhibit severe polyuria that can be attributed to significant changes in the expression of solute carriers, such as the urea transporters encoded by Slc14a2, as well as aquaporins within the inner and outer medulla. Furthermore, Pax8 expression is induced by high-salt levels in collecting duct cells and activates the Slc14a2 gene by recruiting a histone methyltransferase complex to the promoter. Conclusions These data reveal novel functions for Pax proteins in adult renal epithelia that are essential for retaining water and concentrating urine.

Background Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute injury may be repaired, a process that includes a decrease in the number of myofibroblasts in the interstitium and degradation of the accumulated extracellular matrix, leaving little evidence of prior injury. Methods To investigate whether activated fibroblasts demonstrate changes in gene expression that correspond with regression after acute injury but are not observed in chronic models of fibrosis, we used microarrays to analyze gene expression patterns among fibroblast populations at different stages of injury or repair. We then mined the data for signaling pathways in fibroblasts corresponding to the acute proliferative, regression, and chronic phases of renal injury. Results We identified multiple gene clusters with changes that correlate with the three phases of renal injury, including changes in levels of receptors for the antifibrotic factor PGE2. In adult renal fibroblast cultures, PGE2 was able to upregulate many genes that are suppressed by the profibrotic cytokine TGF- β , whereas many PGE2-downregulated genes were activated by TGF- β . High levels of TGF- β suppressed expression of a subset of PG receptors in fibroblast cultures, making these cells resistant to any effects of PGE2. Conclusions Inherent gene expression changes in activated fibroblasts accompany the transition from AKI to repair and regeneration. In chronic models, however, activated fibroblasts are resistant to the antifibrotic effects of PGE2 due to suppression of a subset of PGE receptors.

Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues resembling vestibular sensory epithelia-has sparked interest in applications such as regeneration, drug discovery, and disease modeling. In this study, we adapted this protocol for a novel mouse embryonic stem cell line with a fluorescent reporter for Pax2 expression. We used Pax2EGFP/+ organoid formation to model otic induction, the pivotal developmental event when preplacodal tissue adopts otic fate. We found upregulation of Pax2 and activation of ERK downstream of fibroblast growth factor signaling in organoid formation as in embryonic inner ear development. Pax2 expression was evident from the EGFP reporter beginning at the vesicle formation stage and persisting through generation of the sensory epithelium. The native ventralizing signal sonic hedgehog was largely absent from the cell aggregates as otic vesicles began to form, confirming the dorsal vestibular organoid fate. Nonetheless, cochlear- or vestibular-like neurons appeared to delaminate from the derived otic vesicles and formed synaptic contacts with hair cells in the organoids. Cell lines with transcriptional reporters such as Pax2EGFP/+ facilitate direct evaluation of morphological changes during organoid production, a major asset when establishing and validating the culture protocol.

Epidemiological findings indicate that acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD), although the molecular mechanism remains unclear. Genetic fate mapping demonstrated that nephrons, functional units in the kidney, are repaired by surviving nephrons after AKI. However, the cell population that repairs damaged nephrons and their repair capacity limitations remain controversial. To answer these questions, we generated a new transgenic mouse strain in which mature proximal tubules, the segment predominantly damaged during AKI, could be genetically labelled at desired time points. Using this strain, massive proliferation of mature proximal tubules is observed during repair, with no dilution of the genetic label after the repair process, demonstrating that proximal tubules are repaired mainly by their own proliferation. Furthermore, acute tubular injury caused significant shortening of proximal tubules associated with interstitial fibrosis, suggesting that proximal tubules have a limited capacity to repair. Understanding the mechanism of this limitation might clarify the mechanism of the AKI-to-CKD continuum.

