Summary.A cross-over study of glycosylated and nonglycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 mg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P ¼ 0 . 02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P ¼ 0 . 03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P ¼ 0 . 003). Serum concentrations of G-CSF achieved were significantly higher with the nonglycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.
SUMMARY One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). (Sigma, Poole, Dorset) (50 ig/ml in distilled water) and incubated for one hour at 37°C. Each well was then washed three times with phosphate buffered saline (PBS) (Flow, Ayrshire, Scotland) before the addition of 50 RI of dsDNA (10 Fig/ml) or ssDNA (5 [ig/ml), both in PBS. The dsDNA was prepared by treating calf thymus DNA (Sigma) with 1 U/4g S1 nuclease (Sigma) for 30 minutes at 37°C. The ssDNA was prepared by boiling calf thymus DNA for 10 minutes and cooling on ice for 15 minutes. After overnight incubation at 4°C the plates were washed three times with PBS. These were then treated with 100 RI of
Summary: Methods Daily administration of granulocyte colony-stimulating Study subjects Factor (G-CSF) results in progenitor cell mobilizationTwenty healthy male volunteers were entered into the first with maximum blood levels achieved after 4-7 days. In phase of this study and seven into the second phase. They this study the short-term effects of glycosylated G-CSF were aged between 19 and 35 years and all were normal at a dose of 5 g/kg s.c. were determined so as to allow on physical examination and routine hematological and biooptimization of the timing of progenitor cell collection.chemical screening. The studies were approved by the local In the first study involving 20 normal volunteers, a sigresearch ethics committee and each volunteer gave written nificant fall in neutrophil count and G-CSF levels was informed consent. observed 2 h after the G-CSF injection. To investigateIn both studies each volunteer received glycosylated Gthis phenomenon serial measurements were made in a CSF (lenograstim) at a dose of 5 g/kg/day for 6 days. Volfurther six volunteers after the 6th daily injection of Gunteers were hospitalized throughout this period and the G-CSF. A fall in the neutrophil count occurred which was CSF was administered at 09.00 h each day. In the first maximal at 1 h and recovered to baseline within 3 h.phase of the study baseline full blood counts, GM-CFC and There was also a fall in CD34+ cells (P = 0.034), GM-CD34 measurements were made immediately before the CFC (P = 0.025) and BFU-E (P = 0.066) and recovery to first G-CSF administration (day 1) and on days 4, 5 and 6 baseline levels took 4-12 h. We conclude that glycosylimmediately before the next dose of G-CSF and 2 h after ated G-CSF should not be given immediately prior to its administration. In the second phase of the study full stem cell collection.blood counts and progenitor cell levels were determined
A whole-blood technique was used to measure simultaneously neutrophil migration, uptake, and killing of candida in 27 premature infants of low birth weight (less than 1500 g). Neutrophil migration was consistently reduced, especially in the first two weeks of life. Phagocytosis was also reduced, particularly in the first week of life and in sick patients. Killing was usually normal, except in sick patients. The three functions were not altered when the test was performed in normal adult, rather than autologous, plasma, and the reduced migration and uptake are therefore the result of an intrinsic defect of the cell. The results clarify the previous controversy concerning neutrophil function in premature infants and provide an explanation for their increased susceptibility to infection.
This study examined gingival crevicular polymorphonuclear leucocyte function in periodontosis patients. Cells were examined for viability, function and ultrastructure. Eighty percent or more of the cells in each sample were viable as assessed by the fluorescein diacetate technique, but the test organism, Candida guillermondiae, was not phagocytosed. Gingival crevicular fluid contained many lysing neutrophils and nonphagocytosed organisms. Recognizable polymorphs contained Gram‐negative and Gram‐positive organisms. On the basis of this and previous studies it is concluded that gingival crevice neutrophils from periodontosis sites show reduced phagocytic function compared with cells from normal or periodontitis‐affected gingival crevices. It is possible that the behavior of neutrophils from gingival crevices may be irrelevant. Original changes by that stage may have obscured their capabilities.
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