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1
Senthilan, Pingkalai R., and Charlotte Helfrich-Förster. "Rhodopsin 7–The unusual Rhodopsin inDrosophila." PeerJ 4 (September 6, 2016): e2427. http://dx.doi.org/10.7717/peerj.2427.
Повний текст джерелаАнотація:
Rhodopsins are the major photopigments in the fruit flyDrosophila melanogaster. Drosophilaexpress six well-characterized Rhodopsins (Rh1–Rh6) with distinct absorption maxima and expression pattern. In 2000, when theDrosophilagenome was published, a novelRhodopsingene was discovered:Rhodopsin 7(Rh7).Rh7is highly conserved among theDrosophilagenus and is also found in other arthropods. Phylogenetic trees based on protein sequences suggest that the sevenDrosophilaRhodopsins cluster in three different groups. While Rh1, Rh2 and Rh6 form a “vertebrate-melanopsin-type”–cluster, and Rh3, Rh4 and Rh5 form an “insect-type”-Rhodopsin cluster, Rh7 seem to form its own cluster. Although Rh7 has nearly all important features of a functional Rhodopsin, it differs from other Rhodopsins in its genomic and structural properties, suggesting it might have an overall different role than other known Rhodopsins.
2
Holloway, T., C. Voigt, J. Morton, S. N. Spak, A. P. Rutter, and J. J. Schauer. "An assessment of atmospheric mercury in the Community Multiscale Air Quality (CMAQ) model." Atmospheric Chemistry and Physics Discussions 12, no. 1 (January 23, 2012): 2131–66. http://dx.doi.org/10.5194/acpd-12-2131-2012.
Повний текст джерелаАнотація:
Abstract. Quantitative analysis of three atmospheric mercury species – gaseous elemental mercury (Hg0), reactive gaseous mercury (RGHg) and particulate mercury (PHg) – has been limited to date by lack of ambient measurement data as well as by uncertainties in numerical models and emission inventories. This study employs the Community Multiscale Air Quality Model version 4.6 with mercury chemistry (CMAQ-Hg), to examine how local emissions, meteorology, atmospheric chemistry, and deposition affect mercury concentration and deposition the Great Lakes Region (GLR), and two sites in Wisconsin in particular: the rural Devil's Lake site and the urban Milwaukee site. Ambient mercury exhibits significant biases at both sites. Hg0 is too low in CMAQ-Hg, with the model showing a 6% low bias at the rural site and 36% low bias at the urban site. Reactive mercury (RHg = RGHg + PHg) is over-predicted by the model, with annual average biases >250%. Performance metrics for RHg are much worse than for mercury wet deposition, ozone (O3), nitrogen dioxide (NO2), or sulfur dioxide (SO2). Sensitivity simulations to isolate background inflow from regional emissions suggests that oxidation of imported Hg0 dominates model estimates of RHg at the rural study site (91% of base case value), and contributes 55% to the RHg at the urban site (local emissions contribute 45%). Limited evidence on the lifetime of RHg transported to the rural site suggests that modeled dry deposition rates are too high, possibly compensating for the erroneously high RHg values.
3
Holloway, T., C. Voigt, J. Morton, S. N. Spak, A. P. Rutter, and J. J. Schauer. "An assessment of atmospheric mercury in the Community Multiscale Air Quality (CMAQ) model at an urban site and a rural site in the Great Lakes Region of North America." Atmospheric Chemistry and Physics 12, no. 15 (August 7, 2012): 7117–33. http://dx.doi.org/10.5194/acp-12-7117-2012.
Повний текст джерелаАнотація:
Abstract. Quantitative analysis of three atmospheric mercury species – gaseous elemental mercury (Hg0), reactive gaseous mercury (RGHg) and particulate mercury (PHg) – has been limited to date by lack of ambient measurement data as well as by uncertainties in numerical models and emission inventories. This study employs the Community Multiscale Air Quality Model version 4.6 with mercury chemistry (CMAQ-Hg), to examine how local emissions, meteorology, atmospheric chemistry, and deposition affect mercury concentration and deposition the Great Lakes Region (GLR), and two sites in Wisconsin in particular: the rural Devil's Lake site and the urban Milwaukee site. Ambient mercury exhibits significant biases at both sites. Hg0 is too low in CMAQ-Hg, with the model showing a 6% low bias at the rural site and 36% low bias at the urban site. Reactive mercury (RHg = RGHg + PHg) is over-predicted by the model, with annual average biases >250%. Performance metrics for RHg are much worse than for mercury wet deposition, ozone (O3), nitrogen dioxide (NO2), or sulfur dioxide (SO2). Sensitivity simulations to isolate background inflow from regional emissions suggests that oxidation of imported Hg0 dominates model estimates of RHg at the rural study site (91% of base case value), and contributes 55% to the RHg at the urban site (local emissions contribute 45%).
4
Sambo, Paolo, Franco Sannazzaro, and Michael R. Evans. "Physical Properties of Ground Fresh Rice Hulls and Sphagnum Peat Used for Greenhouse Root Substrates." HortTechnology 18, no. 3 (January 2008): 384–88. http://dx.doi.org/10.21273/horttech.18.3.384.
Повний текст джерелаАнотація:
Ground fresh rice (Oryza sativa) hull materials were produced by grinding whole fresh rice hulls and passing the resulting product through a 1-, 2-, 4- or 6-mm-diameter screen to produce a total of four ground rice products (RH1, RH2, RH4, and RH6, respectively). The physical properties and water release characteristics of sphagnum peatmoss (peat) and the four ground rice hull products were evaluated. All of the ground rice hull products had a higher bulk density (Bd) than peat, and as the grind size of the rice hull particle decreased, Bd increased. Peat had a higher total pore space (TPS) than all of the ground rice hull products except for RH6. As grind size decreased, the TPS decreased. Peat had a lower air-filled pore space (AFP) than all of the ground rice hull products and as the grind size of the rice hull products decreased, AFP decreased. Peat had a higher water holding capacity (WHC) than all of the ground rice hull products. Grind sizes RH4 and RH6 had similar WHC, whereas RH1 and RH2 had a higher WHC than RH4 and RH6. Peat, RH4, and RH6 had similar available water content (AVW), whereas RH2 had higher AVW than these materials and RH1 had the highest AVW. However, peat had the lowest AVW and easily available water (EAW) as a percentage of the WHC. The ground rice hull products RH1 and RH2 had the highest AVW and EAW of the components tested. Peat had the highest water content at container capacity. As pressure was increased from 1 to 5 kPa, peat released water more slowly than any of the ground rice hull products. The RH1 and RH2 ground hull products released water at a significantly higher rate than peat, but RH4 and RH6 released the most water over these pressures. For all rice hull products, most water was released between 1 and 2 kPa pressure. The rice hull products RH1 and RH2 had physical properties that were within recommended ranges and were most similar to those of peat.
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Fan, Zhisong, Yu Su, Long Wang, Yudong Wang, Jing Zuo, Fengling Liu, and Da Jiang. "Bone pain associated with rhG-CSF or PEG-rhG-CSF in oncology patients." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19186-e19186. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19186.
Повний текст джерелаАнотація:
e19186 Background: Recombinant human granulocyte colonystimulating factor (rhG-CSF) and glycoPEGylated G-CSF (PEG-rhG-CSF) are two kinds of drugs in reducing the incidence and duration of neutropenia in oncology patients treated with chemotherapy. Although the acting time is different, bone pain is one of the most common adverse events in rhG-CSF and PEG-rhG-CSF. The purpose of this study is to describe the occurrence and management of bone pain in oncology patients receiving rhG-CSF and PEG-rhG-CSF. Methods: Two hundred and forty patients with malignant tumor received rhG-CSF or PEG-rhG-CSF after chemotherapy were enrolled to finish questionnaires about the side effect of bone pain. The incidence, location, duration, degree and treatment of bone pain after rhG-CSF or PEG-rhG-CSF used were collected and analyzed. Results: A total of 240 patients enrolled and 56.3% (135) patients had bone pain after rhG-CSF or PEG-rhG-CSF delivered. The most common parts of bone pain were thigh (35.6%), back (29.6%), waist (25.9%), shoulder (23.7%) and chest (21.5%). The bone pain of 39.2% patients last for 72h and 27.2% patients last less than 72h. The duration time of bone pain was longer in PEG-rhG-CSF than rhG-CSF. There was no significant difference in the rate of pain occurrence and the proportion of severe pain between rhG-CSF and PEG-rhG-CSF. Only 22.2% patients took drugs to relieve bone pain. Downregulated the doses of rhG-CSF or PEG-rhG-CSF could significantly relieve bone pain. Besides bone pain, 34.0% patients suffered muscle ache which was the second most side effect and occurred more often than runny nose and fever. Conclusions: The percentage of bone pain occurrence are similar in rhG-CSF and PEG-rhG-CSF, but the duration time was longer in PEG-rhG-CSF. For most patients, bone pain need not to deal with, Dose reductions can effectively relieve the mild to severe pain.
