Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report concerns itself with additional experimental evidence to support the immunologic concept for the pathogenesis of Bell's palsy, using the mast cell as an index of immunological activity. In a previous experimental study, we postulated that degranulation of mast cells activated by complement or specific allergens with release of histamine and other substances may be the mechanism leading to nerve edema, ischemia, and paralysis. In this study we observed a loss of granulated mast cells in the more severely damaged facial nerves of immunized dogs after the intrafallopian canal injection of various substances, in contrast with the relative abundance of these cells in nerves that showed little or no evidence of injury. In addition, we demonstrated that cromolyn sodium, a mast cell degranulation inhibitor, when infused intravenously at the time of the intrafacial canal injection of horse serum, very effectively lessened the degree of experimental paralysis and histologic nerve injury.
 ...
PMID:Immunological concept for Bell's palsy: further experimental study. 86 31

Reperfusion of ischemic hindlimbs leads to leukotriene B4 (LTB4) and polymorphonuclear neutrophil (PMN)-dependent lung injury. Pulmonary mast cells are capable of synthesizing LTB4 and are potential mediators of this inflammatory response. This study tests their role in PMN sequestration and pulmonary edema after hindlimb ischemia. Anesthetized, mast cell-sufficient mice (n = 8) or their congeneic mast cell-deficient strain (n = 8) were subjected to 3 hours of hindlimb ischemia. After another 3 hours of reperfusion, plasma LTB4 levels rose to 651 pg/ml, higher than sham ischemic control (n = 8) values of 202 pg/ml (p less than 0.05). At this time there was sequestration of neutrophils in the pulmonary microcirculation (54 PMN/10 high-power fields [HPF]) and an increase in lung wet/dry weight ratio (W/D) of 4.4. Both these values were higher (p less than 0.05) than those in sham ischemic animals that showed sequestration of 18 PMN/10 HPF and a lung W/D of 3.1. In contrast, mast cell-deficient mice showed an attenuation of ischemia- and reperfusion-induced rise in plasma LTB4 (507 pg/ml), fewer sequestered neutrophils (34 PMNs/10 HPF), and a reduction in lung W/D to 3.9 (all p less than 0.05). To test the role of lung LTB4 in determining PMN sequestration, rats (n = 78) were subjected to 3 hours of hindlimb ischemia. After 3 hours of reperfusion, plasma and bronchoalveolar lavage (BAL) LTB4 concentrations rose to 956 and 211 pg/ml, respectively--higher than sham values of 460 and 121 pg/ml (both p less than 0.05). After 4 hours, plasma LTB4 levels had returned to baseline, whereas BAL LTB4 had increased further to 658 pg/ml, indicating lung origin. Treatment of other rats by localized lung lavage of the lipoxygenase inhibitor diethylcarbamazine (80 mg/kg in 0.1 ml twice) prevented the ischemia- and reperfusion-induced rise in BAL LTB4 (267 pg/ml) and limited local neutrophil sequestration (from 51 PMN/10 HPF after saline aspiration to 36 PMN/10 HPF) and lung W/D (from 4.5 to 4.1) (all p less than 0.05). The data indicate that after hindlimb ischemia pulmonary mast cells and localized LTB4 synthesis mediate, in part, the lung inflammatory response.
 ...
PMID:Mast cells and leukotrienes mediate neutrophil sequestration and lung edema after remote ischemia in rodents. 132 74

Recent studies have demonstrated a connection between xanthine oxidase-generated reactive oxygen intermediates and histamine release during ischemia-reperfusion. In the present work, the effect of modulation of the endogenous histamine level on the xanthine oxidase activity was examined during the reperfusion of a canine ileal segment following a 2 hr of complete ischemia. The xanthine oxidase activity and the plasma histamine level peaked simultaneously at the beginning of reperfusion, reaching mean values of 14.9 nmol/ml/min and 12.1 nmol/l, respectively. Pretreatment with aminoguanidine, a blocker of diamine oxidase (histaminase), resulted in significantly higher levels of histamine during reperfusion, but this elevation was not accompanied by a further increase in xanthine oxidase activity. Pretreatment with the mast cell stabilizer cromolyn significantly diminished the rise in plasma histamine level, with an unchanging activity of xanthine oxidase. No significant alteration could be observed in the postocclusive activity of xanthine oxidase following the intra-arterial administration of 0.5, 1, or 5 nmol of histamine during the last 10 min of the ischemic period. These data suggest that the amount of histamine liberated during reperfusion does not result in a further increase in the xanthine oxidase activity. The release of histamine is not a cause, but rather an effect of the elevated activity of intestinal xanthine oxidase.
 ...
PMID:Studies on the relationship between xanthine oxidase and histamine release during intestinal ischemia-reperfusion. 138 3

Experiments were carried out to provide evidence of the effect of L-arginine (L-Arg), its analogue NG-monomethyl-L-arginine (MeArg) and of some nitrovasodilators (sodium nitroprusside, NaNP; 3-morpholino-sydnonimine, SIN-1) which spontaneously release nitric oxide (NO) on ischemia-reperfusion injury, histamine release and mast cell degranulation, occurring after multiple ligature and release of the left anterior descending (LAD) coronary artery in isolated perfused guinea-pig hearts. The reopening of the LAD coronary artery leads to a release of histamine related to a decrease in microdensitometry of cardiac mast cells and to calcium overload. The perfusion of the heart with NO-donors significantly reduces either the release of histamine, the loss of mast cell metachromasia and the overload of calcium. These effects were potentiated by SOD. The results suggest that the endogenous formation of NO and molecules able to generate NO have a role in the prevention of post-ischemic tissue injury.
 ...
PMID:The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart. 171 36

