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Biomedical subjects

D Lagunoff

Publications and source records attributed to D Lagunoff.

At least 37 records · Page 2Linked to original sources
PubMed1988

Aluminum-containing emboli in infants treated with extracorporeal membrane oxygenation.

We found fibrin thrombi or thromboemboli at autopsy in 22 of 23 infants with respiratory failure who had been treated with venoarterial extracorporeal membrane oxygenation (ECMO). In addition, distinctive basophilic aluminum-containing emboli were found in 12 of the infants; the distribution of these emboli was similar to that of the thromboemboli, except that an aluminum-containing embolus was found in a lung in only 1 infant. Sixteen infants had pulmonary thrombi or thromboemboli. We also found friable aluminum-containing concretions adhering loosely to the mixing rods of heat exchangers that had been used to warm the blood flowing through the ECMO circuit; such concretions were not present on unused mixing rods. We propose that these aluminum-containing concretions developed as the silicone coating of the heat exchanger wore away and aluminum metal was exposed to warm, oxygenated blood and that fragments of aluminum-containing concretions formed emboli. This hypothesis is supported by the fact that aluminum-containing emboli were generally not present in the lungs, which are bypassed by ECMO. Although infarcts were found in 16 of the 23 infants, we cannot be certain whether any of the infarcts were caused by the aluminum-containing emboli.

Aluminum↗
PubMed1988

Studies on the growth of mast cells in rats. Changes in granule size between 1 and 6 months.

Mast cells from rats aged 1 month, 3 months and 5 to 7 months were compared with respect to cell size and secretory granule size and number. With increasing age there was an increase in mean total cell volume accounted for almost entirely by an increase in mean total granule volume/cell even though there was no apparent increase in the number of granules. An increase in histamine content closely paralleled the increase in total granule volume. In each age group, the distribution of equivalent volumes of granule profiles exhibited periodic multimodality consistent with a Poisson distribution of granule volume. We have interpreted these observations in terms of a model in which total granule volume/cell increases through the production of unit granules of uniform size; the increasing size of individual granules we attribute to the fusion of unit granules with each other and with larger granules.

Aging↗
PubMed1988

Effect of perioperative myocardial infarction on survival of postcardiotomy patients supported with ventricular-assist devices.

Ventricular-assist devices (VAD) have increased survival in patients with postcardiotomy shock, but the predictors of success need to be elucidated. We evaluated 45 patients treated with centrifugal (n = 18) or pulsatile (n = 27) VAD for postcardiotomy cardiogenic shock to determine the effect of perioperative myocardial infarction (PMI) on survival. The patients ranged in age from 15 to 72 years (mean age, 55.1 years). VAD support was left ventricular in 29, right ventricular in seven, and biventricular in nine, and the flow-rate range was 1.6-5.2 l/min (mean rate, 3.97 l/min) for 0.2-22 days (mean time, 4.1 days). PMI was determined by analysis of postoperative electrocardiogram (EKG), enzyme levels, or at necropsy. PMI was considered "possible" if there were either EKG or enzyme level changes, and "definite" if there were EKG and enzyme level changes or necropsy evidence. Of the 45 patients, 19 were successfully weaned from ventricular assistance; 12 were discharged (Group 1), and seven died (Group 2); the remaining 26 patients could not be weaned from VAD support (Group 3). In Group 1, one patient had a definite PMI, and three had a possible PMI. Among the 33 nonsurvivors (Groups 2 and 3), 24 patients had PMI by necropsy examination. Definite PMI was much more common in nonsurvivors (72.7%) than in survivors (8.3%) (p less than 0.05). However, Group 2 nonsurvivors were weaned despite PMI in 100% of cases. These data suggest that, although PMI is a strong negative determinant of survival in postcardiotomy patients, it cannot be considered a contraindication because it does not preclude myocardial recovery.

Adolescent↗
PubMed1988

Inhibition of endothelial cell retraction by ATP depletion.

