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Biomedical subjects

J Hakim

Publications and source records attributed to J Hakim.

At least 127 records · Page 7Linked to original sources
PubMed1985

Cytochrome b-245 in human alveolar macrophages.

To kill microorganisms, phagocytes exhibit an oxidative burst with, in particular, a NADPH-dependent, superoxide-generating system that consists, in polymorphonuclear leukocytes (PMN), of a flavin enzyme and cytochrome b-245 (cyt b-245). We investigated the existence of this cytochrome in human alveolar macrophages (AM) because its presence would support its wide-spread occurrence in phagocytes and would raise the possibility of similarities in the oxygen-dependent killing mechanisms in AM and PMN. Moreover, we compared the amount of cyt b-245 in AM from patients with lung disorders with that from healthy subjects, by a differential spectroscopic measurement of its 558 to 559 nm characteristic band. This spectrum showed that cyt b-245 was present in AM. In AM of healthy subjects, the amount was similar to that found in PMN of blood. In AM of patients with miscellaneous lung diseases and in Am of infected lungs, the data were not modified.

Cytochrome b Group↗
PubMed1985

New lymphokines produced by SLE sera stimulated lymphocytes: the PNAF (polymorphonuclear activating factors).

Twenty-two SLE sera were assessed for their stimulating properties for lymphocytes. After fixation of specific serum factors, lymphocyte cultures were performed and supernatants of 24, 48, 72 and 96 h tested on two polymorphonuclear functions: chemotaxis and cyanide insensitive O2 consumption; 20 out of 22 SLE sera supernatants led to enhanced chemotaxis. The factors involved were not destroyed by heating for 30 min at 56 degrees C. Fifteen of the SLE sera supernatants increased the O2 consumption by PN. In most cases this second mediator was destroyed by heating. The buffer, the normal sera, the monoclonal antibodies stimulated lymphocytes supernatants and the total lymphocyte lysate did not display such enhancing activities. So it clearly appears that SLE sera contain factors acting on lymphocyte membrane and induce them to secrete new lymphokines called PNAF (polymorphonuclear activating factors) which may play a role in pathogenesis of tissue lesions in SLE.

Antilymphocyte Serum↗
PubMed1985

[Exclusion prenatal diagnosis of chronic familial septic granulomatosis].

We report the prenatal diagnosis in a 20 week male fetus at risk of chronic granulomatous disease (CGD). A previous affected brother was known in the family and the mother was detected as heterozygote. Three different assays were performed on fetal blood obtained under fetoscopy: cytochemical reduction of nitroblue tetrazolium (NBT), chemiluminescence after activation by opsonized zymosan or phorbol myristate acetate (PMA) and production of superoxide anion (O2-.). Results were comparable to those obtained in 6 fetuses investigated for other inherited diseases. Absence of functional polymorphonuclear defects was confirmed at birth. The use of 3 different techniques performed on whole blood for prenatal diagnosis of CGD has to be recommended instead of an isolated technique adapted to whole blood tests.

Female↗
PubMed1984

In vivo effects of indomethacin and flurbiprofen on the locomotion of neutrophils elicited by immune and non-immune inflammation in the rat.

The in vivo effects of indomethacin (3 mg/kg) and flurbiprofen (1.5 mg/kg) were investigated on the development of three different pleural inflammations in the rat and on in vitro locomotion of elicited neutrophils (PMN). Indomethacin and flurbiprofen similarly reduced the development of non-immune pleurisy induced by decomplemented isologous rat serum (DIRS) to a similar degree but had no effect in the delayed hypersensitivity reaction (DHR) model. Flurbiprofen was less effective than indomethacin in the immediate hypersensitivity reaction (IHR) model. PMN elicited by the two immune reactions (IHR and DHR) displayed lower random and directed locomotion than DIRS-elicited PMN. Neither drug interfered with DIRS-elicited PMN locomotion. They inhibited both random migration and directed locomotion of unwashed PMN (i.e. suspended in their original exudate) elicited by IHR or DHR and stimulated by the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) or isologous rat serum (IRS). Locomotion of washed IHR-elicited PMN stimulated with IRS was also inhibited by the two drugs. The data suggest that these drugs could impair PMN movement at inflammatory sites.

Animals↗
PubMed1984

Luminol assay for microdetermination of superoxide dismutase activity: its application to human fetal blood.

