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Biomedical subjects

R S Weening

Publications and source records attributed to R S Weening.

13 recordsLinked to original sources
PubMed1979

Phenylglyoxal is not a selective inhibitor of phagocytosis.

In 1976, it has been reported that phenylglyoxal (C6H5COCHO) selectively inhibits endocytosis in phagocytes of rabbit and mouse. We have tested the specificity of this compound by measuring its effect on human neutrophil chemotaxis, respiration and release of lysosomal enzymes. Pretreatment of human neutrophils with 100 microgram phenylglyoxal/ml for 30 min at 37 degrees C resulted in almost complete inhibition of phagocytosis of opsonized zymosan. However, after treatment with phenylglyoxal, spontaneous mobility as well as chemotaxis of these cells towards casein, rosette formation with opsonized zymosan, stimulation of the oxidative metabolism and release of lysosomal enzymes were also severely decreased. Most of these functions were only partially restored by resuspension of the cells in a medium without phenylglyoxal. The intracellular level of ATP was not affected by phenylglyoxal, but the level of reduced glutathione was decreased. We conclude from the inhibitory action of phenylglyoxal on the stimulated oxygen consumption and its reaction with intracellular glutathione that phenylglyoxal does not necessarily act exclusively on the outside of the plasma membrane. From our studies, it follows that phenylglyoxal is not a specific inhibitor of endo- or exocytosis in human neutrophils. Phenylglyoxal can be used effectively in the bacterial-killing test of phagocytes to inhibit intracellular killing after an initial period of ingestion.

Aldehydes↗
PubMed1979

Immune complex glomerulonephritis in chronic granulomatous disease. Case report of an eighteen-year-old girl.

An 18-year-old girl is described who developed advanced renal sclerotic lesions, probably preceded by local focal glomerulonephritis, which coexisted with a Staphylococcus aureus abscess. It is hypothesized that immune complex glomerulonephritis developed, provoked by long-term antigenic stimulation of Staphylococcus aureus. The cause of these long-term bacterial infections was a defect of the phagocytic cells to kill bacteria effectively, a disease known as chronic granulomatous disease. Therapy with intracellularly active antimicrobial agents restored the renal function till no more haemodialysis was necessary.

Adolescent↗
PubMed1978

Levamisole in Crohn's disease--a double-blind controlled trial.

The efficacy of levamisole in patients with mildly active Crohn's disease was evaluated in a double-blind, placebo-controlled trial by means of clinical, biochemical, and immunological parameters. No immunosuppressive drugs were prescribed during the study. 11 patients received levamisole for 3 months (2.5 mg/kg body weight on 2 consecutive days/week) and 10 patients received placebo. Although the 2 patients groups were not very well comparable, the overall results of this study did not show obvious changes in clinical, biochemical, or immunological parameters in either group. No side effects of levamisole were observed during the study.

Adult↗
PubMed1976

An EPR study of myeloperoxidase in human granulocytes.

1. EPR spectra of human granulocytes (4 - 10(8) cells per ml) show an intense high-spin ferric heme signal with rhombic symmetry (gx = 6.90 and gy = 5.07) for the heme group. These g-values are identical to those of partially purified myeloperoxidase and thus the signal is derived from ferric myeloperoxidase. In chicken granulocytes, which contain little or no myeloperoxidase, only an axial type of heme iron signal, weak in intensity, can be detected at g = 6.0. 2. Upon phagocytosis of latex particles by human granulocytes the high-spin heme signal with rhombic symmetry is slowly converted into a signal with axial symmetry (gx = gy = 6.0), showing that the EPR signals of myeloperoxidase in the intact cell can be used to study the involvement of the enzyme in metabolic changes during phagocytosis.

Animals↗
PubMed1976

Defective initiation of the metabolic stimulation in phagocytizing granulocytes: a new congenital defect.

Two patients suffering from recurrent bacterial infections were studied: a boy and a girl from one family, children of apparently healthy parents. The granulocytes of these patients were capable of normal ingestion of latex particles and DNA-anti-DNA immune complexes. When the metabolic changes in these granulocytes during phagocytosis of latex particles were studied, however, no stimulation of oxygen consumption, superoxide production, or hexose monophosphate shunt activity could be observed. Moreover, zymosan particles were not iodinated. These findings are comparable to those found in chronic granulomatous disease. In sharp contrast to the observations in this latter disease, however, a completely normal stimulation of cell metabolism was found after phagocytosis of IgG-coated latex particles or IgG aggregates. Since latex and IgG-coated latex were equally well ingested, this means that the absence of metabolic stimulation after uptake of tatexf metabolic stimulation after uptake of latex must be due to a defect in the triggering of the oxidative burst. As far as we know, this is the first time that a defect in the triggering of the metabolic stimulation during phagocytosis could be demonstrated. Moreover, these finding suggest that adherence and subsequent ingestion of particles are in themselves not sufficient for the metabolic stimulation of granulocytes.

Adult↗
PubMed1975

Production of hydrogen peroxide by phagocytizing human granulocytes.

A rapid and sensitive method is described for the quantitative determination of H202 produced by phagocytizing human granulocytes. For this purpose, the method of Keston and Brandt was mechanized, which is based on the oxidation of nonfluorescent leukociacetyl-2,7-dichlorofluorescein to a fluorescent compound by H202 in the presence of peroxidase. The optimal conditions for this test were determined. H202 in water can be measured in the range of 0.05 to 0.5 muM, with a standard deviation of 1.2 per cent at 0.4 muM (n = 1-). The production of H2O2 by phagocytizing granulocytes could only be measured in a medium which contained phosphate-buffered salt, albumin, glucose, NaN3, and IgG-coated latex particles. The fluorescence signal was catalase-sensitive. Of known amounts of H202, added to this medium, 97 per cent were recovered. Under optimal conditions we found a H2O2 production of 970 plus or minus 170 mumoles per 10-10 cells per hour (10 different healthy donors), corresponding to 50 to 70 per cent of the observed increase in O2 consumption. No H2O2 was produced by phagocytizing granulocytes from 2 patients with chronic granulomatous disease, while intermediate values were found in the cells from heterozygotes.

Female↗
PubMed1975

Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes.

The production of superoxide radicals (O2-) by human granulocytes after phagocytosis of latex particles has been studied as a function of cell, latex, and cytochrome c concentration. Under the chosen conditions, latex phagocytosis stimulated the reduction of cytochrome c by O2- sevenfold to 420 mumoles per 10-10 granulocytes per hour. At high cytochrome c concentrations, this value increased to 800 to 1,000 mumoles per 10-10 granulocytes per hour. These amounts suggest that O2- plays an important role in the formation of H2O2 during the phagocytic process. We propose that the extra oxygen consumed in the respiratory burst is first reduced to O2-, possibly by ascorbate, before being converted to H2O2. No stimulation of the superoxide radical formation was found in the phagocytizing granulocytes of two patients with chronic granulomatous disease, and intermediate values were found for the heterozygotes of this deficiency.

Animals↗
PubMedDate not supplied

Defects in the oxidative killing of microorganisms by phagocytic leukocytes.

One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.

Blood Bactericidal Activity↗