Helicobacter pylori Infection Significantly Increases Insulin Resistance in the Asymptomatic Japanese Population

Background: Helicobacter pylori infection has been shown to contribute to atherosclerosis and cardiovascular diseases. Insulin resistance is the pathophysiologic background of the clinical features of atherosclerosis and cardiovascular diseases. We examined the association between H. pylori infection and insulin resistance in a large Japanese population. Materials and Methods: Fifteen hundred ninety‐eight consecutive asymptomatic subjects that underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases under medication for hypertension, hyperlipidemia, diabetes mellitus, hyperuricemia, or cardiovascular diseases were excluded from the study. Cases suffering from chronic renal or liver failure were also excluded. The homeostasis model assessment of insulin resistance (HOMA‐IR) score was used to quantitatively estimate insulin resistance. Visceral and subcutaneous adipose tissues (SAT) were measured by computed tomography. The association between H. pylori serostatus and HOMA‐IR score was investigated by multivariate regression analysis. Results: A total of 988 men and 119 women were eventually eligible for this cross‐sectional survey. Helicobacter pylori seropositivity was significantly higher in 99 cases with insulin resistance (HOMA‐IR ≥2.5) compared with 1008 cases without insulin resistance (HOMA‐IR <2.5) (39.4 vs 28.7%, p = .027). There was a significant association between H. pylori serostatus and HOMA‐IR score by multiple linear regression analysis (coefficients = 0.152, 95% CI = 0.058–0.246, p = .001), after adjusting for sex, age, body mass index, waist girth, visceral and subcutaneous adipose tissues, smoking status, alcohol consumption, dietary habits, and physical activity. Conclusions: Helicobacter pylori infection significantly and independently contributed to promoting insulin resistance in a large asymptomatic population.     

Coenzymic activity of NADP derivatives alkylated at 2'-phosphate and 6-amino groups

Coenzymic activities of the following NADP derivatives were investigated: 2'-O-(2-carboxyethyl)phosphono-NAD (I), N6-(2-carboxyethyl)-NADP (II), 2'-O-(2-carboxyethyl)phosphono-N6-(2-carboxyethyl)-NAD (III), 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-NAD (IV), N6-[N-(2-aminoethyl)carbamoylethyl]-NADP (Va), 2',3'-cyclic NADP, and 3'-NADP. Derivatives I and IV show the effects of modification at the 2'-phosphate group, and derivatives II and Va show those at the 6-amino group of NADP. As for enzymes, alcohol, isocitrate, 6-phosphogluconate, glucose, glucose-6-phosphate, and glutamate dehydrogenases were used. These enzymes were grouped on the basis of the ratio of the activities for NAD and NADP into NADP-specific enzymes (ratio less than 0.01), NAD(P)-specific enzymes (0.01 less than ratio less than 100), and NAD-specific enzymes (ratio greater than 100). For NADP-specific enzymes, modifications at the 2'-phosphate group of NADP caused great loss of cofactor activity. The relative cofactor activities (NADP = 100%) of derivatives I and IV for these enzymes were 0.5-20 and 0.01-0.5%, respectively. On the other hand, NAD(P)-specific enzymes showed several types of responses to the NADP derivatives. The relative cofactor activities of I and IV for Leuconostoc mesenteroides and Bacillus stearothermophilus glucose-6-phosphate dehydrogenases and beef liver glutamate dehydrogenase were 60-200%; whereas, for B. megaterium glucose dehydrogenase and L. mesenteroides alcohol dehydrogenase, the values were 0.8-8%. For NAD-specific enzymes, these values were 20-50%. The relative cofactor activities of 2',3'-cyclic NADP and 3'-NADP were very low (less than 0.2%) except for beef liver glutamate dehydrogenase, B. stearothermophilus glucose-6-phosphate dehydrogenase, and horse liver alcohol dehydrogenase. Kinetic studies showed that the losses of the cofactor activity of NADP by these modifications were mainly due to the increase of the Km value. The mechanisms of coenzyme specificity of dehydrogenases are discussed. Unlike the 2'-phosphate group, the 6-amino group is common to NAD and NADP, and the effects of modification at the 6-amino group were independent of the coenzyme specificity of enzymes used for the assay. Derivatives II and Va had high relative cofactor activities (65-130%) for most of the enzymes except for isocitrate and glucose dehydrogenases (less than 1%) and L. mesenteroides alcohol dehydrogenase (20-60%). The cofactor activity of derivative III was generally lower than those of I and II.     

