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Biomedical subjects

D G Wright

Publications and source records attributed to D G Wright.

124 records · Page 7Linked to original sources

Paroxysmal "nightmares". Sequel of a stroke responsive to diphenylhydantoin.

A 65-year-old man had nightmares a few weeks after a right temporal lobe infarction. Electroencephalography showed no epileptic activity. Therapy with diphenylhydantoin produced complete remission of his symptoms. On the bases of their acute onset, their association with sleep, their occasional occurrence while the patient was awake, the lack of effect of diazepam and flurazepam, and the good response to diphenylhydantoin, we propose that these episodes were partial seizures secondary to the right temporal lobe lesion.

Aged↗

Functional abnormalities of human neutrophils collected by continuous flow filtration leukopheresis.

Continuous flow filtration leukopheresis (FL) is a relatively simple, inexpensive, and efficient technique of harvesting blood neutrophils from normal donors for transfusion into neutropenic recipients. There has been concern, however, that neutrophils may be functionally altered druing this leukopheresis procedure. Human neutrophils obtained by various FL techniques were studied for in vitro chemotaxis by a 51Cr-radiolabel method and for in vitro killing and phagocytosis of Staphylococcus aureus. We compared their function with neutrophils obtained by the NCI-IBM cell separator and by dextran sedimentation from whole blood. FL neutrophils eluted from nylon filters after 3-hr collection periods were functionally abnormal by all parameters tested, while neutrophils obtained by cell separator after similar collection times were not significantly different from control cells. However, neutrophils from 3-hr FL collections were found to include both normal and abnormal populations of cells. Loosely adherent cells, eluted after tapping the filters, were functionally normal; more adherent cells, eluted after tapping the filters and representing the bulk of cells collected, were progressively more abnormal the less readily they were eluted. Shortened FL collection times (1-2 hr) were found to decrease the functional defects. Also, administration of dexamethasone to donors prior to filtration leukopheresis diminished the functional defects of FL neutrophils perhaps by altering adherence characteristics of the cells. These studies show that neutrophils obtained by filtration leukopheresis are functionally abnormal in relation to the time and extent of adherence to nylon filters.

Adult↗

The mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis.

The importance of granular (lysosomal) enzymes from neutrophils in producing the tissue damage of acute inflammation has been suggested by much indirect and some direct evidence. This study has investigated the kinetics of release and subsequent fate of granular enzymes from phagocytizing human leukocytes The following observations are made: (a) During phagocytosis, the granular enzyme lysozyme is released from leukocytes into the extracellular medium. (b) Release of lysozyme increases as phagocytic challenge increases, but attains a maximum. (c) Release of lysozyme accompanies phagocytosis and is not a delayed event. (d) The lack of release of a nongranular enzyme, lactic dehydrogenase, indicates that cell damage is not a necessary condition of enzyme release. (e) Like lysozyme, beta-glucuronidase is released from phagocytizing leukocytes. Acid alpha-naphthyl phosphatase and cathepsin also appear to be released, but are not found in appreciable amounts in the extracellular medium, in part because of their lability in solution. These results support the concept that extracellular release of granular enzymes may be a useful secretory function of inflammatory leukocytes which becomes damaging to the host in certain circumstances.

Acid Phosphatase↗

Tiazofurin effects on IMP-dehydrogenase activity and expression in the leukemia cells of patients with CML blast crisis.

Tricot et al have reported that the nucleoside analog tiazofurin can induce hematologic remissions in patients with chronic myelogenous leukemia in blast crisis (CML-BC). These reports prompted us to begin a derivative, phase II trial of tiazofurin in CML-BC to determine if the promising findings reported by these investigators could be reproduced. In our ongoing trial patients receive tiazofurin by IV infusion (2200-4400 mg/m2 over 1 hr) once every 24-48 hrs for up to 10 days. Each of 3 patients, treated to date on this trial, experienced substantial hematologic responses with normalization of WBC counts and complete or partial clearance of blasts from the blood within 4-11 days of treatment. These responses were relatively brief, in that leukemic blasts reaccumulated in the marrow and blood of patients within 4 weeks following treatment, but were re-induced with subsequent courses of treatment. Of interest, the rates of blast cell reaccumulation appeared to increase progressively following sequential courses of treatment. Tiazofurin, which inhibits IMP-dehydrogenase (IMPDH) and blocks guanine ribonucleotide synthesis, has been shown to increase IMPDH mRNA expression in various cell lines in vitro, as an apparently compensatory response to guanylate deprivation. Studies of IMPDH mRNA expression in the leukemic blasts of CML-BC patients receiving tiazofurin treatment showed that this same phenomenon occurs in vivo. Since IMPDH activity is linked to the proliferative activity of neoplastic cells an amplification of IMPDH message expression induced by tiazofurin may lead to an increased sensitivity of the leukemic clone to cycle active agents.

Aged↗