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Yang, Wenyu, Tianfeng Liu, Xiaojuan Chen, Ye Guo, Ting Li, Benquan Qi, Fang Liu, et al. "A single-center, open-label clinical study to evaluate pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte stimulating factor in pediatric patients with acute lymphoblastic leukemia." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e22501-e22501. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e22501.
Повний текст джерелаАнотація:
e22501 Background: The aims of the study were to investigate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony stimulating factor(PEG-rhG-CSF) in pediatric patients with acute lymphoblastic leukemia(ALL), and compare the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) and rhG-CSF. Methods: Pediatric patients with newly diagnosed ALL who planned to use CAM (cyclophosphamide, cytarabine, 6-mercaptopurine) for chemotherapy were assigned to PEG-rhG-CSF group or rhG-CSF group. In the PEG-rhG-CSF group, PEG-rhG-CSF (100ug/kg) was injected subcutaneously once 48 hours after chemotherapy. In the rhG-CSF group, rhG-CSF (150ug/d) was injected subcutaneously daily from 48 hours after chemotherapy until the absolute neutrophil count (ANC) was≥1.0×109/L. The serum concentration of PEG-rhG-CSF was detected by enzyme-linked immunosorbent assay (ELISA). Safety and efficacy of the two groups were evaluated. Results: Between November 2015 to April 2016, 17 pediatric patients were assigned to PEG-rhG-CSF(n = 9) or rhG-CSF(n = 8) groups. The main pharmacokinetic parameters (mean±SD) of PEG-rhG-CSF group were as follows: Cmax was 353.50±136.3 ng/ml, Tmax was 44.00±20.8 h, t1/2 was 14.58± 2.2h. The PEG-rhG-CSF serum concentration and ANC curve were consistent with the mechanism of neutrophil mediated clearance. The average value of ANC nadir in PEG-rhG-CSF group was 0.18 (±0.32)×109/L, and the rhG-CSF group was 0.08 (±0.09)×109/L, there was no significant difference between the two groups ( P = 0.469). Compared with rhG-CSF, the average time of ANC recovery in PEG-rhG-CSF group was earlier (18.33±2.18 vs. 21.50±2.33, P = 0.021). There were no significant differences in the incidence of FN and infection, the duration of grade Ⅳ neutropenia and hospitalization, and the safety of the two groups. Conclusions: PEG-rhG-CSF had favorable efficacy in pediatric patients with ALL receiving chemotherapy, and there was no serious adverse event. Compared with rhG-CSF, PEG-rhG-CSF needed only once in each chemotherapy cycle, which is more suitable for pediatric patients. Clinical trial information: NCT02953730.
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Takatani, H., H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka. "Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts." Antimicrobial Agents and Chemotherapy 40, no. 4 (April 1996): 988–91. http://dx.doi.org/10.1128/aac.40.4.988.
Повний текст джерелаАнотація:
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.
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Pratiwi, Riyona Desvy, Dian Fitria Agustiyanti, Tri Isyani Tungga Dewi, Nina Herlina, Kartika Sari Dewi, Yuliawati Yuliawati, Aminah Aminah, and Asrul Muhamad Fuad. "Bioassay of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) for Neutropenia Treatment in Male Sprague Dawley Rats." Molecular and Cellular Biomedical Sciences 4, no. 1 (March 1, 2020): 10. http://dx.doi.org/10.21705/mcbs.v4i1.81.
Повний текст джерелаАнотація:
Background: Recombinant human granulocyte colony stimulating factor (rhG-CSF) is a first line therapy for neutropenia. However, it is less affordable for most patients in developing and poor countries. Therefore, biosimilar products are developed to suppress the cost of treatment, namely with rhG-CSF. This study aimed to explore the establishment of an affordable rhG-CSF that has similar potential to induce neutrophils recovery as the positive control.Materials and Methods: The rhG-CSF was expressed as inclusion body in Escherichia coli NiCo21(DE3). The inclusion body was then solubilized, refolded, purified and characterized prior to be used in the bioactivity assay. Cyclophosphamide-induced male Sprague Dawley rats were used as animal model and administered with rhG-CSF. Blood sample was collected at several points of time, before and after rhG-CSF treatments. Complete blood count and peripheral blood smear were conducted to investigate the activity of the rhG-CSF on each blood cells type, particularly neutrophil.Results: Specific activity on neutrophil proliferation was shown after treatments with our rhG-CSF and positive control. Positive control dose 40 mg/kg BW was statistically similar with that of the rhG-CSF dose 80 and 120 mg/kg BW. However, in neutropenic condition, recovery of neutrophil counts could not be achieved within 4 days of treatments. Thus, a longer treatment is needed to observe the activity of the rhG-CSF as an antineutropenia agent.Conclusion: The rhG-CSF has been proven having specific activity on neutrophil proliferation. However, improvement in the rhG-CSF preparation is still needed and longer administration of the rhG-CSF has to be applied in the future study.Keywords: rhG-CSF, biosimilar, neutropenia, Sprague Dawley rats
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Andrews, RG, RA Briddell, GH Knitter, T. Opie, M. Bronsden, D. Myerson, FR Appelbaum, and IK McNiece. "In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells." Blood 84, no. 3 (August 1, 1994): 800–810. http://dx.doi.org/10.1182/blood.v84.3.800.bloodjournal843800.
Повний текст джерелаАнотація:
Recombinant human stem cell factor (rhSCF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) are synergistic in vitro in stimulating the proliferation of hematopoietic progenitor cells and their precursors. We examined the in vivo synergy of rhSCF with rhG-CSF for stimulating hematopoiesis in vivo in baboons. Administration of low-dose (LD) rhSCF (25 micrograms/kg) alone did not stimulate changes in circulating WBCs. In comparison, administration of LD rhSCF in combination with rhG-CSF at 10 micrograms/kg or 100 micrograms/kg stimulated increases in circulating WBCs of multiple types up to twofold higher than was stimulated by administration of the same dose of rhG-CSF alone. When the dose of rhG-CSF is increased to 250 micrograms/kg, the administration of LD rhSCF does not further increase the circulating WBC counts. Administration of LD rhSCF in combination with rhG-CSF also stimulated increased circulation of hematopoietic progenitors. LD rhSCF alone stimulated less of an increase in circulating progenitors, per milliliter of blood, than did administration of rhG-CSF alone at 100 micrograms/kg. Baboons administered LD rhSCF together with rhG-CSF at 10, 100, or 250 micrograms/kg had 3.5- to 16-fold higher numbers per milliliter of blood of progenitors cells of multiple types, including colony-forming units granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming and burst-forming units-megakaryocyte (CFU- MK and BFU-MK) compared with animals given the same dose of rhG-CSF without rhSCF, regardless of the rhG-CSF dose. The increased circulation of progenitor cells stimulated by the combination of rhSCF plus rhG-CSF was not necessarily directly related to the increase in WBCs, as this effect on peripheral blood progenitors was observed even at an rhG-CSF dose of 250 micrograms/kg, where coadministration of LD rhSCF did not further increase WBC counts. Administration of very-low- dose rhSCF (2.5 micrograms/kg) with rhG-CSF, 10 micrograms/kg, did not stimulate increases in circulating WBCs, but did increase the number of megakaryocyte progenitor cells in blood compared with rhG-CSF alone. LD rhSCF administered alone for 7 days before rhG-CSF did not result in increased levels of circulating WBCs or progenitors compared with rhG- CSF alone. Thus, the synergistic effects of rhSCF with rhG-CSF were both dose- and time-dependent. The doses of rhSCF used in these studies have been tolerated in vivo in humans.(ABSTRACT TRUNCATED AT 400 WORDS).
