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Complications after hematopoietic stem cell transplantation (HSCT) especially graft versus host disease (GVHD) are serious events and the keys to success of HSCT. Pathological diagnosis of complications is critical but sometimes not definite in GVHD diagnosis. In this review, we focus on the role of macrophages in HSCT complications. In the early period after HSCT, residual recipient macrophages have important roles for engraftment and rejection. Hemophagocytosis is the main feature of activated recipient macrophages. Skin lesions after HSCT are usually skin GVHD but mimicking histology of interface dermatitis is hardly differentiated. Macrophages and lymphocytes of these lesions were studied and increased numbers of macrophages were significantly associated with overall survival of HSCT. It could be suggested macrophages were good predictive markers for skin GVHD‐like lesions. Intestinal type transplantation‐associated microangiopathy (i‐TAM) is an independent pathogenesis from GVHD with serious prognosis. Activated macrophages in these lesions are important and key to the pathogenesis of i‐TAM. These activated macrophages are predominantly residual recipient tissue‐resident macrophages. Cryptogenic organizing pneumonitis is a lung complication around day 100 after HSCT caused by activated alveolar macrophages. They are donor‐derived tissue‐resident macrophages. Residual recipient and donor‐derived macrophages work in different ways in HSCT complications. [ABSTRACT FROM AUTHOR]

An etching process for SiO2 that employs atmospheric-pressure pulsed remote plasma with a mixture gas (CF4/Ar) has been demonstrated. The etch rate increased by increasing the pulse frequency and also increased rapidly with the addition of a small amount of O2 gas. A SiO2 etch rate of 400 nm/min was obtained without any bias supplied to the substrate, and more than 8 μm/min was obtained with H2O addition. The exhaust gas from the plasma source was investigated using ion attachment mass spectrometry (IAMS). With IAMS, the polymerized species were measured without the generation of fragment ions. The results suggest that HF molecules are generated by H2O addition to CF4 and that the etch rate of SiO2 depends on the density of HF molecules. [ABSTRACT FROM AUTHOR]

In situ subsurface reaction measurements of silicon nitride in a selective etching process of silicon oxide over silicon nitride using an x-ray photoelectron spectroscopy (XPS) and a Fourier transform infrared reflection absorption spectroscopy (FTIR RAS) have been carried out. Under low selectivity etching conditions using an electron cyclotron resonance plasma employing a pure octafluorocyclobutane (C[sub 4]F[sub 8]) gas, a clear difference has been observed between time-evolution spectra of FTIR RAS and those of XPS on the etched silicon nitride films. From these results it has been found that the etching reaction layer is thicker than that under highly selective etching conditions and that SiF[sub 3] bonds are located in the deeper region rather than in the shallow region of the reaction layer. On the other hand, under highly selective etching conditions employing C[sub 4]F[sub 8] gas diluted by Ar gas, it has been observed that the shallow region of the reaction layer in the etched silicon nitride films becomes C-C cross-linking-rich and CNsp² bond-rich. From these results, it is concluded that the C-C cross linking prevents CNsp² bonds from reacting with F atoms, resulting in the suppression of the etch by-products such as FCN. [ABSTRACT FROM AUTHOR]

Aims: Refractory cytopenia of childhood (RCC) is subdivided into myelodysplastic syndrome with multilineage dysplasia (MDS‐MLD) and RCC without (w/o) multilineage dysplasia (RCC without MLD). Although RCC is a histomorphological distinct entity, the bone marrow (BM) histology of RCC is not yet characterised in relation to multilineage dysplasia. We investigated the BM histological features of RCC to clarify the characteristics of BM histology of MDS‐MLD in childhood compared to RCC without MLD. Methods and results: The BM histology and cytology in 60 RCC patients from the nationwide registry of Japanese Childhood AA‐MDS Study Group were reviewed retrospectively. Although a thorough genetic assessment, including GATA2 and/or SAMD9, was not performed, inherited BM failure disorders were excluded by a cytogenetic test, a chromosome fragility test and a telomere length measurement along with careful clinical assessments. Among the 60 patients, 20 (33%) of MDS‐MLD and 40 (67%) of RCC w/o MLD were classified according to their BM cytology. We then investigated the BM histological features and compared them between the two groups. The BM cellularity, distribution pattern of haematopoiesis, frequency of left‐shifted granulopoiesis, numbers of micromegakaryocytes and p53 immunostaining‐positive cells were significantly different between the groups. The BM histology of MDS‐MLD in childhood showed higher cellularity, the more common occurrence of diffuse distribution pattern, more frequently left‐shifted granulopoiesis and more micromegakaryocytes and p53 immunostaining‐positive cells than RCC without MLD. Conclusions: Our results showed that MDS‐MLD in childhood had a characteristic BM histology compared to RCC without MLD. The clinical relevance of MDS‐MLD in childhood needs to be evaluated. [ABSTRACT FROM AUTHOR]

We review new trends of agricultural applications of atmospheric‐pressure plasmas for decontaminating agricultural products and enhancing seed germination and growth of plants and beneficial microorganisms. We classify the decontamination techniques into three kinds of treatments, which are gas‐phase, in‐liquid, and plasma‐activated liquid treatments, and introduce recent studies mainly after 2010, discussing the inactivation mechanism of microorganisms in each treatment. Likewise, we categorize the enhancement techniques into the same three kinds of treatments, and introduce the growth enhancements in detail, discussing the mechanisms and future prospects. [ABSTRACT FROM AUTHOR]

Inhalation of molecular hydrogen (H2) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H2 also prevents chronic neurodegenerative diseases including Parkinson’s disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain unclear. Here, we investigated the effect of H2 on mitochondria in cultured human neuroblastoma SH-SY5Y cells. H2 increased the mitochondrial membrane potential and the cellular ATP level, which were accompanied by a decrease in the reduced glutathione level and an increase in the superoxide level. Pretreatment with H2 suppressed H2O2-induced cell death, whereas post-treatment did not. Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H2-treated cells indicated that mild stress caused by H2 induced increased resistance to exacerbated oxidative stress. We propose that H2 functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells. [ABSTRACT FROM AUTHOR]

