Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents.     

Phenotyping of malignant hematopoietic cells

Summary 1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.Abbreviations ALL acute lymphoblastic leukemia - AML acute myeloblastic leukemia - AMMoL acute myelomonoblastic leukemia - AMoL acute monoblastic leukemia - cALL common ALL - CLL chronic lymphocytic leukemia - CML chronic myelocytic leukemia - CML-BC CML in blastic crisis - CMoL chronic monocytic leukemia     

Comparative assessment of in vitro and in vivo toxicity of azinphos methyl and its commercial formulation

The toxic effects of Gusathion (GUS), which is a commercial organophosphate (OP) pesticide, and also its active ingredient, azinphos methyl (AzM), are evaluated comparatively with in vitro and in vivo studies. Initially, the 96‐h LC₅₀ values of AzM and GUS were estimated for two different life stages of Xenopus laevis, embryos, and tadpoles. The actual AzM concentrations in exposure media were monitored by high‐performance liquid chromatography. Also, the sub‐lethal effects of these compounds to tadpoles were determined 24 h later at exposure concentrations of 0.1 and 1 mg/L using selected biomarker enzymes such as acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione S‐transferase (GST), glutathione reductase, lactate dehydrogenase, and aspartate aminotrasferase. Differences in AChE inhibition capacities of AzM and GUS were evaluated under in vitro conditions between frogs and fish in the second part of this study. The AChE activities in a pure electrical eel AChE solution and in brain homogenates of adult Cyprinus carpio, Pelophylax ridibundus, and X. laevis were assayed after in vitro exposure to 0.05, 0.5, 5, and 50 mg/L concentrations of AzM and GUS. According to in vivo studies AChE, CaE and GST are important biomarkers of the effect of OP exposure while CaE may be more effective in short‐term, low‐concentration exposures. The results of in vitro studies showed that amphibian brain AChEs were relatively more resistant to OP exposure than fish AChEs. The resistance may be the cause of the lower toxicity/lethality of OP compounds to amphibians than to fish. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1091–1101, 2015.     

Development and feasibility testing of a Pain Neuroscience Education program for children with chronic pain: treatment protocol

Background

Current treatment for adults with chronic pain often includes Pain Neuroscience Education (PNE) to make people understand the nature underlying their pain and thus provides a clear rational for a biopsychosocial approach. Despite recommendations to use Pain Neuroscience Education as well in children with chronic pain, a specific program, tailored to children aged 6–12 years is lacking.

Neurodegenerative Genes Polymorphisms of the -491A/T APOE,the -877T/C APP and the Risk of Primary Open-angle Glaucoma in the Polish Population

Background: Glaucoma is characterized by optic neuropathy of the retinal ganglion cell. It may be possible that β-amyloid (Aβ) and apolipoprotein E (APOE), the main proteins of the pathogenesis of AD, play a role in glaucoma development. The aim of this study was to evaluate a relationship between the APP and APOE gene polymorphisms and the risk of primary open-angle glaucoma (POAG) occurrence.

Materials and methods: The study consisted of 183 patients with POAG and 209 healthy subjects. Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP.

Results: We found a statistically significant increase of the -491?T allele frequency (p?=?0.02; OR?=?1.48; 95% CI?=?1.06–2.08) of APOE in POAG compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the APP polymorphism between patients and controls group. We also found an association between APOE polymorphic variant and retinal nerve fiber layer (RNFL). There was a statistically significant difference in the APOE gene A/T genotype frequency in the early POAG stage and middle-advanced POAG stage in comparison to the advanced POAG stage (p?=?0.04; OR?=?3.38; 95% CI?=?1.04–10.97).

Conclusions: The -491?T allele of APOE polymorphism may be associated with a risk of POAG occurrence in the Polish population.     

Autoimmune haemolytic anaemia and antiphospholipid antibodies in paediatrics: a systematic review and meta-analysis

Clinical Rheumatology - The relationship between autoimmune haemolytic anaemia (AIHA) and antiphospholipid antibodies (aPL) has never been addressed via a meta-analysis in the paediatric age group....     

Diagnostic value of contrast-enhanced magnetic resonance imaging and single-photon emission computed tomography for detection of myocardial necrosis early after acute myocardial infarction.

OBJECTIVES: This study sought to evaluate the diagnostic value of contrast-enhanced magnetic resonance imaging (CMR) and single-photon emission computed tomography (SPECT) for detection of myocardial necrosis after acute myocardial infarction (AMI). BACKGROUND: Single-photon emission computed tomography is widely accepted in the clinical setting for detection and estimation of myocardial infarction. Contrast-enhanced magnetic resonance imaging offers technical advantages and is therefore a promising new method for identification of infarcted tissue. METHODS: Seventy-eight patients with AMI were examined by CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced magnetic resonance imaging and SPECT images were scored for presence and location of infarction using a 17-segment model. Results were compared with the peak troponin T level, electrocardiographic, and angiographic findings. RESULTS: Acute myocardial infarction was detected significantly more often by CMR than SPECT (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to SPECT in detecting small infarction as assessed by the peak troponin T level <3.0 ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs. 84%; p = 0.03). Non-Q-wave infarctions were more likely to be detected by CMR (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for detection of AMI irrespective of the infarct-related artery, SPECT was less sensitive, particularly within the left circumflex artery territory. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging is superior to SPECT in detecting myocardial necrosis after reperfused AMI because CMR detects small infarcts that were missed by SPECT independent of the infarct location. Thus, CMR is attractive for accurate detection and assessment of the myocardial infarct region in patients early after AMI.