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A lumped model for cell growth and secondary metabolite production in an immobilized live cell bioreactor has been developed. This model is applied here to simulate the performance of an immobilized bioreactor under steady-state conditions and under conditions of periodically varying concentration of a growth-limiting substrate. The results of the simulation study were experimentally verified in the case of the production of the antibiotic candicidin by Streptomyces griseus in an immobilized bioreactor with forced periodic operation. The results of the studies suggest that periodically operated immobilized live cell bioreactors can provide a potent alternative for the production of non-growth-associated biochemicals, as compared to free cell fermentations, pulsed fermentations with process cycle regeneration, and nonregenerated bioreactors. This work has demonstrated that by frequent pulsing of the growth limiting nutrient, stable extended production can be obtained at high specific cellular productivities. 相似文献
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Alkis Constantinides Daleep Bhatia Wolf R. Vieth 《Biotechnology and bioengineering》1981,23(4):899-916
In this study, live cells of Brevibacterium flavum were immobilized for the production of glutamic acid. The reason for such a choice was that glutamic acid fermentation is an extensively studied fermentation and one which requires the viability of entire cellular faculties for the acid production. Brevibacterium flavum was chosen because it is an industrially used bacterium, and is very potent via a vis glutamic acid production. Studies were performed to find aeration and agitation conditions for optimal growth and glutamic acid productivity. Experiments were also done to find the optimum harvesting time. The cell activity peaks during the run of fermentation, and the time at which the peak occurs, was found. Conventional methods for immobilizing the cells on collagen were found to be lacking. The pH and drying were the two main reasons for loss of viability of the cells; the latter being more important. A modified immobilization procedure has been devised, which can immobilize live cells at any given pH and ionic strength, in contrast to the conventional method which requires the pH to be above 11 or below 3. This new method involves dialysis of collagen in suitable dialysis bags against water at pH7 (or buffer at any desired pH). The dialysed collagen blended at 20,000 rpm, resulted in a very smooth dispersion, unnoticeably different from collagen dispersion prepared at pH 11. The dispersed collagen was then cast and dried at an elevated temperature, and high air flow rate over the cast membrane, decreasing the time of drying from 6–8 hr ( in the conventional method) to 1.5–2 hr. The membrane has been tested for glutamic acid producing capabilities in a column reactor with the membrane spirally wound. The reactor has been operated under continuous conditions for 5–10 days with stable activities. 相似文献
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Phenotypic conversion of cultured mouse embryo cells by aza pyrimidine nucleosides. 总被引:14,自引:0,他引:14
Cells of the line, which are nonmyoblastic in nature, form functional myotubes when treated with low concentrations of 5-azacytidine. Further characterization of the myotubes revealed that they arise from the fusion of mononucleated precursors and not as a result of endoreplication. They accumulate histochemically detectable myosin ATPase activity as well as acetylcholine receptors capable of binding radioactively labeled α-bungarotoxin. The deoxy analog, 5-aza-2′-deoxycytidine, induced myogenic conversion at one-tenth of the maximally effective concentration of 5-azacytidine. The ability of both analogs to induce myotube formation and to cause cytotoxicity was strongly influenced by cotreatment with certain pyrimidine nucleosides. These effects were consistent with a requirement for metabolism of both aza compounds to phosphorylated derivatives and with a mechanism of action based on their incorporation into DNA. Concentrations of the analogs causing myogenic conversion did not substantially alter rates of DNA, RNA, or protein synthesis as measured by precursor incorporation into intact cells. The induction of myotubes by 5-azacytidine in cells synchronized by two different methods required that treatment with the analog was carried out at a critical phase early in S phase. Thus the mechanism of drug action appears to be linked to specific DNA synthesis. 相似文献
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Mehmet Esref Alkis Hakki Murat Bilgin Veysi Akpolat Korkut Yegin Mehmet Cihan Yavas 《Electromagnetic biology and medicine》2019,38(1):32-47
