Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GM-CSF represents an important advance in bone marrow transplantation. The drug can be given safely and does not appear to increase the risk of graft-versus-host disease or tumor relapse. This is a rare example of a new technology reducing the cost of health care. By shortening the duration of hospitalization, GM-CSF can significantly reduce the cost of a bone marrow transplant (Table 2). However, there are few data to support the conclusion that the reduction in the duration of neutropenia is associated with a superior survival. This attests to the excellent supportive care that has been developed for patients undergoing bone marrow transplantation. At present, GM-CSF has become a standard therapy in autologous bone marrow transplantation. However, the future will undoubtedly see the development of combinations of hematopoietic growth factors and/or new growth factors that will further improve our ability to perform bone marrow transplantation.
 ...
PMID:The use of granulocyte-macrophage colony-stimulating factor in bone marrow transplantation. 136 21

The results of an open-label, randomized, Phase III trial of r-methionyl human granulocyte-colony-stimulating factor (r-metHuG-CSF) in 41 patients with severe chronic neutropenia (SCN) are reported. Patients with diagnoses of congenital, cyclic, and idiopathic neutropenia, with histories of recurrent infections, were evaluated. The primary objective of the trial was to evaluate the ability of r-metHuG-CSF to increase the ANC to greater than 1500/mm3. A secondary objective was to evaluate variables associated with infection-related morbidity in SCN. r-metHuG-CSF treatment consisted of 1 month of dose titration followed by 4 months of treatment at an optimal dose. Patients were randomized to either immediate treatment with r-metHuG-CSF (Group A) or four months of observation followed by r-metHuG-CSF treatment (Group B). r-metHuG-CSF was administered by daily, subcutaneous injection with initial doses of 3 to 10 micrograms/kg/day. Forty of 41 patients who received r-metHuG-CSF had a complete response (median ANC greater than 1500/mm3 during 4 months of r-metHuG-CSF treatment). All cases of gingivitis and severe mouth ulcers resolved upon treatment with r-metHuG-CSF. Serious infections were also eliminated. Only one patient failed to show clinical improvement in response to r-metHuG-CSF treatment. Adverse reactions during the first 5 months of treatment were mild. Splenomegaly (mild) was noted in some patients. The administration of r-metHuG-CSF in patients with SCN significantly increased the ANC (P less than 0.001) and was accompanied by a marked reduction in infectious complications.
 ...
PMID:Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia. 137 Feb 64

We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G-CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.
 ...
PMID:Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia. 137 12

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.
 ...
PMID:Use of recombinant canine granulocyte colony-stimulating factor to decrease myelosuppression associated with the administration of mitoxantrone in the dog. 137 55

A transient hyporegenerative neutropenia has been reported in neonates, but not in older children or adults, undergoing treatment with recombinant erythropoietin (epo). Monocytopenia has not been reported. We postulated that epo might selectively reduce the responsiveness of neonatal progenitors to Granulocyte Colony-Stimulating Factor (G-CSF), while not similarly affecting their responsiveness to Macrophage Colony-Stimulating Factor (M-CSF). To test this hypothesis two types of experiments were performed. First, progenitors of adult or fetal origin were pre-incubated with epo (or control), then washed, and their responsiveness to G-CSF and M-CSF evaluated in clonogenic culture assays. Second, clonogenic maturation was initiated using either G-CSF or M-CSF, after which the effect of a late addition of epo to the developing clones was evaluated. Indeed, pre-incubation with epo resulted in production of fewer neutrophils from fetal progenitors grown in G-CSF (P less than 0.001), but it did not reduce the number of macrophages generated from progenitors grown in M-CSF. Adding epo to the already-developing G-CSF-responsive and M-CSF-responsive adult and fetal clones did not alter colony development. Thus, epo appears to have an action on G-CSF-responsive, but not-M-CSF-responsive fetal progenitors, resulting in reduced production of neutrophils. This effect is no longer apparent, however, when progenitors have matured to the 8-cell clone stage.
 ...
PMID:Erythropoietin affects the maturation pattern of fetal G-CSF-responsive progenitors. 137 65