TP53 mutation is associated with various hematological malignancies and immunohistochemistry of p53 has been used as a simple method to establish the presence of a TP53 mutation. Since the significance of p53 expression is controversial in myelodysplastic syndrome (MDS) patients treated with azacitidine (Aza), we analyzed the prevalence of p53 expression as a prognostic factor in 60 MDS patients treated with Aza. To assess p53 expression, immunohistochemical analyses of bone marrow clot sections were performed. Overall survival (OS) was significantly lower in p53-positive patients compared with p53-negetive patients (59% vs. 85% at 12 months; P = 0.006). Multivariate analysis demonstrated that p53-positive was a significant prognostic factor for OS along with poor cytogenetics. Here, we propose a new prognostic index to make short-term prognoses of MDS patients in the era of Aza treatment; high: p53-positive and poor cytogenetics, low: p53-negative and absence of poor cytogenetics, and intermediate: the others. OS was significantly different among the three groups according to this index (Low 92%, Intermediate 65% and High 27% at 12 months; P < 0.0001). In conclusion, p53 expression was a significant prognostic factor in MDS patients treated with Aza. In combination with cytogenetic abnormalities, it is possible to make short-term prognoses. [ABSTRACT FROM AUTHOR]

Pyruvate therapy is a promising approach for the treatment of mitochondrial diseases. To identify novel biomarkers for diagnosis and to evaluate therapeutic efficacy, we performed microarray analysis of 2SD cybrid cells harboring a MELAS-causing mutation and control cells treated with either lactate or pyruvate. We found that expression and secretion of growth differentiation factor 15 (GDF15) were increased in 2SD cells treated with lactate and that serum GDF15 levels were significantly higher in patients with mitochondrial diseases than in those with other diseases, suggesting that GDF15 could be a useful marker for diagnosis and evaluating the therapeutic efficacy of pyruvate. [ABSTRACT FROM AUTHOR]

Low-temperature plasma (LTP) science and technology are rapidly establishing their place in agriculture, with already existing or envisaged future commercial applications in (i) sustainable fertilizer production, (ii) food safety "from farm to fork", and (iii) in reducing pollution and pathogens. On-demand local fertilizer production or pathogen inactivation at the farm by LTP technology will reduce the need for complex logistics. This current S.I. consists of one review article and 14 original research papers, focusing on state-of-the-art LTP applications in agricultural and food-related fields, ranging from the basics of activating air and water by electrical discharges and the treatment and decontamination of seeds and plants, to LTP use as a food processing technology. [Extracted from the article]

Nagai S, Ito M, Kamei H, Nakamura T, Ando H, Kiuchi T. Indirect immunohistochemical evaluation of graft fibrosis and interface hepatitis after pediatric liver transplantation. Pediatr Transplantation 2010:14:342–350. © 2009 John Wiley & Sons A/S. Fibrosis or IH following pediatric liver transplantation is recognized as major causes of graft loss, but the etiology remains unclear. To determine this issue, we used an indirect immunohistochemistry technique with post-transplant serum samples from recipients and normal human liver tissues from living liver donors, and the association between occult antibody reaction to the liver and the occurrence of fibrosis or IH was evaluated. Forty-three recipients were evaluated, and both hepatocytes and biliary epithelial cells were evaluated for staining intensity. Fibrosis and IH occurred in 13 and six patients, respectively. According to staining results for the hepatocytes and biliary epithelial cells, 18 and 11 patients, respectively, were classified into the positive group. According to log-rank analysis, positive reaction for hepatocytes was associated with increased rates of fibrosis and IH (p = 0.002 and 0.048, respectively), while positive reaction for biliary epithelial cells was associated with an increased rate of fibrosis (p = 0.014). Multivariate analysis revealed that positive reaction for hepatocytes and biliary epithelial cells was independently associated with fibrosis occurrence (p = 0.020 and 0.047, respectively). In conclusion, immune-mediated reactions by occult antibodies may underlie the pathogeneses of fibrosis and IH. [ABSTRACT FROM AUTHOR]

Whether Bickerstaff's brainstem encephalitis (BBE) is a distinct disease or a subtype of Fisher syndrome (FS) is unclear as there have been no clinical studies with sufficiently large numbers of patients with FS or BBE. Our aim was to clarify the nosological relationship. Medical records of patients suffering acute ophthalmoplegia and ataxia within four weeks of onset were reviewed. BBE was the diagnosis for patients with impaired consciousness, FS for those with clear consciousness and areflexia. Clinical features, neuroimages, and laboratory findings were analyzed. Patients were grouped as having BBE (n = 53), FS (n = 466), or as unclassified (n = 62). The BBE and FS groups had similar features; positive serum anti-GQ1b IgG antibody (68 % versus 83 %), antecedent Campylobacter jejuni infection (23 % versus 21 %), CSF albuminocytological dissociation (46 % versus 76 %), brain MRI abnormality (11 % versus 2 %), and abnormal EEG findings (57 % versus 25 %). BBE (n = 4) and FS (n = 28) subgroups underwent detailed electrophysiological testing. Both groups frequently showed absent soleus H-reflexes, but normal sensory nerve conduction (75 % versus 74 %) and a 1-Hz power spectrum peak on postural body sway analysis (67 % versus 72 %). Common autoantibodies, antecedent infections, and MRI and neurophysiological results found in this large study offer conclusive evidence that Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum with variable CNS and PNS involvement. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial dysfunction caused by mutations in mitochondrial DNA (mtDNA) is related to a variety of diseases including MELAS and NARP syndromes. However, little is known about the intracellular responses induced by mtDNA mutations. In order to identify genes whose expression is altered as a result of the presence of mtDNA mutations, DNA microarray analysis was performed using human 143B osteosarcoma cells harboring 3243A>G [tRNA-Leu (UUR)] and 8993T>G [ATPase6 Leu156Arg] mtDNA mutations associated with MELAS and NARP syndromes (2SD and NARP3-1 cybrid cells), respectively. We found that mRNA and protein levels of ATF4, CHOP and ASNS were upregulated in 2SD and NARP3-1 cells as compared with parental cells. Reporter assays demonstrated that transcription of CHOP and ASNS genes was upregulated through the AARE (amino acid regulatory element) and NSRE-1 (nutrient-sensing response element-1) enhancer elements to which ATF4 binds, respectively. Furthermore, knockdown of ATF4 by RNA interference reduced CHOP and ASNS transcription in 2SD and NARP3-1 cells. These results suggest that the presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively. [Copyright &y& Elsevier]

