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B J Zimmerman

Publications and source records attributed to B J Zimmerman.

At least 19 recordsLinked to original sources
PubMed1992

Effects of SC-41930 on leukocyte adherence and emigration in rat mesenteric venules.

This study demonstrates that SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-p ropyl-2H-1-benzopyran-2-carboxylic acid, an orally active LTB4 receptor antagonist, reduces LTB4-induced leukocyte adhesion and emigration in rat mesenteric venules. The mesentery of Sprague-Dawley rats was prepared for intravital microscopic examination and venules of 25-35 microns were chosen for evaluation. In control animals, LTB4 (20 nM) was superfused over the mesentery for 30 min. In the treatment group SC-41930 (5 microM) was superfused for 30 min, followed by a 30 min superfusion with SC-41930 and LTB4. The LTB4-induced increase in leukocyte adherence and emigration in postcapillary venules was significantly attenuated by pretreatment with SC-41930. Other experiments demonstrated that platelet-activating-factor-induced leukocyte adherence was not affected by SC-41930. These results indicate that SC-41930 is a potent inhibitor of LTB4-induced leukocyte-endothelial cell adhesive interactions in postcapillary venules.

Animals↗
PubMed1992

Reperfusion injury.

In conclusion, a large body of evidence demonstrates that reperfusion of ischemic intestine results in significant microvascular and parenchymal cell injury. Reperfusion injury appears to be mediated by both reactive oxygen metabolites and activated polymorphonuclear leukocytes. Xanthine oxidase-derived oxidants initiate the production and release of proinflammatory agents, which in turn lead to polymorphonuclear leukocyte adherence and emigration. The adherent leukocytes mediate microvascular injury by either release of proteases, physical disruption of the endothelial barrier, or both.

Animals↗
PubMed1992

Neuropeptides promote neutrophil adherence to endothelial cell monolayers.

The objective of this study was to determine whether substance P and calcitonin gene-related peptide (CGRP), at physiologically relevant concentrations, affect leukocyte-endothelial cell adhesion. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated (40 min) with freshly isolated human neutrophils in the presence or absence of substance P or CGRP (10(-11) M). Both substance P and CGRP caused a significant increase (2-fold) in neutrophil adherence to HUVEC. Monoclonal antibodies (MAb) directed against the leukocyte adhesion glycoproteins CD11/CD18 (MAb IB4) and L-selectin (MAb DREG56) did not attenuate substance P-induced adhesion. Antibodies directed against the endothelial cell adhesion molecules E-selectin (MAb CL2) and ICAM-1 (MAb R6.5) were also without effect on substance P-induced neutrophil adhesion. Similar results were obtained when either MAb IB4, DREG56, CL2, or R6.5 was coincubated with CGRP-stimulated neutrophils and endothelial cells. Phorbol 12-myristate 13-acetate-stimulated neutrophil adherence was significantly attenuated by MAb IB4, indicating that CD11/CD18 participates in this adhesion process. The results of this study indicate that 1) the neuropeptides substance P and CGRP promote neutrophil adherence to venular endothelium and 2) the neuropeptide-induced adhesion is not mediated by the adhesion molecules CD11/CD18, L-selectin, E-selectin, or ICAM-1.

Antibodies, Monoclonal↗
PubMed1992

Hemoprotein-dependent production of a neutrophil-activating factor from arachidonic acid.

Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37 degrees C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxyeicosatetraenoic acids. A lipid-extractable substance with significant cross-reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1991

Role of neutrophils in acetic acid-induced colitis in rats.

Intrarectal administration of 4% acetic acid produces diffuse inflammation that ultimately results in erosions and ulcerations of the rat colon. Although this model of colitis has been used extensively over the past several years, there are no quantitative data available regarding the relationship between neutrophil infiltration and mucosal injury during times of active inflammation. Therefore, the objective of this study was to define the role of extravasated neutrophils as mediators of mucosal injury and inflammation in acetic acid-induced colitis. We found the intrarectal administration of 4% acetic acid produced an 11-fold increase in colonic mucosal permeability, a 9-fold increase in colonic MPO activity, and a 1.6-fold increase in colon weight at 48 h following administration of acetic acid. In addition, we found significant correlations between colonic MPO activity and mucosal permeability and between colonic MPO activity and colon weight (P less than 0.01 for both). These data suggested that inflammatory neutrophils may mediate mucosal injury and inflammation in this model of colitis. To assess the role of circulating neutrophils, rats were rendered neutropenic for 48 h by the intraperitoneal administration of antiserum directed toward rat neutrophils (ANS). Although ANS treatment reduced both the number of circulating neutrophils and colonic MPO activity to less than 10% of control values, it did not attenuate the increases in colonic mucosal permeability nor did it attenuate the increases in colon weight produced by acetic acid. Histological inspection confirmed that ANS treatment was not effective in attenuating the injury to the epithelial barrier. These data demonstrate that infiltrating neutrophils do not mediate the mucosal injury and inflammation observed in acetic acid-induced colitis.