Background There are significant differences in the proportion of home death of cancer patients, 8.3% in Japan and 27.4% in the United Kingdom. However 63% of Japanese population hope home palliative care in their last 6 months. The palliative care unit (PCU) at the National Cancer Center Hospital East changed the administrative policy to amend patients unmet needs and strengthen the transition to palliative home care. Previous studies about the discharge from hospice indicated the factor of old age, female and poor performance status (PS). This study aimed to identify the factors tended to transfer to palliative home care in Japan. Methods We reviewed the medical records of 333 consecutive cancer patients admitted to our PCU during period from October 2010 until September 2011. Patients transferred to other hospitals were excluded in this study. We identified variables associated with the discharged group and the deceased at PCU group, using the univariate and multivariate analyses. Results There were 311 patients (Pts) during periods, 68 Pts (21.9%) discharged to palliative home care and 243 Pts (78.1%) deceased in our PCU. Characteristics of discharged group (68 Pts) were below: over 65 year-old (32%), female (53.0%), PS 4 (7.4%), a relatively good amount of oral intake in first hospital day (76.1%), morphine use over 120mg/day at admission (23.5%), living alone (9.7%), married (74.6%), primary caregiver was partner (67.7%). Univariate and multivariate analysis identified: admission from their own home (OR 4.41; 95%CI 2.08-9.75), a good PS of > 4 (OR 6.21; 95%CI 2.11-23.18), a heart rate Conclusion Our study indicated the factors tended to transfer to palliative home care from PCU in Japan, however this study had some limitations. A prospective study is required to validate these factors. Disclosure All authors have declared no conflicts of interest.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

We describe the development of neurological signs in four juvenile black-and-white ruffed lemurs (Varecia variegate), housed at a petting zoo in Japan. The clinical course was severe, with three lemurs dying within 1 day of the appearance of clinical signs. The other lemur was treated and survived. Pathological analyses demonstrated meningitis and the presence of gram-negative bacilli in the cerebrum, cerebellum, palatine tonsil and liver. Klebsiella pneumoniae was isolated from the brain of all of the dead lemurs. Multilocus sequence typing analysis showed that all the isolates were sequence type 86 (ST86). To our knowledge, this is the first determination of K. pneumoniae infection in ruffed lemurs of this genus. K. pneumoniae infection may represent a risk to lemurs and people who come into contact with infected animals.

The possible existence of \eta'-nucleus bound states has been put forward through theoretical and experimental studies. It is strongly related to the \eta' mass at finite density, which is expected to be reduced because of the interplay between the $U_A(1)$ anomaly and partial restoration of chiral symmetry. The investigation of the C(p,d) reaction at GSI and FAIR, as well as an overview of the experimental program at GSI and future plans at FAIR are discussed., Comment: 7 pages, 3 figures; talk at the International Conference on Exotic Atoms and Related Topics (EXA2014), Vienna, Austria, 15-19 September 2014. in Hyperfine Interactions (2015)

The cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from the synovial fluid. The contributions of these two routes as nutritional pathways are not known in detail. In this study, we injected [3H]methyl glucose as a tracer intravenously or directly into the knee of rabbits. Tracer concentrations in plasma, synovial fluid, the posterior cruciate ligament (PCL), and the lateral collateral ligament (LCL) were analysed by a pharmacokinetic compartment model. The contribution of [3H]methyl glucose permeation from the synovial fluid during steady state was calculated at 44.3% in the PCL and at 39.0% in the LCL. Although these results indicated that more than half the nutrition for both ligaments is provided by its vascular supply, synovial fluid permeation is also an important transport route for small molecules for the PCL and the LCL, which is an extra-articular structure.

An ambulatory acceleration monitor was developed and used to evaluate physical activity in the elderly. The ECG and accelerations at the wrist, waist, and ankle were recorded, and the heart rate and frequency and amplitude of accelerations per unit time were evaluated in both working and retired elderly women performing normal daily activities. The heart rate closely paralleled wrist acceleration. The behaviour patterns of the subjects could be differentiated by time interval signals and histogram distributions. This system appears to be an effective method of understanding and describing the characteristic activities of the elderly in a quantitative and objective fashion.

The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.

The anterior cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from synovial fluid. In order to quantitate the relative importance of these two routes and to compare the anterior cruciate ligament with the medial collateral ligament, we injected [3H]methyl-glucose as a tracer intravenously or directly into the knee in rabbits. Tracer concentrations in plasma, synovial fluid, the anterior cruciate ligament and the medial collateral ligament were analysed by a pharmacokinetic compartment model developed for this study. The contribution of [3H]methyl-glucose permeation from the synovial fluid was calculated at 59.7% in the anterior cruciate ligament and at 18.1% in the medial collateral ligament. We concluded from these results that the nutrition for the medial collateral ligament, which is an extraarticular structure, is provided mainly by its vascular supply. In contrast, synovial fluid permeation is an important transport route for small molecules for the normal anterior cruciate ligament.

