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Biomedical subjects

D English

Publications and source records attributed to D English.

162 records · Page 9Linked to original sources
PubMed1981

Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils.

Human neutrophils exposed to chemotactic concentrations of zymosan-activated serum (ZAS) and a formylated chemotactic peptide (FMLP, 10(-7)--10(-9) M) were markedly enhanced in their ability to generate superoxide (O2-) upon stimulation with either sodium fluoride or phorbol myristate acetate (PMA). For both fluoride and PMA, enhancement was characterized by a decrease in the lag from stimulation to initiation of superoxide release and by an increase in the rate of superoxide generation--representing faster activation and increased activity of O2- generating enzyme, respectively. Chemotactic concentrations of casein, normal serum, and casein-treated serum enhanced the activity, but not the rate of activation, of the fluoride-stimulated superoxide generating system. This effect on activity was not so impressive as that obtained with FMLP or ZAS. The mechanisms by which FMLP enhanced responsiveness to fluoride and PMA were found to be different. Optimal enhancement for fluoride-stimulated responses required extracellular Ca++. Extracellular glucose, but not extracellular Ca++, was required for enhancement of FMLP of PMA-stimulated responses. A similar glucose requirement could not be demonstrated for chemotactic peptide enhancement of the superoxide-generating system stimulated by fluoride. Fluoride and PMA apparently activate the neutrophil O2- generating enzyme by pathways that are not identical. However, responsiveness of the enzyme to both agents is susceptible to modulation by cellular responses to chemotactic peptides.

Chemotactic Factors↗
PubMed1980

Superoxide and inflammation: a mechanism for the anti-inflammatory activity of superoxide dismutase.

Several models of inflammation induced in laboratory animals were markedly inhibited by intravenous administration of the enzyme superoxide dismutase. In most cases, the enzyme required chemical modification to increase its circulating lifetime. In all cases, histological examination of the sites of the potential lesions revealed that treatment with superoxide dismutase prevented the accumulation of inflammatory cells. Experiments in vitro demonstrated the existence of a plasma factor which reacts with superoxide to become a potent chemotactic factor for neutrophils. The factor apparently serves to call increasing numbers of neutrophils to the inflammatory locus in response to the superoxide produced by the first cells to encounter the stimulus.

Animals↗
PubMed1977

Chemotaxis radioassays: a simplified, quantitative method using technetium-99m radiocolloid labeled granulocytes.

Selective labeling of phagocytes in human blood can be achieved by incubation of unseparated, heparinized blood with 99mTc-sulfur colloid. We have developed a method for quantitation of granulocyte chemotaxis using granulocytes labeled by this technique. The method was found to be more accurate and less tedious to perform than the conventional Boyden chamber chemotaxis assay. The assay was also less time-consuming and as quantitative as a previously described granulocyte chemotaxis radioassay in which 51Cr-labeled leukocytes were used. The simplicity and reliability of this technique and the ready availability of 99mTc-sulfur colloid may provide one standardized method for granulocyte chemotaxis quantitation in clinical and experimental medicine.

Chemotaxis, Leukocyte↗
PubMed1977

Organ distribution of canine leukocytes labeled with 99mTc-sulfur colloid.

Previous reports have shown that scintigraphic localization of acute inflammation can be achieved using autologous leukocytes labeled in vitro with 99mTc-sulfur colloid (TcSC). The technique is limited, however, by a marked accumulation of radioactivity in the lungs and liver of normal animals. A modified procedure was developed using preparations of TcSC of small particle size to label blood leukocytes in vitro. Markedly decreased levels of lung and liver radioactivity and elevated levels of blood radioactivity were found after intravenous infusion of autologous canine leukocytes labeled by this method. These leukocytes could be used to image areas of acute inflammation resulting from induction of septic or sterile venous thrombi.

Animals↗
PubMed1975

Labeling of phagocytes from human blood with 99mTc-sulfur colloid.