To determine the relationship among endothelial cell (EC) retraction, cell adenosine triphosphate (ATP), and the status of cellular actin, ATP levels, F-actin content, and cytochemical redistribution in bovine pulmonary artery endothelial cells were assessed. EC monolayers 7 days after confluence were exposed to ethchlorvynol (ECV), histamine, or cytochalasin B (cyto B) for time intervals from 5-90 minutes. All 3 agents resulted in endothelial cell retraction without significant effect on cellular ATP content. Sixty-minute incubation of monolayers in glucose-free media containing antimycin A and 2-deoxyglucose depleted cellular ATP to less than 10% of control levels. ATP depleted monolayers failed to retract when incubated with ECV, histamine, or cyto B. ATP depletion resulted in loss of the prominent EC margins but only a rare gap between adjacent cells. When ATP levels were allowed to recover, the ability of EC monolayers to retract was restored. Actin filaments in control monolayers localized to a dense peripheral band of actin, a paranuclear complex, and bundles of microfilaments orientated parallel to the long axis of the cell. ECV induced complete loss of the dense peripheral band and other changes in the actin disposition. Monolayers exposed to histamine showed a retraction of the dense peripheral band of actin to a subcortical position. Cyto B caused loss of the dense peripheral band and the longitudinal microfilament bundles. Monolayers depleted of ATP lost their dense peripheral band and exhibited a disorganized, tangled web of microfilaments. Neither histamine nor ECV modified the actin distribution in ATP-depleted monolayers, whereas exposure to cyto B resulted in substantial change in actin with formation of a rim inside the cell membrane and considerable loss of actin filaments. ECV or histamine induced a small reduction in F-actin content while cyto B resulted in a 50% decline in 15 minutes. ATP depletion resulted in a 19% decrease in F-actin, with no further reduction on subsequent exposure to histamine or ECV. Cyto B treatment of ATP-depleted monolayers caused a drop in F-actin content equivalent to that observed in cells with normal ATP levels. These studies indicate that ATP is essential for changes in actin filament distribution and endothelial cell retraction produced by ECV, histamine or cyto B, and make it unlikely that any of these agents acts simply by depolymerization of actin filaments or modification of the dense peripheral band, although disruption of the dense peripheral band may facilitate retraction in the presence of adequate levels of cell ATP.

Actins↗
PubMed1987

Proton nuclear magnetic resonance studies of mast cell histamine.

The state of histamine in mast cells was studied by 1H NMR spectroscopy. Spectra were measured for histamine in situ in intact mast cells, for histamine in suspensions of mast cell granule matrices that had been stripped of their membranes, and for histamine in solutions of heparin. The 1H NMR spectrum of intact mast cells is relatively simple, consisting predominantly of resonances for intracellular histamine superimposed on a weaker background of resonances from heparin and proteins of the cells. All of the intracellular histamine contributes to the NMR signals, indicating it must be relatively mobile and not rigidly associated with the negatively charged granule matrix. Spectra for intracellular histamine and for histamine in granule matrices are similar, indicating the latter to be a reasonable model for the in situ situation. The dynamics of binding of histamine by granule matrices and by heparin are considerably different; exchange of histamine between the bulk water and the granule matrices is slow on the 1H NMR time scale, whereas exchange between the free and bound forms in heparin solution is fast. The chemical shifts of resonances for histamine in mast cells are pH dependent, decreasing as the intragranule pH increases without splitting or broadening. The results are interpreted to indicate that histamine in mast cells is relatively labile, with rapid exchange between bound histamine and pools of free histamine in water compartments confined in the granule matrix.

Animals↗
PubMed1987

Phosphatidylcholine metabolism in endothelial cells: evidence for phospholipase A and a novel Ca2+-independent phospholipase C.

The metabolism of phosphatidylcholine (PC) was investigated in sonicated suspensions of bovine pulmonary artery endothelial cells and in subcellular fractions using two PC substrates: 1-oleoyl-2-[3H]oleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phospho[14C]choline. When these substrates were incubated with the whole cell sonicate at pH 7.5, all of the metabolized 3H label was recovered in [3H]oleic acid (95%) and [3H]diacylglycerol (5%). All of the 14C label was identified in [14C]lysoPC (92%) and [14C]phosphocholine (8%). These data indicated that PC was metabolized via phospholipase(s) A and phospholipase C. Substantial diacylglycerol lipase activity was identified in the cell sonicate. Production of similar proportions of diacylglycerol and phosphocholine and the low relative activity of phospholipase C compared to phospholipase A indicated that the phospholipase C-diacylglycerol lipase pathway contributed little to fatty acid release from the sn-2 position of PC. Neither phospholipase A nor phospholipase C required Ca2+. The pH profiles and subcellular fractionation experiments indicated the presence of multiple forms of phospholipase A, but phospholipase C activity displayed a single pH optimum at 7.5 and was located exclusively in the particulate fraction. The two enzyme activities demonstrated differential sensitivities to inhibition by p-bromophenacylbromide, phenylmethanesulfonyl fluoride and quinacrine. Each of these agents inhibited phospholipase A, whereas phospholipase C was inhibited only by p-bromophenacylbromide. The unique characteristics observed for phospholipase C activity towards PC indicated the existence of a novel enzyme that may play an important role in lipid metabolism in endothelial cells.