This article concerns the initial ideal computation for toric ideals, which arises in the computational algebraic approach for integer programs. It is known that the initial ideals of toric ideals contain many information about original toric ideals that are beneficial for solving the integer programs. Therefore, their analyses may bring further comprehensions for structure of integer programs and can help us to construct a new type of algorithm. There are two known algorithms for initial ideal computation. One is based on the theory of Gröbner bases and the other is proposed by Thomas and Hoşten. In this article, we propose another type of algorithm to perform the initial ideal computation for the toric ideals defined by unimodular matrices. The unimodular matrices is one of the important matrix classes, that are often looming as the coefficient matrices of some combinatorial optimization problems with the forms of integer programs. Ours are based on a combinatorial relation between the vector matroids of defining matrices and the minimal generators of initial ideals. [ABSTRACT FROM AUTHOR]

Several lines of evidence indicate the clonal nature of juvenile myelomonocytic leukaemia (JMML), involving myeloid, erythroid, megakaryocyte and B-lymphoid lineages. However, it is unclear whether the T-lymphocyte lineage is involved. We demonstrated that cells from six patients with JMML repopulated in non-obese diabetic/severe combined immunodeficient/ γcnull mice and differentiated into granulocytes, monocytes, erythrocytes, B lymphocytes, T lymphocytes and natural killer cells. The percentage of human CD45 antigen-positive cells ranged from 41% to 73% in the murine bone marrow 12 weeks after transplantation. To examine the involvement of lymphocyte subpopulations, we purified human CD3+, CD19+ and CD56+ cells from murine bone marrow cells transplanted from a patient with monosomy 7. Fluorescence in situ hybridization (FISH) showed the clonal marker in 96–100% of purified CD3+, CD19+ and CD56+ subpopulations. These findings support the concept that JMML originates in transplantable multilineage haematopoietic stem cells. This novel murine xenotransplant model should be useful for investigating the nature of stem cells and testing new therapies for patients with JMML. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of hydrosalpinges on embryo implantation.Design: Prospective study.Setting: Private fertility and university hospitals.Patient(s): Eighteen patients with unilateral or bilateral hydrosalpinges who underwent salpingectomy.Intervention(s): Pre- and posttreatment endometrial biopsies for immunohistochemical evaluation.Main outcome measure(s): Pre- and posttreatment lymphocyte populations in endometrial samples, evaluated by immunohistochemical identification.Result(s): Endometrial samples from pretreatment exhibited small lymphocytic clusters of CD3+, CD8+, CD4+, granzyme B positive, and CD56+. After salpingectomy, the numbers of cluster lesions were significantly decreased.Conclusion(s): Because a characteristic distribution of lymphocytes in endometrium with hydrosalpinges was found, activation of T/NK (natural killer) lymphocytes in endometrium might be involved in the impairment of embryo implantation in cases of hydrosalpinges. [Copyright &y& Elsevier]

Background: MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. Results: Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions: These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the precise mechanisms leading to the development of acute gastric mucosal lesions (AGMLs). We investigated whether the pathologic mechanism of AGMLs resulting in damage to epithelial cells is associated with cytotoxic molecules expressed by activated intraepithelial lymphocytes (IELs). Methods: The expression of the lymphocyte markers, CD3, CD4, CD8, CD20, T-cell-restricted intracellular antigen (TIA)-1, and granzyme B (GrB)-7 in IELs and that of single-stranded DNA (ssDNA) in apoptotic epithelial cells were evaluated by immunohistochemistry, using endoscopic biopsy specimens from 20 patients with AGMLs and 20 controls. Results: The number of CD3- and CD8-positive IELs increased in AGML specimens when compared with controls, and this increase was accompanied by a concomitant increase in TIA-1-positive cells. The epithelial cell layers of AGML specimens contained more GrB-7-positive phenotypically activated cytotoxic T cells than those in controls. Apoptotic ssDNA-positive epithelial cells were detected more frequently in AGML specimens than in controls, a feature which was paralleled by an increase in GrB-7-positive IELs in the former group of specimens. Conclusions: The present study showed that activated cytotoxic IELs and apoptotic epithelial cells are increased in number in gastric mucosa affected with AGMLs. These results provide evidence that this condition could be categorized as apoptotic gastritis with activation of the innate immune response. [ABSTRACT FROM AUTHOR]

A PCR-based cDNA subtraction hybridization was performed to identify the genes stimulated by estrogen in the pituitary. A novel tissue-specific calpain (nCL-2′), previously shown to be expressed mainly in the stomach, was markedly induced in the pituitary after estrogen treatment. The 5′-flanking region of the calpain nCL-2′ gene was analyzed to assess the molecular mechanism of estrogen regulation. Sequence analysis of the nCL-2′ promoter (1.9 kb) revealed a perfectly palindromic putative estrogen-response element (ERE), GGTCATGCTGACC. In transient transfection studies, the nCL-2′ promoter was highly responsive to estrogen in the presence of estrogen receptor (ER). Transcriptional activation by estrogen was prevented by an ERE mutation as well as by mutations in the ER DNA-binding domain. An ER antagonist, ICI 182780, blocked estrogen inducibility of the nCL-2′ promoter. We conclude that the nCL-2′ form of calpain is expressed in the pituitary and upregulated by estrogen at the transcription level. [Copyright &y& Elsevier]

Investigates the structural basis of the catalysis of intestinal brush border membrane-associated phospholipase B/lipase (PLB/LIP) by site-directed mutagenesis of recombinant repeat 2 enzyme. Analysis of three essential residues in the PLB/LIP enzymes; Reason why repeat 2 is the catalytic domain; Role of Thr[sup 406] in the structural stability.