Ubiquitous and ever increasing use of mobile phones led to the growing concern about the effects of radiofrequency radiation (RFR) emitted by cell phones on biological systems. The aim of this study is to explore whether long-term RFR exposure at different frequencies affects DNA damage and oxidant-antioxidant parameters in the blood and brain tissue of rats. 28 male Sprague Dawley rats were randomly divided into four equal groups (n = 7). They were identified as Group 1: sham-control, Group 2: 900 MHz, Group 3: 1800 MHz, and Group 4: 2100 MHz. Experimental groups of rats were exposed to RFR 2 h/day for 6 months. The sham-control group of rats was subjected to the same experimental condition but generator was turned off. Specific absorption rates (SARs) at brain with 1 g average were calculated as 0.0845 W/kg, 0.04563 W/kg, and 0.03957, at 900 MHz, 1800 MHz, and 2100 MHz, respectively. Additionally, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), total antioxidant status (TAS), and total oxidant status (TOS) analyses were conducted in the brain tissue samples. Results of the study showed that DNA damage and oxidative stress indicators were found higher in the RFR exposure groups than in the sham-control group. In conclusion, 900-, 1800-, and 2100-MHz RFR emitted from mobile phones may cause oxidative damage, induce increase in lipid peroxidation, and increase oxidative DNA damage formation in the frontal lobe of the rat brain tissues. Furthermore, 2100-MHz RFR may cause formation of DNA single-strand breaks. 相似文献
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Plasma extravasation through neuronal stimulation in human nasal mucosa in the setting of allergic rhinitis 总被引:2,自引:0,他引:2
Sanico Alvin M.; Atsuta Satsuki; Proud David; Togias Alkis 《Journal of applied physiology》1998,84(2):537-543
Sanico, Alvin M., Satsuki Atsuta, David Proud, and AlkisTogias. Plasma extravasation through neuronal stimulation in humannasal mucosa in the setting of allergic rhinitis. J. Appl. Physiol. 84(2): 537-543, 1998.We havepreviously shown that capsaicin nasal challenge in subjects withallergic rhinitis produces a dose-dependent increase in the albumincontent of nasal lavage fluids. In the present set of studies, wedetermined whether this observation represents plasma extravasationthat is neuronally mediated. To evaluate whether glandular secretionscontribute to the albumin increase in nasal lavage fluids, volunteerswith allergic rhinitis were pretreated with atropine or placebo before capsaicin challenge. Atropine significantly reduced the volume ofreturned lavage fluids and their lysozyme content but increased theiralbumin and fibrinogen content. To assess the contribution of sensorynerve stimulation, subjects with allergic rhinitis were pretreated in asecond study with lidocaine or placebo before capsaicin challenge.Lidocaine significantly attenuated the capsaicin-induced increases inthe volume of nasal lavage fluids, as well as their lysozyme andalbumin content. To rule out the possibility of a direct effect oflidocaine on blood vessels rather than on nerves, healthy subjects werepretreated in a third study with lidocaine or placebo before bradykininnasal challenge. Lidocaine did not affect the bradykinin-inducedincrease in the albumin content of nasal fluids. We conclude that, inallergic rhinitis, high-dose capsaicin induces plasma extravasation inthe human nose and that this effect is neuronally mediated. Thisprovides more definitive evidence that neurogenic inflammation canoccur in vivo in the human upper airway. 相似文献
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Rapid reversibility of the allergen-induced pulmonary late-phase reaction by an intravenous beta 2-agonist 总被引:1,自引:0,他引:1
Peebles R. Stokes Jr.; Permutt Solbert; Togias Alkis 《Journal of applied physiology》1998,84(5):1500-1505
This studywas performed to determine the degree to which2-adrenergic receptor agonistscan reverse the allergen-induced late reduction in lungfunction. On two occasions, seven asthmatic subjects wereadministered terbutaline or its vehicle by intravenous infusion 7 hafter inhaled allergen, at which point the forced expiratory volume in1 s was 57% of baseline. On another occasion, terbutaline was infusedat baseline to determine maximal attainable bronchodilation. Afterallergen challenge, terbutaline rapidly improved lung function. At theend of terbutaline infusion, the forced expiratory volume in 1 sreached 100 ± 1.3% of baseline and 84.2 ± 4.3% of maximalattainable value, but the bronchodilating effect of the -agonist didnot plateau. The values for forced vital capacity were 102 ± 1.3%of baseline and 95.1 ± 3% of maximal attainablevalue. The kinetics of the terbutaline effect, when it wasinfused at baseline, were similar to those in the late phase. Becausethe late-phase reduction in lung function is rapidly reversible by2-adrenergic agonists, weconclude that it is caused mainly by bronchial smooth muscle spasm. 相似文献