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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, an increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. We now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an "overlap" region for the facial and some of the skeletal features. We report the clinical, cytogenetic, and molecular analysis of two patients. The first is DUP21JS, who carries both a partial duplication of chromosome 21, including the region 21q21.1-q22.13, or proximal q22.2, and DS features including duodenal stenosis. Using quantitative Southern blot dosage analysis and 15 DNA sequences unique to chromosome 21, we have defined the molecular extent of the duplication. This includes the region defined by DNA sequences for APP (amyloid precursor protein), SOD1 (CuZn superoxide dismutase), D21S47, SF57, D21S17, D21S55, D21S3, and D21S15 and excludes the regions defined by DNA sequences for D21S16, D21S46, D21S1, D21S19, BCE I (breast cancer estrogen-inducible gene), D21S39, and D21S44. Using similar techniques, we have also defined the region duplicated in the second case occurring in a family carrying a translocation associated with DS and congenital heart disease. This region includes DNA sequences for D21S55 and D21S3 and excludes DNA sequences for D21S47 and D21S17.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis. 153 Nov 66

The interactive effects of manganese and iron on true absorption and endogenous losses of manganese were investigated by feeding rats three levels of manganese (0.9, 48 or 188 micrograms Mn/g diet) and two levels of iron (19 or 276 micrograms Fe/g diet) for 7 wk. After 45 d, half of the rats were fed 54Mn and half were injected intraportally with 54Mn complexed to albumin. The relative distribution of 54Mn in tissues was generally similar for rats when 54Mn was administered in these two ways. Manganese-deficient animals retained more of the isotope, had both higher apparent and higher true absorption of manganese, had a greater proportion of 54Mn in their livers and had a lower proportion of 54Mn in their muscles compared with animals fed adequate or high levels of manganese. High iron intake inhibited manganese true absorption, reduced tissue manganese concentrations and inhibited heart manganese-dependent superoxide dismutase activity. However, the greatest effect of dietary iron was on mucosal cell manganese concentrations. Endogenous losses of manganese were approximately 8% of the amount of manganese actually absorbed regardless of intake. Thus, control of absorption in the gut seems to be the major way that manganese homeostasis is maintained. Furthermore, iron seems to be depressing manganese absorption by inhibiting manganese uptake into the mucosal cells.
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PMID:Varying levels of manganese and iron affect absorption and gut endogenous losses of manganese by rats. 158 48

There is a growing body of experimental data to suggest that the chronically inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable sources of these oxidants are the phagocytic leukocytes since these cells are known to be present in large numbers in the inflamed mucosa and are known to produce significant amounts of reactive oxygen species in response to certain inflammatory stimuli. Because the colonic mucosa contains relatively small amounts of antioxidant enzymes (e.g. SOD, catalase, GSH peroxidase) it is possible that the gut mucosa may be overwhelmed during times of active inflammation which could result in intestinal injury. If reactive oxygen species play an important role in mediating mucosal injury in IBD then it should be possible to attenuate this injury by the use of antioxidants. One such drug is the sulfasalazine metabolite 5-ASA. It may not be coincidence that this potent antiinflammatory metabolite is a potent antioxidant that possesses multiple mechanisms of action including nitrogen, carbon and oxygen-centered free radical scavenging properties as well as the ability to decompose HOCl and scavenge hemoprotein-associated oxidants. In addition 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. The reason that 5-ASA is so effective in vivo may be due to this multitude of antioxidant properties. This would also suggest that other, more potent antioxidants may prove beneficial in the treatment of IBD.
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PMID:Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. 166 88

