Consider the following Cauchy problem for the first order quasilinear strictly hy- perbolic system ?u ?u + A(u) = 0, ...Consider the following Cauchy problem for the first order quasilinear strictly hy- perbolic system ?u ?u + A(u) = 0, ?t ?x t = 0 : u = f(x). We let M = sup |f (x)| < +∞. x∈R The main result of this paper is that under the assumption that the system is weakly linearly degenerated, there exists a positive constant ε independent of M, such that the above Cauchy problem admits a unique global C1 solution u = u(t,x) for all t ∈ R, provided that +∞ |f (x)|dx ≤ ε, ?∞ +∞ ε |f(x)|dx ≤ . M∞展开更多
Background The treatment of hypoparathyroidism (HPT) is still a difficult clinical problem, which necessitates a new therapy. Gene therapy of HPT has been valuable, but how to improve the gene transfer efficiency and ...Background The treatment of hypoparathyroidism (HPT) is still a difficult clinical problem, which necessitates a new therapy. Gene therapy of HPT has been valuable, but how to improve the gene transfer efficiency and expression stability is a problem. This study was designed to optimize the gene therapy of HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone (PTH) gene. Methods The human PTH gene was amplified by polymerase chain reaction (PCR) from pcDNA3.1-PTH vectors and inserted into murine stem cell virus (MSCV) vectors with double enzyme digestion (EcoRI and XhoI). The recombinant vectors were transfected into PA317 packaging cell lines by the lipofectin method and screened by G418 selective medium. The condensed recombinant retroviruses were extracted and used to infect HSCs, which were injected into mice suffering from HPT. The change of symptoms and serum levels of PTH and calcium in each group of mice were investigated. Results The human PTH gene was inserted into MSCV vectors successfully and the titres were up to 2×107 colony forming unit (CFU)/ml in condensed retroviral solution. The secretion of PTH reached 15 ng·10-6·cell-1 per 48 hours. The wild type viruses were not detected via PCR amplification, so they were safe for use. The mice suffering from HPT recovered quickly and the serum levels of calcium and PTH remained normal for about three months after the HSCs recombined with PTH were injected into them. The therapeutic effect of this method was better than simple recombinant retroviruses injection.Conclusions The recombinant retroviral vectors MSCV-PTH and the high-titre condensed retroviral solution recombined with the PTH gene are obtained. The recombinant retroviral solution could infect HSCs at a high rate of efficiency. The infected HSCs could cure HPT in mice. This method has provided theoretical evidence for the clinical gene therapy of HPT.展开更多
基金Project supported by the National Natural Science Foundation of China (No.10225102) the 973 Project of the Ministry of Science and Technology of China and the Doctoral Programme Foundation of the Ministry of Education of China.
文摘Consider the following Cauchy problem for the first order quasilinear strictly hy- perbolic system ?u ?u + A(u) = 0, ?t ?x t = 0 : u = f(x). We let M = sup |f (x)| < +∞. x∈R The main result of this paper is that under the assumption that the system is weakly linearly degenerated, there exists a positive constant ε independent of M, such that the above Cauchy problem admits a unique global C1 solution u = u(t,x) for all t ∈ R, provided that +∞ |f (x)|dx ≤ ε, ?∞ +∞ ε |f(x)|dx ≤ . M∞
文摘Background The treatment of hypoparathyroidism (HPT) is still a difficult clinical problem, which necessitates a new therapy. Gene therapy of HPT has been valuable, but how to improve the gene transfer efficiency and expression stability is a problem. This study was designed to optimize the gene therapy of HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone (PTH) gene. Methods The human PTH gene was amplified by polymerase chain reaction (PCR) from pcDNA3.1-PTH vectors and inserted into murine stem cell virus (MSCV) vectors with double enzyme digestion (EcoRI and XhoI). The recombinant vectors were transfected into PA317 packaging cell lines by the lipofectin method and screened by G418 selective medium. The condensed recombinant retroviruses were extracted and used to infect HSCs, which were injected into mice suffering from HPT. The change of symptoms and serum levels of PTH and calcium in each group of mice were investigated. Results The human PTH gene was inserted into MSCV vectors successfully and the titres were up to 2×107 colony forming unit (CFU)/ml in condensed retroviral solution. The secretion of PTH reached 15 ng·10-6·cell-1 per 48 hours. The wild type viruses were not detected via PCR amplification, so they were safe for use. The mice suffering from HPT recovered quickly and the serum levels of calcium and PTH remained normal for about three months after the HSCs recombined with PTH were injected into them. The therapeutic effect of this method was better than simple recombinant retroviruses injection.Conclusions The recombinant retroviral vectors MSCV-PTH and the high-titre condensed retroviral solution recombined with the PTH gene are obtained. The recombinant retroviral solution could infect HSCs at a high rate of efficiency. The infected HSCs could cure HPT in mice. This method has provided theoretical evidence for the clinical gene therapy of HPT.