Inhalation of hydrogen (H2) gas is therapeutically effective for cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders including pathologies induced by anesthetic gases. To understand the mechanisms underlying the protective effects of H2 on the brain, we investigated the molecular signals affected by H2 in sevoflurane‐induced neuronal cell death. We confirmed that neural progenitor cells are susceptible to sevoflurane and undergo apoptosis in the retrosplenial cortex of neonatal mice. Co‐administration of 1–8% H2 gas for 3 h to sevoflurane‐exposed pups suppressed elevated caspase‐3‐mediated apoptotic cell death and concomitantly decreased c‐Jun phosphorylation and activation of the c‐Jun pathway, all of which are induced by oxidative stress. Anesthesia‐induced increases in lipid peroxidation and oxidative DNA damage were alleviated by H2 inhalation. Phosphoproteome analysis revealed enriched clusters of differentially phosphorylated proteins in the sevoflurane‐exposed neonatal brain that included proteins involved in neuronal development and synaptic signaling. H2 inhalation modified cellular transport pathways that depend on hyperphosphorylated proteins including microtubule‐associated protein family. These modifications may be involved in the protective mechanisms of H2 against sevoflurane‐induced neuronal cell death. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. Methods: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38–39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. Results: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3–12.0) and 2.7 (95% CI: 1.1–6.9), respectively. Conclusion: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition. [ABSTRACT FROM AUTHOR]

Ahch (also known as Dax1) encodes a transcription factor that has been implicated in sex determination and gonadal differentiation. Mutations in human AHC cause X-linked, adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH). Duplication of the Xp21 dosage-sensitive sex reversal (DSS) region, which contains the Ahch locus, and transgenic overexpression of Ahch (ref. 6) cause male-to-female sex reversal. Using Cre-mediated disruption of Ahch, we have generated a mouse model of AHC-HH that allows the function of Ahch to be examined in both males and females. Although Ahch has been postulated to function as an ovarian determination gene, the loss of Ahch function in females does not affect ovarian development or fertility. Ahch is instead essential for the maintenance of spermatogenesis. Lack of Ahch causes progressive degeneration of the testicular germinal epithelium independent of abnormalities in gonadotropin and testosterone production and results in male sterility. Ahch is thus not an ovarian determining gene, but rather has a critical role in spermatogenesis. [ABSTRACT FROM AUTHOR]

Mitochondria are multifunctional organelles that regulate diverse cellular processes. Mitochondrial stress, including stress generated by electron transport chain defects and impaired mitochondrial proteostasis, is intimately involved in various diseases and pathological conditions. Sepsis is a life-threatening condition that occurs when an imbalanced host response to infection leads to organ dysfunction. Metabolic disturbances and impaired immune responses are implicated in the pathogenesis and development of sepsis. Given that mitochondria play central roles in cellular metabolism, mitochondrial stress is predicted to be involved in the pathological mechanism of sepsis. Under mitochondrial stress, cells activate stress response systems to maintain homeostasis. This mitochondrial stress response transcriptionally activates genes involved in cell survival and death. Mitochondrial stress also induces the release of distinctive secretory proteins from cells. Recently, we showed that growth differentiation factor 15 (GDF15) is a major secretory protein induced by mitochondrial dysfunction. In this article, we provide a brief overview of mitochondrial stress response and GDF15, and discuss the potential role of GDF15 in the pathophysiology of sepsis. • Mitochondrial stress response is partly mediated by the ISR pathway. • GDF15 is induced by mitochondrial dysfunction through the ISR pathway. • Septic patients and animals present mitochondrial dysfunction in multiple organs. • Circulating GDF15 level is elevated in patients and animals with sepsis. • GDF15 plays an important role in the pathophysiology of sepsis. [ABSTRACT FROM AUTHOR]

The authors have developed a simultaneous measurement technique of multimetallic atom densities in process plasmas using absorption spectroscopy employing a multimicrohollow cathode plasma as a light source. The optical emissions of four metallic atoms of Cu, Zn, Fe, and Mo were simultaneously produced from the multimicrohollow cathode plasma of millimeter size. The absolute densities of Cu and Mo in the magnetron sputtering plasma were simultaneously measured using this technique. The simultaneous monitoring of multimetallic atoms is very useful for controlling the plasma processes precisely. [ABSTRACT FROM AUTHOR]

Examines electronic structure at a surface of diamond film synthesized by a capacitively coupled radio frequency plasma chemical vapor deposition. Characterization of the electronic structure; Role of hydrogen for the selective etching of the nondiamond phase in the plasma; Elements synthesizing diamond films; Implications for device applications of diamond films.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8‐positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3‐positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1‐positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T‐cell profile of MNT, that of MNCA was more suppressive to patients′ antitumor immune response. [ABSTRACT FROM AUTHOR]

This Special Issue highlights the topics from the PLASMA Conference 2017, which was held in Himeji, Japan, on November 20–24, 2017. This conference was jointly organized by the Japan Society of Applied Physics, The Japan Society of Plasma and Nuclear Fusion Research, The Physical Society of Japan, and the Japan Society for the Promotion of Science 153 Committee (Plasma Science for Materials). [ABSTRACT FROM AUTHOR]