A microtechnique for determining the superoxide dismutase activity in erythrocytes is described. This technique involves the inhibition of luminol-enhanced chemiluminescence of superoxide anion generated by xanthine-xanthine oxidase. Measurements required a steady-state chemiluminescence whether superoxide dismutase was present or absent; the level of luminescence was correlated to enzyme activity. Superoxide dismutase activity measured by this technique was 836 +/- 112 micrograms/g of hemoglobin for whole blood and 834 +/- 109 micrograms/g of hemoglobin for erythrocytes. When the reference technique was applied to larger amounts of blood, the results were 862 +/- 58 and 858 +/- 116 micrograms/g of hemoglobin for whole blood and washed erythrocytes, respectively. The enzymatic activity of superoxide dismutase from fetal blood (obtained by venipuncture in utero and of 19-26 weeks gestational age) was similar to that of adult blood, when measured by the new technique.

Adult↗
PubMed1984

In vivo interaction of nonsteroidal anti-inflammatory drugs on the locomotion of neutrophils elicited by acute non-specific inflammations in the rat--effect of indomethacin, ibuprofen and flurbiprofen.

The in vivo effects of Flurbiprofen, Ibuprofen and Indomethacin (1.5, 6 and 3 mg/kg respectively) were studied on two acute non-specific pleurisies induced by calcium pyrophosphate crystals (CaPP) or decomplemented isologous rat serum (DIRS) in the rat. Drug effects on the exudation phase (pleural exudate volume), leukocyte emigration (number of leukocytes in the fluid) and on random and directed locomotion of elicited neutrophils (PMN) under agarose were investigated. In the CaPP model, Indomethacin, Flurbiprofen and Ibuprofen reduced the pleural exudate volume by approximately 48, 57 and 22% respectively while leukocyte emigration was inhibited 50, 45 and 50% respectively. In the DIRS model Indomethacin and Flurbiprofen reduced the exudate volume by 54 and 52% and leukocyte emigration by 51 and 31% respectively. Ibuprofen administration produced a decrease in exudate volume of only 27%. The three drugs did not alter in vitro locomotion of DIRS-elicited PMN. On the other hand, Flurbiprofen reduced both random and directed locomotion of CaPP-elicited PMN stimulated with peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), isologous rat serum (IRS) or cell-free exudates. Ibuprofen induced a slight increase in random migration of CaPP-elicited PMN while Indomethacin was without effect. None of the three drugs altered the chemotactic activity of inflammatory exudate. These data suggest that therapeutic doses of anti-inflammatory drugs interfere with PMN at inflammatory sites and induce modifications in their movement per se which persist after cell washing.

Animals↗
PubMed1984

Impaired metabolic activity of phagocytosing neutrophils in agnogenic osteomyelofibrosis with splenomegaly: a longitudinal study.

Functional and enzyme activity of neutrophils in patients with agnogenic osteomyelofibrosis (AOM) is still a subject of controversy, probably owing to the heterogeneity of the abnormalities observed from patient to patient, and the absence of longitudinal studies performed during the course of the disease. For a better definition of these abnormalities, 40 patients with untreated AOM were studied from the time of diagnosis, and in 12 cases, neutrophil function and enzyme activity were reassessed at one-year intervals for 3-5 years. The results showed that all abnormalities were serum-independent. Mean ingestion rate in neutrophils from patients were similar to that of the controls but individual values were more varied, with some very high and some low ingestion rates. Histochemical latex ingestion and nitroblue tetrazolium reduction were lower in patients than in controls, as were cyanide-insensitive O2 consumption and superoxide anion and H2O2 production. Mean iodination was also decreased and, in most patients, was related to a decrease in H2O2 production. However, in eight patients H2O2 production was normal, although an iodination deficiency was found. Myeloperoxidase activity was low in five of these cases. In the other three patients this discrepancy was not explained. The longitudinal study of 12 patients showed that defects observed in the early stages of the disease remained or were aggravated, and that new abnormalities appeared during the course of the disease.

Adult↗
PubMed1984

Ingestion rate and glycolytic enzymes in neutrophils of patients with agnogenic osteomyelofibrosis and splenomegaly.

Ingestion rate of granulocytes in osteomyelofibrosis with splenomegaly, which is still a matter of controversy, was measured in 32 patients. The mean ingestion rate in patients' granulocytes was similar to that of the controls; the results, however, were more dispersed in the patients than in the controls, with very high (three patients) and very low (three patients) ingestion rates. Ingestion alterations were serum-independent. Neutrophil glycolytic enzymes and adenylate-kinase were measured in order to assess: (1) if they could be responsible for the observed abnormalities and (2) if enzyme abnormalities, previously described in red blood cells, also occur in the neutrophils. Major increases in phosphofructoaldolase and in 3-phosphoglycerate kinase activities, contrasting with a decrease in pyruvate kinase activity were observed. These, however, did not correlate with ingestion alterations. In conclusion, we showed that the granulocyte ingestion rate is altered in a few patients only, that the alterations are unrelated to the serum, to adenylate kinase or to glycolytic enzyme abnormalities. The latter, however, are important. The mechanisms of their occurrence are unknown and hypotheses such as those proposed for red blood cells enzyme modifications in myeloproliferative disorders could be applicable.