Animals↗
PubMed1987

Absence of tubular myelin in lungs of infants dying with hyaline membrane disease.

Immaturity of the pulmonary surface active material synthesizing system with deficiency of surface active material in the premature lung is an accepted cause of hyaline membrane disease. Lamellar bodies, the intracellular form of surface active material, are produced and secreted from Type II pneumocytes and converted to tubular myelin in the alveolar lumen. Tubular myelin, in turn, gives rise to the surface monolayer, which has the greatest surface active property. Thus, lung sections were studied by light and electron microscopy from 35 infants who died of histologically confirmed hyaline membrane disease and 19 infants who died of other causes. Tubular myelin was not identified ultrastructurally in lungs of infants who died of hyaline membrane disease, despite the presence of abundant lamellar bodies. In contrast, 16 of 19 infants dying of other causes had easily identifiable tubular myelin in addition to lamellar bodies. The absence of tubular myelin in the hyaline membrane disease patients suggests an abnormality in the conversion of lamellar bodies to tubular myelin. The authors speculate that this abnormal lamellar body turnover may be important in the pathogenesis of hyaline membrane disease.

Freeze Fracturing↗
PubMed1986

Amine uptake into intact mast cell granules in vitro.

Histamine, the principal amine of rat peritoneal mast cells, is taken up into isolated granules with intact membranes. Uptake is pH- and concentration-dependent and is not stimulated by the addition of Mg2+-ATP. The saturable uptake has a Km of 91.1 microM and a Vmax of 95.4 pmol (mg of protein)-1 min-1. Uptake is abolished by 5 mM ammonium ion. 5-HT, the other endogenous amine of the granules, and dopamine and tyramine, which do not occur naturally in rat mast cells, each competitively inhibits [3H]-histamine uptake with Ki's close to 1 microM. Reserpine, a putative amine carrier blocker, inhibits uptake at nanomolar concentrations. At high concentrations, uptake of [3H]-5-HT is nonsaturable; at low concentrations, a saturable component is observed with a Km of 1.6 microM. Uptake of [3H]-5-HT is not enhanced by Mg2+-ATP. It is pH-dependent but with a lower apparent pKa than that of histamine. [3H]-5-HT uptake can be completely inhibited by ammonium ions. Amine inhibition of [3H]-5-HT gives nonlinear Dixon plots, and high concentrations of the competing amines or reserpine cannot completely block uptake. We propose a model consistent with these results in which amine uptake occurs by several distinct saturable transport systems. According to the model, histamine is transported by a single system, which also transports 5-HT and dopamine. 5-HT and dopamine are transported by one or more other systems.

Adenosine Triphosphate↗
PubMed1986

Antagonism of the final common pathway of mast cell histamine secretion by arylalkylamines.

The antagonism of histamine secretion from rat peritoneal mast cells by a range of drugs (e.g., antihistamines, local anesthetics, tranquilizers, antidepressants, adrenergics and antiadrenergics) and arylalkylamines was studied. Simple arylalkylamines, those without quaternary ammonium, phenolic or anionic groups, uniformly inhibited histamine secretion induced via three major secretory pathways of mast cells (compound 48/80, A23187 and concanavalin A). That is, each simple arylalkylamine nonselectively inhibited all three secretagogues at about the same concentration (avg. range = 2.2). This nonselective inhibition was rapid in onset (seconds), readily reversible by washing and not related to a decrease in ATP. It is likely that these agents act nonspecifically at a step in the final common pathway in the cell membrane, possibly to inhibit fusion of the secretory granules with the plasma membrane. Other, more complex arylalkylamines were selective in their antagonism of histamine secretion. Quaternary arylalkylammonium compounds selectively antagonized polyamine secretagogues (48/80 and polymyxin B), whereas arylalkylamines, with other hydrophilic groups, selectively inhibited one or another of the secretory pathways. These complex arylalkylamines must act before the final common pathway because of their selective inhibition. At higher concentrations most of the arylalkylamines caused disruption of the mast cells and liberated histamine.

