The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying

Background  

Previous studies have shown that non-erosive reflux disease (NERD) patients are less sensitive to proton pump inhibitor (PPI) treatment than patients with erosive reflux disease. The aim of this study was to investigate whether treatment with prokinetics in addition to omeprazole therapy would improve clinical symptoms, gastric emptying and esophageal peristalsis in PPI-resistant NERD patients with or without delayed gastric emptying.     

Predictors of a better outcome of pneumatic dilatation in patients with primary achalasia

Objective  

Pneumatic dilatation (PD) has been widely used in the treatment of primary achalasia. The aim of this study was to evaluate the effectiveness of PD and its predictive factors in Japanese patients with primary achalasia.     

Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan

Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T, Urabe S, Ogawara S, Yonemasu H, Matsushita Y, Karube K & Iwashita A
(2011) Histopathology 58 , 395–407
Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy‐associated T cell lymphoma in Japan Aims: To elucidate the clinicopathological findings of primary intestinal enteropathy‐associated T cell lymphoma (EATL) in Japan, a non‐endemic area for coeliac disease. Methods and results: Of the 24 cases, four (17%) had large‐cell lymphoma (type I), and the remaining 20 (83%) had medium‐sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56‐positive. Only one (4%) case showed typical CD56‐ and CD8‐negative and CD30‐positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy‐like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy‐like lesions in five (24%) cases expressed T‐bet, with no cases of CD30‐positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele. Conclusions: Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs.     

Pleural Mesothelioma Instigates Tumor-Associated Fibroblasts To Promote Progression via a Malignant Cytokine Network

The tumor microenvironment is crucial to the progression of various malignancies. Malignant pleural mesothelioma (MPM), which originates from the pleura, grows aggressively in the thoracic cavity. Here we describe an orthotopic implantation SCID mouse model of MPM and demonstrate that α-SMA-positive fibroblast-like cells accumulate in the tumors produced by the human MPM cell lines MSTO-211H and Y-Meso-14. We assessed the interaction between MPM cells and their microenvironments, focusing on tumor-associated fibroblasts. MSTO-211H and Y-Meso-14 cells produced fibroblast growth factor-2 (FGF-2) and/or platelet-derived growth factor-AA (PDGF-AA); they also enhanced growth, migration, and production of hepatocyte growth factor (HGF) by human lung fibroblast MRC-5 cells. MRC-5 cells stimulated HGF-mediated growth and migration of MSTO-211H and Y-Meso-14 cells in an in vitro coculture system. In the orthotopic model, tumor formation by MSTO-211H and Y-Meso-14 cells was significantly inhibited by TSU-68, an inhibitor of FGF, VEGF, and PDGF receptors; imatinib, an inhibitor of PDGF receptors; and NK4, an antagonist of HGF. Histological analyses of clinical specimens from 51 MPM patients revealed considerable tumor-associated fibroblasts infiltration and expression of HGF, together with FGF-2 or PDGF-AA, in tumors. These findings indicate that MPM instigates tumor-associated fibroblasts, promoting tumor progression via a malignant cytokine network. Regulation of this cytokine network may be therapeutically useful for controlling MPM.Malignant pleural mesothelioma (MPM) is a unique form of tumor, the development of which is highly related to asbestos exposure.¹ Even after bans on asbestos were initiated in the 1970s, MPM remains a serious problem worldwide because of its long latency period (30 to 40 years) and high mortality rate. In the United States, 2000 to 3000 patients die of MPM every year. Deaths from this disease are expected to peak in 2020 to 2025, with more than 250,000 deaths expected to occur in Western Europe and Japan over the next 40 years.² MPM grows aggressively, with dissemination in the thoracic cavity, and frequently produces a malignant pleural effusion.³ MPM is rarely diagnosed at an operable stage, and it is refractory to conventional chemotherapy and radiotherapy. Thus, the prognosis of patients with this disease is extremely poor, with median survival varying between 8 and 14 months after diagnosis, despite the recent development of a chemotherapy regimen combining cisplatin and an antifolate agent such as pemetrexed or raltitrexed.⁴The tumor microenvironment is crucial for the progression and chemosensitivity of various malignant diseases.⁵ For example, the tumor microenvironment mediates endocrine instigation of indolent metastatic tumor progression via osteopontin.⁶ Moreover, EGFR-TKI resistance may be induced by microenvironmental fibroblasts in epidermal growth factor receptor mutant lung cancer.⁷ Thus, innovative therapies may target the microenvironment. For example, antiangiogenic therapy targeting host endothelial cells and bisphosphonate targeting host osteoclasts have been successfully used to treat several malignant diseases, including colon cancer,⁸ non-small cell lung cancer,^9,10 and metastatic bone tumors.¹¹In MPM, angiogenesis inhibition using an anti-VEGF antibody targeting endothelial cells can successfully control the progression of MPM cells that produce high concentrations of VEGF.¹² Tumor-associated fibroblasts (TAFs), also known as cancer-associated fibroblasts, are the major component of tumor microenvironments.¹³ TAFs regulate tumor behavior through several mediators. Although recent studies show that many populations of MPM contain TAFs,¹⁴ little is known about interactions between TAFs and MPM. We therefore investigated the molecular interaction between MPM and TAFs, using an orthotopic implantation SCID mice model and clinical specimens taken from MPM patients. We show here that MPMs produce fibroblast-growth factor 2 (FGF-2) and platelet-derived growth factor-AA (PDGF-AA), and that these growth factors stimulate TAFs to produce hepatocyte growth factor (HGF), thus promoting tumor progression through a malignant cytokine network.     

Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1

Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive cerulein-induced (50 μg/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, α-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-β1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wild-type pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wild-type mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wild-type mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in pancreatitis.     

Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors alpha and beta

Neurogenesis persists throughout life under normal and degenerative conditions. The adult subventricular zone (SVZ) generates neural stem cells capable of differentiating to neuroblasts and migrating to the site of injury in response to brain insults. In the present study, we investigated whether estradiol increases neurogenesis in the SVZ in an animal model of stroke to potentially promote the ability of the brain to undergo repair. Ovariectomized C57BL/6J mice were implanted with capsules containing either vehicle or 17beta-estradiol, and 1 week later they underwent experimental ischemia. We utilized double-label immunocytochemistry to identify the phenotype of newborn cells (5-bromo-2'-deoxyuridine-labeled) with various cellular markers; doublecortin and PSA-NCAM as the early neuronal marker, NeuN to identify mature neurons, and glial fibrillary acidic protein to identify astrocytes. We report that low physiological levels of estradiol treatment, which exert no effect in the uninjured state, significantly increase the number of newborn neurons in the SVZ following stroke injury. This effect of estradiol is limited to the dorsal region of the SVZ and is absent from the ventral SVZ. The proliferative actions of estradiol are confined to neuronal precursors and do not influence gliosis. Furthermore, we show that both estrogen receptors alpha and beta play pivotal functional roles, insofar as knocking out either of these receptors blocks the ability of estradiol to increase neurogenesis. These findings clearly demonstrate that estradiol stimulates neurogenesis in the adult SVZ, thus potentially facilitating the brain to remodel and repair after injury.     

Identification of lipomatous metaplasia in old infarcted myocardium by cardiovascular magnetic resonance and computed tomography

Epididymitis, as an unusual side-effect of amiodarone use, in a patient with dilated cardiomyopathy is reported along with a pertinent literature review. The diagnosis was one of exclusion after the patient received several regimens of antimicrobials and was only established after a dose reduction of the amiodarone regimen. Cardiologists should be aware of this rare but existing side effect of amiodarone, in order promptly intervene with dose adjustment or discontinuation of amiodarone and to avoid prolonged use of unnecessary antimicrobial regimens.     

Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation

BACKGROUND AND AIMS: There is a need for genetic biomarkers to guide prognosis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphomas. We assessed the incidence and clinical significance of the MALT lymphoma-associated genetic abnormalities t(11;18)/API2-MALT1, t(1;14)/BCL10-IGH, t(14;18)/IGH-MALT1, t(3;14)/FOXP1-IGH, and extra copies of MALT1 and FOXP1 in gastric MALT lymphomas from Japan. METHODS: The presence of translocations and copy number changes involving MALT1, IGH and FOXP1 were assessed in 90 cases of gastric MALT lymphoma using interphase fluorescence in situ hybridisation (FISH). In cases carrying a MALT1 translocation, FISH for API2-MALT1 was performed, whereas in those carrying an IGH translocation, FISH was performed for BCL10, BCL6, BCL2, c-MYC and/or CCND1. RESULTS: t(11;18)/API2-MALT1 was detected in 18 of 87 (21%) cases and was significantly associated with Helicobacter pylori-negativity, resistance to H pylori eradication and Bcl10 nuclear expression. Four of 68 (6%) cases carried a translocation involving IGH and FOXP1 (n = 1), BCL2 (n = 1) or an unknown partner (n = 2). Neither t(1;14)/BCL10-IGH nor t(14;18)/IGH-MALT1 was detected. Extra copies of MALT1 and FOXP1 were detected in 18 of 71 (25%) cases and 10 of 59 (17%) cases, respectively. The presence of extra copies of MALT1 was significantly associated with progression or relapse of lymphoma, and was an independent adverse prognostic factor for event-free survival as determined by multivariate analysis. CONCLUSIONS: t(11;18)/API2-MALT1 is frequent, whereas IGH-involved translocations are rare in gastric MALT lymphoma in Japan. The presence of extra copies of MALT1, often suggestive of partial or complete trisomy 18, is a frequent genetic aberration in gastric MALT lymphoma, which appears to predict adverse clinical behaviour.