Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to lethally irradiated mice increased the rate of animal survival. Dose modification factor was 1.20 when 4.5 micrograms/mouse of rhG-CSF was given daily for 14 days after whole body irradiation. Haematological examinations revealed that rhG-CSF increased the number of blood-circulating leukocytes, neutrophils, monocytes and erythrocytes, but not that of lymphocytes and thrombocytes. Spleen weight and number of endogenous spleen colonies were also increased by rhG-CSF treatment compared with the values for mice irradiated only.
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PMID:Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. 137 42

In order to examine the effect of recombinant growth factors on hemopoietic stem cells, these cells were enriched using wheat germ agglutinin (WGA) and monoclonal antibodies for lineage markers (Lin) such as B220, L3T4, Lyt-2, asialo GM1, Mac-1, and AL-21. Spleen colony-forming units (CFU-S) and in vitro colony-forming units were highly enriched in the fraction of WGA+Lin- spleen cells. To eliminate committed progenitor cells, spleen cells of 5-fluorouracil (5-FU)-treated mice were used. By this treatment, day-8 CFU-S disappeared but day-14 CFU-S were preserved. Day-14 CFU-S were also contained in the fraction of WGA+Lin- cells, which made up about 0.5% of total nucleated spleen cells. Moreover, this fraction contained primitive stem cells that could reconstitute the hemopoiesis of irradiated mice. Sorted WGA+Lin- spleen cells obtained from male 5-FU-treated mice were injected into lethally irradiated female mice. Southern hybridization using a mouse Y chromosome-specific probe showed that the bone marrow, spleen, and thymus of the recipients was reconstituted by male mouse-derived cells. When sorted WGA+Lin- spleen cells of the 5-FU-treated mice were cultured in vitro in the presence of recombinant interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), colony formation was observed only in wells with IL-3, whereas unfractionated spleen cells formed colonies in the presence of IL-3, IL-6, or G-CSF. However, IL-6 but not G-CSF acted synergistically on enriched hemopoietic stem cells in the presence of IL-3. These data suggest that G-CSF or IL-6 did not affect primitive stem cells independently but showed the effect on these cells indirectly or synergistically with IL-3.
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PMID:Effects of interleukin 3, interleukin 6, and granulocyte colony-stimulating factor on sorted murine splenic progenitor cells. 170 93

The in vivo effects of the subcutaneous administration of the granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced hematopoietic injury were evaluated in BALB/c mice. Mice treated with chemotherapeutic drugs were injected once a day for up to 12 days with 2 micrograms of recombinant human G-CSF, and following this, bone marrow cellularity, spleen weight, and peripheral blood cell counts were measured 24 h after cessation of the G-CSF treatment. Treatment of normal mice had minimal effect on the elevation of the white blood cell (WBC) count or on the hosts' resistance to K. pneumoniae infection. Spleen weight was significantly higher in normal mice treated with G-CSF, and the platelet counts were slightly lower. In mice treated with cyclophosphamide (150 mg/kg), G-CSF treatment caused an elevation of WBC and an enhancement of antibacterial resistance. Variable amounts of an accelerated recovery of neutrophils by G-CSF treatment was also observed in nimustine hydrochloride (50 mg/kg)-, mitomycin c (MMC) (8 mg/kg)-, or vindesine sulfate (VDS) (4 mg/kg)-treated mice. A significant decrease in PLT counts was observed in MMC- or VDS-treated hosts given G-CSF. These results indicate that administration of G-CSF may facilitate hematopoietic recovery in chemotherapy-treated cancer patients and that it may help them to increase their resistance to life-threatening infection. Conversely, treatment with G-CSF and chemotherapeutic drugs may cause a more severe thrombocytopenia than is observed with only chemotherapy treatment.
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PMID:Effects of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice. 170 61

We have investigated the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on hemopoietic reconstitution after bone marrow transplantation (BMT) following lethal irradiation in mice. Mice received a daily administration of 10 micrograms/kg rG-CSF or control vehicle one through 21 days after BMT. Spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg), and erythroid burst-forming units (BFU-E) increased in both bone marrow and spleen of the rG-CSF-treated mice as compared with the control. This increase was evident during the administration period. In spite of the increase in the progenitor cells in bone marrow and spleen, only a recovery of neutrophils was accelerated in peripheral blood. Thus rG-CSF accelerated granulopoietic recovery in the BMT mice, with an enhanced recovery of the stem cells and the progenitors for erythrocytes and megakaryocytes. These results indicate the potential clinical usefulness of rG-CSF in the treatment of patients undergoing BMT.
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PMID:Acceleration of the hemopoietic reconstitution in mice undergoing bone marrow transplantation by recombinant human granulocyte colony-stimulating factor. 171 Aug 41