Molecular hydrogen (H2) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H2 is more soluble in lipids than in water. A recent study demonstrated that H2 reduces radical polymerization-induced cellular damage by suppressing fatty acid peroxidation and membrane permeability. Thus, we sought to examine the effects of short exposure to H2 on lipid composition and associated physiological changes in SH-SY5Y neuroblastoma cells. We analyzed cells by liquid chromatography-high-resolution mass spectrometry to define changes in lipid components. Lipid class analysis of cells exposed to H2 for 1 hour revealed transient increases in glycerophospholipids including phosphatidylethanolamine, phosphatidylinositol, and cardiolipin. Metabolomic analysis also showed that H2 exposure for 1 hour transiently suppressed overall energy metabolism accompanied by a decrease in glutathione. We further observed alterations to endosomal morphology by staining with specific antibodies. Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H2-exposed cells. We speculate that H2-induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells. [ABSTRACT FROM AUTHOR]

Purpose: Less-invasive early diagnosis of lung cancer is essential for improving patient survival rates. The purpose of this study is to demonstrate that serum comprehensive miRNA profile is high sensitive biomarker to early-stage lung cancer in direct comparison to the conventional blood biomarker using next-generation sequencing (NGS) technology combined with automated machine learning (AutoML). Methods: We first evaluated the reproducibility of our measurement system using Pearson's correlation coefficients between samples derived from a single pooled RNA sample. To generate comprehensive miRNA profile, we performed NGS analysis of miRNAs in 262 serum samples. Among the discovery set (57 patients with lung cancer and 57 healthy controls), 1123 miRNA-based diagnostic models for lung cancer detection were constructed and screened using AutoML technology. The diagnostic faculty of the best performance model was evaluated by inspecting the validation samples (74 patients with lung cancer and 74 healthy controls). Results: The Pearson's correlation coefficients between samples derived from the pooled RNA sample ≥ 0.98. In the validation analysis, the best model showed a high AUC score (0.98) and a high sensitivity for early stage lung cancer (85.7%, n = 28). Furthermore, in comparison to carcinoembryonic antigen (CEA), a conventional blood biomarker for adenocarcinoma, the miRNA-based model showed higher sensitivity for early-stage lung adenocarcinoma (CEA, 27.8%, n = 18; miRNA-based model, 77.8%, n = 18). Conclusion: The miRNA-based diagnostic model showed a high sensitivity for lung cancer, including early-stage disease. Our study provides the experimental evidence that serum comprehensive miRNA profile can be a highly sensitive blood biomarker for early-stage lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: Intermittent claudication (IC) refers to leg pain that is induced by walking and relieved by rest. Neurogenic IC is usually associated with lumbar canal stenosis (LCS). We present rare findings from an autopsied patient who had neurogenic IC caused by vasculitis in the cauda equina. Methods: We performed antemortem neurological and electrophysiological assessments, sural nerve biopsy, and post-mortem examination of the spinal cord and brain. Results: A 61-year-old man noted sudden-onset leg pain that was not associated with any traumatic trigger. His leg pain consistently appeared when the patient walked and quickly faded on stopping. Spine surgery and cardiovascular departments both made a diagnosis of IC. However, magnetic resonance imaging (MRI) did not show LCS, and all ankle-brachial pressure indices were normal. He subsequently developed diffuse muscle weakness of the legs a month after disease onset. Myeloperoxidase antineutrophil cytoplasmic autoantibody was seropositive (140 IU/mL), and a sural nerve biopsy revealed axonal injury and angiitis. MRI showed multiple cerebral infarctions. He was diagnosed with microscopic polyangiitis (MPA) and underwent corticosteroid therapy. He died from complications two months after the onset. A post-mortem study revealed vasculitis in the subarachnoid space of the cauda equina, spinal cord, and brain parenchyma. The cauda equina showed a combined loss of small and large axonal fibres. The lumbar cord displayed central chromatolysis of the lower motor neurons. Conclusion: MPA is a rare cause of neurogenic IC when the symptom is acute and multimodal. Small-vessel vasculitis affecting the cauda equina may underlie MPA-associated IC. [ABSTRACT FROM AUTHOR]

Studies the association between a mutation in the gene encoding steroidogenic factor-1 (SF-1) and XY sex reversal and adrenal failure in humans. Heterozygous mutation in exon 3; Creation of a novel EcoR1 site; Expression of mutant SF-1.

Background: Acquired erythrocytosis can be classified into polycythemia vera (PV) and non‐neoplastic erythrocytosis (NNE). The vast majority of PV patients harbor JAK2 mutations, but differentiating JAK2 mutation‐negative PV from NNE is challenging due to a lack of definitive molecular markers. Methods: We studied the clinical features of 121 patients with erythrocytosis of which 47 (38.8%) were JAK2 mutation‐positive and also fulfilled the diagnostic criteria for PV, and 67 (55.4%) JAK2 mutation‐negative erythrocytosis patients who were diagnosed as NNE. Diagnosis was strictly based on driver mutation analysis and central pathology review. Results: No JAK2 mutation‐negative PV patients were found in our cohort. The NNE group showed significantly younger (p < 0.01) age with higher frequency of smoking (p < 0.001), alcohol consumption (p < 0.001), and diabetes mellitus (p < 0.05), whereas the PV group (n = 47) showed significantly higher white blood cell count, platelet count, and lactate dehydrogenase (p < 0.001). Although serum erythropoietin (EPO) levels were significantly higher in NNE compared to PV (p < 0.001), approximately 40% of the NNE patients had EPO levels below the lower range of normal, fulfilling a minor diagnostic criterion of PV and raising the possibility of PV misdiagnosis. Conclusion: Low EPO levels in JAK2 mutation‐negative erythrocytosis may not be a reliable diagnostic criterion for distinguishing PV from NNE. [ABSTRACT FROM AUTHOR]

