Changes in serum granulocyte colony-stimulating factor (G-CSF) in burned patients

Serum G-CSF level was assayed in 20 burned patients (TBSA > or = 30%) 2 weeks postburn. In 11 of them plasma endotoxin was also measured. The results showed serum G-CSF level was increased in 87.5% (7/8) of burned patients with exceeding 50% TBSA and in 58.3% (7/12) of patients with 30%-50% TBSA, and in the former it was earlier increased (1-5 day postburn) than the latter (5-11 day postburn). Serum G-CSF was increased in 90% of the burned patients with wound sepsis. Increased of serum G-CSF in burned patients, especially in those exceeding 50% TBSA, indicates the occurrence of sepsis.     

Clinical use of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in neutropenia associated with malignancy

G-CSF and GM-CSF have been shown in each clinical setting to reduce the duration of neutropenia, with the exception of the scant data available in the unrelated bone marrow transplant setting. These growth factors also have been shown to have no leukemogenic effect during the observation periods of the trials discussed. In MDS, one major randomized trial has demonstrated a reduction in incidence of infection. This has not yet been demonstrated in AML and allogeneic BMT. Data from ongoing and future trials will be helpful in elucidating their effect on treatment-related morbidity and overall survival.     

Recombinant human granulocyte colony-stimulating factor attenuates inflammatory responses in septic patients with neutropenia

OBJECTIVE: The objective of this study was to determine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in septic patients with neutropenia. METHODS: Twenty consecutive septic patients were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days (group G). They were compared with 14 septic patients treated earlier without rhG-CSF (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL. Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an indicator of the tissue injury were evaluated in group G. RESULTS: In group G, TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL-6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI. Consequently, the APACHE II score and MOF index improved. In group N, however, CRP showed no change concomitant with the APACHE II score and MOF index. CONCLUSION: Administration of rhG-CSF attenuates inflammatory responses without inducing tissue injury in septic patients with neutropenia.     

A mesenteric liposarcoma with production of granulocyte colony-stimulating factor

A 77-year-old female was admitted to our hospital because of pyrexia and a right retroperitoneal mass. Leukocytosis and other inflammatory findings were noted. Bone-marrow aspiration revealed hypercellularity with no malignant cells. An additional mass was detected sonographically in the pelvis. The serum concentration of granulocyte colony-stimulating factor (G-CSF) was highly elevated (299 pg/ml). The tumors were removed at laparotomy, and the pelvic mass was found to arise from the ileocecal mesentery. Postoperatively, white blood cell count and serum G-CSF concentrations decreased to normal levels. The mesenteric tumor showed weakly positive immunostaining for human G-CSF, and Northern and polymerase chain reaction (PCR) analyses detected CSF and its mRNA in the mesenteric tumor.     

Effects of granulocyte colony-stimulating factor in cirrhotic rats with pneumococcal pneumonia

A rat model was used to study the effects of granulocyte colony-stimulating factor (G-CSF) on the pathogenesis of pneumococcal pneumonia in cirrhosis. G-CSF or 5% dextrose in water was administered subcutaneously to cirrhotic and control rats before or after transtracheal infection with type 3 Streptococcus pneumoniae. In both groups, G-CSF significantly increased the total number and percentage of polymorphonuclear leukocytes (PMNL) in peripheral blood (P < .002) and bronchoalveolar lavage fluid (P < .01). An in vivo phagocytosis assay revealed no increase in uptake of pneumococci by PMNL within the lungs of cirrhotic or control rats receiving G-CSF. G-CSF administered before infection did not protect cirrhotic or control rats, but G-CSF treatment after infection significantly reduced mortality in control (P = .04) but not cirrhotic rats. These data suggest that despite increasing numbers of circulating and pulmonary PMNL, G-CSF does not protect against fatal pneumococcal pneumonia in cirrhotic rats.     

Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia

Adiabatic pulses, although useful in generating uniform spin nutation in the presence of inhomogeneous B1 fields, are limited for NMR imaging applications due to the lack of slice-selective excitation capability. Selective excitation techniques using gradient modulation have been introduced; however, present methods require either a minimum of two excitations or eight adiabatic segments. Here, a scheme is presented that allows single-shot, arbitrary flip-angle, and slice-selective excitation with only four adiabatic half-passage segments. The technique is demonstrated via computer simulation and experimental tests on a phantom. Furthermore, issues associated with the implementation of these gradient-modulated adiabatic pulses are discussed.     

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor

PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.     