Acetates↗
PubMed1991

Ischemia-reperfusion-induced mucosal dysfunction: role of neutrophils.

The ability of the small intestine to absorb and transport lipid into lymph is markedly reduced 24 h after a 10-min total occlusion of the superior mesenteric artery (SMA). The aim of this study was to define the role of neutrophils in the ischemia-reperfusion (I/R)-induced decrement in lipid absorption. A lipid test meal containing 40 mumol of radioactive triolein was infused intraduodenally at 3 ml/h for 8 h, and radioactive lipid output in lymph was monitored during lipid infusion in intestinal lymph fistula rats. Animals rendered neutropenic with antineutrophil serum (ANS) did not exhibit the reduction in lipid absorption and transport in lymph normally observed 24 h after I/R. This protective effect of ANS was specifically related to the reduction in the number of neutrophils in the intestinal mucosa. The amount of radioactive lipid detected in the liver of untreated rats was significantly higher than in control rats, suggesting an increased portal transport of infused radioactive lipid. Neutropenia reduced the liver lipid level toward the control value. The intestinal blood flow response to SMA occlusion was not altered by neutropenia. Our results suggest that neutrophils play an important role in the mucosal dysfunction associated with ischemia-reperfusion.

Animals↗
PubMed1990

Role of oxyradicals in cold water immersion restraint-induced gastric mucosal injury in the rat.

Cold water immersion restraint of the rat results in focal gastric mucosal erosions. The lesions are associated with powerful, prolonged-duration gastric contractions. Phasic gastric contractions may attenuate gastric mucosal blood flow, resulting in ischemia followed by reperfusion. Therefore, the conditions of cold-water-immersion restraint might lead to mucosal injury by an oxyradical-mediated mechanism. To test this hypothesis, we studied the effect of oxyradical inhibition on cold water immersion restraint-induced lesions. In separate groups of rats subjected to cold water immersion restraint (6-10 animals per group), oxyradical inhibition was achieved by chronic feeding of a sodium tungstate diet, oral administration of allopurinol, or intraperitoneal administration of dimethylsulfoxide. None of these regimens significantly attenuated the number of lesions per stomach, the total lesion area, or the percent of corpus mucosa containing lesions. We conclude that oxyradicals do not play a role in the pathogenesis of cold water immersion restraint-induced lesions.

Allopurinol↗
PubMed1990

Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine.

Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel.

Analysis of Variance↗
PubMed1990

Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration.

The objective of this study was to determine whether hydrogen peroxide, iron, and/or hydroxyl radicals play a role in ischemia/reperfusion (I/R)-induced granulocyte infiltration in the feline small intestine and whether a chemoattractant is formed when superoxide or hydrogen peroxide reacts with feline extracellular fluid. In vivo determinations of granulocyte infiltration consisted of measurements of tissue myeloperoxidase activity in either the intestinal mucosa (I/R studies) or dermis (chemotaxis studies), whereas in vitro measurements of granulocyte migration were obtained using a Boyden chamber. Treatment with either catalase or the iron chelator deferoxamine significantly attenuated granulocyte infiltration into the mucosa induced by reperfusion of the ischemic intestine. Two hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU), were also evaluated for their ability to modulate I/R-induced granulocyte infiltration. DMTU significantly attenuated the I/R-induced granulocyte accumulation, whereas DMSO had no effect. In other experiments, we were unable to stimulate granulocyte migration with feline plasma exposed to superoxide-generating systems using both in vitro and in vivo models of leukocyte chemotaxis. However, hydrogen peroxide in the presence of either ferrous iron or hemoglobin did significantly increase the chemotactic activity of cat plasma. The results obtained from our studies suggest that either hydrogen peroxide or radical species derived from the interaction of superoxide and hydrogen peroxide with iron elicit I/R-induced granulocyte infiltration in the intestine.