Adenosine Triphosphate↗
PubMed1986

Porphyrin content of the cysticercus of Taenia solium.

The strong red fluorescence of the cysticercus of Taenia solium depends on the presence of several porphyrins in the vesicular fluid of the parasite: probably protoporphyrin IX, coproporphyin I or III, and 2 decarboxylated porphyrins intermediate between uroporphyrin and coproporphyrin. Cyst porphyrins associated to form conglomerates of high molecular weight that dissociated in acid solutions and were not antigenic themselves nor associated with antigenic molecules. An appreciable fraction of the porphyrins was capable of undergoing oxidation and reduction, indicating that some of the porphyrins were complexed with metal ions. The metabolic basis for the accumulation of porphyrins is unknown. Preliminary results suggest that conditions deleterious to the cysticercus cause release of porphyrins so that the appearance of porphyrins in the cerebrospinal fluid of neurocysticercotic patients may prove useful in monitoring therapeutic attacks on the parasite.

Animals↗
PubMed1986

Enhancement of human polymorphonuclear leukocyte adherence to plastic and endothelium by phorbol myristate acetate. Comparison with human C5a.

The adherence of circulating neutrophils to vascular endothelium represents a necessary step in the chemotactic emigration of neutrophils to extravascular inflammatory sites. Studies of neutrophil adherence induced by phorbol myristate acetate (PMA) were undertaken to determine the ability of a nonchemotactic neutrophil stimulus to provoke increased adherence. The authors found that the adherence of human neutrophils to plastic surfaces or confluent monolayers of endothelial cells is enhanced in a concentration-dependent fashion by exposure of neutrophils to PMA. The effect of PMA concentration (0.1-5.0 ng/ml) on increased neutrophil adherence parallels that observed for superoxide anion generation and release of lysosomal enzymes from specific granules. Whereas complement C5a-treated neutrophils exhibited a fourfold to fivefold increase in adherence to endothelial cells, PMA-treated neutrophils showed a 10-fold to 20-fold increase. The ability of PMA to cause increased neutrophil adherence to endothelium appeared to be directed primarily at the neutrophil. Pretreatment of neutrophils with PMA was as effective as coincubation in causing increased adherence to plastic surfaces or confluent cultured endothelial cells, but pretreatment of endothelial cells with PMA failed to promote neutrophil adherence. Alteration of neutrophil cytoskeletal structures by cytochalasin B treatment did not prevent subsequent PMA-stimulated neutrophil adherence. These results demonstrate that increased neutrophil adherence to surfaces can be induced by a nonchemotactic stimulus and that neutrophil adherence is independent of organized microfilaments.

Cell Adhesion↗
PubMed1985

Effect on mast cell histamine of inhibiting histamine formation in vivo with alpha-fluoromethylhistidine.

An irreversible inhibitor of histidine decarboxylase, alpha-fluoromethylhistidine (FMH), was used to inhibit histamine formation by mast cells in vivo. Even at doses of FMH sufficient to reduce histamine formation more than 95%, the ability of mast cells to synthesize histamine recovered rapidly. It was possible, however, to sustain levels of histamine-forming activity below 10% of normal with continuous administration of FMH from subcutaneously implanted osmotic pumps. Administration of FMH under these conditions did not deplete significantly mast cell histamine but did prevent the increase in total mast cell histamine that occurs over 14 days and also prevented the reconstitution of mast cell histamine stores after depletion by treatment with polymyxin B.

Animals↗
PubMed1985

Activation of human platelets by N-substituted aminophospholipids.

