Objective To investigate a new strategy of bone marrow transplantation (BMT) for donor-specific tolerance induction after heart transplantation. Methods Donor bone marrow cells (BMCs)were harvested simultaneously with donor cardiac graft using modified perfusion method (PM) ,then stored in a -80 ℃ refrigerator after filtration and centrifugation. Whole BMCs (IBM-BMT) (monocytes 1.2 ×107/kg,CD34+ cells 2.38× 105/kg) in host iliac bones were injected into the bone marrow cavity 40 days after heart transplantation. Preconditoning regimens that consisted of fludarabine, antithymoctye globin and total lymphoid irradiation were performed 3 days before BMT. Tacrolimus (Tac) was administrated intravenously after BMT or orally in conjunction with mycophenolate mofetil (MMF) 3 weeks later.Cyclosporine and MMF were orally administrated 6 weeks later. Donor chimerism was detected using short tandem repeats-polymerase chain reaction in monocytes from peripheral blood at the 2nd,4th, 8th or 12th week after BMT or BMCs at the 4th, 8th or 12th week after BMT. Intramyocardium electrocardiography examination or endomyocardial biopsy was performed weekly or monthly respectively. Mixed lymphocyte reactions (MLR) were performed 3 months after BMT. Results Donor chimerism in monocytes in peripheral blood or BMCs in iliac bones measured at the 1 st,2nd and 3rd month after BMT was 26.3%, 19.1%,4.8% ,and 46.3%, 24.4%, 7.6%, respectively. After 3-month follow-up, there was no rejection confirmed by endomyocardial biopsy or intramyocardium electrocardiography. Echocardiography revealed that the diastolic and systolic function of the cardiac graft was maintained well 3 months after BMT. MLR revealed donor-specific hyporesponsiveness while immunocompetence was preserved to third-party antigens. Conclusion These findings indicate that the two-stage BMT strategy is a safe and feasible method for the induction of donor-specific tolerance via stable mixed chimerism and needs to be further confirmed after a long-term observation. 相似文献
Unilateral spinal anesthesia (USpA) has been reported to potentiate spinal anaesthesia and is used in geriatric patients. The purpose of this study was to determine the median effective dose (ED50) of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine USpA for geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.
Methods
A total of 60 geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery were enrolled in this study. The patients were randomized into 2 groups to receive either intrathecal 0.5% hypobaric bupivacaine USpA (group B) or 0.5% hypobaric ropivacaine USpA (group R). Effective anesthesia was defined as a T10 sensory blockade level maintained for more than 60 min, and a Bromage score of 3 on the operation side within 10 min after injection with no additional epidural anesthetic required during surgery. The ED50 of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine was calculated using the Dixon and Massey formula.
Results
No significant differences were found between the two groups in terms of demographic data. The ED50 of 0.5% hypobaric bupivacaine USpA was 4.66 mg (95% confidence interval CI 4.69–4.63 mg) mg and that of 0.5% hypobaric ropivacaine USpA was 6.43 mg (95% CI 6.47–6.39 mg) for geriatric patients undergoing hip replacement surgery.
Conclusion
We find the ED50 were lower, and the ED50 of 0.5% hypobaric bupivacaine and ropivacaine was 4.66 mg (95% CI 4.69–4.63 mg) and 6.43 mg (95% CI 6.47–6.39 mg), respectively, for USpA in geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.
A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). Behavioral analysis and electrophysiological H-reflex recordings revealed that mice transplanted with GFAP-L1 NSCs showed enhanced locomotor recovery in comparison to mice injected with wild type (WT) NSCs or control mice injected with phosphate-buffered saline (PBS). This functional recovery was further accelerated in mice transplanted with L1-expressing radial glial cells that had been immunoisolated from GFAP-L1 NSCs (GFAP-L1-i cells). Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells. 相似文献
To evaluate the prognostic efficacy of the 7th edition tumor–node–metastasis (TNM) classification compared with the 6th edition in gastric cancer patients.
Methods
A total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations.
Results
Significant differences in 5-year survival rates were observed for the T, N, and M subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio χ2 scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification.
Conclusions
Our study suggests that the 7th edition system performs better than the 6th edition in several aspects. 相似文献
The ability of the skeleton to adapt to mechanical stimuli diminishes with age in diaphyseal cortical bone, making bone formation difficult for adults. However, the effect of aging on adaptation in cancellous bone, tissue which is preferentially lost with age, is not well characterized. To develop a model for early post-menopausal women and determine the effect of aging on cancellous bone adaptation in the adult mouse skeleton, in vivo tibial compression was applied to adult (26 week old) osteopenic female mice using loading parameters, peak applied load and peak diaphyseal strain magnitude, that were previously found to be osteogenic in young, growing (10 week old) mice. A Load-Matched group received the same peak applied loads (corresponding to +2100 με at the medial diaphysis of the tibia) and a Strain-Matched group received the same peak diaphyseal strains (+1200 με, requiring half the load) as the young mice. The effects of mechanical loading on bone mass and architecture in adult mice were assessed using micro-computed tomography and in vivo structural stiffness measures. Adaptation occurred only in the Load-Matched group in both the metaphyseal and diaphyseal compartments. Cancellous bone mass increased 54% through trabecular thickening, and cortical area increased 41% through medullary contraction and periosteal expansion. Adult mice were able to respond to an anabolic stimulus and recover bone mass to levels seen in growing mice; however, the adaptive response was reduced relative to that in 10 week old female mice for the same applied load. Using this osteogenic loading protocol, other factors affecting pathological bone loss can be addressed using an adult osteopenic mouse model. 相似文献