Relationship between local immune response to Helicobacter pylori and the diversity of disease: investigation of H. pylori-specific IgA in gastric juice

In order to evaluate the relationship between local immune response to Helicobacter pylori and the diversity of disease, 77 asymptomatic subjects who underwent a health examination were studied. Helicobacter pylori-specific IgG in serum and H. pylori-specific IgA in gastric juice were measured by ELISA, and the measured IgA titre was classified into two grades, low or high. Histological classification of gastritis was performed according to the Sydney system. Cytokines in gastric juice were also measured, and the cytotoxin-associated gene A (cagA) status of H. pylori was tested by PCR. Of the 65 subjects who were positive for H. pylori-specific IgG in serum, 38 (58.5%) were classified as H. pylori-specific IgA low titre in gastric juice and 27 (41.5%) had high titres. In the IgG-positive, IgA-low group, the rate of peptic ulcers (especially duodenal ulcers) in endoscopic findings was higher (P < 0.05); the score of activity and the density of H. pylori were higher (P < 0.001 and P < 0.05, respectively); the score of metaplasia was lower (P < 0.05); and the level of interleukin-1 beta was lower (P < 0.05) than in the IgG-positive, IgA-high group. The positive rate of the cagA gene was 84.4% and there was no significant difference between the two groups. There were differences in endoscopic and histological findings between the IgG-positive, IgA-low and the IgG-positive, IgA-high groups. It is suggested that persons infected with H. pylori can be divided into two different states of disease according to local immune response.     

Fine structure of the supramammillary nucleus of the rat: analysis of the ultrastructural character of dopaminergic neurons

The islets of Langerhans are richly innervated, and an inhibitory effect on insulin secretion, mediated through alpha 2-adrenergic receptors, appears to be an important physiological neural modulator of beta-cell function. An alpha 2-receptor was cloned from isolated newborn rat islets using a polymerase chain reaction (PCR) approach. This receptor was shown by sequencing to be a new rat alpha 2-receptor very similar to the human alpha 2-C2 receptor. No other alpha 2-receptor subtype was identified in normal islets by the PCR using alpha 2-receptor primers. This was also the only alpha 2-receptor subtype present in the exocrine pancreas and liver. In contrast, in the beta-cell line, beta TC3, the alpha 2-C2 receptor was not detected, but the alpha 2-C4 and alpha 2-C10 receptor subtypes were detected. It is suggested that the alpha 2-C2 subtype may be the principal alpha 2-receptor mediating inhibitory autonomic nervous system activity in the gastrointestinal tract. A comparison of the rat islet, pancreas, and liver alpha 2-receptor sequences reported here with previously reported alpha 2-receptor sequences indicates that the rat islet alpha 2-receptor is not the rat alpha 2-C2 homologue previously denoted as RNG alpha 2, but is a new, fourth rat subtype with an even higher similarity to the human alpha 2-C2 receptor.     

Autonomic nervous function of the patients with neurally mediated syncope

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.     

Coexistence of proguanylin (1-15) and somatostatin in the gastrointestinal tract

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1-15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1-15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1-15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1-15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.     

Effects of vitamin B6 deficiency on cytokine levels and lymphocytes in mice

The effects of vitamin B6 (B6) deficiency on cytokine levels and proportions of lymphocyte subsets in BALB/c mice were investigated. The proportion of lymphocytes from the thymus and spleen of mice given no B6, that were CD4+ CD8- T cells, was larger than in mice given B6, and the ratio of CD8+ to CD4+ T cells in the thymus of mice given no B6 was lower. The concentrations of interleukin-5 and -10 in spleen cells stimulated in vitro with concanavalin A were significantly higher in the mice with B6 deficiency, as was their plasma corticosterone concentrations. These results suggested that B6 is necessary to maintain cytokine levels and lymphoid function in the thymus and spleen of mice.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.     

Functional metal-porphyrazine derivatives and their polymers, 10. Secondary fuel cells based on oxygen reduction on platinum electrode modified by polymers and metal-phthalocyanines

Secondary fuel cells based on oxygen reduction of platinum electrode modified by polymers and metal-phthalocyanine (Mt = Fe(III), Co(II), Ni(II), and Cu(II)) were studied. The discharge curves for the platinum electrode modified by poly(2-vinylpyridine) (or polystyrene) and Co-phthalocyanine in 30% KOH aqueous solution, for a 30 min charge at 500 μA, followed by a 100 μA discharge showed a stable plateau at about ?0.24 V SCE (Saturated Calomel Electrode). The open circuit voltage (vs. Zn) of the cell was 1.2 V, and the discharge capacity was of 46 A · h/kg. For this battery there was no significant decay in its characteristics after more than 30 charge-discharge cycles. In Mt-phthalocyanines, the values decreased in the order of Co(II) > Fe(III) > > Cu(II) > Ni(II). From a cyclic voltammogram for the electrode modified by the polymer and Co-Pc, the cathodic reactions were discussed.     

Oxidative coupling of methane over LaCoO3−δ-based mixed oxides

The catalytic activity of LaCoO_3–-based mixed oxides for the oxidative coupling of methane has been tested by TPR and cyclic reaction. Characterization has been done by XRD, TGA and Mössbauer spectrometry. It is likely that the perovskite-crystal structure containing hypervalent metal ions has an important role and that unique structural oxygen species in the perovskite contribute to the partial oxidation of methane.     

Lysozyme requires fluctuation of the active site for the manifestation of activity

Mutations around His15 which lie far away from the active site,stimulated glycol chitin activity of lysozyme at physiologicaltemperature. Del-Argl4Hisl5 lysozyme, a mutant lysozyme whoseArgl4 and Hisl5 were deleted together, and has the highest activityamong these mutant lysozymes, had a similar binding abilityto a trimer of N-acetyl-glucosamine, a substrate analogue, relativeto native lysozyme. This suggests that the increased activitywas due to an increased k_cat in the catalysis reaction. TheH-D exchange rate of the N-1 proton in the Trp63 which is locatedin the active site cleft, was enhanced in the Del-Argl4Hisl5lysozyme, while 2-D proton NMR analysis revealed no conformationalchange around Trp63. We conclude that some sort of fluctuationat the active site might be required for the manifestation ofactivity. This theory is supported by the finding that the Del-Argl4Hisl5lysozyme showed a shift in temperature dependency of activityto lower temperatures compared with that of native lysozyme.