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Ohsaka, A., S. Kitagawa, S. Sakamoto, Y. Miura, N. Takanashi, F. Takaku, and M. Saito. "In vivo activation of human neutrophil functions by administration of recombinant human granulocyte colony-stimulating factor in patients with malignant lymphoma." Blood 74, no. 8 (December 1, 1989): 2743–48. http://dx.doi.org/10.1182/blood.v74.8.2743.2743.
Повний текст джерелаАнотація:
Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (50 to 800 micrograms/m2) once daily as a half-hour intravenous (IV) infusion for 14 days to seven patients with malignant lymphoma. In all patients, administration of rhG-CSF not only ameliorated the decrease in absolute neutrophil count after the cytotoxic chemotherapy but also enhanced superoxide (O2-) release in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The priming effect of rhG-CSF on neutrophil O2- release was rapid (evident within 6.5 hours) and sustained at least for 24 hours after a single IV administration of rhG-CSF. The responsiveness to further in vitro challenge of rhG-CSF was lost or reduced in neutrophils isolated after rhG-CSF treatment, indicating that neutrophils already primed in vivo by rhG-CSF are desensitized to this factor. In contrast to the results obtained with FMLP, when phorbol myristate acetate (PMA) was used as stimulus, no consistent enhancement of O2- release was observed, suggesting that rhG-CSF modulates the signal transduction pathways linked to FMLP receptors rather than increases the components of the O2- producing enzyme complexes. Administration of rhG-CSF also rapidly (evident within 15 minutes) caused an increase in expression of neutrophil C3bi-receptors that was sustained for at least 24 hours after a single IV administration of rhG- CSF. Pharmacokinetic study of rhG-CSF showed a half-life (t1/2) of 114 min. These findings show that rhG-CSF is a potent activator for neutrophil functions both in vivo and in vitro.
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Ohsaka, A., S. Kitagawa, S. Sakamoto, Y. Miura, N. Takanashi, F. Takaku, and M. Saito. "In vivo activation of human neutrophil functions by administration of recombinant human granulocyte colony-stimulating factor in patients with malignant lymphoma." Blood 74, no. 8 (December 1, 1989): 2743–48. http://dx.doi.org/10.1182/blood.v74.8.2743.bloodjournal7482743.
Повний текст джерелаАнотація:
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (50 to 800 micrograms/m2) once daily as a half-hour intravenous (IV) infusion for 14 days to seven patients with malignant lymphoma. In all patients, administration of rhG-CSF not only ameliorated the decrease in absolute neutrophil count after the cytotoxic chemotherapy but also enhanced superoxide (O2-) release in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The priming effect of rhG-CSF on neutrophil O2- release was rapid (evident within 6.5 hours) and sustained at least for 24 hours after a single IV administration of rhG-CSF. The responsiveness to further in vitro challenge of rhG-CSF was lost or reduced in neutrophils isolated after rhG-CSF treatment, indicating that neutrophils already primed in vivo by rhG-CSF are desensitized to this factor. In contrast to the results obtained with FMLP, when phorbol myristate acetate (PMA) was used as stimulus, no consistent enhancement of O2- release was observed, suggesting that rhG-CSF modulates the signal transduction pathways linked to FMLP receptors rather than increases the components of the O2- producing enzyme complexes. Administration of rhG-CSF also rapidly (evident within 15 minutes) caused an increase in expression of neutrophil C3bi-receptors that was sustained for at least 24 hours after a single IV administration of rhG- CSF. Pharmacokinetic study of rhG-CSF showed a half-life (t1/2) of 114 min. These findings show that rhG-CSF is a potent activator for neutrophil functions both in vivo and in vitro.
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Andrews, RG, RA Briddell, GH Knitter, SD Rowley, FR Appelbaum, and IK McNiece. "Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates." Blood 85, no. 1 (January 1, 1995): 15–20. http://dx.doi.org/10.1182/blood.v85.1.15.bloodjournal85115.
Повний текст джерелаАнотація:
We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG- CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG- CSF alone.
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Andrews, RG, RA Briddell, GH Knitter, T. Opie, M. Bronsden, D. Myerson, FR Appelbaum, and IK McNiece. "In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells." Blood 84, no. 3 (August 1, 1994): 800–810. http://dx.doi.org/10.1182/blood.v84.3.800.800.
Повний текст джерелаАнотація:
Abstract Recombinant human stem cell factor (rhSCF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) are synergistic in vitro in stimulating the proliferation of hematopoietic progenitor cells and their precursors. We examined the in vivo synergy of rhSCF with rhG-CSF for stimulating hematopoiesis in vivo in baboons. Administration of low-dose (LD) rhSCF (25 micrograms/kg) alone did not stimulate changes in circulating WBCs. In comparison, administration of LD rhSCF in combination with rhG-CSF at 10 micrograms/kg or 100 micrograms/kg stimulated increases in circulating WBCs of multiple types up to twofold higher than was stimulated by administration of the same dose of rhG-CSF alone. When the dose of rhG-CSF is increased to 250 micrograms/kg, the administration of LD rhSCF does not further increase the circulating WBC counts. Administration of LD rhSCF in combination with rhG-CSF also stimulated increased circulation of hematopoietic progenitors. LD rhSCF alone stimulated less of an increase in circulating progenitors, per milliliter of blood, than did administration of rhG-CSF alone at 100 micrograms/kg. Baboons administered LD rhSCF together with rhG-CSF at 10, 100, or 250 micrograms/kg had 3.5- to 16-fold higher numbers per milliliter of blood of progenitors cells of multiple types, including colony-forming units granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming and burst-forming units-megakaryocyte (CFU- MK and BFU-MK) compared with animals given the same dose of rhG-CSF without rhSCF, regardless of the rhG-CSF dose. The increased circulation of progenitor cells stimulated by the combination of rhSCF plus rhG-CSF was not necessarily directly related to the increase in WBCs, as this effect on peripheral blood progenitors was observed even at an rhG-CSF dose of 250 micrograms/kg, where coadministration of LD rhSCF did not further increase WBC counts. Administration of very-low- dose rhSCF (2.5 micrograms/kg) with rhG-CSF, 10 micrograms/kg, did not stimulate increases in circulating WBCs, but did increase the number of megakaryocyte progenitor cells in blood compared with rhG-CSF alone. LD rhSCF administered alone for 7 days before rhG-CSF did not result in increased levels of circulating WBCs or progenitors compared with rhG- CSF alone. Thus, the synergistic effects of rhSCF with rhG-CSF were both dose- and time-dependent. The doses of rhSCF used in these studies have been tolerated in vivo in humans.(ABSTRACT TRUNCATED AT 400 WORDS).
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Terashi, Kenji, Mikio Oka, Shigehiro Ohdo, Taku Furukubo, Chizuko Ikeda, Minoru Fukuda, Hiroshi Soda, Shun Higuchi, and Shigeru Kohno. "Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients." Antimicrobial Agents and Chemotherapy 43, no. 1 (January 1, 1999): 21–24. http://dx.doi.org/10.1128/aac.43.1.21.
Повний текст джерелаАнотація:
ABSTRACT Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r 2 = 0.91; P < 0.0001) and neutrophil count (r 2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.
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Liu, Lihong, Lili Wu, Chen Huang, Guimin Zhao, Guangyu Ma, Yuhuan Gao, Lanping Diao, Yingzhen Yao, Xiaolin Wu, and Zhe Gao. "A retrospective observational study on the efficacy and safety of pegylated recombinant human granulocyte-colony stimulating factor and recombinant human granulocyte-colony stimulating factor in patients with lymphoma." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e20066-e20066. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e20066.