In an ischemia-reperfusion model obtained in isolated perfused guinea pig heart by means of a double ligature of the left anterior descending coronary artery, the reperfusion of the ischemic myocardium leads to a release of lactate dehydrogenase and histamine, related to a decrease in the microdensitometry of cardiac mast cells and to a tissue calcium overload. The perfusion of the heart with L-arginine and with nitric oxide donors significantly reduces the release of histamine, the loss of mast cell metachromasia and calcium overload. These effects were potentiated by superoxide dismutase.
 ...
PMID:Effect of nitric oxide generators on ischemia-reperfusion injury and histamine release in isolated perfused guinea pig heart. 171 88

Myofiber injury-repair was studied in the rat following blunt trauma to the lower leg in order to understand how the inflammatory and regenerative responses of muscles are altered when myofiber rupture is accompanied by bleeding and clotting reactions. A contusion injury to the muscles of the lower hindlimb of the rat was induced by applying an impact force of 4.7 N-m/cm2 to one leg. The gastrocnemius and soleus muscles were removed bilaterally and evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations for several days following insult (6-120 hr). A significant increase in wet weight of the gastrocnemius muscle was noted 24 hr postinjury as fluid accumulation and bruising were evident in the muscles resulting from bleeding and inflammation. Vascular disruption was confirmed by the localization of some plasma constituents (fibrinogen, albumin, and complement C3) throughout the interstitial space and even inside some of the damaged myofibers. Inflammation was present and persisted for 5 days as evidenced by continued mast cell degranulation and increased vascular permeability. Using antibodies to identify specific proteoglycans which appear or disappear at various times during muscle regeneration, muscle repair could be followed. The repair process required approximately 10 days for restoration of morphologically intact myofibers. Thus, myofiber repair processes appear to be maintained even after disruption of the vascular system and ischemia following blunt trauma.
 ...
PMID:Extracellular matrix changes following blunt trauma to rat skeletal muscles. 230 15

Histamine has been proved to be released during myocardial infarction and ischemic arrhythmias in dogs. The aim of the present experiments was to evaluate if ischemia and reperfusion modify histamine and lactate dehydrogenase (LDH) release in isolated guinea-pig heart. The results obtained show a steady increase of LDH release both in the ischemic and reperfusion phases. The release of histamine was reduced during the ischemic phase and increased significantly during reperfusion. A significant diminution of mast cell granule metachromasia was observed in the right auricles at the end of the reperfusion period. D-mannitol and reduced glutathione (GSH) modified the kinetics of histamine and LDH release. Cimetidine was able to decrease significantly the release of histamine during the ischemic and reperfusion phases and also reduced the release of LDH; triprolidine was completely ineffective. The results suggest that oxygen-derived free radicals may be involved in the pathogenesis of myocardial dysfunction after ischemia and reperfusion.
 ...
PMID:Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea-pig. 244 Feb 79

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia. Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples. The perfusion of the heart with FeCl3/ADP (10 microM/100 microM), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 microM) a "spin-trapper" molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 microM) and of calcium-activated proteases (leupeptin, 10 microM) modified the kinetics of histamine and LDH release.
 ...
PMID:Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart. 245 99

Intravascular complement activation with either zymosan or cobra venom factor (CVF) impairs hepatic blood flow. Oxygen radical scavengers given at the time of complement activation attenuate the resulting hepatic ischemia. It is not clear whether complement-stimulated phagocytes or transiently ischemic then reperfused endothelial and parenchymal cells generated the toxic oxygen radicals. In this study, a group of rats were given allopurinol (50 mg/kg/day postoperatively X 3 days plus 100 mg/kg iv at t = 0), a specific inhibitor of xanthine oxidase, prior to complement activation with CVF (20 units/kg iv at t = 30 and 60 min) to determine whether xanthine oxidase-derived oxygen radicals contributed significantly to the hepatic perfusion abnormalities. Additional rats received lodoxamide tromethamine (10 mg/kg iv bolus at t = 0 followed by 20 mg/kg/hr iv infusion), a novel and potent inhibitor of mast cell release and inhibitor of xanthine oxidase, prior to the same CVF challenge to determine whether mast cell mediators were involved in the flow disturbance. Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and effective hepatic blood flow (EHBF) by galactose clearance were determined at t = 2 hr. The percentage change in total hemolytic complement activity (% delta CH50) was determined between serum obtained prior to sacrifice and at t = 0. Systemic hemodynamics and HCT were for the most part unaffected regardless of pretreatment group or challenge with CVF or saline. CVF challenge produced a 25% reduction (P less than 0.05) in EHBF in vehicle-pretreated rats compared to saline challenge. Neither allopurinol nor lodoxamide tromethamine significantly improved EHBF when given prior to CVF challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Allopurinol and lodoxamide in complement-induced hepatic ischemia. 326 Jun 42

Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
 ...
PMID:Nitric oxide in the gut. 758 76


1 2 3 4 5 6 7 8 9 10 Next >>