Experments in this report have shown that peripheral blood leukocytes can be readily labeled with 99mTc-sulfur colloid during in vitro incubation. Phagocytic cells were preferentially labeled by this method. Labeling was enhanced in the presence of normal serum. The data suggest that labeling was accomplished by phagocytosis of the radiocolloid. Labeled granulocytes responded normally to chemotactic stimuli and excluded trypan blue dye normally. Buffy coat cells from 50 ml of peripheral blood could be labeled with 8 mCi of 99mTc after incubation with 20 mCi of TcSC. This report offers a method by which phagocytic cells can be selectively labeled with 99mTc in amounts suitable for scintillation scanning.

Chemotaxis↗
PubMed1975

Inflammatory lesions localized with technetium Tc 99m-labeled leukocytes.

Canine leukocytes were labeled with a gamma-ray emitting isotope by permitting them to phagocytize technetium Tc 99m sulfur colloid particles in vitro and removing the unphagocytized particles by washing the cells. The labeled cells were reinfused intravenously into the donor dogs. Scintigraphic scans were performed 4 and 24 hours following the leukocyte infusion. In animals with sterile and infected intramuscular abscesses and pulmonary infections, it was possible to localize the lesions by scintigraphic scanning four hours following administration of labeled leukocytes. In one experiment, a positive scan was observed 24 hours after the leukocyte infusion. It was also shown that labeled leukocytes tend to concentrate in abscess fluid. These results suggest that technetium Tc 99m sulfur colloid-labeled leukocytes may be a useful diagnostic tool in localizing abscesses and inflammatory lesions in humans.

Abscess↗
PubMedDate not supplied

Effects of perfluorochemical on phagocytic function of leukocytes.

Oxygen-carrying perfluorochemical emulsions may become useful for transfusions when red cells cannot be used. Since accumulation of perfluorochemicals in reticuloendothelial cells has been demonstrated, we tested the phagocytic function of monocytes and neutrophils in rabbit and human blood exposed in vivo and in vitro, respectively, to perfluorotributylamine (Oxypherol) a perfluorochemical blood substitute. Neutrophil and monocyte phagocytosis was assessed by determining the uptake of serum-coated fluorescent beads by monocytes and neutrophils in whole blood. Morphologic changes were assessed by electron microscopy. The phagocytic activity of monocytes and neutrophils in the blood of four rabbits injected 4 hours earlier with 70 to 85 ml of Oxypherol (28 ml/kg) was depressed by 87 +/- 1.0 percent. Neutrophils in this blood showed morphological alterations characterized by swelling and extensive vacuole formation. Similar changes were found in neutrophils and monocytes of human blood incubated with Oxypherol (10-50%, V/V) at 37 degrees C for 1 hour. The phagocytic activity of human neutrophils and monocytes exposed to 20 percent, V/V Oxypherol was depressed by 35 +/- 9.9 percent. We conclude that caution should be exercised when administering perfluorochemical blood substitutes in patients exposed or at risk of infection.

Animals↗
PubMedDate not supplied

Effect of perfluorochemical blood substitutes on human neutrophil function.

This investigation was undertaken to determine the influence of perfluorochemical blood substitutes (PFCs) on human neutrophil function. Neutrophils isolated from blood of healthy donors were incubated at 37 degrees C for 1 hour with 25 percent Oxypherol (perfluorotributylamine) or Fluosol-DA (perfluorodecalin and perfluorotripropylamine) in the presence of fresh autologous serum. In comparison to cells incubated with Hank's balanced salt solution (buffer), neutrophils exposed to PFCs were markedly inhibited in their chemotactic and phagocytic responses. With 25 percent PFCs, chemotaxis to zymosan-activated serum was inhibited to approximately 25 percent of control by Fluosol-DA and 11 percent by Oxypherol. Phagocytosis of polystyrene beads in the presence of fresh serum was decreased to 52 and 50 percent of control by both Oxypherol and Fluosol-DA, respectively. Neutrophils exposed to PFCs aggregated slower and with an extended activation time upon addition of phorbol myristate acetate (PMA). When activated with n-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophils exposed to PFCs aggregated at a faster rate but with a longer lag phase in comparison to control cells. Neutrophil superoxide (O-2) release stimulated by PMA also was depressed by prior exposure of cells to Oxypherol (6 nmoles O-2/1.5 X 10(6) neutrophils) compared to buffer (32 nmoles O-2/1.5 X 10(6) neutrophils). PMA-stimulated neutrophil adherence was depressed significantly by prior exposure to Fluosol-DA compared to control. In contrast, Oxypherol had insignificant influence on stimulated adherence. Since PFCs have a profound influence on several important neutrophil functions, patients receiving PFC should be monitored closely for possible infectious complications.