We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor for cholinergic neurons. However, it has not yet been determined whether the action is derived from the interaction of IL-3 with IL-3 receptors. As the first step to study IL-3 receptors in the central nervous system, we examined the presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal transduction for IL-3 in hematopoietic cells, was demonstrated in neurons throughout the brain. This was confirmed in primary cultured neurons and neuronal cell lines by immunocytochemistry and flow cytometry. The staining intensity varied among regions and the most intense immunoreactivity for IL-3RAA was found in large neurons in the magnocellular basal nuclei, pyramidal cells in the cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only cholinergic cell lines derived from the septal region but also other neuronal cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we conclude that IL-3RAA is present in a wide variety of neurons in the brain including cholinergic neurons of the basal forebrain. Western blot analysis revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both in neuronal and IL-3-dependent cell lines.

Abdominal ultrasonographic screening for cancer was performed in 6001 Hiroshima and Nagasaki A-bomb exposed and comparison subjects, all members of the Adult Health Study of the Radiation Effects Research Foundation, formerly the Atomic Bomb Casualty Commission. This study yielded 20 cancers, including 7 hepatocellular, 3 gastric, 3 renal and 2 urinary bladder cancers; one cancer each of the ovary, pancreas, colon and ureter; and one cancer metastatic to the liver, whose primary was unknown. Seventeen of these 20 subjects manifested no symptoms or signs of their disease. A variety of additional tumors, unproven and probably benign, including uterine myomata, and other abnormalities were also detected. Abdominal ultrasonographic screening greatly assisted in the detection of cancers, most of which neither the patients nor their physicians were aware. In this screened fixed population sample the cancer detection rate was 0.33%, exceeding any such rates previously reported in the medical literature.

This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.

金沢大学医薬保健研究域医学系, The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3 -/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

The indication for sleeve lobectomy of the middle lobe is limited, because the frequency of cancer occupying both the middle lobe and its bifurcation is low and the more commonly used middle and lower lobectomy is an alternate procedure. However, if a patient has accompanying cardiopulmonary restriction, lung preservation is paramount. We present a patient with hilar lung cancer (TisN0M0) associated with progressive cardiomyopathy, who underwent sleeve lobectomy of the middle lobe; the cancer took a favorable course.

A pedometer is popular as a quantitative evaluator of walking. However it may not measure the number of steps for elderly. In this study, we attempted to propose a step count algorithm based on a filter bank and a threshold processing to improve the accuracy of an accelerometer-type step counter for elderly. The waist acceleration signals during a self-paced walking were recorded form 74 participants of the gait training at the commuting rehabilitation services center using triaxial accelerometer. A conventional accelerometer-type pedometer was also attached close to the accelerometer. They walked approximately 20 m. As a result of the algorithm verification using 74 elderly data sets, 57 subjects could be estimated with less than 10% error. We suggest that our step count algorithm is suitable for estimating the number of steps for elderly.

An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome P-450-dependent monooxygenases. To investigate its effect on steroid oxidoreductases, in vitro studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3 beta-hydroxy-5-ene-steroid oxidoreductase/isomerase and NADH-linked 20 alpha-hydroxysteroid oxidoreductase for steroid substrate and the Ki values were 2.9 and 0.9 microM, respectively. In contrast, ketoconazole inhibited neither 17 beta-hydroxysteroid oxidoreductase nor NADPH-linked 20 alpha-hydroxysteroid oxidoreductase, indicating that the two 20 alpha-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome P-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides.

We investigated the time course of cortical activity in the brain related to cold epidermal touch stimulation at 4 degree Celsius and touch stimulation at a normal temperature of 14 degree Celsius to the palm of the hand in 20 normal human subjects (average age of 29.1plusmn6.0 years), using magneto-encephalography (MEG). The time course of cortical activities with cold touch stimulation to the right palm showed cortical activities in the posterior portion of the posterior cingulate cortex at an average of 214plusmn 101.2 ms before cold touch stimulation, in the ipsilateral somatosensory area at an average of 39.6plusmn37.5 ms, in the contralateral primary somatosensory area at an average of 64.8plusmn28.4 ms, and then in the anterior cingulate cortex, including a portion of the corpus callosum, at an average of 302plusmn126 ms, following cold touch stimulation. It was noted that the time course of cortical activities to cold touch stimulation to the palm showed a difference, compared with normal temperature touch stimulation: cortical activities were observed in the ipsilateral sensory region at an average of 39.6plusmn37.5 ms following cold touch stimulation, but such activities were not observed following normal temperature touch stimulation. On the other hand, there were no significant differences in the time courses of cortical activities in the contralateral primary sensory area and in cingulate regions between the two types of stimulation. The time course of brain activities in response to epidermal stimulation showed no laterality or gender difference.