Mitochondria are dysfunctional in post-senescent cells. Therefore, age-dependent impairment of mitochondrial energy production accompanied by excessive mitochondrial reactive oxygen species (ROS) is proposed to be a key driver of cellular senescence, which is a state of irreversible cell cycle arrest. However, it remains to be clarified whether mitochondrial dysfunction initiates or accelerates replicative senescence. In this study, we observed no increase in mitochondrial ROS or decrease in mitochondrial respiratory function in human TIG-1 fibroblasts in the transition phase, during which the population doubling rate gradually decreases due to the development of replicative senescence. The integrated stress response and expression of growth differentiation factor 15, which are triggered by respiratory chain deficiency, were also not induced in the transition phase. Mitochondria were elongated without aberrant cristae structures in the transition phase. Mitophagy-related protein levels started to decrease in the transition phase, but autophagic flux slightly increased during replicative senescence. These results suggest that mitochondrial dysfunction and excessive mitochondrial ROS generation do not occur predominately in the transition phase and may not play a role in the development of replicative senescence in normal diploid TIG-1 fibroblasts. • Mitochondrial dysfunction does not occur in the transition phase before senescence. • Excess ROS generation does not occur in the transition phase before senescence. • GDF15 expression through ISR is not induced during replicative senescence. • Mitochondria are elongated without aberrant cristae structures in senescent cells. • Mitophagy-related proteins decline during replicative senescence. [ABSTRACT FROM AUTHOR]

Neurolymphomatosis is a neurological manifestation of lymphoma that involves the cranial or spinal peripheral nerves, nerve roots, and plexus with direct invasion of neoplastic cells. Neurolymphomatosis is rare among patients with low‐grade lymphoma. We report an autopsied case of neurolymphomatosis that arose from follicular lymphoma. A 49‐year‐old woman who presented with pain of her neck and shoulder and numbness of her chin. Computed tomography revealed enlarged lymph nodes in her whole body, and biopsy from the axillary lymph node revealed grade 2 follicular lymphoma. Although the patient underwent chemotherapy, she gradually developed muscle weakness in the upper limbs and sensory disturbances of the trunk and limbs. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) revealed increased tracer uptake of the cervical nerve roots. Repeated FDG‐PET after additional therapy revealed progression of disease within the nerve roots and brachial plexus, whereas gadolinium‐contrast magnetic resonance imaging (MRI) showed weak enhancement of the cervical nerve roots without formation of mass lesions. She died after a total disease duration of 12 months. Postmortem observations revealed invasion of lymphoma cells into the cervical nerve roots, dorsal root ganglia, and subarachnoid spaces of the spinal cord. Neurolymphomatosis was prominent at the segments of C6–Th2. Combined loss of axons and myelin sheaths was observed in the cervical nerve roots and posterior columns. Lymphoma cells also invaded the cranial nerves. The subarachnoid and perivascular spaces of the brain demonstrated focal invasion of the lymphoma. Mass lesions were not observed in the central nervous system. The lymphoma cells did not show histological transformation to higher grades, and the density of the centroblasts remained at grade 2. Our report clarifies that low‐grade follicular lymphoma can manifest as neurolymphomatosis and central nervous system invasion in the absence of transformation toward higher histological grades. FDG‐PET may be more sensitive to non‐mass‐forming lesions, including neurolymphomatosis, than gadolinium‐contrast MRI. [ABSTRACT FROM AUTHOR]

Aim: Wood creosote (WC), an over‐the‐counter (OTC) drug, has been used as an anti‐diarrheal agent for many years; however, its safety in combination with other drugs has not been adequately investigated. The current study was conducted to evaluate whether WC may cause drug interactions through the inhibition of cytochrome P450 (CYP). Methods: The inhibitory effects of WC on ethoxyresorufin O‐deethylation, paclitaxel 6α‐hydroxylation, S‐warfarin 7‐hydroxylation, S‐mephenytoin 4′‐hydroxylation, bufuralol1′‐hydroxylation, and midazolam (MDZ) 1′‐hydroxylation were investigated using human liver microsomes as the marker activities for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. In addition, the effects of single and three‐day multiple treatments of WC (30 mg/kg) on CYP2C‐mediated tolbutamide (TB, 20 mg/kg) and CYP3A‐mediated MDZ (15 mg/kg) metabolism were investigated in rats in vivo. Results: WC at clinical doses did not show a considerable inhibitory effect on any of the CYP activities examined in the in vitro study. CYP2C9 and CYP2C19 activities were inhibited by high concentrations of the WC (100 μg/mL); however, the IC50 values were approximately 70 times higher than the reported circulating levels of the main ingredients in WC. Furthermore, there were no marked changes in the pharmacokinetic parameters of TB and MDZ (area under the serum concentration–time curve, maximum serum concentrations, and elimination half‐life) after single or three‐day multiple treatments with WC. Conclusion: These results suggest that clinical doses of WC are unlikely to cause drug interactions mediated by the inhibition of CYPs. [ABSTRACT FROM AUTHOR]

Summary: In 2008, the World Health Organization proposed a new entity of childhood myelodysplastic syndrome (MDS), which was referred to as refractory cytopenia of childhood (RCC). However, whether this morphological classification reflects clinical outcomes remains unclear. We performed a prospective evaluation of bone marrow morphology in 252 children with acquired bone marrow failure between 2009 and 2013. Of 252 patients, 63 were diagnosed with aplastic anaemia (AA), 131 with RCC without multilineage dysplasia (RCC‐w/o‐MLD) and 58 with RCC with MLD (RCC‐MLD). One patient with AA, three with RCC‐w/o‐MLD and nine with RCC‐MLD presented with chromosomal abnormalities at diagnosis (P = 0·001). The response rates to immunosuppressive therapy (IST) at 6 months and the cumulative incidence of clonal evolution at 5 years did not significantly differ among the three groups. A multivariate analysis revealed that the morphological classification of RCC‐MLD was a significant risk factor for secondary graft failure after haematopoietic cell transplantation (HCT) (P = 0·003). In view of these findings, RCC could be divided into two categories, RCC‐w/o‐MLD and RCC‐MLD, because children with this condition exhibited a distinct morphology, frequent chromosomal abnormalities at diagnosis and a high frequency of secondary graft failure after HCT. [ABSTRACT FROM AUTHOR]