Повний текст джерелаАнотація:
e20066 Background: To evaluate the efficacy and safety of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) in patients with lymphoma. Methods: This retrospective study included patients with newly diagnosed lymphoma who received CHOP ± R (cyclophosphamide, doxorubicin, vincristine, prednisone ± rituximab) between January 2014 to October 2018. PEG-rhG-CSF(brand name: jinyouli) was injected subcutaneously once 24-72 hours after chemotherapy as primary prevention. rhG-CSF was used as prevention or treatment. The primary endpoint was the incidence of febrile neutropenia (FN), and the secondary endpoints included the incidence of grade III/IV neutropenia, the incidence of chemotherapy dose adjustment, the incidence of chemotherapy delay, the rate of antibiotics application and safety. Results: 178 patients with lymphoma were included, of which 76 were in the PEG-rhG-CSF group (256 cycles) and 102 were in the rhG-CSF group (336 cycles). The incidence of FN was 1.17% (3/256) in the PEG-rhG-CSF group and 5.95% (20/336) in the rhG-CSF group, P= 0.003. The incidence of grade Ⅲ/Ⅳ neutropenia and chemotherapy delay in the PEG-rhG-CSF group were significantly lower than those in the rhG-CSF group (12.89%[33/256] vs 50.30%[169/336], P < 0.0001; 3.13%[8/256] vs 9.52% [32/336], P= 0.002). However, there was no significant difference between the two groups in the incidence of dose adjustment (6.25% vs 3.57%, P = 0.128) and the rate of antibiotics application (34.77% vs 33.33%, P= 0.715). And there was no significant difference in the incidence of fever, bone pain and fatigue between the two groups. Conclusions: Compared with rhG-CSF, prophylactic use of PEG-rhG-CSF can significantly reduce the incidence of FN, grade III/IV neutropenia and chemotherapy delay in patients with lymphoma with good safety.
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Yuo, A., S. Kitagawa, A. Ohsaka, M. Ohta, K. Miyazono, T. Okabe, A. Urabe, M. Saito, and F. Takaku. "Recombinant human granulocyte colony-stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor- mediated agonists and stimulation of C3bi receptor expression and adherence." Blood 74, no. 6 (November 1, 1989): 2144–49. http://dx.doi.org/10.1182/blood.v74.6.2144.2144.
Повний текст джерелаАнотація:
Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide release and membrane depolarization in parallel in human granulocytes stimulated by the receptor-mediated agonists, N- formyl-methionyl-leucyl-phenylalanine and wheat germ agglutinin, but not by the Ca2+ ionophore ionomycin and phorbol myristate acetate, which bypass the receptors to stimulate the cells. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL (1.3 to 2.6 nmol/L) rhG-CSF for 10 minutes at 37 degrees C. rhG-CSF produced by bacteria and mammalian cells had identical biological effects on a molar basis. rhG-CSF neither affected stimulus-induced increase in cytoplasmic free Ca2+ nor changed the number and affinity of N-formyl- methionyl-leucyl-phenylalanine receptors. The priming effect of rhG-CSF was temperature dependent and did not require new protein synthesis. rhG-CSF increased the expression of C3bi receptors on human granulocytes and enhanced granulocyte adherence to nylon fiber. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL rhG-CSF for 30 minutes at 37 degrees C. rhG-CSF had no effect on human monocytes. These findings demonstrate that rhG-CSF can selectively stimulate mature granulocyte functions.
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Yuo, A., S. Kitagawa, A. Ohsaka, M. Ohta, K. Miyazono, T. Okabe, A. Urabe, M. Saito, and F. Takaku. "Recombinant human granulocyte colony-stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor- mediated agonists and stimulation of C3bi receptor expression and adherence." Blood 74, no. 6 (November 1, 1989): 2144–49. http://dx.doi.org/10.1182/blood.v74.6.2144.bloodjournal7462144.
Повний текст джерелаАнотація:
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide release and membrane depolarization in parallel in human granulocytes stimulated by the receptor-mediated agonists, N- formyl-methionyl-leucyl-phenylalanine and wheat germ agglutinin, but not by the Ca2+ ionophore ionomycin and phorbol myristate acetate, which bypass the receptors to stimulate the cells. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL (1.3 to 2.6 nmol/L) rhG-CSF for 10 minutes at 37 degrees C. rhG-CSF produced by bacteria and mammalian cells had identical biological effects on a molar basis. rhG-CSF neither affected stimulus-induced increase in cytoplasmic free Ca2+ nor changed the number and affinity of N-formyl- methionyl-leucyl-phenylalanine receptors. The priming effect of rhG-CSF was temperature dependent and did not require new protein synthesis. rhG-CSF increased the expression of C3bi receptors on human granulocytes and enhanced granulocyte adherence to nylon fiber. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL rhG-CSF for 30 minutes at 37 degrees C. rhG-CSF had no effect on human monocytes. These findings demonstrate that rhG-CSF can selectively stimulate mature granulocyte functions.
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Liu, Kaiqi, Hui Wei, Ying Wang, Yingchang Mi, and Jianxiang Wang. "Comparison of PEG-rhG-CSF and common rhG-CSF after induction chemotherapy in patients with newly diagnosed acute myeloid leukemia." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e18507-e18507. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e18507.
Повний текст джерелаАнотація:
e18507 Background: To compare the PEG-rhG-CSF (brand name:jinyouli) with ordinary rhG-CSF in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients promotes the recovery of neutrophils. At the same time, the effects of the two drugs on the incidence of infection and hospitalization were compared. Methods: A prospective randomized controlled trial was conducted in which patients with newly diagnosed AML who met the enrollment criteria were randomized into 1:1 groups: 1. PEG-rhG-CSF group: patients ≥45 kg for 6 mg/time, <45 kg for 3 mg/time, subcutaneous injection once on the 5th day after stopping chemotherapy; 2. rhG-CSF group: 5 μg/kg/day until neutrophils count ≥0.5×109/L and/or leukocytes count ≥1.0×109/L. The neutrophil recovery time (duration from day 1 of chemotherapy to neutrophils count ≥0.5×109/L and/or leukocytes count ≥1.0×109/L), infection rate and hospitalization time were collected from the two groups, and the two groups were analyzed and compared using SAS 9.4. Results: From August 2014 to December 2017, 60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. Except for the gender composition (P=0.018), there were no significant differences in age, chemotherapy regimen, neutrophils count before chemotherapy, leukocytes count before chemotherapy, and induction efficacy between the two groups. The median time (range) of neutrophils recovery in patients with PEG-rhG-CSF and rhG-CSF was 19 (14-35) days and 19 (15-26) days, P=0.36. The number of patients (ratio) with infection during neutropenia in the PEG-rhG-CSF group and the rhG-CSF group were 27 (90.0%) and 28 (93.3%), P=1. The median length of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, P=0.53. Conclusions: In patients with AML induction chemotherapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in neutrophil recovery time, infection incidence and hospitalization time.
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Friedrich, Markus. "Deep Conservation of Hid-Like RHG Gene Family Homologs in Winged Insects Revealed by “Taxon Hopping” BLAST." Insects 12, no. 11 (October 21, 2021): 957. http://dx.doi.org/10.3390/insects12110957.
Повний текст джерелаАнотація:
Together with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera, Hymenoptera, Hemiptera, and Dictyoptera. Analyses of gene structure and protein sequence conservation revealed aconserved splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily-derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their previous elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.
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Hassan, Yang Rafidah, Kwan Lok Tse, Balvinder Khambay, Ricky Wing Kit Wong, Min Gu, and Yanqi Yang. "Dental Arch Relationships and Reverse Headgear Effects in Southern Chinese Patients with Unilateral Cleft Lip and Palate." Cleft Palate-Craniofacial Journal 55, no. 7 (February 26, 2018): 925–34. http://dx.doi.org/10.1597/15-155.
Повний текст джерелаАнотація:
Objective: To evaluate the severity of the dental arch relationships and the treatment outcomes of reverse headgear (RHG) in southern Chinese patients with unilateral cleft lip and palate (UCLP). Design: A retrospective study. Setting: Faculty of Dentistry, The University of Hong Kong. Patients: Thirty-eight UCLP patients with complete records. Among them, 14 were later treated with RHG (RHG group) and 24 were under review (non-RHG group) before definitive orthodontic or in conjunction with orthognathic surgery. Interventions: Study models at T1 (aged 9.4 ± 0.4 years old), prebone grafting and before any orthodontic treatment started; T2 (aged 11.3 ± 0.6 years old), after bone grafting, and RHG treatment (RHG group) or under review (non-RHG group); and T3 (aged 15.3 ± 3.2 years old), pretreatment of definitive orthodontic or in conjunction with orthognathic surgery. Main Outcome Measures: With satisfactory intra- and interexaminer agreement proven by the kappa value, the dental arch relationships of the study models at T1, T2, and T3 were assessed by a solo calibrated examiner using the GOSLON Yardstick. Results: The median GOSLON score for southern Chinese patients with UCLP at T1 was 4.0. Sixty percent of the patients were categorized as “poor” at T1. RHG significantly improved dental arch relationships from T1 to T2, and the improvement was maintained until T3 assessed by the GOSLON Yardstick. Conclusions: The dental arch relationships in southern Chinese UCLP patients at 8 to 10 years old are unfavorable. RHG treatment shows positive effects in improving the dental arch relationships in UCLP patients, as assessed by the GOSLON Yardstick.