We have developed a telemonitoring system of television's operation state (TVOS) in caring for elderly people living alone. A feasibility study was achieved for over three months in a home of a subject of 80-years-old female living alone. It was shown that the consistency of the daily rhythms of the TVOS and TVOS of the different pattern on every day of the week. The accumulation time of TV use of a day correlated inversely with an activity evaluated from a pedometer attached to the volunteer. The TVOS would reflect a living condition of the elderly person living alone.

This study examined the use of telecommunications for home health care and described an alternative telemedicine framework. The framework aims to transmit small but sufficient amounts of data for daily monitoring of residential subjects' basic health status. We tested the remote monitoring of heart rate and respiration. The system was tested in real home-visit rehabilitation environments and was found to be useful both for the therapist and the patients in planning and evaluating daily rehabilitation training.

The mass of the {\eta}' meson is theoretically expected to be reduced at finite density, which indicates the existence of {\eta}'-nucleus bound states. To investigate these states, we perform missing-mass spectroscopy for the (p, d) reaction near the {\eta}' production threshold. The overview of the experimental situation is given and the current status is discussed., Comment: 6 pages, 3 figures; talk at II Symposium on applied nuclear physics and innovative technologies, September 24th - 27th, 2014, Jagiellonian University, Krak\'ow Poland; to appear in Acta Physica Polonica B

Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

The load-bearing surface of the mandibular condyle presents a unique arrangement of tissues consisting of an avascular layer composed largely of collagen bundles. Fibroblasts are interspersed amongst these bundles and are generally agreed to produce the collagen. The mechanisms controlling development of these tissues have not been determined. This study was conducted to explore the role of epidermal growth factor (EGF), which appears to be important in the development of many oral tissue types as well as in the growth and differentiation of the mandibular condyle. Superficial cells of the fibrous zone of the condyle were isolated from fetal rabbit condyles and [ 3 H]thymidine incorporation into DNA measured. The application of EGF produced a significant increase in radiolabel incorporation after 2 days compared to 4 days in the controls, suggesting that EGF induced cells to enter S-phase more rapidly. Fetal condyles were also cultured on gelfoam surgical sponges for up to 21 days. Autoradiography of cultured condyles showed that cells of all three zones may potentially replicate, as indicated by incorporation of [ 3 H]thymidine. All three regions displayed greater increases in cell numbers in samples exposed to EGF than in control samples. The measurement of zone thickness in condyles cultured on gelfoam sponges with or without EGF showed that this peptide was able to re-establish thickness, bringing it in line with the relation observed when the condyles were isolated initially, particularly of the intermediate zone over a period of 21 days. As very little autoradiographic labelling occurred at this time-point in any of the zones, the increase in thickness must primarily be due to matrix production. It is concluded that EGF is one factor potentially regulating both replication and differentiation in mandibular condyle and its associated cells.

The pharmacokinetic behavior of S-allylcysteine (SAC), one of the biologically active transformation products from garlic, was investigated after oral administration to rats, mice, and dogs. SAC was rapidly and easily absorbed in the gastrointestinal tract and distributed mainly in plasma, liver, and kidney. The bioavailability was 98.2, 103.0, and 87.2% in rats, mice, and dogs, respectively. SAC was mainly excreted into urine in the N-acetyl form in rats; however, mice excreted both SAC and the N-acetyl form. The half-life of SAC was longer in dogs than in rats and mice.