Forty dogs were divided randomly into four groups. The portal circulation was reduced to 50%-60% for one hour by partially occluding the superior mesenteric artery (SMA) for the purpose of determining the relationship between the reperfusion injury, bacterial translocation, and multiple system organ failure. Escherichia coli 0111 B4 (1 x 10(10)/kg) was fed to each animal 12 hours before operation. Group I constituted the controls, in which a sham operation was done. The experimental procedure was completed in all the animals of the other three groups. The group-II animals received no further manipulation. Rubia yunnanensis, an antioxidant, was given to the animals in group III. Amikacin was given to the animals in group IV. The results showed that the animals in group II developed bacteremia, hypoxemia, and hypotension compared with the animals in group I. The levels of superoxide dismutase (SOD) in whole blood were markedly lowered in group-II animals, with malondialdehyde (MDA) values significantly elevated after reperfusion when compared with group I. Plasma levels of anaphylatoxin C5a and thromboxane B2 (TXB2) were significantly raised in group-II animals beginning from reperfusion when compared with the animals in group I, group III, and group IV. Pathologic changes in the intestine, liver, and lung were marked only in the group-II animals, including acute necrosis of the intestinal mucosa, granulocyte infiltration, and bacterial invasion of the liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development of MSOF by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations, where it fuels the septic process. Oxygen free radicals, anaphylatoxin, and thromboxane may be potential factors in the development of gut barrier failure and MSOF.
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PMID:Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion. 174 Jul 93

Portal circulation was reduced to 50-60% for one hour by partial occlusion of the superior mesenteric artery for the purpose of studying the relationship between reperfusion injury, bacterial translocation and multiple system organ failure. Forty dogs were divided randomly into four groups, and 1 x 10(10)/kg E. coli O111B4 were fed to each animal 12 hours before operation. Group I constituted the controls, in which sham operations were performed. The experimental procedure was completed in all the animals of the other three groups. Rubia yunnanensis, an anti-oxidant, was given to group III. Amikacin was given to group IV. The results showed that group II was characterized by bacteremia, hypoxemia, and hypotension as compared with group I. The levels of superoxide dismutase (SOD) in the whole blood were markedly lowered and malondialdehyde (MDA) values significantly elevated in group II after reperfusion compared with group I. Plasma levels of anaphylatoxin C5a and B2 (TXB2) were significantly raised in group II beginning with the reperfusion when compared with groups I, III and IV. Pathological changes in the intestine, liver and lung were remarkable only in group II, including acute necrosis of the intestinal mucosa, granulocyte infiltration, hemorrhage and edema of the lung, degenerative changes of myocardial and hepatic cells, and bacterial invasion of the blood, liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development to multiple system organ failure (MSOF) by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations where it fuels the septic process. Oxygen free radicals, anaphylatoxin and thromboxane may be potential factors in the development of gut barrier failure and MSOF.
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PMID:Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion. 180 29

The changes in short circuit current (electrogenic Cl- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H2O2, and the lack of effect of preincubation with deferoxamine or thiourea implicate H2O2, and not O2- or OH., as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H2O2 stimulated colonic PGE2 and PGI2 production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl- secretion was reduced by cyclooxygenase inhibition. Also, the Cl- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H2O2 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H2O2 response. H2O2 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.
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PMID:Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport. 216 49

Delayed fluid resuscitation during burn shock is thought to compromise the integrity of gut mucosa and allow enteric bacteria to cross the luminal wall and infect other sterile organ systems. Superoxide dismutase, a free-oxygen radical scavenger; leupeptin, a protease inhibitor; and verapamil, a calcium channel blocker, were studied to evaluate their efficacy in maintaining cellular integrity in the gut of thermally burned rats whose fluid resuscitation had been delayed. Fifty male rats weighting 280 to 320 gm were given a full-thickness scald burn covering 50% total body surface area. Ten received early fluid resuscitation beginning half an hour after burn, and 40 received fluid resuscitation delayed by 6 hours. Those receiving delayed resuscitation were given superoxide dismutase (n = 10), leupeptin (n = 10), verapamil (n = 10), or a placebo of normal saline solution (n = 10) at the time of fluid resuscitation. Ileal mucosa samples were harvested, and adenosine triphosphate, diphosphate, and monophosphate were measured. Adenosine triphosphate, total nucleotides, and energy charge potential were significantly lower in the placebo group without therapy compared with those of the early resuscitation group. Superoxide dismutase and leupeptin therapy prevented this drop in cellular energy. Total water content was significantly increased in the placebo group compared with that of the early resuscitation group; superoxide dismutase was able to prevent this increase. Data indicate that intestinal reperfusion injury in burned rats can be effectively modulated with superoxide dismutase or leupeptin therapy.
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PMID:Superoxide dismutase and leupeptin prevent delayed reperfusion injury in the rat small intestine during burn shock. 777 3

