UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hereby report profound effects of long-term granulocyte colony-stimulating factor (G-CSF) administration on murine erythropoiesis. Recombinant human (rh)G-CSF (150 micrograms/kg body weight/day) was administered over 24 days to female C57Bl mice. Marrow erythroid colony-forming units (CFU-E) and erythroblast numbers declined to less than 5% of normal, whereas splenic erythropoiesis simultaneously increased. Splenic erythropoiesis effectively compensated for the loss of marrow erythropoiesis as indicated by the maintenance of a normal hematocrit. In the marrow the numbers of spleen colony-forming units (CFU-S) and erythroid burst-forming units (BFU-E) declined as well. Simultaneously, however, these numbers increased both in the spleen and in the peripheral blood by a factor of 20 to 30. These findings suggest a continuous migration of stem cells and progenitor cells out of the marrow and an efficient seeding in the spleen, directly or indirectly induced by G-CSF. In addition the differentiation and/or amplification of BFU-E to CFU-E was impaired in the marrow but not in the spleen. The marrow and splenic microenvironment also behaved differently with respect to granulopoiesis. G-CSF did not lead to an enhanced granuloid amplification in the spleen but exerted its proliferation activity mainly in the marrow. These findings imply that prolonged G-CSF treatment might cause erythroid depression in animals and humans when spleen erythropoiesis is less efficient than in mice.
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PMID:Long-term recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment severely depresses murine marrow erythropoiesis without causing an anemia. 137 61

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastase, were markedly elevated during therapy. A dose-dependent depression of platelet counts occurred in the second third of the treatment course, followed by a spontaneous recovery despite continuing therapy. G-CSF was well-tolerated; minor to moderate bone pain was the most common side effect. The primary course of the malignant diseases studied was not significantly altered. G-CSF appears to be an appropriate means to selectively increase the number of functionally competent polymorphonuclear phagocytes.
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PMID:Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy. 247 25

Septicemia in hematologic malignancies and infection of herpes zoster in cancer patients were studied, and trend in organisms in a cancer hospital was investigated. 1) Septicemia in hematologic malignancies. The success rate of antibiotic therapy for septicemia was 76% if the patients were not under antibiotic therapy when septicemia developed. But recovery from septicemia was only 25% if the patients were undergoing antibiotic therapy when septicemia developed. Some 90% of neutropenic patients under 500/microliters, who were not under antibiotic therapy when septicemia developed, recovered from septicemia if the neutrophil count increased in the following 5 days. Change in the neutrophil count was an important factor determining the success or failure of antibiotic therapy for septicemia. The use of granulocyte colony-stimulating factor may prevent chemotherapy-induced neutropenia. Shortening of the period of neutropenia or preventing its occurrence should reduce the incidence and the severity of infection. 2) Infection of herpes zoster in cancer patients. Thirty-four cancer patients were associated with herpes zoster. Eleven of them were patients with malignant lymphoma and ten of them were patients of breast cancer. Most patients were heavily pretreated by chemotherapy and/or radiotherapy before the development of herpes zoster. Marked lymphocytopenia was observed at the onset of herpes zoster. Absolute lymphocyte count was under 1000/microliters in 71% of these patients. Development of herpes zoster in cancer patients was considered to be due to the depression of cell-mediated immunity which was the result of repeated and continued anticancer therapy. Acyclovir was found to be effective to treat herpes zoster in these patients. 3) Trend of organisms detected in cancer hospital. The frequency of organisms isolated from clinical materials in the National Cancer Center Hospital was compared during the period from 1978 to 1982 and the period from 1983 to 1987. The most common organism detected in both periods was P. aeruginosa and no change in frequency was observed. But the frequency of gram-negative bacilli, E. coli, Klebsiella and Serratia, decreased significantly in the latter period while the frequency of gram-positive cocci, Enterococcus and Staphylococcus increased markedly in the latter period. The use of cephems of third generation in the latter period could be one reason for the recent change of organisms detected in the hospital. Appropriate therapy for infection based on the latest and accurate information should be used.
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PMID:[Infection and immunosuppression in cancer patients]. 273 15