Animals↗
PubMed1990

Reperfusion-induced leukocyte infiltration: role of elastase.

Polymorphonuclear leukocytes are known to accumulate in tissues subjected to ischemia and reperfusion. Studies on endothelial cell monolayers suggest that limited release of elastase plays an important role, via basement membrane degradation, in the leukocyte diapedesis and extravasation elicited by proinflammatory mediators. Thus the objective of this study was to define the role of elastase in the leukocyte infiltration associated with reperfusion of the ischemic bowel. In one series of experiments the cat small intestine was subjected to 3 h of ischemia (blood flow reduced to 20% of base line) and 1 h of reperfusion. Neutrophil accumulation was quantified by measurement of tissue myeloperoxidase activity in mucosal biopsies obtained during base-line, ischemic, and reperfusion periods. Pretreatment with either of the elastase inhibitors Eglin C and L658,758 significantly attenuated the neutrophil infiltration induced by reperfusion but not by ischemia per se. In another series of experiments, leukocyte adherence and extravasation were monitored in cat mesenteric venules subjected to 1 h of ischemia and reperfusion. Pretreatment with L658,758 significantly attenuated the increased rates of leukocyte adherence and extravasation induced by reperfusion, with a proportionately greater reduction in leukocyte extravasation rate. These results indicate that elastase release is an important factor in reperfusion-induced neutrophil infiltration.

Animals↗
PubMed1988

Mechanisms of oxidant-mediated microvascular injury following reperfusion of the ischemic intestine.

Based on work from our laboratory and studies by others, we propose the following hypothesis to explain the interaction among xanthine oxidase, PMNs, and tissue injury in the postischemic small intestine (Figure 2). During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase via a protease. When the intestine is reperfused, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of ferric iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytoxic free radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that activate, attract, and promote the adherence of PMN to microvascular endothelium. The adherent PMN then causes further endothelial cell injury via the release of superoxide and various proteases.

Animals↗
PubMed1988

Intestinal microvascular exchange in the rat during luminal perfusion with formyl-methionyl-leucyl-phenylalanine.

Formyl-methionyl-leucyl-phenylalanine (FMLP), a peptide released from bacteria in the gut lumen, is known to both attract and activate neutrophils. The aim of this study was to determine whether luminal perfusion with 1 microM FMLP alters microvascular permeability, blood flow, and neutrophil migration in the small intestine of control rats and rats treated with antineutrophil serum. Microvascular permeability to total plasma proteins was determined from an analysis of lymphatic protein fluxes. Myeloperoxidase activity was used as an index of tissue neutrophil count. Intestinal blood flow was measured using radiolabeled microspheres and the reference blood sample method. In control rats, luminal perfusion with FMLP caused significant increases in blood flow, lymph flow, lymph protein clearance, and microvascular permeability, but it did not alter tissue myeloperoxidase activity. In rats treated with antineutrophil serum, tissue myeloperoxidase levels were reduced by approximately 55%, and the FMLP-induced changes in lymph flow, lymph protein clearance, and microvascular permeability were significantly attenuated. In vitro experiments with isolated rat neutrophils revealed that 1 microM FMLP elicits significant chemotaxis and degranulation yet minimally enhances superoxide production. The results of this study indicate that peptides produced by microorganisms in the gut lumen can increase intestinal microvascular permeability. The FMLP-induced alterations in microvascular exchange appear to be mediated by activated neutrophils.

Animals↗
PubMed1988

Vascular injury in dogs during ischemia-reperfusion: improvement with ATP-MgCl2 pretreatment.