Perforin secreted from cytotoxic lymphocytes plays a critical role in cancer immunosurveillance. The aim of this study was to investigate the therapeutic potential of liposomes containing perforin expression vector driven by the promotor of prostate-specific antigen (PSA). The anti-tumor effect of perforin was analyzed using prostate cancer (PC) PC-3 cells in which perforin expression was controlled by Tet-on system (PC-3PRF cells). Liposomes encapsulating PSA promoter-driven perforin expression vector (pLipo) were constructed for its specific expression in PC. The anti-tumor effect of pLipo was evaluated in vitro using docetaxel-resistant PC 22Rv1 PC cell line, 22Rv1DR, and PC-3 cells in the presence of human peripheral blood mono nuclear cells (PBMCs) and also in vivo using male nude mice bearing 22Rv1DR cell-derived tumor xenograft. Induction of perforin significantly inhibited growth of PC-3PRF cells. Treatment with pLipo induced perforin expression in 22Rv1DR cells expressing PSA but not in PC-3 cells lacking it. Treatment with pLipo at a low concentration was prone to inhibit growth of both cell lines and significantly inhibited growth of 22Rv1DR cells when co-incubated with PBMCs. The combined use of pLipo at a high concentration with PBMCs showed nearly complete inhibition of 22Rv1DR cell growth. Intravenous administration of pLipo via tail vein increased the level of perforin in tumor and serum and significantly decreased the tumor volume. Our results suggest that liposome-mediated PC-specific expression of perforin could be a novel therapy for advanced PC. [ABSTRACT FROM AUTHOR]

The WBC count (C), Hb value (D), platelet count (E), and LDH level (F) for the patients classified based on driver mutation status are shown. Finally, in the Results, under the subheading 'Noncanonical JAK2 and MPL mutant exhibits wild-type-equivalent levels of STAT5 activation', "One such patient was found to harbor MPL S204F in the abovementioned screening of noncanonical JAK2 and MPL mutations." now reads "One such patient was found to harbor MPL S204F." NC-JAK2/MPL: noncanonical JAK2 and MPL mutation. [Extracted from the article]

Finally, in the Results, under the subheading 'Noncanonical JAK2 and MPL mutant exhibits wild-type-equivalent levels of STAT5 activation', "One such patient was found to harbor MPL S204F in the abovementioned screening of noncanonical JAK2 and MPL mutations." now reads "One such patient was found to harbor MPL S204F." Comparison of TPO (C) and IL-6 (D) concentrations in the serum among the patients with TN-ET, patients with ET harboring driver mutations, and healthy controls. Graph: Figure 1 Comparison of clinical parameters between the TN-ET patients and mutated ET patients. [Extracted from the article]

Abstract: Long-range propagation characteristics of an annular beam were examined from the viewpoint of lidar application. The annular beam permits to use a reflecting telescope for transmission and improves the transmission efficiency because it can pass through the telescope without the obstruction of the telescope’s secondary mirror. As the annular beam can enlarge up to the telescope diameter, it can be eye-safe and its divergence is also reduced. The annular beam generated by a couple of Axicon prisms; conical prisms, transforms its beam shape into the central peak narrow beam; nearly non-diffractive beam, through the far-field propagation. We evaluated how the central peak intensity and its width of the transformed beam change in long-range of 3–100km. The difficulty of the optical arraignment and the requirement of the beam quality to obtain the enough performance of the beam shape transformation were also examined theoretically and experimentally for the lidar application. The stability of the transformed beam was also confirmed in the atmospheric fluctuation. [Copyright &y& Elsevier]

Abstract: Microcrystalline diamond has been successfully synthesized in a low-pressure inductively coupled plasma using di-t-alkyl peroxide. Di-t-alkyl peroxides are thermally decomposed into acetones and methyl radicals, which presumably serve as precursors for the formation of diamond on the silicon substrate at 943 K and 993 K. The deposits on the substrate were examined by scanning electron microscopy, Raman spectroscopy and X-ray photoelectron spectroscopy. It was found that the deposits contained a microcrystalline diamond phase even at a low pressure of 11 Pa. Diamond formation over a large area in low-pressure plasmas has been demonstrated by the present novel diamond deposition process using di-t-alkyl peroxide thermally decomposed as a feed gas. [Copyright &y& Elsevier]

In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)–rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17∼20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]–2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions. [Copyright &y& Elsevier]

A subset of essential thrombocythemia (ET) cases are negative for disease-defining mutations on JAK2, MPL, and CALR and defined as triple negative (TN). The lack of recurrent mutations in TN-ET patients makes its pathogenesis ambiguous. Here, we screened 483 patients with suspected ET in a single institution, centrally reviewed bone marrow specimens, and identified 23 TN-ET patients. Analysis of clinical records revealed that TN-ET patients were mostly young female, without a history of thrombosis or progression to secondary myelofibrosis and leukemia. Sequencing analysis and human androgen receptor assays revealed that the majority of TN-ET patients exhibited polyclonal hematopoiesis, suggesting a possibility of reactive thrombocytosis in TN-ET. However, the serum levels of thrombopoietin (TPO) and interleukin-6 in TN-ET patients were not significantly different from those in ET patients with canonical mutations and healthy individuals. Rather, CD34-positive cells from TN-ET patients showed a capacity to form megakaryocytic colonies, even in the absence of TPO. No signs of thrombocytosis were observed before TN-ET development, denying the possibility of hereditary thrombocytosis in TN-ET. Overall, these findings indicate that TN-ET is a distinctive disease entity associated with polyclonal hematopoiesis and is paradoxically caused by hematopoietic stem cells harboring a capacity for cell-autonomous megakaryopoiesis. [ABSTRACT FROM AUTHOR]