18209 Background: Amrubicin, a totally synthetic 9-amino-anthracycline, has been demonstrated to have excellent antitumor activity against previously untreated SCLC. However, severe hematological toxicities were observed in previously treated SCLC when given at doses of 40 to 45 mg/m2, days 1–3. We sought to determine the maximum tolerable dose (MTD) and toxicity of amrubicin for pts with previously treated SCLC. Methods: Pts with confirmed SCLC, ECOG PS 0–1, and 20 to 74 years of age, with a history of receiving one or two regimens were eligible for the study. Pts were divided into two groups. Group R (-) consisted of pts without history of radiotherapy except prophylactic cranial irradiation. Group R (+) consisted of pts with history of irradiation up to two fields including thoracic radiotherapy. AMR was initially given at 35 mg/m2, iv, days 1–3, every 3 weeks in both groups. The dose was then increased to 40 and 45 mg/m2. Three pts were treated at each dose level in the absence of a dose limiting toxicity (DLT). All pts received prophylactic hG- CSF between days 8–13. DLT was defined as neutrophil nadir 2. A response rate of 62% was observed. Median survival time was 12 months. No treatment-related death was observed. Conclusions: The MTD in group R (-) was not determined. The MTD in group R (+) was determined as 40 mg/m2. Further data will be presented. No significant financial relationships to disclose.

7090 Background: Efficacy of high dose chemotherapy with autologous PBSCT has been demonstrated in the treatment of lymphoma. The purpose of this trial is to determine progression-free survival and long-term survival for LD-SCLC patients (pts) who responded to first-line concurrent chemo-radiotherapy followed by HD-ICE with PBSCT. Methods: Patients (pts) with pathologically proven SCLC without malignant pleural and pericardial effusion, stage II-IIIB, ECOG-PS 0–1 were eligible. All pts were treated with cisplatin (P) 60 mg/m2 day1 and etoposide (E) 100 mg/m2, days 1–3, with concurrent hyperfractionted radiotherapy initially (1.5Gy X 2/day X 15 days, total 45Gy) and then two or three cycles of chemotherapy consisted of P 60 mg/m2, day 1, and E 120 mg/m2, days 1–3, or APE (adriamycin 30 mg/m2, day 1, P 60 mg/m2, day1 and E 100 mg/m2, days 1–3) were repeated. Pts with tumor shrinkage more than 90% after initial therapy received HD-ICE (ifosfamide 3 g/m2, days 1–3, carboplatin 400 mg/m2, days 1–3, etoposide 400 mg/m2, days 1–3) followed by PBSCT. All pts received prophylactic cranial irradiation (1.5 Gy × 2/day × 9 days, total 27 Gy). Results: Between 1996 and 2001, 15 pts were eligible and all 15 pts received HD-ICE with PBSCT. Patient characteristics included M/F:14/1, median age: 55 (47–62), PS 0/1: 7/8 stage IIIA/IIIB: 7/8. Grade IV neutropenia and thorombocytopenia were observed in all pts and 93% of pts experienced neutropenic fever after HD-ICE. There was no toxic death. Median follow up time was 83.2 months. Median progression free survival time was 10. 7 months and overall median survival time (MST) was 30.9 months. Two, 3 and 5-year survival rates after initial chemoradiotherapy were 67%, 33%, 25%, respectively. Conclusion: HD-ICE with PBSCT for LD-SCLC revealed promising MST and a 5-year survival rate with manageable treatment-related toxicity. A randomized phase III study comparing chemo-radiotherapy followed by HD-ICE with PBSCT to standard chemo-radiotherapy for LD-SCLC is ongoing. No significant financial relationships to disclose.

Deuteron inelastic scattering experiments on 14 N are made at E d = 10.03, 11.65, 14.82 and 17.88 MeV, with emphasis on the isospin-forbidden excitation of the 2.31 MeV (0 + , T = 1) state. In order to clarify the reaction mechanism, we have performed analyses assuming both a direct reaction mechanism and compound nucleus formation. Direct reaction calculations using second-order DWBA reproduce fairly well the strong energy dependence of the angular distributions and of the integrated cross sections. Hauser-Feshbach (HF) calculations reproduce the pattern of the angular distributions in the lower energy region. For the isospin-allowed transitions the simple DWBA calculation gives reasonable agreement with the experiment. The present calculation shows that the observed isospin violation is well accounted for by a direct multi-step reaction mechanism assuming isospin mixing in the intermediate channels.

In measurements of the fusion cross sections of the systems 16 O + 27 Al and 19 F + 24 Mg in the energy range of 43Sc∗, 40 MeV ≲ E ∗ ≲ 80 MeV , it has been observed that the Z-distributions of the evaporation residues and the extracted critical angular momenta are the same for the two entrance channels. These features confirm that the fusion cross sections at relatively high energies are rather determined by the properties of the compound nucleus like the “statistical yrast line”.