Adenylate Kinase↗
PubMed1984

Glutathione reductase and nitroblue tetrazolium reduction deficiencies in neutrophils of patients with primary idiopathic myelofibrosis.

Latex ingestion and nitroblue tetrazolium reduction were measured in neutrophils of 40 patients with primary idiopathic myelofibrosis. The percentage of neutrophils that ingested latex, in the presence of either autologous or control sera, was lower (P less than 0.001) than that of the controls. The percentage of the ingesting neutrophils that reduced nitroblue tetrazolium was also lower (P less than 0.001) in the patients than in the controls. Activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione peroxidase and NAD(P)H oxidases were not different from those of the controls. In contrast, glutathione reductase activity was significantly lower (P less than 0.001) in the patients than in the controls either with or without the addition of flavin adenine dinucleotide. Glutathione reductase and nitroblue tetrazolium reduction activities were correlated (r = 0.913). These results are discussed within the framework of the acquired enzymopathies and the increased susceptibility to infection observed in these patients.

Adult↗
PubMed1982

Chemokinetic activity of N-formyl-methionyl-leucyl-phenylalanine on human neutrophils, and its modulation by phenylbutazone.

Phenylbutazone (PBZ) is known to inhibit the oriented migration of human polymorphonuclear leukocytes (PMNs) induced by formyl-methionyl-leucyl-phenylalanine (FMLP), and to protect these cells against the deactivation caused by their prior incubation with FMLP. To gain insight into the mechanism of these effects, we measured the oriented PMN migration under agarose induced, in the presence and absence of PBZ, by FMLP, zymosan-activated serum and Klebsiella pneumoniae culture supernatant. The two components of this migration, i.e. the speed (chemokinesis), and direction of locomotion (chemotaxis), were also assessed. At concentrations ranging from 10(-8) to 10(-5) M, FMLP displayed similar chemotactic activity but the speed of PMN locomotion was maximal for 10(-7) M, and lower for concentrations above and below this level. Oriented migration was proportional to the mean cell locomotion speed during the experiments. PBZ inhibited both the oriented migration and locomotion speed induced by 10(-7) M FMLP, but did not affect its chemotactic activity. At concentrations of 10(-6) and 10(-5) M, PBZ increased oriented migration and locomotion speed, again without influencing FMLP chemotactic activity. Oriented migration induced by zymosan-activated serum was not affected by PBZ but the migration induced by Klebsiella pneumoniae culture supernatant diminished slightly. These results demonstrate that PBZ modulates the chemokinetic effect of FMLP on PMNs and thus alters oriented PMN migration.

Chemotaxis, Leukocyte↗
PubMed1982

[Functional anomalies of polymorphonuclears in Papillon-Lefèver disease (author's transl)].

Polymorphonuclear functions were studied in 3 patients of the same brotherhood with Papillon-Lefèvre disease (hyperkeratosis palmaris and plantaris and acute periodontosis resulting in loss of teeth) who developed severe and recurrent infections. Chemotaxis, oxygen consumption and production of H2 O2 were investigated by polarography, O2 production by quantitative reduction of nitroblue tetrazolium and iodination by the Pinus and Klebanoff technique. functional anomalies of polymorphonuclears involving chemotaxis, induced O2 consumption and H2 O2 production were detected in all three patients. This study confirms the presence of polymorphonuclear functional anomalies in patients with Papillon-Lefèvre disease. Analysis of the family tree of the patients, which went back to 1761, showed that this was probably not a chance association.

Adult↗
PubMed1981

Monocyte alpha-naphtyl esterase deficiency in chronic granulomatous disease.

Monocytes from five unrelated children (four boys and a girl) with chronic granulomatous disease were studied for their ability to reduce nitroblue tetrazolium dye after stimulation with zymosan, and for their alpha-naphtyl butyrate esterase activity. As expected, monocytes ingested zymosan particles but failed to reduce nitroblue tetrazolium dye. However, monocytes from two boys out of the five patients were alpha-naphtyl butyrate esterase-negative, whereas both their neutrophils and monocytes were positive for granular naphtol AS-D esterase activity.

Carboxylic Ester Hydrolases↗