Characterization of antimutagenic mechanism of 3-allyl-5-substituted 2-thiohydantoins against 2-amino-3-methylimidazo[4,5-f]quinoline.

3-Allyl-5-substituted 2-thiohydantoins (ATH-amino acids) derived from allyl isothiocyanate and amino acids can inhibit the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. In this report, we studied possible mechanisms for the inhibition using rat liver S9 in assays for ethoxyresorufin O-deethylase (EROD), a marker activity for cytochrome P450 1A (CYP1A), which activates heterocyclic amines, and the Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). Quantitative analysis of ATH-amino acids and IQ during incubation with rat liver S9 fraction by HPLC showed that ATH-amino acids could act as S9-inhibitors, thereby inhibiting metabolic activation of IQ. Among the tested ATH-amino acids, ATH-Phe, ATH-Trp, ATH-Leu and ATH-Val showed a dose-dependent inhibition of EROD activity. ATH-Gly, ATH-Glu, and ATH-Asp behaved as blocking agents toward N-hydroxy-IQ, but exhibited no inhibition of EROD activity.     

Acid-suppression Therapy Offers Varied Laryngopharyngeal and Esophageal Symptom Relief in Laryngopharyngeal Reflux Patients

It is widely accepted that laryngopharyngeal reflux requires more aggressive and prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness, cough, and globus pharyngeus, are slower to resolve than esophageal symptoms, such as heartburn and regurgitation. The aim of this was to provide empirical evidence to support this observation and to carry out a detailed investigation of the differences between these symptoms. Forty-five patients with laryngopharyngeal and esophageal symptoms received acid-suppression therapy that involved the continuous administration of a proton-pump inhibitor for up to 6 months. We investigated the differences in response to acid-suppression therapy between patients suffering from laryngopharyngeal and esophageal symptoms, respectively, who received upper gastrointestinal endoscopy and were assayed for serum Helicobacter pylori antibodies. The significance of the rate of symptom improvement was estimated by Kaplan-Meier analysis and the logrank test. Laryngopharyngeal symptoms improved significantly more slowly than esophageal symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the start of acid suppression; P = 0.003). These differences were observed both in patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative patients (P = 0.001).     

Randomized controlled trial: PPI-based triple therapy containing metronidazole versus clarithromycin as first-line treatment for Helicobacter pylori in adolescents and young adults in Japan

Background/Aims

Treating Helicobacter pylori infection in young people is effective for preventing gastric cancer. This study compares the efficacy of triple therapies in adolescents and young adults in Japan.

A Case Report of an Adult With Severe Hyperlipidemia During Acute Lymphocytic Leukemia Induction Therapy Successfully Treated With Plasmapheresis

Plasmapheresis for the treatment of hypertriglyceridemia has previously been performed in patients with sudden onset severe hypertriglyceridemia and acute pancreatitis; however, only a few reports of this procedure have been published. We report here on a case showing severe hypertriglyceridemia during asparaginase (Asp) treatment for acute lymphocytic leukemia (ALL), and give an overview of a lipid‐lowering apheresis therapy. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange (PE) three times using fresh frozen plasma. PE remarkably reduced both serum triglyceride and total cholesterol levels from 5430 mg/dL to 403 mg/dL and from 623 mg/dL to 204 mg/dL, respectively. The causes of severe hyperlipidemia in this patient were considered to include: the Asp treatment for ALL, and a genetic background with a heterozygote of familial lipoprotein lipase (LPL) defect syndrome, because the patient's plasma LPL level after intravenous heparin injection was low at 137 ng/mL. Hence, PE using fresh frozen plasma may be useful not only to remove lipoproteins, but also to supply defective factors, such as LPL, in similar cases.     

Oscillatory brain states and learning: Impact of hippocampal theta-contingent training

Eyeblink classical conditioning is a relatively simple form of associative learning that has become an invaluable tool in our understanding of the neural mechanisms of learning. When studying rabbits in this paradigm, we observed a dramatic modification of learning rate by conducting training during episodes of either hippocampal theta or hippocampal non-theta activity as determined by on-line slow-wave spectral analysis. Specifically, if animals were given trials only when a computer analysis verified a predominance of slow-wave oscillations at theta frequencies (3-8 Hz), they learned in half as many trials as animals trained during non-theta hippocampal activity (58 vs. 115). This finding provides important evidence from awake, behaving animals that supports recent advances in our knowledge of (i) brain sites and neurobiological mechanisms of learning and memory, specifically hippocampus and theta oscillations, (ii) the biological plausibility of current models of hippocampal function that posit important roles for oscillatory potentials, and (iii) the design of interfaces between biological and cybernetic (electronic) systems that can optimize cognitive processes and performance.     

Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.     

FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer

Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of 135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as a prognostic biomarker and be involved in cancer-cell survival in NSCLC.     

Efficacy of carbon dioxide-insufflating colonoscopy in patients with irritable bowel syndrome: A randomized double-blind study

Background and Aim: Colonoscopy has the disadvantage of pain and discomfort for patients. It has been shown in randomized controlled trials that carbon dioxide (CO₂) insufflations significantly reduce pain and discomfort in patients undergoing colonoscopy. However, there have been no studies in which CO₂ insufflation in colonoscopy of patients with irritable bowel syndrome (IBS) was investigated. Methods: Randomized double‐blind controlled study was conducted to assess the suffering from colonoscopy in patients with IBS and the efficacy of CO₂ insufflation in colonoscopy for patients with IBS. Patients with IBS and controls who received colonoscopy were randomized into an air or CO₂ insufflation group. Patients' symptoms such as distension and pain were compared using a 10‐cm visual analog scale (VAS). Results: There were 18 patients in the IBS/air group, 19 patients in the IBS/CO₂ group, 25 patients in the control/air group and 26 patients in the control/CO₂ group. The mean value of severity of distension after colonoscopy and the mean value of severity of pain from during examination to one hour after the examination were higher in the IBS group than in the control group. The severity of these symptoms was reduced earlier in the CO₂ group. CO₂ insufflation in colonoscopy was more effective in the IBS group than in the control group from 15 min to one hour after the examination. Conclusion: Regarding colonoscopy‐related suffering, IBS patients showed significant differences from non‐IBS patients. CO₂ insufflation in colonoscopy is effective for IBS patients, particularly for patients who commence activities after colonscopy.