N-(7-nitro-2,1,3-benzoxadiazol-4-yl) phosphatidylserine (NBD-PS), a fluorescent phospholipid synthesized from phosphatidylserine by reaction with NBD-chloride, caused platelet shape change and aggregation when added at micromolar concentrations to suspensions of washed human platelets in the absence of added fibrinogen. Platelet aggregation by NBD-PS was accompanied by thromboxane synthesis and secretion of contents from dense, alpha-, and lysosomal granules in the absence of appreciable platelet damage. Indomethacin completely inhibited NBD-PS-induced thromboxane synthesis, but platelet aggregation and [14C]serotonin secretion were only slightly inhibited. Neither inhibition of the ADP-dependent pathway with creatine phosphate/creatine kinase plus ATP, alone or in combination with indomethacin, nor maximum elevation of cyclic AMP by treatment with prostaglandin I2 and theophylline completely inhibited NBD-PS-induced platelet aggregation or [14C]serotonin secretion. Platelet effects of NBD-PS were specific in that neither phosphatidylserine nor lyso-NBD-PS were similarly active. The activation of platelets by NBD-PS is not attributable to the NBD moiety exclusively since acylation of the amino group with 5-dimethylaminonaphthalene-1-sulfonyl-chloride yielded a similarly active derivative. Dansylated phosphatidylethanolamine was also active. The findings indicate that NBD-PS and other N-substituted aminophospholipids can activate a central pathway of platelet secretion and aggregation that is independent of released ADP and thromboxane formation and is only partially controlled by platelet cyclic AMP.

4-Chloro-7-nitrobenzofurazan↗
PubMed1985

The importance of biventricular failure in patients with postoperative cardiogenic shock.

To evaluate the importance of severe biventricular failure in patients with postcardiotomy ventricular failure, we analyzed the data from 30 patients treated with ventricular assist devices (VADs) over a five-year period. All patients had profound postoperative ventricular failure refractory to drugs and an intraaortic balloon (IAB). Evaluation of preoperative ventricular function did not allow prediction of which patients would require VADs. However, the development of perioperative myocardial infarction was an important determinant of the need for postoperative support with a VAD. Twenty patients received only a left VAD (LVAD). Four of them had isolated left ventricular failure; 3 were weaned, and 2 survived. None of the 16 patients with biventricular failure who received only an LVAD were weaned. Ten other patients with biventricular failure received biventricular support, either with a right VAD and IAB, or with two VADs. Of these 10 patients, 5 were weaned and 3 survived. Considering all 26 patients with biventricular failure, those receiving biventricular mechanical support (10) had a better chance (p less than 0.025) of being weaned (5/10) and surviving (3/10) than those who received only an LVAD (0/16). We conclude that biventricular failure is common in patients with postcardiotomy ventricular failure and is often the result of perioperative infarction. While patients with isolated left ventricular failure did well with an LVAD only, those with biventricular failure required biventricular mechanical support for survival.

Adolescent↗
PubMed1985

The effect of ethchlorvynol on cultured endothelial cells. A model for the study of the mechanism of increased vascular permeability.

Ethchlorvynol (ECV), an agent which produces reversible pulmonary edema, was studied for its effects on cultured bovine pulmonary artery endothelial cell (BPAE) and human umbilical vein endothelial cell (HUVE) monolayers. Endothelial cell monolayers 6 days post-confluent were treated with 1 mg/ml ECV for time intervals of from 5 minutes to 15 hours. ECV treatment caused a mild endothelial cell retraction evident at 10 minutes which increased in severity with increasing duration of exposure to ECV. Retraction of endothelial cells resulted in the formation of irregularly delineated gaps between cells, which remained attached to one another by slender filamentous processes. Despite the severity of the endothelial cell lesion, no cell lysis or cell detachment from the substratum occurred. Furthermore, removal of ECV from cell cultures resulted in the reversal of the endothelial cell lesion. Cytochemical distribution of actin microfilaments in control monolayers localized to a dense peripheral band of actin filaments and to a set of interconnected central microfilaments oriented in general parallel to the long axis of the cell. Endothelial cells treated with ECV for as little as 10 minutes showed a loss of F-actin from the dense peripheral band of microfilaments progressing until the dense peripheral band was entirely lost after 4 hours' exposure to ECV. By 4 hours central microfilaments had reorganized into a prominent series of microfilament bundles aligned parallel to each other and to the long axis of the cell. For investigation of a possible loss of attachment sites of actin filaments as the basis for the lesion, the localization of vinculin was examined in control and ECV-treated BPAE monolayers. After 2 hours' exposure to ECV, vinculin localization within monolayers was affected little, if at all. No effects of ECV on intermediate filaments were observed either. It is proposed that the dense peripheral band of actin bundles is important in maintaining well-spread endothelial cells in monolayers and that ECV acts to destroy the integrity of this structure. It is further proposed that a reaction of endothelial cells to ECV in vivo analogous to that seen in tissue culture accounts for the production of pulmonary edema by creating gaps between cells.

Animals↗