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101.
Optimal HIV treatment by maximising immune response 总被引:1,自引:1,他引:0
We present an optimal control model of drug treatment of the human immunodeficiency virus (HIV). Our model is based upon ordinary differential equations that describe the interaction between HIV and the specific immune response as measured by levels of natural killer cells. We establish stability results for the model. We approach the treatment problem by posing it as an optimal control problem in which we maximise the benefit based on levels of healthy CD4+ T cells and immune response cells, less the systemic cost of chemotherapy. We completely characterise the optimal control and compute a numerical solution of the optimality system via analytic continuation.Research supported by the Natural Science and Engineering Research Council (NSERC) and the Mathematics of Information Technology and Complex Systems (MITACS) of Canada 相似文献
102.
Ruan Z Koizumi T Sakai A Ishizaki T Wang Z Chen Q Wang X 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2004,174(7):549-554
To compare the role of nitric oxide in an adaptive process to chronic hypoxia, we examined the effects of endogenous nitric oxide synthase inhibition on pulmonary vascular tone in conscious sheep and pigs living at high altitude. Unanesthetized male sheep (n=6) and pigs (n=5), born and residing in the highlands of Qinghai Province, China (2,300–3,000 m a.s.l.) were studied at that altitude. Pulmonary artery pressure (Ppa), pulmonary artery wedge pressure (Pcwp), and cardiac output (CO) were measured. Pulmonary vascular resistance (PVR) was calculated as (Ppa—Pcwp)/CO. Using a climatic chamber, hemodynamic measurements during exposures to atmospheric pressures corresponding to altitudes of 0, 2,300, and 4,500 m a.s.l. were performed with and without NO inhibition, using Nw-nitro-l-argine (NLA; 20 mg kg–1), a potent stereospecific competitive inhibitor of nitric oxide synthase. Ppa and PVR at baseline (2,300 m) and during hypoxic exposure (4,500 m) were significantly higher in pigs than in sheep. After NLA administration, Ppa increased and CO decreased in both animals, resulting in significantly increased PVR at baseline and during hypoxic exposure. However, there were no significant differences in the percent increase in basal or hypoxic PVR after NLA administration between sheep and pigs. We conclude that augmented endogenous NO production could contribute to the regulation of pulmonary vascular tone at high altitude in sheep and pigs. However, it is unlikely that NO is responsible for the different pulmonary vascular tones between sheep and pigs at basal condition at moderately high altitude.Communicated by G. Heldmaier 相似文献
103.
Detection of tumor marker CA125 in ovarian carcinoma using quantum dots 总被引:11,自引:0,他引:11
The fluorescent labeling of biological materials usingsmall-molecule organic dyes is widely employed in bio-logical imaging and clinical diagnosis. Organic fluoro-phores, however, have certain characteristics that limittheir advantages in some applications. These limitationsinclude narrow excitation bands and broad emissionbands with red spectral tails, which make the simultaneousevaluation of several light-emitting probes difficult due tospectral overlap. Also, many organic dyes exhibit highp… 相似文献
104.
Silva MD Savinainen A Kapadia R Ruan J Siebert E Avitahl N Mosher R Anderson K Jaffee B Schopf L Chandra S 《Molecular imaging》2004,3(4):312-318
Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10) stored in formalin consisted of approximately 600 30-mum slices acquired on a 512 x 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents. 相似文献
105.
Ruan W Lindner E Langosch D 《Protein science : a publication of the Protein Society》2004,13(2):555-559
An oligo-leucine sequence has previously been shown to function as an artificial transmembrane segment that efficiently self-assembles in membranes and in detergent solution. Here, a novel technique, asparagine-scanning mutagenesis, was applied to probe the interface of the self-assembled oligo-leucine domain. This novel approach identifies interfacial residues whose exchange to asparagine leads to enhanced self-interaction of transmembrane helices by interhelical hydrogen bond formation. As analyzed by the ToxR system in membranes, the interface formed by the oligo-leucine domain is based on a leucine-zipper-like heptad repeat pattern of amino acids. In general, the strongest impacts on self-assembly were seen with asparagines located around the center of the sequence, indicating that interaction is be more efficient here than at the termini of the transmembrane domains. 相似文献
106.
We consider a two-dimensional model of cell-to-cell spread of HIV-1 in tissue cultures, assuming that infection is spread
directly from infected cells to healthy cells and neglecting the effects of free virus. The intracellular incubation period
is modeled by a gamma distribution and the model is a system of two differential equations with distributed delay, which includes
the differential equations model with a discrete delay and the ordinary differential equations model as special cases. We
study the stability in all three types of models. It is shown that the ODE model is globally stable while both delay models
exhibit Hopf bifurcations by using the (average) delay as a bifurcation parameter. The results indicate that, differing from
the cell-to-free virus spread models, the cell-to-cell spread models can produce infective oscillations in typical tissue
culture parameter regimes and the latently infected cells are instrumental in sustaining the infection. Our delayed cell-to-cell
models may be applicable to study other types of viral infections such as human T-cell leukaemia virus type 1 (HTLV-1).