Preparation and characterization of NADP derivatives alkylated at 2'-phosphate and 6-amino groups

Reaction of NADP with 3-propiolactone at pH 6 gave new NADP derivatives carboxyethylated at the 2'-phosphate or 6-amino group, or both: 2'-O-(2-carboxyethyl)phosphono-NAD (I), N6-(2-carboxyethyl)-NADP (II), and 2'-O-(2-carboxyethyl)phosphono-N6-(2-carboxyethyl)-NAD (III). Their structures were assigned on the basis of ultraviolet, 1H-NMR and 31P-NMR spectra, and also treatment with nucleotide pyrophosphatase or alkaline phosphatase. Carbodiimide-promoted reaction of derivative I with 1,2-diaminoethane gave 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-NAD (IV); derivative III gave 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-N6-[N-(2-aminoethyl ) carbamoylethyl]-NAD (IV). The same reaction of derivative II, on the other hand, gave a mixture of N6-[N-(2-aminoethyl)carbamoylethyl]-NADP (Va) and its 3'-phosphate isomer (Vb). The mixture was converted to Va via the 2',3'-cyclic derivative (Vc). Their structures were assigned on the basis of ultraviolet and 1H-NMR spectra, and also treatment with alkaline phosphatase or 3'-nucleotidase. All the NADP derivatives obtained in this work could be reduced with yeast glucose-6-phosphate dehydrogenase.     

Expression of the functional erythropoietin receptors on interleukin 3-dependent murine cell lines

Two distinct hemopoietic growth factors, interleukin 3 (IL-3) and erythropoietin (EPO), support the growth and development of erythroid cells in a sequential manner in vitro. Stimulation of multipotential stem cells by IL-3 appears to develop committed erythroid progenitor cells that respond to EPO. When several murine IL-3-dependent cell lines were assayed for their ability to respond to EPO, the growth and survival of the three cell lines showing the profiles of either myeloid or mast cell lineage (IC-2, DA-1, FDC-P2) were stimulated by EPO in a dose-dependent fashion. To determine whether the biologic effects were mediated through the specific receptors for EPO, we performed binding experiments on these cells with radioiodinated EPO. All of these cells displayed significant levels of specific binding for EPO. Among a family of hemopoietic growth factors, only unlabeled EPO was able to compete for the binding of radioiodinated EPO to the cells. Analysis of the binding data revealed the existence of a single case of binding sites in extremely low abundance. IC-2 cells were used to study the effects of IL-3 on the regulation of expression of EPO receptors. It was demonstrated that a decrease in IL-3 concentration in the culture medium increased the responsiveness to EPO and the amount in specific binding of EPO as well. These results suggest that some IL-3-dependent cell lines have functional EPO receptors and their expression may be modulated by IL-3.     

Outbreaks of paralytic poliomyelitis and polio surveillance in Shandong province of China.

Widespread outbreaks of paralytic poliomyelitis occurred in Shandong province, China, starting from 1988. In 1989, 484 cases were recorded, which was the peak during the past 4 years. Although emergency immunization with trivalent oral poliovirus vaccine (OPV) was carried out in selected counties in 1989 and 1990, control of the outbreak was not satisfactory. OPV mass immunization campaigns were introduced to cover the whole province in early 1991, and the number of patients with paralytic poliomyelitis decreased to 95. In addition to this new immunization strategy, we began to construct new polio surveillance systems. These were a network for case-negative reporting and an immediate reporting system of acute flaccid paralysis (AFP). As for the case-negative reporting, presently more than 90% of counties have been reporting presence or absence of new AFP cases. Monitoring of AFP immediate reporting has also shown a gradual improvement in several aspects. These polio surveillance activities are crucial to polio eradication programme management.     

Midsummer succession of rotifer plankton in a shallow eutrophic pond

Temporal changes in the density of rotifer plankton were examinedin a shallow eutrophic pond during July to September 1990, whenabiotic environmental variables were relatively stable. In earlyJuly when Daphnia similis was abundant, rotifer populationsremained at a low density. This is probably due to interferenceby the large cladoceran, because possible food was abundantand the rotifers showed high egg ratio. After late July, whenthe large cladoceran disappeared, a striking succession wasfound in the rotifer plankton. In late July, when Filinia longisetaand Conochilus dossuarius dominated, and in mid- to late Septemberwhen F.opoliensis and Brachionus falcatus dominated, there wasa causal relationship between the density and egg ratio, suggestingthat temporal changes in rotifer density were regulated mainlyby food abundance. However, in August, changes in the densityof most rotifers were not necessarily related with those inthe egg ratio. Brachionus angularis, B.forficula and Keratellaspp. decreased or remained at a low density regardless of theegg ratio, when the population of Asplanchna brightwelli wasdeveloped. However, Polyarthra vulgaris, B.calyciflorus andH.intermedia increased or maintained a high density at thistime. Stomach contents of A.brightwelli revealed that B.angularis,B.forficula and Keratella spp. were the preferred prey, whereasP.vulgaris, B.calyciflorus and H.intermedia were not. Theseresults provide strong evidence that the structure of rotiferplankton can change strikingly within a season due to species-specificdifferences not only in diet, but also in the ability to escapepredation, even if abiotic environmental variables are stable.     