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Carlo-Stella, Carmelo, Massimo Di Nicola, Raffaella Milani, Anna Guidetti, Michele Magni, Marco Milanesi, Paolo Longoni, et al. "Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers." Blood 103, no. 9 (May 1, 2004): 3287–95. http://dx.doi.org/10.1182/blood-2003-07-2428.
Повний текст джерелаАнотація:
Abstract The activity of recombinant human growth hormone (rhGH) in enhancing CD34+ cell mobilization elicited by chemotherapy plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated in 16 hard-to-mobilize patients, that is, those achieving a peak of circulating CD34+ cells 10/μL or less, or a collection of CD34+ cells equal to or less than 2 × 106/kg. Patients who had failed a first mobilization attempt with chemotherapy plus rhG-CSF (5 μg/kg/d) were remobilized with chemotherapy plus rhG-CSF and rhGH (100 μg/kg/d). As compared with rhG-CSF, the combined rhGH/rhG-CSF treatment induced significantly higher (P ≤ .05) median peak values for CD34+ cells/μL (7 versus 29), colony-forming cells (CFCs)/mL (2154 versus 28 510), and long-term culture-initiating cells (LTC-ICs)/mL (25 versus 511). Following rhG-CSF and rhGH/rhG-CSF, the median yields of CD34+ cells per leukapheresis were 1.1 × 106/kg and 2.3 × 106/kg (P ≤ .008), respectively; the median total collections of CD34+ cells were 1.1 × 106/kg and 6 × 106/kg (P ≤ .008), respectively. No specific side effect could be ascribed to rhGH, except a transient hyperglycemia occurring in 2 patients. Reinfusion of rhGH/rhG-CSF-mobilized cells following myeloablative therapy resulted in prompt hematopoietic recovery. In conclusion, our data demonstrate that in poor mobilizers addition of rhGH to rhG-CSF allows the patients to efficiently mobilize and collect CD34+ cells with maintained functional properties. (Blood. 2004;103: 3287-3295)
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Zidi-Yahiaoui, Nedjma, Isabelle Callebaut, Sandrine Genetet, Caroline Le Van Kim, Jean-Pierre Cartron, Yves Colin, Pierre Ripoche, and Isabelle Mouro-Chanteloup. "Functional analysis of human RhCG: comparison with E. coli ammonium transporter reveals similarities in the pore and differences in the vestibule." American Journal of Physiology-Cell Physiology 297, no. 3 (September 2009): C537—C547. http://dx.doi.org/10.1152/ajpcell.00137.2009.
Повний текст джерелаАнотація:
Rh glycoproteins are members of the ammonium transporter (Amt)/methylamine permease (Mep)/Rh family facilitating movement of NH3 across plasma membranes. Homology models constructed on the basis of the experimental structures of Escherichia coli AmtB and Nitrosomonas europaea Rh50 indicated a channel structure for human RhA (RhAG), RhB (RhBG), and RhC (RhCG) glycoproteins in which external and internal vestibules are linked by a pore containing two strictly conserved histidines. The pore entry is constricted by two highly conserved phenylalanines, “twin-Phe.” In this study, RhCG function was investigated by stopped-flow spectrofluorometry measuring kinetic pH variations in HEK293E cells in the presence of an ammonium gradient. The apparent unitary NH3 permeability of RhCG was determined and was found to be close to that of AmtB. With a site-directed mutagenesis approach, critical residues involved in Rh NH3 channel activity were highlighted. In the external vestibule, the importance of both the charge and the conformation of the conserved aspartic acid was shown. In contrast to AmtB, individual mutations of each phenylalanine of the twin-Phe impaired the function while the removal of both resulted in recovery of the transport activity. The impact of the mutations suggests that, although having a common function and a similar channel structure, bacterial AmtB and human Rh vary in several aspects of the NH3 transport mechanisms.
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Tanikawa, S., M. Nose, Y. Aoki, K. Tsuneoka, M. Shikita, and N. Nara. "Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice." Blood 76, no. 3 (August 1, 1990): 445–49. http://dx.doi.org/10.1182/blood.v76.3.445.445.
Повний текст джерелаАнотація:
Abstract We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony- forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.
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Tanikawa, S., M. Nose, Y. Aoki, K. Tsuneoka, M. Shikita, and N. Nara. "Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice." Blood 76, no. 3 (August 1, 1990): 445–49. http://dx.doi.org/10.1182/blood.v76.3.445.bloodjournal763445.
Повний текст джерелаАнотація:
We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony- forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.
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Yan, XQ, R. Briddell, C. Hartley, G. Stoney, B. Samal, and I. McNiece. "Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor." Blood 84, no. 3 (August 1, 1994): 795–99. http://dx.doi.org/10.1182/blood.v84.3.795.795.
Повний текст джерелаАнотація:
Abstract In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.
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Yan, XQ, R. Briddell, C. Hartley, G. Stoney, B. Samal, and I. McNiece. "Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor." Blood 84, no. 3 (August 1, 1994): 795–99. http://dx.doi.org/10.1182/blood.v84.3.795.bloodjournal843795.
Повний текст джерелаАнотація:
In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.
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Zhen, Changqing, Mei Ding, Kang Lu, Xueling Ge, Na Chen, Xiaosheng Fang, Xiaohui Sui, et al. "A Randomized Controlled Clinical Study of Peg-Rhg-CSF for Preventing Chemotherapy-Induced Neutropenia in Patients with B-Cell Non-Hodgkin Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 5323. http://dx.doi.org/10.1182/blood-2019-128438.
Повний текст джерелаАнотація:
Introduction: B-cell non-Hodgkin lymphoma is the most frequent type of non-Hodgkin's lymphoma. RCHOP regimen is established as the standard therapy for aggressive and indolent B-cell NHL, which has a 10%-20% rate of febrile neutropenia (FN). Recently, pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) is frequently used in clinical practice. This randomized controlled clinical study was conducted to investigate the efficacy and safety of prophylactic PEG-rhG-CSF in patients with B-cell non-Hodgkin lymphoma on RCHOP chemotherapy. Methods:We included 162 patients with pathological diagnosis of B-cell non-Hodgkin lymphoma including diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma (MCL),from October 2016 to May 2019 at Shandong Provincial Hospital Affiliated to Shandong University. All patients gave written informed consent in accordance with the Declaration of Helsinki. The patients were randomized into PEG-rhG-CSF and rhG-CSF groups. Each patient received three cycles of chemotherapy with identical RCHOP regimens. In the study group, the patients received PEG-rhG-CSF 6mg(weight≥45Kg)or 3mg(weight≤45Kg)once 24 hours after the end of chemotherapy drugs of every chemotherapy cycle. In the control group, they weren't preventively administered rhG-CSF. If their neutrophil count (ANC)≤1.0×109/L, they were administered rhG-CSF:5ug/kg/day until their neutrophil count (ANC)≥2.0×109/L. The primary endpoint was the incidence of III/IV grade neutropenia and febrile neutropenia(FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application and safety were observed. Analyses were performed with SPSS Statistics 20.0 (IBM-SPSS, Chicago, Illinois). The numerical data was presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance and chi-square test. A p-value<0.05 was considered statistically significant. Results: Clinical characteristics for PEG-rhG-CSF and rhG-CSF groups were shown in Table1. There were no significant differences in age, gender,height, body weight, body mass index, Ann Arbor and IPI staging. The incidence of IV grade neutropenia during cycle 1 in 81 evaluable study cycles and 81 evaluable control cycles were 7.41% and 35.80%( P<0.01), with durations of 2.85±0.62 days and 3.11±1.23 days (P>0.05). The differences in I/II/III grade neutropenia between study and control groups weren't statistically significant (Table2,Fig.1). After secondary prophylactic use of PEG-rhG-CSF In the study group, the incidences of III/IV grade neutropenia decreased from 77.78% to 14.81% (P<0.01).Statistically significant differences were observed in the incidences of FN (12.35% and 34.57% for the PEG-rhG-CSF and rhG-CSF groups, respectively; P<0.01) and in the proportion of patients who received antibiotic therapy (11.11% and 37.04%, respectively; P<0.01) during cycle 1(Table2,Fig .2). The safety profiles of PEG-rhG-CSF and rhG-CSF were similar. Bone pain occurred in 7.41% of the cases during the study cycles and 2.47% in the control cycles (P>0.05 ), which were mostly mild or moderate. Patients receiving PEG-rhG-CSF who developed III/IV grade neutropenia were significantly older than those without neutropenia (53.41±14.96 vs. 63.64±4.65;years; p=0.01) (Fig.3).The incidence of III/IV grade neutropenia in patients older than 60 years was significantly higher than that in patients younger than 60 years(24.44% vs. 6.38%; P =0.038). Conclusions: Prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade III/IV neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve prognosis. III/IV grade neutropenia after prophylactic use of PEG-rhG-CSF were more likely to occur in patients older than 60 years. After the use of PEG-rhG-CSF, the elderly patients should be pay more attention to them. Disclosures No relevant conflicts of interest to declare.