Blood Substitutes↗
PubMedDate not supplied

Haemodynamic and neuroendocrine consequences of stopping smoking--a controlled study.

The haemodynamic and neuroendocrine consequences of stopping smoking for a 6 week period were studied in thirty-three smokers and their matched controls. Complete smoking cessation was associated with a significant fall in adrenaline and cortisol levels, consistent with the withdrawal of a nicotine stimulus to adrenomedullary and cortical activity. Supine systolic and diastolic blood pressure did not change significantly. However, the response to a cold pressor stimulus was altered with a delay in return of systolic blood pressure to basal values. This study has been unable to confirm findings from epidemiological studies of lower blood pressure in smokers. However, the possibility is raised that this phenomenon may be due to modification by smoking of the normal physiological response to stressful stimuli.

Blood Pressure↗
PubMedDate not supplied

Issues in stem cell plasticity.

Experimental biology and medicine work with stem cells more than twenty years. The method discovered for in vitro culture of human embryonal stem cells acquired at abortions or from "surplus" embryos left from in vitro fertilization, evoked immediately ideas on the possibility to aim development and differentiation of these cells at regeneration of damaged tissues. Recently, several surprising observations proved that even tissue-specific (multipotent) stem cells are capable, under suitable conditions, of producing a whole spectrum of cell types, regardless, whether these tissues are derived from the same germ layer or not. This ability is frequently called stem cell plasticity but other authors also use different names - "non-orthodox differentiation" or "transdifferentiation". In this paper we wish to raise several important questions and problems related to this theme. Let us remind some of them: Is it possible to force cells of one-type tissue to look and act as cells of another tissue? Are these changes natural? Could these transformations be used to treat diseases? What about the bioethic issue? However, the most serious task "still remains to be solved - how to detect, harvest and culture stem cells for therapy of certain diseases".

Animals↗
PubMedDate not supplied

Neutrophil activation and lung injury associated with chronic endotoxemia in rabbits.

Chronic endotoxemia produces emphysematous lung destruction in several animal models. The present study was designed to examine changes in the polymorphonuclear leukocytes (PMN) and the lung parenchyma of rabbits that received either saline (control, n = 6) or Escherichia coli endotoxin (LPS, n = 6) 2-3 times weekly for 15 to 28 weeks. Peripheral blood was collected just before and after each intravenous injection and lung tissue was processed at the end of the experiment. PMN myeloperoxidase was stained with diaminobenzidine tetrahydrochloride (DAB)-H2O2, and CD11/CD18 was detected with immunogold. The changes in the PMN and the lung parenchyma were quantitatively analyzed. The results show that each dose of LPS produced an initial fall, followed by a rise in the circulating mature and immature PMN cell counts. Repeated doses of LPS induced PMN activation, degranulation, and an increase in the mean thickness of the alveolar wall (control, 4.1 +/- 0.2; LPS, 5.1 +/- 0.5; p < .05) at 28 weeks without evidence of alveolar septa destruction. Morphometric analysis of intravascular PMN showed an increase in the volume (V) of myeloperoxidase-containing azurophil granules (control, 6.1 +/- 1.3 microns3; LPS, 13.1 +/- 2.8 microns3; p < .05); a trend for a decrease in the V of specific granules (control, 15.8 +/- 3.4 microns3; LPS, 10.2 +/- 1.5 microns3; p = .09); an increase in the V of the cytoplasm (control, 37.3 +/- 6.4 microns3; LPS, 54.5 +/- 7.1 microns3; p < .05); and an increase in CD11/CD18 expressed as the number of gold particles per micrometer of cell surface membrane (G/micron) (control, 7.1 +/- 1.4 G/micron; LPS, 18.1 +/- 7.8 G/micron; p < .05). The results indicate that chronic endoxemia in rabbits, accelerates the release of PMN from the bone marrow, enhances the retention of both mature and immature activated PMN in the pulmonary microvessels, and causes alveolar wall thickening rather than emphysematous lung destruction.

Animals↗