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Biomedical subjects

D G Wright

Publications and source records attributed to D G Wright.

At least 109 records · Page 6Linked to original sources
PubMed1981

Lymphocytapheresis.

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Arthritis, Rheumatoid↗
PubMed1980

Development of chemotactic responsiveness in myeloid precursor cells: studies with a human leukemia cell line.

We have studied the events that occur during the development of chemotaxis in HL60, a promyelocytic leukemia cell line that acquires the features of mature neutrophils when exposed to dimethylformamide (DMF). Chemotactic function first appears between 48 and 96 hr of DMF induction and is associated not only with the coincidental development of deformability, spontaneous motility, greatly increased binding of fMet-Leu-Phe, and orientation but also with decreasing cell size and pleomorphism of nuclei. Surface adhesiveness develops earlier (36-48 hr) and is coincident with a 10-fold increase in protein synthesis not seen in other DMF-inducible cell lines. This burst of protein synthesis precedes the expression of chemotactic function. These studies show that the HL60 cell line can provide a useful model for delineating control mechanisms responsible for the development of complex cellular functions present in differentiated myeloid cells in humans.

Animals↗
PubMed1980

Disorders of phagocyte chemotaxis.

Recent advances in understanding the physiologic and biochemical bases for recruitment of phagocytes to inflammatory sites has led to the recognition of patients who have recurrent infections because of abnormalities of phagocyte chemotaxis. In some of these patients there is abnormal chemoattractant mediator production or regulation, whereas in others there are defects in phagocytic cell function. The cellular defects in chemotaxis can be characterized as either intrinsic defects of the cellular motility apparatus or acquired defects from mediators influencing cell function or from shifts in circulating phagocyte subpopulations. Systematic study of these defects has resulted in functional, biochemical, and ultrastructural characterization of abnormal phagocyte chemotaxis in certain patients, and in some patients study has led to rational approaches for treatment. Clinical trials assessing the efficacy of such pharmacologic agents are underway.

Adolescent↗
PubMed1979

Lymphocyte depletion by continuous flow cell centrifugation in rheumatoid arthritis: clinical effects.

Four patients with active, severe rheumatoid arthritis were subjected to the removal of circulating lymphocytes (lymphapheresis) for a 6-week period by use of a continuous flow cell centrifuge. Repetitive venous access was gained through forearm arteriovenous fistulae. In all patients the Ritchie-Camp articular index declined rapidly in the first week and more slowly therafter for a total mean drop of 61% below the initial value. The index continued to decline after lymphapheresis but exacerbation of disease activity developed at an average of 19 weeks. No significant untoward effects of the procedure were observed; occasional transfusions were required to compensate for the small, unavoidable erythrocyte loss.

Adult↗
PubMed1979

Pontine and extrapontine myelinolysis.

No coherent theory has been advanced to explain either the particular localization of the myelinolytic lesions of central pontine myelinolysis or their pathogenesis. However, several lines of evidence support the generalization that the centre of the basis pontis has a special susceptibility to a metabolic fault. The constancy of localization of the lesion and its bilateral symmetry are the very attributes that characterize other metabolic (nutritional) disorders, such as the assymmetrical degeneragion of the papillomacular bundles within the optic nerves and tracts in deficiency amblyopia and the specific affection of the paraventricular regions in the Wernicke-Korsakoff syndrome. And clinically, the frequent occurrence of central pontine myelinolysis in a setting of severe metabolic derangement, particularly of the serum sodium, points in the same direction.

Adult↗
PubMed1978

Correction of human cyclic neutropenia with prednisolone.

A 70-year-old woman with cyclic neutropenia was treated with 16 mg of etiocholanolone and 25 mg of prednisolone intramuscularly every other day. During 14 weeks' treatment amplitude of cyclic fluctuations in neutrophil counts gradually decreased, but pretreatment cycles returned promptly after treatment was stopped. Prednisolone alone every other day (25 mg) reproduced this result, and by 23 weeks, neutrophil counts became stable at about 1500 per cubic millimeter. tcycling of monocytes, platelets and reticulocytes was also eliminated, as were symptoms that had accompanied neutropenic periods. In addition, bone-marrow neutrophil precursors and neutrophil marrow reserves were stabilized. The patient was subsequently maintained satisfactorily with oral prednisolone, 20 mg every other day. These studies demonstrate that the discontinuous myeloid maturation that occurs in cyclic neutropenia can be corrected with prednisolone every other day.

Aged↗
PubMed1978

Role of secretory events in modulating human neutrophil chemotaxis.

