Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy

Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) cou

The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy

Background. The present study was undertaken to determine the role of preformed and induced anti-non-Gal antibodies in the rejection of hDAF pig-to-baboon kidney xenotransplants after anti-Gal antibody neutralization therapy. Methods. Seven baboons receiv

TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival

In xenotransplantation, donor endothelium is the first target of immunological attack. Activation of the endothelial cell by preformed natural antibodies leads to platelet binding via the interaction of the glycoprotein (GP) Ib and von Willebrand factor (vWF). TMVA is a novel GPIb-binding protein purified from the venom of Trimeresurus mucrosquamatus. In this study, the inhibitory effect of TMVA on platelet aggregation in rats and the effect on discordant guinea pig-to-rat cardiac xenograft survival were investigated. Three doses (8, 20 or 40 mug/kg) of TMVA were infused intravenously to 30 rats respectively. Platelet aggregation rate was assayed 0.5, 12, and 24 h after TMVA administration. Wister rats underwent guinea pig cardiac cervical heterotopic transplantation using single dosing of TMVA (20 mug/kg, i.v., 0.5 h before reperfusion). Additionally, levels of TXB2 and 6-keto-PGF(1alpha) within rejected graft tissues were determined by radioimmunoassay. Treatment with TMVA at a dose of 20 or 40 mug/kg resulted in complete inhibition of platelet aggregation 0.5 h after TMVA administration. Rats receiving guinea pig cardiac xenografts after TMVA therapy had significantly prolonged xenograft survival. Histologic and immunopathologic analysis of cardiac xenografts in TMVA treatment group showed no intragraft platelet microthrombi formation and fibrin deposition. Additionally, the ratio of 6-keto-PGF(1alpha) to TXB2 in TMVA treatment group was significantly higher than those in control group. We conclude that the use of this novel GPIb-binding protein was very effective in preventing platelet microthrombi formation and fibrin deposition in a guinea pig-to-rat model and resulted in prolongation of xenograft survival. The increased ratio of PGI(2)/TXA(2) in TMVA treatment group may protect xenografts from the endothelial cell activation and contribute to the prolongation of xenograft survival.

Excision of Sleeping Beauty transposons: parameters and applications to gene therapy

A major problem in gene therapy is the determination of the rates at which gene transfer has occurred. Our work has focused on applications of the Sleeping Beauty (SB) transposon system as a non-viral vector for gene therapy. Excision of a transposon from a donor molecule and its integration into a cellular chromosome are catalyzed by SB transposase. In this study, we used a plasmid-based excision assay to study the excision step of transposition. We used the excision assay to evaluate the importance of various sequences that border the sites of excision inside and outside the transposon in order to determine the most active sequences for transposition from a donor plasmid. These findings together with our previous results in transposase binding to the terminal repeats suggest that the sequences in the transposon-junction of SB are involved in steps subsequent to DNA binding but before excision, and that they may have a role in transposase-transposon interaction. We found that SB transposons leave characteristically different footprints at excision sites in different cell types, suggesting that alternative repair machineries operate in concert with transposition. Most importantly, we found that the rates of excision correlate with the rates of transposition. We used this finding to assess transposition in livers of mice that were injected with the SB transposon and transposase. The excision assay appears to be a relatively quick and easy method to optimize protocols for delivery of genes in SB transposons to mammalian chromosomes in living animals. Copyright (C) 2004 John Wiley Sons, Ltd.

HORMONAL REPLACEMENT THERAPY IN FISH - HUMAN GROWTH-HORMONE GENE-FUNCTION IN HYPOPHYSECTOMIZED CARP

Transgenic common carp, Cyprinus carpio, produced by the microinjection of fertilized eggs with a linearized chimeric plasmid pMThGH, a human growth hormone (hGH) gene with a mouse metallothionein-I (MT) gene promoter in pBR322, were used to produce F1 and F2 transgenics. Following hypophysectomy of the transgenic F2 common carp, non-transgenic common carp and non-transgenic crucian carp, growth was monitored for up to 110 days. In addition, recombinant hGH was injected subcutaenously into a group of the non-transgenic crucian carp. Growth rate analyses indicated that (1) hypophysectomy of non-transgenic common carp and crucian carp results in the cessation of growth, (2) hGH administration can stimulate the growth of hypophysectomized crucian carp and (3) hypophysectomized hGH-transgenic common carp continue to grow in the absence of their own growth hormone, suggesting that the hGH-transgene is being expressed in tissues other than the pituitary.