Our in vivo model of mesenteric ischemia/reperfusion (I/R) has shown that the gut serves as a priming bed for neutrophils (PMN). Activation of phospholipase A2 (PLA2) during ischemia temporally precedes PMN sequestration in the gut and the appearance of primed PMN in the portal circulation. Therefore, we hypothesized that reperfused gut secretes platelet activating factor (PAF) via PLA2 activation that is responsible for increased PMN chemotaxis and priming for superoxide (O2-) generation. Sprague-Dawley rats underwent gut ischemia/reperfusion (45 min SMA occlusion/2 hr reperfusion) or sham laparotomy. Distal ileum was harvested, rinsed with bacteriostatic saline/neomycin, and incubated for 1 hr at 37 degrees C in RPMI 1640 and the cell-free supernatant was collected. Normal human PMNs, isolated by plasma-Percoll gradients, were pretreated with or without a PAF receptor antagonist (WEB 2170). Chemotaxis toward gut supernatant was then measured by the agarose method. Additionally, PMNs were preincubated with or without WEB 2170 and their O2- release in response to 1 microM FMLP was measured by the Vmax of SOD-inhibitable cytochrome c reduction. Reperfused gut produced a chemotactic index of 2.1 +/- 0.1 compared to 0.2 +/- 0.9 following sham laparotomy (P < 0.05); this was reduced to 0.4 +/- 0.9 with PAF receptor blockade. Similarly, gut I/R supernatant primed PMNs for O2- (P < 0.05) compared to laparotomy, and this effect was abrogated by a PAF antagonist. These data suggest that reperfused gut can elaborate PAF which chemoattracts and primes PMNs for O2- generation.
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PMID:Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. 779 40

We hypothesized that manganese deficient animals fed high vs moderate levels of polyunsaturated fat would either manifest evidence of increased oxidative stress or would experience compensatory changes in antioxidant enzymes and/or shifts in manganese utilization that result in decreased endogenous gut manganese losses. Rats (females in Study 1, males in Study 2, n = 8/treatment) were fed diets that contained 5 or 20% corn oil by weight and either 0.01 or 1.5 mumol manganese/g diet. In study 2, 54Mn complexed to albumin was injected into the portal vein to assess gut endogenous losses of manganese. The manganese deficient rats: 1. Had 30-50% lower liver, tibia, kidney, spleen, and pancreas manganese concentrations than manganese adequate rats; 2. Conserved manganese through approximately 70-fold reductions in endogenous fecal losses of manganese; 3. Had lower heart manganese superoxide dismutase (MnSOD) activity; and 4. Experienced only two minor compensatory changes in the activity of copper-zinc superoxide dismutase (CuZnSOD) and catalase. Gut endogenous losses of manganese tended to account for a smaller proportion of absorbed manganese in rats fed high-fat diets; otherwise fat intake had few effects on tissue manganese concentrations.
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PMID:Manganese status, gut endogenous losses of manganese, and antioxidant enzyme activity in rats fed varying levels of manganese and fat. 798 58

The role of nitric oxide (NO) as a mediator of colonic circular smooth muscle relaxation by human leucocytes was investigated. Granulocytes and mononuclear cells were obtained by gradient centrifugation of venous blood from healthy volunteers. Both cell types relaxed precontracted distal colonic circular smooth muscle in a concentration dependent manner. Muscle relaxation was inhibited by preincubation of cells with NG-monomethyl-L-arginine (100 microM/l) but not by preincubation with NG-monomethyl-D-arginine (100 microM/l). Muscle relaxation by cells was reduced by 200 nM oxyhaemoglobin and 10 microM methylene blue but was increased by 60 units/ml superoxide dismutase. Non-viable cells did not produce muscle relaxation. Activation of mononuclear cells by incubation with 100 nM/l FMet-Leu-Phe increased muscle relaxation, whereas activation of granulocytes did not. Granulocytes and mononuclear cells relax precontracted distal colonic circular smooth muscle in vitro by the release of NO that may contribute to motility disorders of the gut associated with inflammation.
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PMID:Relaxation of distal colonic circular smooth muscle by nitric oxide derived from human leucocytes. 831 15


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