The relationship between neutrophil polymorphonuclear leukocyte (PMN) locomotion and the exocytosis of neutrophil cytoplasmic granules was studied by assessing these processes in cells migrating through micropore filters and by measuring the effects of degranulating stimuli on PMN chemotaxis, orientation, adhesiveness, and ability to bind the chemoattractant f-Met-Leu-[3H]Phe. Studies of cells migrating through cellulose nitrate filters indicated that concentrations of f-Met-Leu-Phe optimal for exocytosis were greater than those optimal for chemotaxis and actually inhibited cell migration. In other studies incubation of PMNs with concentrations of secretagogues causing exocytosis of 30% or greater PMN lysozyme increased cell adhesiveness and inhibited chemotaxis. PMNs that had secreted more than 30% lysozyme appeared round, did not orient in a gradient of chemoattractant, and were capable of significantly less f-Met-Leu-[3H]Phe binding than were control cells. The decreased binding of f-Met-Leu-Phe was not associated with hydrolysis of chemotactic peptide by washed cells, although peptide hydrolysis was caused by cell products secreted extracellularly after vigorous exocytosis. In contrast, when only 10--15% cellular lysozyme was released f-Met-Leu-Phe binding was enhanced significantly and there was no depression of chemotaxis. The data indicate limited exocytosis of intracellular granule contents is associated with increased availability of PMN cehmotactic factor receptors. Vigorous exocytosis is associated with inactivation of chemotactic responsiveness related to increase cell adhesiveness, decreased PMN binding of chemotactic factors, and to hydrolysis of chemoattractants by factors secreted extracellularly.

Binding Sites↗
PubMed1977

Effects of levamisole on normal and abnormal leukocyte locomotion.

The anti-helminthic drug levamisole hydrochloride has been reported to stimulate immune responses in humans and experimental animals. We have investigated levamisole effects on human leukocyte locomotion in vitro in studies of neutrophils and mononuclear cells from normal adults, from patients with Chediak-Higashi disease and from patients with the syndrome of hyperimmunoglobulin E, recurrent pyogenic infections, and defective leukocyte chemotaxis. Directed migration (chemotaxis) of neutrophils and mononuclear cells from normal adults and from the hyperimmunoglobulin E syndrome patients, but not from Chediak-Higashi patients, were stimulated by levamisole at concentrations of 0.01-1.0 micronM, with stimulation observed most consistently at 0.1 micronM. These concentrations of drug also increased cyclic GMP levels in mononuclear cells and enhanced hexose monophosphate shunt activity in neutrophils, but did not alter chemotactic factor-induced changes in the surface charge of neutrophils. Other concentrations of levamisole did not affect leukocyte locomotion except for a high concentration (5.0 mM) which stimulated both random and directed leukocyte migration. When patients with the hyperimmunoglobulin E syndrome took levamisole by mouth, the abnormal chemotactic responses of their neutrophils were significantly improved towards normal. These studies are the first to show pharmacologic improvement of in vitro leukocyte locomotion in patients in whom recurrent infections have been attributed to a defect of this leukocyte function.

Adolescent↗
PubMed1977

Efficacy of intermittent colchicine therapy in familial Mediterranean fever.

Nine patients with familial Mediterranean fever (FMF) were admitted to a controlled, double-blind trial to determine if there are patients with this disease who are able to abort their acute episodes of pain and fever with short courses of colchicine taken at the onset of attacks. Five patients completed their treatment assignments, and colchicine was significantly effective in aborting the attacks of three but was ineffective in two. The remaining four patients could not be assessed because of insufficient numbers of courses. During the 10 months of the trial, 28 courses of colchicine and 31 of placebo were taken during the early stages of FMF attacks. Twenty-one (75%) colchicine courses were followed by attacks considered to have been aborted, compared to only three (10%) placebo courses. This trial shows that patients can recognize the prodrome of their FMF attacks and that some patients can consistently abort their attacks with short courses of colchicine taken at the very onset of symptoms.

Adolescent↗
PubMed1977

The differential mobilization of human neutrophil granules. Effects of phorbol myristate acetate and ionophore A23187.

Phorbol myristate acetate (PMA, 2 to 100 ng/ml) and ionophore A23187 (10(-7) to 10(-6) M) cause human neutrophils to release up to 50% of the granule-associated enzyme lysozyme extracellularly without release of beta-glucuronidase or the cytoplasmic enzyme LDH. When azurophil and specific granules are separated from neutrophil lysates by sucrose density centrifugation, it is found that lysozyme release from neutrophils exposed to PMA or to A23187 reflects a selective disappearance of the small, peroxidase-negative (specific) granules from the cells. These studies demonstrate that neutrophils can mobilize the specific and azurophil granules independently. These studies also demonstrate that under certain conditions the specific granules of human neutrophils behave like the storage granules of secretory cells. Finally, these studies show that techniques of separating neutrophil granules according to their sedimentation characteristics successfully divide these granules into populations that are distinct not only by cytochemical and morphologic criteria but also according to their availability for mobilization and extracellular release. (APM J Pathol 87:273-284, 1977).

Anti-Bacterial Agents↗