Received: 18 November 2000 /
Published online: 28 February 2003
RID="*"
ID="*" Research was partially supported by the NSERC and MITACS of Canada and a start-up fund from the College of Arts and
Sciences at the University of Miami. On leave from Dalhousie University, Halifax, Nova Scotia, Canada.
Current address: Department of Mathematics, Clarke College, Dubuque, Iowa 52001, USA
Key words or phrases: HIV-1 – Cell-to-cell spread – Time delay – Stability – Hopf bifurcation – Periodicity 相似文献
107.
Germinal vesicle (GV) breakdown in mammalian oocytes is regulated by the activation of maturation promoting factor (MPF). We investigated a specific cdc2 kinase inhibitor, roscovitine, to maintain pig oocytes in the GV stage. Cumulus-oocyte complexes (COCs) were aspirated from slaughterhouse ovaries and cultured for 44 hr in NCSU#23 medium containing different levels of roscovitine (0, 10, 20, 30, 40, 50 microM in Experiment 1 and 0, 40, 60, 80, 100, 120 microM in Experiment 2). The COCs were cultured for another 44 hr after removal of the chemical. Twenty oocytes in each group were fixed at 44 hr for immunocytochemical labeling of the cytoskeleton and the rest (approximately 20/group) were fixed at the end of 88 hr after culture. Results showed that the inhibition of the oocyte in the GV stage was not effective when 10-50 microM (Experiment 1) of roscovitine were used (19-34%). When oocytes were released from the inhibitor, similar proportions (70-83%) of oocytes were observed in the MII or advanced stages among treatments. However, when higher concentrations of roscovitine were used (Experiment 2), significantly greater inhibitory effect was observed at the levels of 80-120 microM with 83-91% oocytes being blocked in the GV stage when compared to the control (9%) and the 40-60 microM (27-43%) groups (P < 0.05). Although 15-21% of the oocytes showed abnormal MII morphology with aberrant meiotic spindles and/or formation of cytoplasmic microtubules, a substantial number of oocytes resumed meiosis and reached MII stage at 44 hr after removal of this chemical. In Experiment 3, different concentrations of roscovitine (0, 20, 40, and 80 microM) were tested to examine the length of intervals (0, 11, 22, 33, and 44 hr) for an effective inhibition. Results showed that the inhibitory effect was significantly more prominent at 22 hr than that at 33 and 44 hr after roscovitine treatment in all treatment groups (P < 0.05). This study demonstrated that roscovitine-treated oocytes resumed meiosis after removal of the inhibitor. This could provide flexibility for studying porcine oocyte development and embryo cloning and may have application in other species. 相似文献
108.
Yang J Si T Ling Y Ruan Y Han Y Wang X Zhou M Zhang D Zhang H Kong Q Liu C Li X Yu Y Liu S Shu L Ma D Wei J Zhang D 《Life sciences》2003,72(26):3017-3021
An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with the abnormal immune system, and cytokines may be important in schizophrenia. Among these cytokines, interleukin-1beta may play a role in the pathogenesis of the disease. In the present study, we investigated the genetic association between a TaqI polymorphism in interleukin-1beta gene (IL-1beta) and schizophrenia by restriction fragment length polymorphism (RFLP) analysis among 132 Chinese families of Han descent. The transmission disequilibrium test (TDT) did not demonstrate an allelic association with schizophrenia. Our results suggested that the TaqI polymorphism in IL-1beta gene might not confer increased susceptibility for schizophrenia. 相似文献
109.
From our topological arrangement model of prostaglandin I(2) synthase (PGIS) created by homology modeling and topology studies, we hypothesized that the helix F/G loop of PGIS contains a membrane contact region distinct from the N-terminal membrane anchor domain. To provide direct experimental data we have explored the relationship between the endoplasmic reticulum (ER) membrane and the PGIS F/G loop using a constrained synthetic peptide to mimic PGIS residues 208-230 cyclized on both ends through a disulfide bond with added Cys residues. The solution structure and the residues important for membrane contact of the constrained PGIS F/G loop peptide were investigated by high-resolution 1H two-dimensional nuclear magnetic resonance (2D NMR) experiments and a spin label incorporation technique. Through the combination of 2D NMR experiments in the presence of dodecylphosphocholine (DPC) micelles used to mimic the membrane environment, complete 1H NMR assignments of the F/G loop segment have been obtained and the solution structure of the peptide has been determined. The PGIS F/G loop segment shows a defined helix turn helix conformation, which is similar to the three-dimensional crystallography structure of P450BM3 in the corresponding region. The orientation and the residues contacted with the membrane of the PGIS F/G loop were evaluated from the effect of incorporation of a spin-labeled 12-doxylstearate into the DPC micelles with the peptide. Three residues in the peptide corresponding to the PGIS residues L217 (L11), L222 (L16), and V224 (V18) have been demonstrated to contact the DPC micelles, which implies that the residues are involved in contact with the ER membrane in the native membrane-bound PGIS. These results provided the first experimental evidence to localize the membrane contact residues in the F/G loop region of microsomal P450 and are valuable to further define and understand the membrane topology of PGIS and those of other microsomal P450s in the native membrane environment. 相似文献
110.