Neutrophil function in primary cilia dyskinesia.
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Chemotaxis, Leukocyte↗
Biomedical subjects
N H Valerius
Publications and source records attributed to N H Valerius.
Effect of antimalarial drugs on human neutrophil chemotaxis in vitro.
The effect of several antimalarial drugs, commonly used for prophylaxis and therapy of human malaria, on polymorphonuclear leukocyte chemotaxis was studied. A modified, reversible Boyden chamber method was used. Various concentrations of each drug was mixed with neutrophils and incubated in the chambers for 2 1/2 hours. After the incubation period percent inhibition of chemotaxis was determined. It was shown that chloroquine, quinine, proguanil, and tetracycline at concentrations frequently obtained in clinical situations significantly inhibited chemotaxis of neutrophils towards casein. There was a direct correlation between increasing drug concentration and percent inhibition of chemotaxis. Drugs such as pyrimethamine and fansidar at any concentration tested had no effect on chemotaxis.
Antimalarials↗
Prenatal diagnosis of chronic granulomatous disease.
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Adult↗
Distribution of actin-binding protein and myosin in neutrophils during chemotaxis and phagocytosis.
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Animals↗
Neutrophil and lymphocyte function in patients with diabetes mellitus.
Neutrophil granulocyte chemotaxis and intraneutrophilic and plasma levels of lysozyme as well as the number of T and B lymphocytes and lymphocyte transformation in vitro on stimulation with mitogens and microbial antigens were studied in four groups of patients with diabetes mellitus (DM). Twelve patients with insulin-dependent diabetes mellitus (IDDM) and ketoacidosis and 4 patients with non-insulin-dependent diabetes mellitus were studied at the time of diagnosis and before and after start of treatment. Ten patients with IDDM of less than 10 years' duration which had been difficult to regulate well and 10 patients with IDDM well regulated for more than 20 years were studied at their regular outpatient visits. Apart from a slight increase in plasma lysozyme in group 1 from the first to the second examination, we found no differences between diabetics and healthy control persons. It is concluded that if patients with DM are more susceptible to infections, it is probably caused by elements of neutrophil or lymphocyte function not examined in this study or by factors unrelated to immunity.
Adolescent↗
Distribution of actin-binding protein and myosin in polymorphonuclear leukocytes during locomotion and phagocytosis.
Polymorphonuclear (PMN) leukocytes, highly motile ameboid cells vital for mammalian defense against infection, acquire a distinct polarized morphology during locomotion and phagocytosis. An organelle-excluding pseudopod extends in the direction of movement and surrounds objects during phagocytosis. The anterior pseudopod contains a three-dimensional network of actin filaments. Actin-binding protein (ABP) and myosin cause the crosslinking and contraction, respectively, of actin filaments in vitro. We used indirect immunofluorescence to study the redistribution of myosin and ABP molecules in rabbit PMN leukocytes during locomotion and phagocytosis. In unpolarized PMN leukocytes, ABP and myosin had a diffuse distribution with some predilection for the cortex. In polarized PMN leukocytes crawling toward yeast particles, myosin and ABP staining concentrated in the anterior pseudopod. In PMN leukocytes fixed during phagocytosis of the yeast particles, antimyosin and anti-ABP staining concentrated strikingly in the distal portions of the pseudopod embracing the yeasts. Staining for catalase, a cytoplasmic protein in PMN leukocytes, for lactoferrin, a protein of specific granules, and for myeloperoxidase, a protein of azurophilic granules, was not concentrated in pseudopods. Taken together with available morphologic and biochemical information, these findings are consistent with a mechanism wherein interactions of actin, ABP and myosin redistribute cortical cytoplasm into pseudopods involved in locomotion and phagocytosis.
Actins↗
Effect of in vitro X-irradiation on lymphocyte and granulocyte function.