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MacVittie, TJ, AM Farese, F. Herodin, LB Grab, CM Baum, and JP McKearn. "Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor." Blood 87, no. 10 (May 15, 1996): 4129–35. http://dx.doi.org/10.1182/blood.v87.10.4129.bloodjournal87104129.
Повний текст джерелаАнотація:
Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine- SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [QD], 15 micrograms/kg/d, n = 10), Synthokine (twice daily [BID], 100, micrograms/kg/d, n = 15), rhG-CSF (QD, 10 micrograms/kg/d, n = 5), or a combination of Synthokine and rhG-CSF (BID, 100 and 10 micrograms/kg/d, respectively, n = 5) for 23 days beginning on d1. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count < 500/microL) and thrombocytopenia (platelet count < 20,000/microL) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period neutropenia (P < .05). The combined Synthokine/rhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The Synthokine/rhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animals for Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA. These data showed that the combination of Synthokine, SC-55494, and rhG-CSF further decreased the cytopenic periods and nadirs for both platelets and neutrophils relative to Synthokine and rhG-CSF monotherapy and suggest that this combination therapy would be effective against both neutropenia and thrombocytopenia consequent to drug- or radiation- induced myelosuppression.
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Uckun, FM, L. Souza, KG Waddick, M. Wick, and CW Song. "In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice." Blood 75, no. 3 (February 1, 1990): 638–45. http://dx.doi.org/10.1182/blood.v75.3.638.638.
Повний текст джерелаАнотація:
Abstract The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.
30
Uckun, FM, L. Souza, KG Waddick, M. Wick, and CW Song. "In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice." Blood 75, no. 3 (February 1, 1990): 638–45. http://dx.doi.org/10.1182/blood.v75.3.638.bloodjournal753638.
Повний текст джерелаАнотація:
The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.
31
Neidhart, J., A. Mangalik, W. Kohler, C. Stidley, J. Saiki, P. Duncan, L. Souza, and M. Downing. "Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation." Journal of Clinical Oncology 7, no. 11 (November 1989): 1685–92. http://dx.doi.org/10.1200/jco.1989.7.11.1685.
Повний текст джерелаАнотація:
Bone marrow colony-stimulating factors (CSF) ameliorate hematologic toxicity of standard chemotherapy regimens and may allow relatively safe use of intensive and more efficacious doses of anticancer drugs. Twenty-four patients with cancers for which no standard regimens were likely to be effective received repeated courses of a combination of cisplatin (150 mg/m2), etoposide (1,500 mg/m2), and cyclophosphamide (5,000 mg/m2) at doses for which bone marrow transplantation is usually used. A total of 10 patients received escalating doses of recombinant human granulocyte CSF (rhG-CSF); 11 patients receiving identical chemotherapy and supportive therapy without rhG-CSF served as controls for the first cycle of therapy. Five of these patients and 3 additional patients also served as their own controls, receiving rhG-CSF for all cycles after the first. No patient received bone marrow transplantation. rhG-CSF shortened the median duration of severe granulocytopenia (less than or equal to 100/mm3) in a dose-related fashion (P less than .03; Kruskal-Wallis test). Patients not receiving rhG-CSF had a median of 8.5 days of granulocytopenia. Those receiving 40 micrograms/kg of rhG-CSF for approximately 20 days from the third day after chemotherapy had a median of 7.0 days (P less than .23) and those receiving 60 micrograms/kg had a median of 5.5 days (P less than .007) of granulocytopenia. An rhG-CSF dose of 20 micrograms/kg had no effect. Recovery to a granulocyte count of at least 500/mm3 took a median of 12 days in the control group and 8 days (P less than .03) in patients receiving rhG-CSF at a dose of 60 mg/kg. The duration of antibiotic therapy (a median, 9.0 days v 5.0 days) was shortened with the two higher and effective doses of rhG-CSF compared with control patients. The duration of hospitalization (median of 20 days v 19 days) was not shortened. These findings that rhG-CSF decreases the risk of granulocytopenia associated with this particular dose-intensive chemotherapy regimen therapy administered without bone marrow transplantation.
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Cairo, MS, JM Plunkett, D. Mauss, and C. Van de ven. "Seven-day administration of recombinant human granulocyte colony- stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis." Blood 76, no. 9 (November 1, 1990): 1788–94. http://dx.doi.org/10.1182/blood.v76.9.1788.1788.
Повний текст джерелаАнотація:
Abstract Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats.
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Cairo, MS, JM Plunkett, D. Mauss, and C. Van de ven. "Seven-day administration of recombinant human granulocyte colony- stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis." Blood 76, no. 9 (November 1, 1990): 1788–94. http://dx.doi.org/10.1182/blood.v76.9.1788.bloodjournal7691788.
Повний текст джерелаАнотація:
Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats.
34
Medlock, ES, DL Kaplan, M. Cecchini, TR Ulich, J. del Castillo, and J. Andresen. "Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis." Blood 81, no. 4 (February 15, 1993): 916–22. http://dx.doi.org/10.1182/blood.v81.4.916.916.
Повний текст джерелаАнотація:
Abstract We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.
35
Medlock, ES, DL Kaplan, M. Cecchini, TR Ulich, J. del Castillo, and J. Andresen. "Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis." Blood 81, no. 4 (February 15, 1993): 916–22. http://dx.doi.org/10.1182/blood.v81.4.916.bloodjournal814916.
Повний текст джерелаАнотація:
We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.
36
Chou, W. H., A. Huber, J. Bentrop, S. Schulz, K. Schwab, L. V. Chadwell, R. Paulsen, and S. G. Britt. "Patterning of the R7 and R8 photoreceptor cells of Drosophila: evidence for induced and default cell-fate specification." Development 126, no. 4 (February 15, 1999): 607–16. http://dx.doi.org/10.1242/dev.126.4.607.
Повний текст джерелаАнотація:
Opsin gene expression in the R7 and R8 photoreceptor cells of the Drosophila compound eye is highly coordinated. We have found that the R8 cell specific Rh5 and Rh6 opsins are expressed in non-overlapping sets of R8 cells, in a precise pairwise fashion with Rh3 and Rh4 in the R7 cells of individual ommatidia. Removal of the R7 cells in sevenless, boss or sina mutants, disrupts Rh5 expression and dramatically increases the number of Rh6-expressing R8 cells. This suggests that the expression of Rh5 may be induced by an Rh3-expressing R7 cell, whereas Rh6 expression is most likely a default state of the R8 cell. We found that the paired expression of opsin genes in the R7 and R8 cells occurs in a sevenless and boss independent manner. Furthermore, we found that the generation of both Rh3- and Rh4-expressing R7 cells can occur in the absence of an R8 cell. These results suggest that the specification of opsin expression in the R7 cells may occur autonomously, whereas the R7 photoreceptor cell may be responsible for regulating a binary developmental switch between induced and default cell-fates in the R8 cell.