Laser irradiation cell photothermal therapy assisted by gold nanoparticles

The strong absorption of gold nanoparticles in the visible spectral range allows the localized generation of heat in a volume of only a few tens of nanometer. The efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest that the gold nanoparticles can be used as selective photothermal agents in molecular cell targeting. The selective destruction of alkaline phosphatase, the permeabilization of the cell membrane and the selective killing of cells by laser irradiating gold nanoparticles were demonstrated. The potential of using this selective technique in molecularly targeted photothermal therapy and transfection is discussed.

Design of slow extraction system for therapy synchrotron

Based on the optimized design of the lattice for therapy synchrotron and considering the requirement of radiation therapy, the third order resonant extraction is adopted. Using the momentum-amplitude selection method, the extraction system is designed and optimized. An extraction efficiency of more than 97% and a momentum spread less than 0.11% are obtained.

Progresses of heavy-ion cancer therapy

The status of heavy-ion cancer therapy has been reviewed. The existing and constructing heavy-ion beam facilities for cancer therapy in the world are introduced. The first clinical trials of superficially placed tumor therapy at heavy ion research facility in Lanzhou (HIRFL) are presented.

Rotating wheel filter design and optimization for a uniform depth dose distribution in heavy ion therapy

Treatment planning of heavy-ion radiotherapy involves predictive calculation of not only the physical dose but also the biological dose in a patient body. The goal in designing beam-modulating devices for heavy ion therapy is to achieve uniform biological effects across the spread-out Bragg peak (SOBP). To achieve this, a mathematical model of Bragg peak movement is presented. The parameters of this model have been resolved with Monte Carlo method. And a rotating wheel filter is designed basing on the velocity of the Bragg peak movement.

Injection system design for a hadron therapy synchrotron

A synchrotron is designed for tumour therapy with C6+ ions or proton. Its injector is a cyclotron, which delivers C5+ or H-2(+) ions to the synchrotron. After comparing the methods of the single-turn injection, the multi-turn injection and the stripping injection, this paper chooses the stripping injection method. In addition, the concept design of the injection system is presented, in which the synchrotron lattice is optimized.

Design of synchrotron for hadron therapy

According to the operation and development of radiation therapy in the world, in order to further promote the radiation therapy of tumour in China, a design of a special synchrotron with two super-periodicity for hadron therapy is presented, including lattice, injection system, RF acceleration and slow extraction of the third order resonance. The synchrotron accelerates the proton beam to 250MeV and the carbon beam to 4000MeV/u.

Heavy-ion conformal irradiation in the shallow-seated tumor therapy terminal at HIRFL

Basic research related to heavy-ion cancer therapy has been done at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Now a plan of clinical trial with heavy ions has been launched at IMP. First, superficially placed tumor treatment with heavy ions is expected in the therapy terminal at the Heavy Ion Research Facility in Lanzhou (HIRFL), where carbon ion beams with energy up to 100 MeV/u can be supplied. The shallow-seated tumor therapy terminal at HIRFL is equipped with a passive beam delivery system including two orthogonal dipole magnets, which continuously scan pencil beams laterally and generate a broad and uniform irradiation field, a motor-driven energy degrader and a multi-leaf collimator. Two different types of range modulator, ripple filter and ridge filter with which Guassian-shaped physical dose and uniform biological effective dose Bragg peaks can be shaped for therapeutic ion beams respectively, have been designed and manufactured. Therefore, two-dimensional and three-dimensional conformal irradiations to tumors can be performed with the passive beam delivery system at the earlier therapy terminal. Both the conformal irradiation methods have been verified experimentally and carbon-ion conformal irradiations to patients with superficially placed tumors have been carried out at HIRFL since November 2006.