Granulocyte transfusions have been complicated by graft-versus-host disease (GVHD) in the recipients. This risk can be eliminated by irradiation of the cell product. The effect of in vitro irradiation on elements of lymphocyte and granulocyte function was therefore studied in order to determine the dose of irradiation which blocked lymphocyte function without affecting the function of granulocytes. Lymphocyte blast transformation after stimulation with mitogens was reduced by 90% after irradiation with 1500 rad and by 97% after 5 000 rad. The response to microbial agents and allogeneic cells was far more radio-sensitive, being completely abolished after irradiation with 1 000 and 500 rad, respectively. Mobility was the function of polymorphonuclear leucocytes (PMN) most affected by irradiation, being slightly but significantly reduced after irradiation with 10 000-20 000 rad. The bactericidal activity was reduced only after irradiation with 40 000 rad or more, while the hexose monophosphate shunt activity and the myeloperoxidase activity were largely unaffected by irradiation with doses of up to 120 000 rad. Hence the results indicate that the irradiation of leucocytes intended for transfusion with a dose of 2 000 rad is likely to prevent GVHD without causing any apparent damage to the PMN.
Chemotaxis, Leukocyte↗
Severe combined immunodeficiency associated with hyperimmunoglobulinaemia E, eosinophilia and impaired neutrophil chemotaxis.
A boy with severe combined immunodeficiency was found to have coexistent hyperimmunoglobulinaemia E, eosinophilia and impaired neutrophil chemotaxis. Based on the literature, a deficient regulatory function of the T-cell system is proposed as the basic defect leading to the observed impairment of the cellular and humoral immunity and, probably through hyper-immunoglobulinaemia E, to defective neutrophil chemotaxis.
Chemotaxis, Leukocyte↗
Defective leukocyte metabolism.
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Blood Bactericidal Activity↗
Refractory Pneumocystis carinii infection in chronic granulomatous disease: successful treatment with granulocytes.
Pneumocystis carinii pneumonia developed in an 11-year-old girl with chronic granulomatous disease who had normal cellular and humoral immunity. The patient remained febrile during treatment with sulfamethoxazole-trimethoprim and pentamidine but became afebrile when treated with a series of 12 granulocyte transfusions combined with sulfamethoxazole-trimethoprim. In addition to documenting P carinii infection in chronic granulomatous disease our findings suggest that granulocyte transfusions may be of value in the treatment of severe infections in chronic granulomatous disease.
Blood Transfusion↗
In vitro effect of R 17934, a new drug with antitubulin activity, on neutrophil granulocyte locomotion and orientation.
R 17934 is a new synthetic antimicrotubule drug, which binds to tubulin at the same site as does colchicine. The interaction of this drug with human neutrophil granulocyte locomotion and orientation was examined, using a modified reversible Boyden chamber and a gradient chamber offering a direct visual assay of cell orientation. R 17934 at concentrations as low as 5 x 10(-6) M was found to inhibit chemokinesis to an equal degree in gradient chambers, and in Boyden chambers using checkerboard experiments, in which the absolute concentrations and the concentration gradients of the chemotactic agent were varied. At higher concentrations (10(-5) M) R 17934 also inhibited chemotaxis in Boyden chambers. Much lower concentrations of R 17934 (10(-7) M) were found to affect the ability of neutrophils to orient in gradient chambers. This finding may show that filters form a more suitable substrate for oriented pseudopod formation of microtubule-deficient cells than do glass or plastic slides. In conclusion this study has provided evidence that in the absence of functioning microtubules neutrophils can still orient and migrate directionally towards the source of a concentration gradient, but that they do so less precisely. The finding that R 17934 inhibited chemokinesis suggests that this drug may interfere with the mechanism translating a recognition signal into locomotion. The previous finding that colchicine also had this effect supports the hypothesis that this process may be microtubule-dependent.
Benzimidazoles↗
Neutrophil kinetics in acute bacterial infection. A clinical study.
Neutrophil kinetics in peripheral blood were studied with DF32P-labeled cells in eight patients during severe acute bacterial infection. Contrary to previous studies in man, the blood transit time of labeled neutrophils was short and the neutrophil turnover rate increased, up to ten times the normal, during the early phases of infection. This early phase was followed by a period in which the specific neutrophil radioactivity in the blood remained constant for up to 50 hours, probably indicating that in early convalescence neutrophil egress from the bone marrow to the blood is almost stopped. The demonstration of increased neutrophil turnover may seem to illustrate what might be considered an obvious fact, but is in contrast to previous findings and seems to obviate the prevailing theory of quantitatively unchanged but redistributed neutrophil kinetics during bacterial infection in man. The mechanism which apparently abruptly stops neutrophil egress from the bone marrow to the blood during early convalescence is unknown.