Neutrophils from AIDS patients treated with granulocyte colony-stimulating factor demonstrate enhanced killing of Mycobacterium avium

Neutrophils isolated from AIDS patients have demonstrated improved growth inhibition of Mycobacterium avium when incubated with exogenous granulocyte colony-stimulating factor (G-CSF). In this clinical study, 30 AIDS patients without M. avium infection were randomized to receive 5 days of treatment with rifabutin, G-CSF, or both agents. The M. avium killing capacity of neutrophils harvested from each patient before intervention, during (day 4), and after therapy (day 7) was assessed. The mean change in human immunodeficiency virus load in the group receiving G-CSF alone was -0.07 log of viral RNA. There was a 90% reduction in M. avium growth after therapy for patients treated with G-CSF alone (P=.01), 59% for patients treated with both agents (P=.06), and 11% for patients treated with rifabutin alone (P=.84). Thus, neutrophils isolated from AIDS patients treated with G-CSF demonstrated a significant enhancement of killing of M. avium; there was no notable effect on virus load.     

Enhancement of cytosine arabinoside cytotoxicity by granulocyte/macrophage colony-stimulating factor and granulocyte colony-stimulating factor in a human myeloblastic leukemia cell line

Enhancement of the cytotoxicity of cytosine arabinoside (ara-C) by granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), and the mechanisms involved, were studied in the AML-193 human leukemia cell line. AML-193 cells require GM-CSF and G-CSF(CSFs) for optimum growth, and 24 h deprivation of CSFs decreased DNA synthesis measured in terms of 3H-thymidine incorporation. The DNA synthesis gradually recovered upon addition of CSFs. To examine the sensitivity to ara-C under different growth conditions, two groups of cell suspensions, one pretreated with CSFs after 24 h deprivation (CSFs(+) cells), and the other held continuously under CSFs-free conditions (CSFs(-) cells), were exposed to 1.0 microgram/ml of ara-C for 16 h. In clonogenic assays, CSFs(+) cells showed higher sensitivity to ara-C than CSFs(-) cells. These cell groups showed no significant difference in ara-C triphosphate accumulation or retention, though the amount of ara-C incorporated into the acid-insoluble fraction was two times greater in CSFs(+) cells than CSFs(-) cells, and that difference became even clearer in the retention pools. These data suggest that the enhancement of cytotoxicity by CSFs was due to the promotion of ara-C incorporation into DNA as a result of an increase of the cell fraction in the S phase.     

Soluble complement receptor 1 is increased in patients with leukemia and after administration of granulocyte colony-stimulating factor

The morphologically uniform species Gonium pectorale is a colonial green flagellate of worldwide distribution. The affinities of 25 isolates from 18 sites on five continents were assessed by both DNA sequence comparisons and sexual compatibility. Complete sequences were obtained (i) for the internal transcribed spacer ITS-1 and ITS-2 regions of ribosomal DNA and (ii) for each of three single-copy spliceosomal introns, two in a small G protein and one in the actin gene. ITS sequences appeared to homogenize sufficiently rapidly to behave as a single copy gene. Intron sequence differences between isolates in this species reached nucleotide substitution saturation, while ITS sequences did not. Parsimony and evolutionary distance analysis of the two types of DNA data gave essentially the same tree conformation. By all these criteria, the group of G. pectorale isolates fell into two main clades, A and B. Clade A, with isolates from four continents, was comprised of four subclades of quite closely related isolates, plus one strain of ambiguous affinity. Clade B was comprised of two subclades represented by South African and South American isolates, respectively; thus, only subclades of clade B showed geographical localization. With respect to mating, all isolates except one homothallic strain and one apparently sterile strain fell into either one or the other of two mating types. Pairings in all possible combinations revealed that isolates from the same site formed abundant zygotes, which germinated to produce new, sexually active organisms. Zygotes were also formed in many pairings of other combinations, including crosses of clade A with clade B organisms, but none of the latter produced viable germlings. The ability to mate and produce viable progeny that were themselves capable of sexual reproduction was restricted to members of subclades established on the basis of DNA sequence similarities. Thus, the grades of difference in both nuclear intron sequences and rDNA ITS sequences paralleled those observed in the sexual analysis.     

A case of multiple myeloma producing granulocyte colony-stimulating factor

A case of multiple myeloma (IgA-lambda) with marked granulocytosis, which measured up to 9.9 x 10(4)/mm3, is described. Matured neutrophils were predominant and blasts were not found in the peripheral blood. The serum granulocyte colony-stimulating factor (G-CSF) was notably elevated. The disease ran a chronic course and granulocytosis and elevated serum G-CSF continued. The patient developed atelectasis and bronchopneumonia, and died of respiratory failure. At autopsy, bone marrow showed marked myeloid hyperplasia in varying states of differentiation. The enlarged spleen also disclosed numerous myeloid cells of varying differentiation. Small aggregations of atypical plasma cells were present in the marrow and spleen. Immunohistochemically, atypical plasma cells were positive for anti-G-CSF antibody, which indicated G-CSF secretion from the myeloma cells. To our knowledge, this is the first reported case of G-CSF-producing multiple myeloma.