Human Granulocyte (human + granulocyte)

Distribution by Scientific Domains

Selected Abstracts

Biocompatibility Assessment of Peritoneal Dialysis Solutions With a New In Vitro Model of Preconditioned Human HL60 Cells

Sebastian Koball
Abstract The purposes of this study were to test the human promyelocytic cell line HL60 for its usability as a new cell model for the immune barrier of the peritoneum, and to investigate the impact of different peritoneal dialysis (PD) solutions in the model. HL60 cells were stimulated by retinoic acid and recombinant human granulocyte and macrophage colony-stimulating factor to differentiate into neutrophilic granulocytes. Cells were incubated in different commercially available PD solutions. After a 4-h incubation, functional (chemiluminescence phagocytosis) and viability tests (Live-Dead, XTT) were performed. High glucose concentrations (>1.36%) and low pH values (<7.0) appeared to be detrimental for neutrophil functions and for neutrophil viability. There is a quantitative correlation between glucose concentration and the cytotoxicity of standard PD solutions (PD 1.36% glucose shows 42.6% higher chemiluminescence than PD 3.86% glucose [P < 0.05]). PD solution containing icodextrin shows 74.3% higher chemiluminescence than PD 3.86% glucose, and PD solution with amino acids shows 52.4% higher chemiluminescence than PD 3.86% glucose which is a sign for better biocompatibility in these tests (P < 0.05). The test system is useful for biocompatibility investigations of PD solutions and their effect on immune cells, for example, neutrophil granulocytes. It does not depend on donor variability and availability in comparison to models based on primary isolated leukocytes. [source]

Immune-stimulating effects of low-dose perioperative recombinant granulocyte,macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma,

A. K. Mels
Background: Surgery induces a postoperative immunosuppression, thereby possibly facilitating the outgrowth of pre-existing occult metastases or the seeding of disseminated tumour cells in patients with primary colorectal carcinoma operated on with curative intent. The hypothesis that adjuvant therapy with perioperative recombinant human granulocyte,macrophage colony-stimulating factor (rhGM-CSF) would minimize postoperative immunosuppression was investigated in this pilot study. Methods: Patients were allocated randomly to receive daily subcutaneous injections with either saline (n = 8) or rhGM-CSF 28 g per kg body-weight (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR expression and the extent of the acute-phase response, by determination of white blood cell count and differentiation, plasma interleukin (IL) 6 levels and body temperature in the perioperative period, were examined. Results: rhGM-CSF treatment minimized postoperative suppression in PHA skin test reactivity and increased the numbers of neutrophils and monocytes while enhancing the expression of HLA-DR in the postoperative period. Additionally, both postoperative plasma IL-6 levels and the incidence of fever tended to be higher in the rhGM-CSF group. Conclusion: In this pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain immune functions that are normally depressed after operation. The implications for the antitumour responses directly after operation and the formation of liver metastases are currently under investigation. 2001 British Journal of Surgery Society Ltd [source]

High-dose ifosfamide with mesna and granuloctye,colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesothelioma

CANCER, Issue 2 2003
A Southwest Oncology Group study
Abstract BACKGROUND The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte,colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. METHODS Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 ,g/kg/day was administered subcutaneously on days 6,15. RESULTS Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0,14%) and 1 was an unconfirmed response (3%; 95% CI, 5,14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3,7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6,9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. CONCLUSIONS This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma. Cancer 2003;98:331,6. 2003 American Cancer Society. DOI 10.1002/cncr.11512 [source]

The identification of a phospholipase B precursor in human neutrophils

FEBS JOURNAL, Issue 1 2009
Shengyuan Xu
A phospholipase B (PLB) precursor was purified from normal human granulocytes using Sephadex G-75, Mono-S cation-exchange and hydroxyapatite columns. The molecular mass of the protein was estimated to be , 130 kDa by gel filtration and 22 and 42 kDa by SDS/PAGE. Tryptic peptide and sequence analyses by MALDI-TOF and tandem mass spectrometry (MS/MS) identified the protein as a FLJ22662 (Homo sapiens) gene product, a homologue of the amoeba Dictyostelium discoideum PLB. The native protein needed modifications to acquire deacylation activity against phospholipids including phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and lysophospholipids. Enzyme activity was associated with fragments derived from the 42 kDa fragment. The enzyme revealed a PLB nature by removing fatty acids from both the sn -1 and sn -2 positions of phospholipids. The enzyme is active at a broad pH range with an optimum of 7.4. Immunoblotting of neutrophil postnuclear supernatant using antibodies against the 42 kDa fragment detected a band at a molecular mass of 42 kDa, indicating a neutrophil origin of the novel PLB precursor. The existence of the PLB precursor in neutrophils and its enzymatic activity against phospholipids suggest a role in the defence against invading microorganisms and in the generation of lipid mediators of inflammation. [source]

Determination of medullasin levels for the diagnosis of multiple sclerosis

Y. Aoki
Objectives , To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. Patients and methods, Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. Results, A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals+2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. Conclusion, This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis. [source]