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.
 ...
PMID:[Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]. 137 86

The pathogenesis of the neutropenia that occurs in some patients with chronic T cell lymphocytosis is not well understood. We have investigated a 15-year-old girl with this syndrome. Initial committed bone marrow progenitor numbers (CFUgm) were low but markedly increased in vitro following T cell depletion. Similarly a transient correction of neutropenia was observed following in vivo lymphocyte depletion with antilymphocyte globulin. A sustained neutrophil recovery was achieved with daily therapy using recombinant human granulocyte colony stimulating factor (rhG-CSF) despite persistence of the lymphocytosis; during successful therapy CFUgm numbers remained low, and were not increased by the in vitro addition of rhG-CSF. These observations suggest the possibility of an inhibitory regulatory mechanism specifically acting on neutrophil granulopoiesis.
 ...
PMID:Childhood polyclonal T cell lymphocytosis with neutropenia: effects of antilymphocyte globulin and granulocyte colony stimulating factor in vitro and in vivo. 137 32

The mechanism(s) driving cyclic hematopoiesis in human cyclic neutropenia remains unknown. Clinical trials suggest that an abnormal responsiveness of bone marrow progenitor cells to hematopoietic growth factors might cause oscillatory blood counts. Studies were performed to determine whether an abnormal responsiveness to multiple growth factors exists in this disorder and whether the defect could be shown in highly enriched populations of marrow progenitor cells. Bone marrow mononuclear cells from patients with congenital cyclic neutropenia required higher concentrations of added granulocyte-colony-stimulating factor (G-CSF) to achieve half-maximal colony growth than cells from normal subjects (478 +/- 90 pmol/L v 53 +/- 12 pmol/L, P less than .01). Patients also differed in requirement for granulocyte-macrophage-CSF (P less than .05), but not for interleukin-3 (P greater than .30). CD34+ bone marrow cells from three patients also showed this difference in G-CSF responsiveness (P less than .05). These data suggest that the defect in congenital cyclic hematopoiesis lies in growth factor receptor binding or the postreceptor signal transduction system that drives granulocytopoiesis.
 ...
PMID:Abnormal responsiveness of granulocyte-committed progenitor cells in cyclic neutropenia. 137 3

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.
 ...
PMID:[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance]. 137 67

The in-vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and function (phagocytosis and superoxide production) of peripheral neutrophils were studied in time sequence in cyclophosphamide (CPA) treated mice. The neutrophil function was evaluated by the phagocytosis of fluorescent particles, analyzing the number of fluorescence-positive cells and the fluorescence intensity of each neutrophil by flow cytometry and also by the superoxide production, measuring chemiluminescence of the leukocyte suspension by a photometer. In CPA-treated (100 mg/kg) mice, the neutrophil function including both the phagocytosis and the superoxide production declined significantly (p less than 0.01) as the peripheral neutrophil count (PNC) decreased, reached the nadir on the same day as PNC and returned to the normal level 8 days after first CPA treated day (day 0). When rhG-CSF (100 micrograms/kg) was administered subcutaneously daily for 5 consecutive days initiating at day 1, a decrease in PNC and a decline in the neutrophil function were prevented and a significant (p less than 0.05-p less than 0.01) increase of PNC was observed after day 4. In addition, the function of increased neutrophils was significantly (p less than 0.05-p less than 0.01) enhanced after day 4 and even at day 3, when an increase in PNC was not observed yet. The study shows that rhG-CSF appears to enhance neutrophil function by a direct effect on mature neutrophils, which have been impaired by CPA at the phase of progenitor cells in the bone marrow and subsequently have appeared in the peripheral blood and that rhG-CSF is effective on the impaired host defense mechanism in CPA-treated mice, improving not only drug-induced neutropenia but also the deteriorated function of neutrophils.
 ...
PMID:[In-vivo enhancement of neutrophil function by administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in cyclophosphamide (CPA) treated mice]. 137 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>