: ObjectivesTo estimate the relationship between serum prostate-specific antigen (PSA) and prostatic epithelial volume, a new simple method for measuring epithelial volume was developed and its efficacy evaluated in patients with benign prostatic hyperplasia.: MethodsBetween March 1998 and June 2001, 122 patients without prostate cancer in the transurethral resected specimen were enrolled in this study. Of the 122 patients, 55 had a serum PSA level of 4.0 ng/mL or greater and negative sextant biopsies before surgery. First, we measured the epithelium/glandular lumen ratio by computer image analysis in 20 specimens. Second, we measured the percentage of glandular lumen in all 122 patients. The prostatic epithelial volume was then calculated as follows: calculated epithelium volume (in cubic centimeters) = epithelium/glandular lumen ratio percentage of glandularlumen × total prostate volume (in cubic centimeters).: ResultsThe epithelium/glandular lumen ratio was 1.01 in the 20 specimens. In the 122 patients with benign prostatic hyperplasia, the calculated epithelial volume correlated more strongly with the serum PSA level than did the total prostate volume, transition zone volume, or percentage of epithelium (γ = 0.672, P <0.0001). The mean PSA level per calculated epithelial volume was 1.27 ng/mL/cm3. The calculated epithelial volumes from the biopsy specimens correlated significantly with those from transurethral resection specimens (γ = 0.956, P <0.0001).: ConclusionsSerum PSA levels correlated significantly with prostatic epithelial volumes in patients with benign prostatic hyperplasia. The method of measuring prostatic epithelial volume used in this study is very convenient for clinical practice. [Copyright &y& Elsevier]

Investigates the regulation of aromatase expression by targeted disruption of Dax1 gene. Repression of transcription by steroidogenic factor-1; Measurement of aromatase activity; Application of Western Blot assay.

We aimed to develop a sandwich ELISA to detect prostate-specific membrane antigen (PSMA) on small extracellular vesicles (EVs) using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) as a capture molecule for EVs and to evaluate its diagnostic potential in urologic malignancies. First, we optimized the conditions for sandwich ELISA measuring the PSMA level on EVs captured from serum by Tim4 and found that the use of highly-purified EVs released from Tim4 that had captured EVs in serum reduced the background. Second, we confirmed its validity by studying mouse xenograft model for prostate cancer (PC). Lastly, we measured PSMA-EVs in serum of patients with urologic malignancies. The PSMA-EV levels were significantly higher in metastatic PC and castration-resistant PC (CRPC) patients than in therapy-naïve PC patients. In renal cell carcinoma (RCC) patients, PSMA-EVs were elevated in those with metastasis compared with those without metastasis, which may reflect the development of the neovasculature positive for PSMA in tumors. In conclusion, we developed a sandwich ELISA for detection of PSMA-EVs using highly-purified EVs isolated from serum by Tim4. Our results suggest that PSMA-EVs may be useful to diagnose and monitor not only PC but also RCC and possibly other hypervascular solid tumors. [ABSTRACT FROM AUTHOR]

To identify the key neutral species from atmospheric‐pressure plasma for promoting the proliferation of fibroblast cells, an atmospheric‐pressure radical generator was employed. A cell viability assay showed that the proliferation of fibroblasts was significantly promoted through radical treatment, resulting in the highest promotion ratio of 24%. The densities of the neutral radicals supplied by the radical generator were measured via mass spectrometry at atmospheric pressure. To determine an effective factor for the promotion, the dose dependencies of these radicals on the promotion ratio were investigated. The promotion ratio exhibited a strong correlation only with the NO• dose. These results confirmed that NO• is a direct trigger of plasma‐enhanced cell proliferation. [ABSTRACT FROM AUTHOR]

Secretory immunoglobulin A (sIgA) plays an important role in local immune defense mechanisms. Although skin is always exposed to external antigens, the role of local immune defenses involving sIgA in the skin has not been adequately studied. In order to evaluate the presence of sIgA in sweat, we have measured the concentration of sIgA in human sweat by enzyme immunoassay and have localized the components of sIgA in the sweat glands of human axillary skin. The concentration of sIgA in sweat was found to be 10 times higher in men than in women (13.0 ± 0.9 μg/ml versus 1.6 ± 0.9 μg/ml). Secretory component (SC) was localized immunohistochemically in protein synthetic organelles, such as the perinuclear spaces and Golgi complex, in cytoplasmic vesicles, and along the external surface membranes of mucous cells on the terminal segment of eccrine sweat glands. IgA and J chain were present in plasma cells in the protein synthetic organelles. The luminal aspects of eccrine sweat ducts also strongly express SC, as well as IgA and J chain. Neither SC, IgA, or J chain were identified in epithelial cells of apocrine sweat glands. These findings are consistent with the theory that J chain complexed with dimeric IgA is synthesized in plasma cells and is transported by SC-mediated endocytosis transfer across mucous cells of eccrine sweat glands and thus into sweat. [ABSTRACT FROM AUTHOR]

The differential diagnoses included inflammatory myofibroblastic sarcoma, undifferentiated pleomorphic sarcoma, inflammatory leiomyosarcoma, Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma, malignant gastrointestinal stromal tumour, and sarcomatoid carcinoma. HS has a poor prognosis, with most patients dying within 2 years.1,2 Our patient received TKI therapy, and has remained healthy without HS or CML recurrence for 3 years. Histiocytic sarcoma (HS) is a rare myeloid-derived neoplasm with histiocytic differentiation and an aggressive clinical course.1 Recent studies have suggested a common clonal origin for various haematolymphoid disorders.2 However, HS coexisting with chronic myeloid leukaemia (CML) without tyrosine kinase inhibitors (TKIs) has not been reported.3 We report a case of CML, and an intestinal mass caused by HS, that showed a I BCR::ABL1 i translocation. [Extracted from the article]