The aim of this study was to determine whether ATP-MgCl2 or isoproterenol pretreatment would attenuate the increase in canine gracilis muscle vascular resistance and permeability associated with 4 h of occlusive ischemia followed by 1 h of reperfusion. To this end, the osmotic reflection coefficient for total plasma proteins (omega), isogravimetric capillary pressure (Pci), precapillary resistance (Ra), postcapillary resistance (Rv), and total vascular resistance (Rt) were determined for the following conditions: control, ischemia, and ischemia plus pretreatment with ATP-MgCl2 or isoproterenol. Reperfusion, after ischemia, significantly reduced omega from 0.94 +/- 0.02 to 0.64 +/- 0.02, whereas Pci was decreased by 50 +/- 4%, indicating a dramatic increase in vascular permeability. Ischemia-reperfusion was also associated with an increase in Rt of 230 +/- 22%. Similar results were obtained in muscles pretreated with isoproterenol. However, in muscles pretreated with ATP-MgCl2, omega averaged 0.98 +/- 0.09, Pci was reduced by only 15 +/- 8%, and Rt was increased by just 25 +/- 12%. The effect of ATP-MgCl2 on neutrophilic oxidative metabolism was evaluated by measuring superoxide production by activated neutrophils in the presence and absence of ATP-MgCl2. Superoxide production by activated neutrophils was significantly attenuated by ATP-MgCl2. The results of these studies indicate that pretreatment with ATP-MgCl2, but not isoproterenol, is remarkably effective in attenuating the increase in skeletal muscle vascular resistance and permeability induced by ischemia-reperfusion. The protective effect of ATP-MgCl2 may be related in part to its ability to inhibit neutrophilic superoxide production.

Adenosine Triphosphate↗
PubMed1988

Allopurinol does not enhance antioxidant properties of extracellular fluid.

Allopurinol has been shown to provide significant protection against ischemia/reperfusion-induced microvascular and parenchymal cell injury. It has been hypothesized that the protection seen with allopurinol after ischemia/reperfusion (I/R) is caused by inhibition of xanthine oxidase. However, recent reports suggest that the beneficial effects of allopurinol in I/R may be caused by direct free radical scavenging. The objective of this study was to determine whether the regimen of allopurinol administration used in most I/R studies leads to a significant modification of the free radical scavenging properties of extracellular fluid (ECF), i.e., plasma and lymph. Plasma and intestinal lymph samples obtained from both control and allopurinol-treated cats were used to assess the following: 1) allopurinol and oxypurinol concentrations, 2) xanthine oxidase inhibition, 3) myoglobin-catalyzed linolenic acid peroxidation, 4) hypochlorous acid scavenging, and 5) protein and nonprotein sulfhydryl content. ECF from allopurinol-treated animals contained approximately 10 microM each of allopurinol and oxypurinol. Ten percent ECF resulted in 80% inhibition of xanthine oxidase activity. Comparable volumes of control ECF did not inhibit xanthine oxidase. Furthermore, allopurinol treatment did not enhance the antioxidant properties of ECF. The results of this study do not support the contention that the beneficial effects of allopurinol in I/R injury are caused by the scavenging of oxidants produced in ECF by activated granulocytes.

Allopurinol↗
PubMed1976

Vicarious effects on the creative behavior of retarded and nonretarded children.

The effects of observing a model's overt display of a creative drawing response and hearing a description of these actions were assessed with 54 retarded and 68 nonretarded children. The modeled creative strategy was designed to be high in the dimension of elaboration. A multivariate research design was employed to assess the target dimension of elaboration, as well as to determine transfer to tasks of varying degrees of similarity to the model's task and to creative dimensions other than elaboration. The overt modeling of a creative strategy was most effective in improving elaboration, although verbal descriptions also aided performance. Retarded children were less able than nonretarded children to discriminate the essential elements of the model's elaboration strategy and displayed less acquisition of the elaboration strategy but showed comparable gradients of transfer.

Child↗
PubMed1975

A field study of coliform mastitis in sows.

Three sows with agalactia and mastitis were compared with 3 normally lactating sows at 8, 16, 24, and 32 hours postpartum. Bacteriologic examination of milk resulted in isolation of Klebsiella pneumoniae or Escherichia coli from affected glands of all 3 agalactic sows. Milk from clinically normal glands of affected sows and from glands of normal sows was culture-negative for coliforms. Affected sows had higher rectal temperatures and lower milk yields, and pigs from affected sows had lower mean weights, but these differences were not significant. Mean total white blood cell counts and plasma protein to fibrinogen ratios were lower in mastitic sows at all 4 periods; differences were significant at certain periods in both cases. Evidence indicated that leukopenia appeared early, 8 to 16 hours postpartum, and was followed by increasing plasma fibrinogen content. Packed cell volumes and plasma concentrations of corticoid, estrone, and estradiol did not differ. Plasma progesterone content was higher in mastitic sows at all periods, but the differences were not significant.

Adrenal Cortex Hormones↗