Patients with aplastic anemia were tested for natural killer (NK) activity, and the roles of granulocytes and granulocyte colony-stimulating factor (G-CSF) in the regulation of cytotoxicity were evaluated. Blood lymphocytes showed low or no NK activity against K562 targets. The depression of NK activity was more frequently recorded for patients who were not in remission and those who received G-CSF administration. Granulocytes of aplastic anemia patients with impaired NK activity suppressed the lytic activity of NK cells. By contrast, granulocytes from normal controls and aplastic anemia patients with normal NK activity had no suppressive activity. There was a good correlation between NK activity of lymphocytes and suppressive activity of granulocytes. Blocking of direct contact of suppressor and effector cells by cell chambers abolished suppression of cytotoxicity. NK suppression by granulocytes was resistant to treatment with catalase or superoxide dismutase. In vitro stimulation with G-CSF of granulocytes that naturally had no suppressive activity resulted in development of suppressive function, whereas granulocytes with natural suppressive activity were not further stimulated in vitro by G-CSF to express augmented activity. These results suggest that the presence of suppressor granulocytes in the blood could be one cause of the impaired NK activity in patients with aplastic anemia.
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PMID:Suppression of natural killer cell activity by granulocytes in patients with aplastic anemia: role of granulocyte colony-stimulating factor. 751 63

To examine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophilic recovery after cytotoxic agents, the variations of marrow colony-forming units of granulocytes and macrophages (CFU-GM) and morphologically identifiable bone marrow cells were investigated in cyclophosphamide (CPA)-treated mice. In mice treated with CPA at 200mg/kg intraperitoneally (day 0), marked decreases in peripheral neutrophils and nucleated cells in the femur were observed. In the femur of mice treated with CPA, the greatest depression in number occurred firstly with CFU-GM and the most immature granulocytes, such as myeloblasts and promyelocytes, followed in turn by myelocytes, metamyelocytes and mature neutrophils. Administration of rhG-CSF for four successive days (days 1-4) after CPA treatment completely prevented the neutropenia. In the femur, rhG-CSF enhanced the recovery of progenitors and immature granulocytes from their depression in the order of their differentiation, and recovery of marrow neutrophils was also promoted. From these studies, we confirmed that rhG-CSF effects an increase in peripheral neutrophils by enhancing the proliferation and differentiation of CFU-GM and immature marrow granulocytes.
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PMID:Effect of recombinant human granulocyte colony-stimulating factor on variations of morphologically identifiable bone marrow cells in myelosuppressed mice. 753 36

The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-6-treated dogs were compared with the data obtained from dogs who received TBI of 2.4 Gy and were treated with the carrier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradiated control animals. The thrombocyte counts in the period from day 1 to 16 after TBI were similar for both groups of dogs, showing a sharp decrease in counts between days 6 and 12 with a stabilization thereafter at approximately 30 x 10(3)/microL. In three of the four IL-6-treated dogs, however, thrombocyte counts increased at day 18 after the beginning of treatment. This increase occurred 7 days earlier than in the controls. In two of the three dogs showing an accelerated recovery of platelet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reticulocyte concentration. There was no influence on the recovery of blood granulocytes. In one of the animals responding with an accelerated thrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. However, IL-6 forced the recovery of blood granulocytes in the period beyond day 10 after TBI. Another animal showed no influence of IL-6 on thrombocyte recovery but a strong depressive effect on erythrocyte and reticulocyte counts. The results show that for standardized conditions of radiation-induced bone marrow damage, the pattern of response to IL-6 in different hematopoietic lineages may show considerable variations between individuals, in contrast to what has been observed in irradiated animals treated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM- or G-CSF).
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PMID:Hematologic effects of recombinant human interleukin-6 in dogs exposed to a total-body radiation dose of 2.4 Gy. 801 70

Recent studies in human bone-marrow culture and healthy human volunteers suggest that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in vivo potency than filgrastim [nonglycosylated, methionine-extended recombinant human granulocyte colony-stimulating factor (rmetHuG-CSF) produced in Escherichia coli]. To confirm and extend these results we investigated the in vivo potency of both products in normal rats and neutropenic CD rats as an animal model of chemotherapy-induced neutropenia. In normal rats, groups of eight normal male CD rats received four subcutaneous doses of 10, 30, or 100 micrograms/kg filgrastim or lenograstim on days 1-4 of the study, whereas a control group received the vehicle. Blood samples were collected from each animal before treatment (day -5) and on days 2, 3, 5, 8, and 12 of the study for determination of red blood cell (RBC), platelet, white blood cell (WBC), and differential counts. rHuG-CSF and r-metHuG-CSF produced increased WBC counts, principally due to elevated absolute neutrophil counts (ANCs); on days 2, 3, and 5, all groups receiving rG-CSF had ANCs that increased in a progressive and dose-related manner. With the exception of a single value, mean ANCs obtained on days 2, 3, and 5 in lenograstim-treated groups were higher (statistically significant on day 3 at 30 and 100 micrograms/kg and on day 5 at 10, 30, and 100 micrograms/kg) than the respective values obtained in filgrastim-treated groups. No compound-related effect was noted in RBC or platelet parameters. Neutropenia was induced in male CD rats (12 animals/group) with a single intraperitoneal dose of 50 mg/kg cyclophosphamide (CPA) on day 0. On days 1-4, CPA-treated groups were treated with the vehicle (control) or with filgrastim or lenograstim at 30 or 100 micrograms/kg per day. An additional group was not treated with CPA and served as the absolute control group. Blood was collected from alternating subgroups on study day -5 (pretest) and on days 2, 3, 4, 5, 6, 8, 9, and 12 for determination of RBC, platelet, WBC, and differential counts. No major adverse in-life effect was noted in neutropenic rats. Maximal depression of WBCs and ANCs occurred on day 5, followed by recovery to normal values by days 9 (ANC) and 12 (WBC). On day 3 and days 5-9, rHuG-CSF- and metHuG-CSF-treated groups had marked and dose-related increases in WBCs as compared with CPA-treated controls, principally due to elevated ANCs. With the exception of a few values, mean ANC values obtained in lenograstim-treated groups were consistently higher than the respective values obtained in filgrastim-treated groups; the difference was statistically significant on day 3 (30-microgram/kg groups) and on days 6 and 8 (100-microgram/kg groups). In conclusion, treatment of normal and neutropenic CD rats with lenograstim resulted in a dose-related elevation of ANCs that was consistently and significantly higher than the response to identical doses of filgrastim. These results suggest that lenograstim, the glycosylated form of rG-CSF, has superior in vivo potency in normal and neutropenic animals as compared with filgrastim, the nonglycosylated form of rG-CSF.
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PMID:Comparison of the potency of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factors in neutropenic and nonneutropenic CD rats. 899 30