Acute Disease↗
Harvesting of granulocytes for transfusion therapy by haemonetics 30. Yield, morphology and in vitro functions of collected granulocytes.
By means of a Haemonetics 30 blood cell separator white blood cells (WBC) were collected for transfusion purposes from 21 normal unstimulated donors. Citrated Hydroxyethyl Starch (HES) was used as anticoagulant. A mean yield of 1.13 x 10(10) WBC was obtained in 2 1/2-3 h. Half of the collected WBC were PMN cells containing a few per cent band forms, the other half lymphocytes and monocytes (12%). No shift in the distribution of WBC was found during the leucapheresis. Light and electron microscopy did not reveal any damage or changes in the structure of the processed granulocytes. The Trypan blue exclusion test showed 99% vital cells. In vitro assessment of the chemotactic and bactericidal activity of the collected granulocytes showed normal function. Also the content of myeloperoxidase was within normal range.
Blood Cell Count↗
Immunosuppressive measles encephalopathy.
A case of measles infection without a rash, which was followed by a severe encephalopathy after two months, is described in a 2 1/2 year old boy. At the age of 8 months he had been irradiated for an inoperable intrathoracic neuroblastoma, and at the time of exposure to measles he was being treated with cyclophosphamide and vincristine. This case closely resembles other cases recently described and termed immunosuppressive measles encephalopathy. The syndrome is believed to represent the effect of measles virus in patients with deficient cellular immunity induced by antineoplastic treatment. The importance of protecting children on immunosuppressive treatment for contracting measles is stressed.
Child, Preschool↗
Intrauterine supraventricular tachycardia.
Four cases of intra-uterine ectopic supraventricular tachycardia are described. In three there were none or only minor symptoms immediately after delivery and subsequently. The fourth baby having a congenital W-P-W-syndrome was born with severe hydrops fetalis and was asphyxiated. From these cases and from data reported in the literature it is concluded that intra-uterine heart failure is a significant risk when the fetal heart rate persistently exceeds 230 per minute. It is suggested that digoxin administered to the mother may be beneficial to the fetus in cases of intra-uterine ectopic tachycardia.
Apgar Score↗
In vitro effect of colchicine on neutrophil granulocyte locomotion. Assessment of the effect of colchicine on chemotaxis, chemokinesis and spontaneous motility, using a modified reversible Boyden chamber.
The effect of colchicine on human neutrophil granulocyte chemotaxis, chemokinesis and spontaneous motility was examined, using a modified reversible Boyden chamber. Colchicine was shown to inhibit the attraction of neutrophils to casein and to a bacterial chemotactic factor at concentrations as low as 10(-7) M. Experiments in which the absolute concentrations and the concentration gradients of the chemotactic agent were varied, revealed that colchicine inhibited chemokinesis rather than chemotaxis. The spontaneous motility measured in the absence of chemotactic agents was not inhibited by colchicine. Pre-incubation of the cells with a bacterial chematactic factor did not change the sensitivity of the cells to colchicine. It is concluded that the integrity of microtubule function is not necessary for the ability of the cells to discern a concentration gradient or to react to this with directional locomotion. Thus the inhibitory effect of colchicine on neutrophil granulocyte chemokinesis may not depend on its inhibition of microtubule function. It is suggested that colchicine may block the still unidentified membrane mechanism involved in the translation of the recognition signal into an appropriate locomotory cell response.
Caseins↗
Lymphocyte unresponsiveness to mitogens in vitro is not equivalent with severe immunodeficiency.
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Adolescent↗
Neutrophil granulocyte chemotaxis in vitro. Comparison of the response to casein and a bacterial chemotactic factor, and evaluation of an automatic method for counting cells on a membrane filter surface.
A method is described for evaluating neutrophil granulocyte chemotaxis in vitro, using a modified reversible Boyden chamber. The variation in cell detachment from the attractant surface of the filter after the migration through the filter was shown to be eliminated by reversing the chambers during the incubation period. In unreversed chambers, the loss of cells from the bottom surface of the filter was much higher on attraction with casein than with a bacterial chemotactic factor (BCF). The finding of a different kinetic response to casein and to BCF may suggest differing affinity to various chemoattractants within circulating neutrophils. The results obtained after introducing an automatic quantitative image analysis system for the counting of the cells at the filter surface are found to be very well correlated to those with conventional direct microscope counting.
Automation↗