The mobilization of hematopoietic stem cells (HSCs) into the peripheral blood of mice was induced by recombinant human granulocyte colony-stimulating factor (rhG-CSF) (250 microgram/kg/d) alone or combined with recombinant rat stem cell factor (rrSCF) (34 microgram/kg/d), injected subcutaneously (s.c.) once a day for 10 and 17 days. After administering G-CSF plus SCF or G-CSF alone for 10 days, the level of day-11 spleen colony-forming units (CFU-S-11) in the peripheral blood increased 169- and 93-fold, respectively. The effect was lower--30- and 17-fold--after 17 days of treatment. A 1.5- to three-fold decrease in CFU-S-11 content in the bone marrow of treated mice was observed. In normal mice, the content of long-term culture initiating cells (LTC-IC) in blood was below the threshold level. Cytokine treatment mobilized LTC-IC in the circulation. Following a 10- and 17-day course of G-CSF plus SCF, the proliferation of CFU-S-11 in the peripheral blood but not in the bone marrow increased from <10% in the controls to 44 and 72%, respectively, as measured by hydroxyurea (HU) suicide. Spleen-repopulating ability (SRA) of CFU-S (daughter CFU-S-8 content in an 11-day-old spleen colony) increased two-fold in the peripheral blood after a 10-day course and seven-fold after a 17-day course of combined cytokines. One month after the final cytokine injection, all hematopoietic indexes (including the number of different precursors, their proliferative rate, and their SRA) were near normal. The results suggest that the age structure of the mobilized progenitor population depends on both the cytokines used and the duration of the treatment: more immature CFU-S with higher proliferative activity and an increased SRA were mobilized preferentially after a 17-day course of combined cytokines.
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PMID:Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. 864 32

Granulocyte colony-stimulating factor (G-CSF) administration in vivo has been shown to improve the defence mechanisms against infection by different microbes. Here we evaluated a possible protective role of this molecule in a mouse model of mycobacterial infection. The administration of recombinant G-CSF promoted an extensive blood neutrophilia but failed to improve the course of Mycobacterium avium infection in C57Bl/6 or beige mice. G-CSF administration also failed to improve the efficacy of a triple chemotherapeutic regimen (clarithromycin + ethambutol + rifabutin). G-CSF treatment did not protect interleukin-10 gene disrupted mice infected with M. avium. Spleen cells from infected mice treated with G-CSF had a decreased priming for antigen-specific production of interferon gamma compared to control infected mice. Our data do not substantiate previous reports on the protective activity of G-CSF in antimycobacterial immunity using mouse models.
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PMID:Effects of recombinant granulocyte-colony stimulating factor administration during Mycobacterium avium infection in mice. 1142

A leukemoid reaction with granulocytosis and splenomegaly has been observed in animals and humans with a variety of tumors. We have employed four color flow cytometry to characterize the leukemoid reaction induced by the transplantable mouse mammary carcinoma 4T1 in female BALB/c mice. Gr-1(+) myeloid cells with the morphology of granulocytes increased in peripheral blood from <15% pre-transplant to nearly 80% of total CD45(+) leukocytes at four weeks post-transplant. Though the granulocyte:lymphocyte ratio increased markedly, the absolute numbers of CD19(+) B lymphocytes, CD4(+) and CD8(+) T lymphocytes, and the CD4/CD8 ratio in peripheral blood did not change significantly. Femurs from tumor-bearing mice showed myeloid hyperplasia of the fatty marrow. There was a notable increase in cells with a Gr-1(dim)/CD11b(bright) immature granulocyte phenotype, and these cells were also found in peripheral blood and spleen. Spleen weights had increased 8.5-fold by four weeks post-tumor transplant, mainly due to granulocytic hyperplasia. Cultured 4T1 tumor cells constitutively expressed mRNA for the myeloid colony-stimulating factors G-CSF and GM-CSF, and IFN-gamma-inducible M-CSF transcripts were also detected. Tumors excised from mice had transcripts for G-CSF and GM-CSF, but only G-CSF protein was found in high levels in serum of tumor-bearing mice. These data demonstrate that 4T1 tumor-bearing mice exhibit a leukemoid reaction that apparently is caused by the production of colony-stimulating factors produced by the tumor. The 4T1 tumor may serve as an excellent model for the study of this reaction.
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PMID:Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors. 1691 66

Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs.
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PMID:Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience. 1918 33

Rare reports of splenic rupture have been associated with filgrastim treatment during peripheral blood progenitor cell (PBPC) mobilization in allogeneic donors. We performed a prospective study of spleen volume change in 309 normal donors who received filgrastim according to local institutional practices. Splenic assessments consisted of ultrasonography and clinical examination at baseline and on the first day of leukapheresis in 304 donors. Of these, 90 donors were also examined 2 and 4 days after the first leukapheresis and 7 days after the last leukapheresis. Median spleen volume increased 1.47-fold (range: 0.63 to 2.60) on the first leukapheresis day and declined to near pretreatment levels at 7 days after last leukapheresis. Nine percent of donors had > or =2-fold increase in splenic volume. Spleen palpability did not correlate with change in spleen volume. No donors experienced a splenic rupture. There was no correlation between change in spleen volume and filgrastim dosage, number of doses/day, peak absolute neutrophil count (ANC), CD34+ yield, or donor baseline weight. Most donors experienced > or =1 adverse event, with 6 donors reporting serious adverse events. We conclude that the increase in splenic volume during PBPC mobilization in donors was transient, and that filgrastim was well tolerated in this study. This trial was registered at www.ClinicalTrials.gov as NCT00115128.
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PMID:Clinical and ultrasonic evaluation of spleen size during peripheral blood progenitor cell mobilization by filgrastim: results of an open-label trial in normal donors. 1953 14