Effects of recombinant interferons on the clonogenic growth of leukemic cells and normal hemopoietic progenitors

We have examined the effects of recombinant immune and leukocyte interferons (rIFN-gamma and rIFN-alpha) on the clonogenic growth of leukemic cells and normal hemopoietic progenitors using in vitro colony assays. Both interferons suppressed the colony formation by granulocyte-macrophage progenitors (CFU-gm) and erythroid progenitors (CFU-e and BFU-e) in a dose-dependent manner. Six myeloid leukemic cell lines were less sensitive to rIFN-gamma than CFU-gm. The colony formation of some myeloid leukemic cell lines was suppressed more potently by rIFN-alpha than by CFU-gm. Four lymphoid leukemic cell lines of the T-cell type were very resistant to both recombinant interferons. Reduced sensitivity of leukemic cells to rIFN-gamma, a possible hemopoietic regulator, may explain partially the unregulated proliferation of leukemic cells in vivo.     

Evidence of multiple introductions and genetic admixture of the Asian brush-clawed shore crab <Emphasis Type="Italic">Hemigrapsus takanoi</Emphasis> (Decapoda: Brachyura: Varunidae) along the Northern European coast

The Asian brush-clawed shore crab Hemigrapsus takanoi is a non-indigenous species along the Northern European coast. Although the history of range expansion of European H. takanoi has been well-documented, little is known about the genetic compositions of either the introduced European populations or the native Asian ones. We therefore collected H. takanoi broadly from their native Asian sites and introduced European ranges, and genotyped them by sequencing the mitochondrial 16S RNA gene and by analyzing nuclear microsatellite loci. Our results revealed that the H. takanoi Bay of Seine (France) populations consisted of a genetic admixture between populations in Japan and those in the Yellow Sea region. These French populations should be carefully monitored in the future, since the genetic admixture of multiple source populations may accelerate range expansion in non-indigenous organisms. Our results also suggested that shipping lines from East Asia were more probable vectors than historical juvenile oyster transportations from Japan for the foundation of present European H. takanoi populations. Interestingly, gene flow between populations in Japan and those in the Yellow Sea region (i.e., domestic invasion) was not observed despite the higher potential for artificial translocations via shipping lines in the native Asian range compared with those from Asia to Europe. The lack of domestic invasions implied that intra-specific priority effects of the resident H. takanoi populations played an important role in preventing the successful colonization of artificially-transferred individuals.     

Synthesis and characterization of 1-substituted 5-alkylphenazine derivatives carrying functional groups

The following 1-substituted derivatives of 5-methylphenazine and 5-ethylphenazine were synthesized: 1-(3-carboxypropyloxy)-5-methylphenazine (1B), 1-(3-carboxypropyloxy)-5-ethylphenazine (2B), 1-(3-ethoxycarbonylpropyloxy)-5-ethylphenazine (2C) and 1-[N-(2-aminoethyl)carbamoylpropyloxy]-5-ethylphenazine (2D); their spectra, stability and reactivity as electron mediators were investigated, together with those of 5-methylphenazine (1A) and 5-ethylphenazine (2A). The 1-substituted derivatives are all insensitive to light and the derivatives of 5-ethylphenazine are more stable than those of 5-methylphenazine under neutral and alkaline conditions; 2B is the most stable of all the derivatives. The spectral properties of the decomposed compounds showed that photodecomposition of 1A and 2A is associated with hydroxylation at position 1, alkali decomposition of 1A and 1B with elimination of the 5-methyl group and alkali decomposition of 2A, 2B, and 2D with a ring-opening reaction. The second-order rate constant k1 for the reaction of the phenazine derivatives with NADH was measured under steady-state conditions. The k1 values vary depending on the substituents at positions 1 and 5: the values for 1A, 1B, 2A, 2B, 2C and 2D are 1.83 mM-1 s-1, 3.33 mM-1 s-1, 0.75 mM-1 s-1, 1.42 mM-1 s-1, 1.68 mM-1 s-1 and 2.03 mM-1 s-1, respectively. The rate constants, k2 and k3, for the reactions of the reduced form of 2B with oxygen and with 3-(4',5'-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium ion, respectively, were k2 = 1.21 mM-1 s-1 and k3 = 91 mM-1 s-1. These phenazine derivatives have potential applications in the biochemical field.