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Aoki, Y., K. Hiromatsu, N. Kobayashi, T. Hotta, H. Saito, H. Igarashi, Y. Niho, and Y. Yoshikai. "Protective effect of granulocyte colony-stimulating factor against T- cell-meditated lethal shock triggered by superantigens." Blood 86, no. 4 (August 15, 1995): 1420–27. http://dx.doi.org/10.1182/blood.v86.4.1420.bloodjournal8641420.
Повний текст джерелаАнотація:
The bacterial superantigens (SAg), toxic shock syndrome toxin-1 (TSST- 1) and staphylococcal enterotoxin B (SEB), are powerful T-cell stimulators, triggering systemic release of lymphokines causing lethal shock in D-galactosamine (D-Gal)-sensitized mice. We show that pretreatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) protects mice against T-cell-mediated SAg-shock. In mice challenged with D-Gal/TSST-1, lethal shock was caused within 30 hours. In contrast, animals pretreated with two consecutive subcutaneous injections of 2 micrograms rhG-CSF with a 12-hour time interval showed only marginal signs of illness and no lethality after challenge with D-Gal/TSST-1. Mice treated with 5 micrograms rhG-CSF either 12 or 6 hours in advance also survived otherwise lethal doses of D-Gal/TSST-1. The protective effects of rhG-CSF pretreatment was also evident against lethal doses of D-Gal/SEB challenge and this protection was accompanied by suppression of systemic interleukin-2. However, rhG- CSF affected neither the proliferative responses of SAg-reactive T cells in vivo or in vitro nor their interleukin-2 production in vitro, implying that rhG-CSF may indirectly interfere with cytokine synthesis in T cells but not with T-cell-SAg binding itself. These results represent another beneficial effect of rhG-CSF as an anti-inflammatory agent against T-cell-mediated toxicity triggered by SAg.
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Gillan, ER, RD Christensen, Y. Suen, R. Ellis, C. van de Ven, and MS Cairo. "A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia." Blood 84, no. 5 (September 1, 1994): 1427–33. http://dx.doi.org/10.1182/blood.v84.5.1427.1427.
Повний текст джерелаАнотація:
Abstract Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG- CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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Gillan, ER, RD Christensen, Y. Suen, R. Ellis, C. van de Ven, and MS Cairo. "A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia." Blood 84, no. 5 (September 1, 1994): 1427–33. http://dx.doi.org/10.1182/blood.v84.5.1427.bloodjournal8451427.
Повний текст джерелаАнотація:
Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG- CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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Grzegorzewski, KJ, KL Komschlies, JL Franco, FW Ruscetti, JR Keller, and RH Wiltrout. "Quantitative and cell-cycle differences in progenitor cells mobilized by recombinant human interleukin-7 and recombinant human granulocyte colony-stimulating factor." Blood 88, no. 11 (December 1, 1996): 4139–48. http://dx.doi.org/10.1182/blood.v88.11.4139.4139.
Повний текст джерелаАнотація:
Abstract Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.
41
Grzegorzewski, KJ, KL Komschlies, JL Franco, FW Ruscetti, JR Keller, and RH Wiltrout. "Quantitative and cell-cycle differences in progenitor cells mobilized by recombinant human interleukin-7 and recombinant human granulocyte colony-stimulating factor." Blood 88, no. 11 (December 1, 1996): 4139–48. http://dx.doi.org/10.1182/blood.v88.11.4139.bloodjournal88114139.
Повний текст джерелаАнотація:
Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.
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Welte, K., M. A. Bonilla, A. P. Gillio, T. C. Boone, G. K. Potter, J. L. Gabrilove, M. A. Moore, R. J. O'Reilly, and L. M. Souza. "Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates." Journal of Experimental Medicine 165, no. 4 (April 1, 1987): 941–48. http://dx.doi.org/10.1084/jem.165.4.941.
Повний текст джерелаАнотація:
We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.
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Yuo, A., S. Kitagawa, T. Okabe, A. Urabe, Y. Komatsu, S. Itoh, and F. Takaku. "Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia." Blood 70, no. 2 (August 1, 1987): 404–11. http://dx.doi.org/10.1182/blood.v70.2.404.404.
Повний текст джерелаАнотація:
Abstract We examined the in vitro effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was determined in nine MDS patients and eight CML patients by a scoring method. NAP scores were decreased in six of the nine patients with MDS and in all of the patients with CML. In all patients with these diseases, NAP scores increased by incubating the blood with rhG- CSF. An increase in NAP scores by rhG-CSF was observed even at a concentration of 1 U/mL in patients with MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL) in patients with CML. Significant increases in NAP scores occurred at 12 hours' incubation in patients with MDS, whereas the increase was more gradual in patients with CML. This time course difference was thought to be due mainly to the difference in cell populations of circulating myeloid cells between MDS patients and CML patients. Induction of NAP activity by rhG-CSF in patients with both these diseases was suppressed by the addition of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2- ) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was determined in the other 11 patients with MDS. This neutrophil function was decreased in seven of the 11 patients with MDS, normal in two patients, and increased in two patients. Preincubation with rhG-CSF caused a significant increase in fMLP-induced O2- production in nine of the 11 patients with MDS. rhG-CSF enhanced this neutrophil function in a time- and dose-dependent manner, and maximal stimulation was observed at 2,000 to 4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present results show that rhG-CSF is able to repair at least in part the neutrophil anomalies in these patients, and our data, especially for patients with MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic disorder.
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Yuo, A., S. Kitagawa, T. Okabe, A. Urabe, Y. Komatsu, S. Itoh, and F. Takaku. "Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia." Blood 70, no. 2 (August 1, 1987): 404–11. http://dx.doi.org/10.1182/blood.v70.2.404.bloodjournal702404.
Повний текст джерелаАнотація:
We examined the in vitro effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was determined in nine MDS patients and eight CML patients by a scoring method. NAP scores were decreased in six of the nine patients with MDS and in all of the patients with CML. In all patients with these diseases, NAP scores increased by incubating the blood with rhG- CSF. An increase in NAP scores by rhG-CSF was observed even at a concentration of 1 U/mL in patients with MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL) in patients with CML. Significant increases in NAP scores occurred at 12 hours' incubation in patients with MDS, whereas the increase was more gradual in patients with CML. This time course difference was thought to be due mainly to the difference in cell populations of circulating myeloid cells between MDS patients and CML patients. Induction of NAP activity by rhG-CSF in patients with both these diseases was suppressed by the addition of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2- ) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was determined in the other 11 patients with MDS. This neutrophil function was decreased in seven of the 11 patients with MDS, normal in two patients, and increased in two patients. Preincubation with rhG-CSF caused a significant increase in fMLP-induced O2- production in nine of the 11 patients with MDS. rhG-CSF enhanced this neutrophil function in a time- and dose-dependent manner, and maximal stimulation was observed at 2,000 to 4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present results show that rhG-CSF is able to repair at least in part the neutrophil anomalies in these patients, and our data, especially for patients with MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic disorder.
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Opal, Steven M., Jhung W. Jhung, James C. Keith, Samuel J. Goldman, John E. Palardy, and Nicolas A. Parejo. "Additive Effects of Human Recombinant Interleukin-11 and Granulocyte Colony-Stimulating Factor in Experimental Gram-Negative Sepsis." Blood 93, no. 10 (May 15, 1999): 3467–72. http://dx.doi.org/10.1182/blood.v93.10.3467.410k10_3467_3472.