Bone marrow aplasia is a frequent complication of colchicine poisoning. This typically occurs on day 3 to 5 postexposure, and the blood cell counts remain depressed for a week or more. Unfortunately, because patients suffering from colchicine toxicity develop multiple organ complications and sepsis, the morbidity and mortality associated with bone marrow depression is high. In this article, we present three cases of colchicine toxicity in which granulocyte colony-stimulating factor (G-CSF) was used to treat bone marrow depression. In all three cases, there was a dramatic increase in the white cell count and, to a lesser extent, the platelet count. In view of the critical nature of the bone marrow depression and multi-organ toxicity induced by colchicine, we believe that consideration of the use of G-CSF to shorten the duration of neutropenia is warranted.
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PMID:Colchicine-induced bone marrow suppression: treatment with granulocyte colony-stimulating factor. 1080 21

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated for its effects on granulopoiesis recovery in mice pretreated with cyclophosphamide. The cytotoxic agent was administered on days 0 and 7. rhG-CSF therapy (injected from days 8 to 28) accelerated the recovery and maintained an increased level of peripheral blood neutrophils. Marrow granuloid precursors depression, due the second dose of cyclophosphamide, was prevented by rhG-CSF, but this hemopoietic growth factor was unable to increase these cells in a similar way to that observed in normal mice. This suggests a decreased granuloid marrow proliferation capacity in cyclophosphamide treated mice. In contrast, in the spleen, rhG-CSF highly increased granuloid precursors. However, the contribution of spleen to granuloid recovery was scarce. Mice receiving rhG-CSF after cyclophosphamide demonstrated a biphasic recovery pattern in bone marrow GM-CFU population. A first rebound of GM-CFUs was followed by a nadir and then a second recovery where GM-CFU progenitor cells were significantly increased was observed. On the other hand, rhG-CSF therapy highly increased the spleen GM-CFU numbers at days 24 to 28. Although rhG-CSF increased splenic granulopoiesis, this result shows that the bulk of granulopoiesis recovery due to rhG-CSF therapy in cyclophosphamide pretreated mice occurred in the marrow.
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PMID:The influence of recombinant human granulocyte colony-stimulating factor on granulopoiesis in mice recovering from cyclophosphamide treatment. 1103 27

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with neuroprotective and antiinflammatory properties. By real-time polymerase chain reaction we show that G-CSF transcripts are induced 485-fold at 4 h and 65-fold at 16 h in ischemic lesions after middle cerebral artery occlusion compared to control brains. Further analysis in photochemically induced focal ischemia revealed that G-CSF induction involved both the infarct area and remote nonischemic brain regions. Remote responses could be blocked by the noncompetitive NMDA receptor antagonist MK-801, suggesting periinfarct depolarizations as a trigger. To further confirm this notion, cortical spreading depression (CSD) was induced by focal application of KCl to the brain surface. CSD led to a 90-fold increase in G-CSF mRNA. Contrastingly, the induction of granulocyte-monocyte (GM)-CSF, another member of the hematopoietic growth factor family, was only moderate (sixfold) and restricted to ischemic brain lesions. In conclusion, G-CSF induction in the brain may be part of an intrinsic stress response aimed at limitation of neuronal damage.
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PMID:Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression. 1553 Jun 54

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