Background Factors of Reflux Esophagitis and Non-Erosive Reflux Disease: A Cross-Sectional Study of 10,837 Subjects in Japan

Background

Despite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of Helicobacter pylori infection and gastric atrophy.

Methods

We analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20–87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and p-value.

Results

Of the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), HP non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, HP infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic HP infection and successful HP eradication denotes significant difference (2.3% and 8.8%; p<0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; p = 0.064).

Conclusions

Significantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of Helicobacter pylori may have disadvantageous effects on RE but not on NERD.     

Fine root turnover of Japanese white birch (<Emphasis Type="Italic">Betula platyphylla</Emphasis> var. <Emphasis Type="Italic">japonica</Emphasis>) grown under elevated CO<Subscript>2</Subscript> in northern Japan

Key message

Elevated CO ₂ reduced fine root dynamics (production and turnover) of white birch seedlings, especially grown in volcanic ash soil compared with brown forest soil.

Abstract

Increased atmospheric CO₂ usually enhances photosynthetic ability and growth of trees. To understand how increased CO₂ affects below-ground part of trees under varied soil condition, we investigated the responses of the fine root (diameter <2 mm) dynamics of Japanese white birch (Betula platyphylla var. japonica) which was planted in 2010. The three-year-old birch seedlings were grown in four experimental treatments comprising two levels of CO₂, i.e., ambient: 380–390 and elevated: 500 μmol mol^?1, in combination with two kinds of soil: brown forest (BF) soil and volcanic ash (VA) soil which has few nutrients. The growth and turnover of fine roots were measured for 3 years (2011–2013) using the Mini-rhizotron. In the first observation year, live fine root length (standing crop) in BF soil was not affected by CO₂ treatment, but it was reduced by the elevated CO₂ from the second observation year. In VA soil, live fine root length was reduced by elevated CO₂ for all 3 years. Fine root turnover tended to decrease under elevated CO₂ compared with ambient in both soil types during the first and second observation years. Turnover of fine root production and mortality was also affected by the two factors, elevated CO₂ and different soil types. Median longevity of fine root increased under elevated CO₂, especially in VA soil at the beginning, and a shorter fine root lifespan appeared after 2 years of observation (2011–2012). These results suggest that elevated CO₂ does not consistently stimulate fine root turnover, particularly during the plant seedlings stage, as it may depend on the costs and benefits of constructing and retaining roots. Therefore, despite the other uncontrollable environment factors, carbon sequestration to the root system may be varied by CO₂ treatment period, soil type and plant age.

     

Multiscale spatial genetic structure within and between populations of wild cherry trees in nuclear genotypes and chloroplast haplotypes

Spatial genetic structure (SGS) of plants mainly depends on the effective population size and gene dispersal. Maternally inherited loci are expected to have higher genetic differentiation between populations and more intensive SGS within populations than biparentally inherited loci because of smaller effective population sizes and fewer opportunities of gene dispersal in the maternally inherited loci. We investigated biparentally inherited nuclear genotypes and maternally inherited chloroplast haplotypes of microsatellites in 17 tree populations of three wild cherry species under different conditions of tree distribution and seed dispersal. As expected, interpopulation genetic differentiation was 6–9 times higher in chloroplast haplotypes than in nuclear genotypes. This difference indicated that pollen flow 4–7 times exceeded seed flow between populations. However, no difference between nuclear and chloroplast loci was detected in within‐population SGS intensity due to their substantial variation among the populations. The SGS intensity tended to increase as trees became more aggregated, suggesting that tree aggregation biased pollen and seed dispersal distances toward shorter. The loss of effective seed dispersers, Asian black bears, did not affect the SGS intensity probably because of mitigation of the bear loss by other vertebrate dispersers and too few tree generations after the bear loss to alter SGS. The findings suggest that SGS is more variable in smaller spatial scales due to various ecological factors in local populations.     

Intravascular heavy chain-modification of hyaluronan during endotoxic shock

During inflammation, the covalent linking of the ubiquitous extracellular polysaccharide hyaluronan (HA) with the heavy chains (HC) of the serum protein inter alpha inhibitor (IαI) is exclusively mediated by the enzyme tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6). While significant advances have been made regarding how HC-modified HA (HC-HA) is an important regulator of inflammation, it remains unclear why HC-HA plays a critical role in promoting survival in intraperitoneal lipopolysaccharide (LPS)-induced endotoxemia while exerting only a modest role in the outcomes following intratracheal exposure to LPS. To address this gap, the two models of intraperitoneal LPS-induced endotoxic shock and intratracheal LPS-induced acute lung injury were directly compared in TSG-6 knockout mice and littermate controls. HC-HA formation, endogenous TSG-6 activity, and inflammatory markers were assessed in plasma and lung tissue. TSG-6 knockout mice exhibited accelerated mortality during endotoxic shock. While both intraperitoneal and intratracheal LPS induced HC-HA formation in lung parenchyma, only systemically-induced endotoxemia increased plasma TSG-6 levels and intravascular HC-HA formation. Cultured human lung microvascular endothelial cells secreted TSG-6 in response to both TNFα and IL1β stimulation, indicating that, in addition to inflammatory cells, the endothelium may secrete TSG-6 into circulation during systemic inflammation. These data show for the first time that LPS-induced systemic inflammation is uniquely characterized by significant vascular induction of TSG-6 and HC-HA, which may contribute to improved outcomes of endotoxemia.     

Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens

The eye lens is composed of fiber cells that differentiate from epithelial cells on its anterior surface. In concert with this differentiation, a set of proteins essential for lens function is synthesized, and the cellular organelles are degraded. DNase II-like acid DNase, also called DNase IIbeta, is specifically expressed in the lens, and degrades the DNA in the lens fiber cells. Here we report that DNase II-like acid DNase is synthesized as a precursor with a signal sequence, and is localized to lysosomes. DNase II-like acid DNase mRNA was found in cortical fiber cells but not epithelial cells, indicating that its expression is induced during the differentiation of epithelial cells into fiber cells. Immunohistochemical and immunocytochemical analyses indicated that DNase II-like acid DNase was colocalized with Lamp-1 in the lysosomes of fiber cells in a relatively narrow region bordering the organelle-free zone, and was often found in degenerating nuclei. A comparison by microarray analysis of the gene expression profiles between epithelial and cortical fiber cells of young mouse lens indicated that some genes for lysosomal enzymes (cathepsins and lipases) were strongly expressed in the fiber cells. These results suggest that the lysosomal system plays a role in the degradation of cellular organelles during lens cell differentiation.     

Mercuric chloride mediates a protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase which is independent of the phosphorylation / dephosphorylation of a carboxyl terminal tyrosine

Little is known about the regulatory mechanism of c-Src kinase in cells except the suggested regulation through phosphorylation and dephosphorylation of its carboxyl terminal tyrosine residue (Y527). We here demonstrated that exposure of NIH3T3 cells to mercuric chloride (HgCl₂) induces both aggregation and activation of Src kinase protein through a redox-linked mechanism. The aggregation of Src proteins was suggested to be induced by the sulfhydryl groups-to-Hg²⁺ reaction-mediated polymerization of cell membrane proteins to which the Src proteins associate noncovalently. The possibility was ruled out that the aggregation occurred secondarily to the promotion of protein tyrosine phosphorylation. Further study revealed that the Src kinase was activated by HgCl₂ at least in part independent of the known Csk kinase-linked or Y527-phosphorylation/dephosphorylation-mediated control. Correspondingly, CNBr cleavage mapping of phosphopeptides for autophosphorylated c-Src protein demonstrated selective promotion of phosphorylation at Y416 in HgCl₂-treated cells without obvious change in the phosphorylation level at Y527. These results suggest a unique protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase in NIH3T3 cells. © 1996 Wiley-Liss, Inc.     

Effect of arylidene-cyclopentenedione radiosensitizers on ATP synthesis in mitochondria: action as potent inhibitors of phosphate transport

The effects of the arylidene-cyclopentenedione radiosensitizers, KIH-200, 201 and 202 on ATP synthesis in mitochondria were examined. In spite of the close similarity of their chemical structure to that of the most potent known weakly acidic uncoupler, SF 6847, they did not show any uncoupling activity at concentrations of up to 50 microM. However, these three compounds were found to have very potent inhibitory effects on Pi-transport into mitochondria, all causing 50% inhibition (I50%) at about 7 microM. Thus they are much more potent than the commonly used Pi-transport inhibitors N-ethylmaleimide (I50% = about 40 microM), and mersalyl (I50% = about 30 microM). They may act as SH-reagents, and inhibit Pi-transport by modifying an SH-group(s) in the Pi-transporter.     

Effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, CS622, and a vasodilator, hydralazine, on atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR)

We studied the effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, alpha-[(2S,6R)-6-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino-5-oxo-2- (2-thienyl)perhydro-1,4-thiazepin-4-yl]acetic acid.HCl (CS622), and a vasodilator, hydralazine, on plasma atrial natriuretic factor (ANF) levels and kidney ANF receptors in spontaneously hypertensive rats (SHR). Plasma ANF level was decreased and cardiac hypertrophy reduced in CS622 treated SHR, but not in hydralazine treated SHR, although blood pressure was lowered similarly in both SHR groups. The binding capacity of kidney ANF receptors increased and the affinity decreased in CS622 treated SHR compared to untreated SHR. These results suggest that decrease of plasma ANF results from decreased cardiac load but not from lowered blood pressure, and that changes in ANF receptors result from increased plasma ANF.     

Distribution of immunoreactive mesotocin and vasotocin in the brain and pituitary of chickens

The distribution of vasotocin and mesotocin in the pituitary and central nervous system in male chickens was determined using radioimmunoassays. Neither peptide was detected in the pineal. Mesotocin, but not vasotocin, was detected in the cerebellum. Both peptides were found in the septal area, archistriatum, paleostriatum, optic lobe, anterior, medial and posterior hypothalamus, midbrain, pons, medulla oblongata, and the anterior and posterior pituitary. Equal amounts of the 2 peptides were present in the septal area, archistriatum and anterior hypothalamus whereas vasotocin was more abundant (2- to 10-fold) in the paleostriatum, optic lobe, midbrain, and pituitary. The amount of mesotocin was about twice that of vasotocin in the medulla oblongata and the medial and posterior hypothalamus. The wide distribution of vasotocin and mesotocin in extrahypothalamic sites in the central nervous system suggests that the peptides may, as in mammals, have a role in a variety of autonomic and endocrine regulatory processes in chickens.