Повний текст джерелаАнотація:
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to promote granulocyte recovery from a variety of pathologic states. Recombinant human interleukin-11 (rhIL-11) has recently become available clinically as a platelet restorative agent after myelosuppressive chemotherapy. Preclinical data has shown that rhIL-11 limits mucosal injury after chemotherapy and attenuates the proinflammatory cytokine response. The potential efficacy of combination therapy with recombinant human forms of rhIL-11 and rhG-CSF was studied in a neutropenic rat model of Pseudomonas aeruginosa sepsis. At the onset of neutropenia, animals were randomly assigned to receive either rhG-CSF at a dose of 200 μg/kg subcutaneously every 24 hours for 7 days; rhIL-11 at 200 μg/kg subcutaneously every 24 hours for 7 days; the combination of both rhG-CSF and rhIL-11; or saline control. Animals were orally colonized with Pseudomonas aeruginosa 12.4.4 and then given a myelosuppressive dose of cyclophosphamide. rhG-CSF resulted in a slight increase in absolute neutrophil counts (ANC), but did not provide a survival advantage (0 of 12, 0% survival) compared with the placebo group (1 of 12 , 8% survival). rhIL-11 was partially protective (4 of 10, 40% survival); the combination of rhG-CSF and rhIL-11 resulted in a survival rate of 80% (16 of 20; P < .001). rhIL-11 alone or in combination with rhG-CSF resulted in preservation of gastrointestinal mucosal integrity (P < .001), lower circulating endotoxin levels (P < .01), and reduced quantitative levels of P. aeruginosa in quantitative organ cultures. These results indicate that the combination of rhIL-11 and rhG-CSF is additive as a treatment strategy in the prevention and treatment of experimental Gram-negative sepsis in immunocompromised animals. This combination may prove to be efficacious in the prevention of severe sepsis in neutropenic patients.
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Ohara, Akira, Seiji Kojima, Nobuyuki Hamajima, Masahiro Tsuchida, Shinsaku Imashuku, Shigeru Ohta, Hideki Sasaki, et al. "Myelodysplastic Syndrome and Acute Myelogenous Leukemia as a Late Clonal Complication in Children With Acquired Aplastic Anemia." Blood 90, no. 3 (August 1, 1997): 1009–13. http://dx.doi.org/10.1182/blood.v90.3.1009.
Повний текст джерелаАнотація:
Abstract The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF ) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 μg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.
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Ohara, Akira, Seiji Kojima, Nobuyuki Hamajima, Masahiro Tsuchida, Shinsaku Imashuku, Shigeru Ohta, Hideki Sasaki, et al. "Myelodysplastic Syndrome and Acute Myelogenous Leukemia as a Late Clonal Complication in Children With Acquired Aplastic Anemia." Blood 90, no. 3 (August 1, 1997): 1009–13. http://dx.doi.org/10.1182/blood.v90.3.1009.1009_1009_1013.
Повний текст джерелаАнотація:
The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF ) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 μg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.
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Piao, Xiang Min, Yue Huo, Jong Pyo Kang, Ramya Mathiyalagan, Hao Zhang, Dong Uk Yang, Mia Kim, Deok Chun Yang, Se Chan Kang, and Ying Ping Wang. "Diversity of Ginsenoside Profiles Produced by Various Processing Technologies." Molecules 25, no. 19 (September 24, 2020): 4390. http://dx.doi.org/10.3390/molecules25194390.
Повний текст джерелаАнотація:
Ginseng is a traditional medicinal herb commonly consumed world-wide owing to its unique family of saponins called ginsenosides. The absorption and bioavailability of ginsenosides mainly depend on an individual’s gastrointestinal bioconversion abilities. There is a need to improve ginseng processing to predictably increase the pharmacologically active of ginsenosides. Various types of ginseng, such as fresh, white, steamed, acid-processed, and fermented ginsengs, are available. The various ginseng processing methods produce a range ginsenoside compositions with diverse pharmacological properties. This review is intended to summarize the properties of the ginsenosides found in different Panax species as well as the different processing methods. The sugar moiety attached to the C–3, C–6, or C–20 deglycosylated to produce minor ginsenosides, such as Rb1, Rb2, Rc, Rd→Rg3, F2, Rh2; Re, Rf→Rg1, Rg2, F1, Rh1. The malonyl-Rb1, Rb2, Rc, and Rd were demalonylated into ginsenoside Rb1, Rb2, Rc, and Rd by dehydration. Dehydration also produces minor ginsenosides such as Rg3→Rk1, Rg5, Rz1; Rh2→Rk2, Rh3; Rh1→Rh4, Rk3; Rg2→Rg6, F4; Rs3→Rs4, Rs5; Rf→Rg9, Rg10. Acetylation of several ginsenosides may generate acetylated ginsenosides Rg5, Rk1, Rh4, Rk3, Rs4, Rs5, Rs6, and Rs7. Acid processing methods produces Rh1→Rk3, Rh4; Rh2→Rk1, Rg5; Rg3→Rk2, Rh3; Re, Rf, Rg2→F1, Rh1, Rf2, Rf3, Rg6, F4, Rg9. Alkaline produces Rh16, Rh3, Rh1, F4, Rk1, ginsenoslaloside-I, 20(S)-ginsenoside-Rh1-60-acetate, 20(R)-ginsenoside Rh19, zingibroside-R1 through hydrolysis, hydration addition reactions, and dehydration. Moreover, biological processing of ginseng generates the minor ginsenosides of Rg3, F2, Rh2, CK, Rh1, Mc, compound O, compound Y through hydrolysis reactions, and synthetic ginsenosides Rd12 and Ia are produced through glycosylation. This review with respect to the properties of particular ginsenosides could serve to increase the utilization of ginseng in agricultural products, food, dietary supplements, health supplements, and medicines, and may also spur future development of novel highly functional ginseng products through a combination of various processing methods.
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Ericson, Solveig G., Yue Zhao, Huilan Gao, Kathryn L. Miller, Laura F. Gibson, Joseph P. Lynch, and Kenneth S. Landreth. "Interleukin-6 Production by Human Neutrophils After Fc-Receptor Cross-Linking or Exposure to Granulocyte Colony-Stimulating Factor." Blood 91, no. 6 (March 15, 1998): 2099–107. http://dx.doi.org/10.1182/blood.v91.6.2099.
Повний текст джерелаАнотація:
Abstract Polymorphonuclear neutrophils (PMNs) are essential effector cells in host defense and tissue inflammatory responses. These responses may be initiated after cross-linking of cell surface Fc receptors that bind the constant portion of IgG (FcγR). We evaluated the effect of cross-linking FcγRI or FcγRII on interleukin-6 (IL-6) production by purified PMNs from normal donors or from patients being treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In PMNs from normal donors, IL-6 mRNA was detected by reverse transcriptase-polymerase chain reaction only after FcγRI or FcγRII cross-linking. We also found that IL-6 mRNA could be detected in PMNs after either in vitro or in vivo rhG-CSF treatment in the absence of FcγR cross-linking. IL-6 protein was found to be produced intracellularly and secreted by PMNs after cross-linking FcγRI or FcγRII or after rhG-CSF stimulation. Cross-linking FcγRI or FcγRII on PMNs from patients treated with rhG-CSF resulted in a synergistic increase in IL-6 secretion. Upregulation of IL-6 production by PMNs after rhG-CSF treatment may contribute to a clinical engraftment syndrome that occurs during periods of rapid increase in PMN numbers in patients receiving rhG-CSF.
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Ericson, Solveig G., Yue Zhao, Huilan Gao, Kathryn L. Miller, Laura F. Gibson, Joseph P. Lynch, and Kenneth S. Landreth. "Interleukin-6 Production by Human Neutrophils After Fc-Receptor Cross-Linking or Exposure to Granulocyte Colony-Stimulating Factor." Blood 91, no. 6 (March 15, 1998): 2099–107. http://dx.doi.org/10.1182/blood.v91.6.2099.2099_2099_2107.
Повний текст джерелаАнотація:
Polymorphonuclear neutrophils (PMNs) are essential effector cells in host defense and tissue inflammatory responses. These responses may be initiated after cross-linking of cell surface Fc receptors that bind the constant portion of IgG (FcγR). We evaluated the effect of cross-linking FcγRI or FcγRII on interleukin-6 (IL-6) production by purified PMNs from normal donors or from patients being treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In PMNs from normal donors, IL-6 mRNA was detected by reverse transcriptase-polymerase chain reaction only after FcγRI or FcγRII cross-linking. We also found that IL-6 mRNA could be detected in PMNs after either in vitro or in vivo rhG-CSF treatment in the absence of FcγR cross-linking. IL-6 protein was found to be produced intracellularly and secreted by PMNs after cross-linking FcγRI or FcγRII or after rhG-CSF stimulation. Cross-linking FcγRI or FcγRII on PMNs from patients treated with rhG-CSF resulted in a synergistic increase in IL-6 secretion. Upregulation of IL-6 production by PMNs after rhG-CSF treatment may contribute to a clinical engraftment syndrome that occurs during periods of rapid increase in PMN numbers in patients receiving rhG-CSF.