scholarly journals Colony-stimulating factor in patients with chronic neutropenia

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 861-867
Author(s):  
JR Wewerka ◽  
DC Dale
Keyword(s):  
Neutrophil Count ◽  
Normal Subjects ◽  
Target Cells ◽  
Blood Neutrophil ◽  
Colony Stimulating Factor ◽  
Normal Individuals ◽  
Chronic Idiopathic Neutropenia ◽  
Significant Difference ◽  
Csf Levels ◽  
Stimulating Factor

Urinary and serum colony-stimulating factor (CSF) levels were measured in 11 patients with chronic idiopathic neutropenia without infections and in 10 normal individuals. Urinary CSF output was determined using mouse marrow target cells, and serum CSF activity was assayed with human marrow target cells by the double agar layer technique. Using these methods, there was no significant difference between CSF levels of neutropenic and normal subjects. These data indicate that CSF levels are not inversely related to the blood neutrophil count in chronic idiopathic neutropenia and suggest that CSF is not a hormone regulating the blood neutrophil count in a manner analogous to the erythropoietin regulation of circulating erythrocyte levels.

scholarly journals Colony-stimulating factor in patients with chronic neutropenia

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 861-867 ◽  
Author(s):  
JR Wewerka ◽  
DC Dale
Keyword(s):  
Neutrophil Count ◽  
Normal Subjects ◽  
Target Cells ◽  
Blood Neutrophil ◽  
Colony Stimulating Factor ◽  
Normal Individuals ◽  
Chronic Idiopathic Neutropenia ◽  
Significant Difference ◽  
Csf Levels ◽  
Stimulating Factor

Abstract Urinary and serum colony-stimulating factor (CSF) levels were measured in 11 patients with chronic idiopathic neutropenia without infections and in 10 normal individuals. Urinary CSF output was determined using mouse marrow target cells, and serum CSF activity was assayed with human marrow target cells by the double agar layer technique. Using these methods, there was no significant difference between CSF levels of neutropenic and normal subjects. These data indicate that CSF levels are not inversely related to the blood neutrophil count in chronic idiopathic neutropenia and suggest that CSF is not a hormone regulating the blood neutrophil count in a manner analogous to the erythropoietin regulation of circulating erythrocyte levels.

scholarly journals Quantitative in vivo assay of human granulocyte colony-stimulating factor using cyclophosphamide-induced neutropenic mice

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1228-1233 ◽  
Author(s):  
K Hattori ◽  
K Shimizu ◽  
M Takahashi ◽  
M Tamura ◽  
M Oheda ◽  
...  
Keyword(s):  
Linear Relationship ◽  
Neutrophil Count ◽  
Peripheral Blood ◽  
Assay Method ◽  
Blood Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Neutrophil ◽  
Stimulating Factor

Abstract Administration of human granulocyte colony-stimulating factor (hG-CSF) to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose-dependent increase in the peripheral blood neutrophil count 6 hours after the final hG-CSF injection. Within the hG-CSF dose range of 0.1 to 10 micrograms per mouse per day, there was a strong linear relationship (r greater than .9) between the logarithm of the dose and the peripheral blood neutrophil count in the treated mice. Using the same hG-CSF preparation, 38 experiments indicated that the regression lines are highly reproducible. Such an association never occurred with intact mice, and 100 mg/kg of CPA induced the highest response to hG- CSF. This linear relationship between the two variables allows us to determine the biologic potency of a test hG-CSF preparation relative to a reference standard using a parallel line assay, with a coefficient of precision of around .2. When assayed by this bioassay procedure, which we have termed CPA-mouse assay, natural hG-CSF and recombinant hG-CSF (produced by Chinese hamster ovary cells) were nearly equipotent in specific biologic activity. These results confirm the CPA-mouse assay as an especially useful assay method for quantifying the in vivo activity of hG-CSF.

Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 117-122 ◽  
Author(s):  
K Watari ◽  
S Asano ◽  
N Shirafuji ◽  
H Kodo ◽  
K Ozawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Aplastic Anemia ◽  
Enzyme Immunoassay ◽  
Blood Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Csf Levels ◽  
Stimulating Factor ◽  
Healthy Persons

Abstract In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.

scholarly journals Levels of serum granulocyte colony-stimulating factor in patients with infections

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1962-1964 ◽  
Author(s):  
M Kawakami ◽  
H Tsutsumi ◽  
T Kumakawa ◽  
H Abe ◽  
M Hirai ◽  
...  
Keyword(s):  
Tract Infection ◽  
Recovery Phase ◽  
Acute Stage ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Serum Samples ◽  
Significant Difference ◽  
Csf Levels ◽  
Stimulating Factor

Abstract To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

scholarly journals Levels of serum granulocyte colony-stimulating factor in patients with infections

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1962-1964 ◽  
Author(s):  
M Kawakami ◽  
H Tsutsumi ◽  
T Kumakawa ◽  
H Abe ◽  
M Hirai ◽  
...  
Keyword(s):  
Tract Infection ◽  
Recovery Phase ◽  
Acute Stage ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Serum Samples ◽  
Significant Difference ◽  
Csf Levels ◽  
Stimulating Factor

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

scholarly journals Quantitative in vivo assay of human granulocyte colony-stimulating factor using cyclophosphamide-induced neutropenic mice

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1228-1233
Author(s):  
K Hattori ◽  
K Shimizu ◽  
M Takahashi ◽  
M Tamura ◽  
M Oheda ◽  
...  
Keyword(s):  
Linear Relationship ◽  
Neutrophil Count ◽  
Peripheral Blood ◽  
Assay Method ◽  
Blood Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Neutrophil ◽  
Stimulating Factor

Administration of human granulocyte colony-stimulating factor (hG-CSF) to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose-dependent increase in the peripheral blood neutrophil count 6 hours after the final hG-CSF injection. Within the hG-CSF dose range of 0.1 to 10 micrograms per mouse per day, there was a strong linear relationship (r greater than .9) between the logarithm of the dose and the peripheral blood neutrophil count in the treated mice. Using the same hG-CSF preparation, 38 experiments indicated that the regression lines are highly reproducible. Such an association never occurred with intact mice, and 100 mg/kg of CPA induced the highest response to hG- CSF. This linear relationship between the two variables allows us to determine the biologic potency of a test hG-CSF preparation relative to a reference standard using a parallel line assay, with a coefficient of precision of around .2. When assayed by this bioassay procedure, which we have termed CPA-mouse assay, natural hG-CSF and recombinant hG-CSF (produced by Chinese hamster ovary cells) were nearly equipotent in specific biologic activity. These results confirm the CPA-mouse assay as an especially useful assay method for quantifying the in vivo activity of hG-CSF.

scholarly journals Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 117-122
Author(s):  
K Watari ◽  
S Asano ◽  
N Shirafuji ◽  
H Kodo ◽  
K Ozawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Aplastic Anemia ◽  
Enzyme Immunoassay ◽  
Blood Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Csf Levels ◽  
Stimulating Factor ◽  
Healthy Persons

In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.

Auditory Selective Attention in Cerebral-Palsied Individuals

1985 ◽  
Vol 16 (4) ◽  
pp. 260-266 ◽  
Author(s):  
Lee Ann Laraway
Keyword(s):  
Selective Attention ◽  
White Noise ◽  
Normal Subjects ◽  
Auditory Selective Attention ◽  
Normal Individuals ◽  
Significant Difference

The purpose of this study was to determine whether there is a statistically significant difference between the auditory selective attention abilities of normal and cerebral-palsied individuals. Twenty-three cerebral-palsied and 23 normal subjects between the ages of 5 and 21 were asked to repeat a series of 30 items consisting of from 2 to 4 digits in the presence of intermittent white noise. Results of the study indicate that cerebral-palsied individuals perform significantly poorer than normal individuals when the stimulus is accompanied by noise. Noise was not a significant factor in the performance of the normal subjects regardless of age.

scholarly journals Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Andrew B. Kelly ◽  
Ellen Cheung ◽  
Aaron Tomer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Neutrophil Count ◽  
Growth And Development ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Colony Stimulating Factor ◽  
Platelet Counts ◽  
Development Factor ◽  
Trough Serum ◽  
Stimulating Factor

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.

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