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71.
George Karpati Djordje Ajdukovic Douglas Arnold Robert B. Gledhill Ronald Guttmann Paul Holland Penelope A. Koch Eric Shoubridge Desmond Spence Michel Vanasse Gordon V. Watters Michael Abrahamowicz Catherine Duff Ronald G. Worton 《Annals of neurology》1993,34(1):8-17
One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent. 相似文献
72.
Insulin and IGF-1 binding in chick sclera 总被引:2,自引:0,他引:2
R J Waldbillig D R Arnold R T Fletcher G J Chader 《Investigative ophthalmology & visual science》1990,31(6):1015-1022
The sclera of embryonic (days 10 and 14) and young adult (2-week posthatching chicks) contains distinct binding sites for insulin and for insulin-like growth factor-1 (IGF-1). Since there is a nearly 50% decrease in insulin and IGF-1 binding between embryonic day 10 and the 2nd week posthatching, it is clear that these sites are developmentally regulated. The affinity of each binding site for its ligand is stable across development. This suggests that the developmental decrease in binding is the result of a decrease in the number of binding sites. The insulin binding site in the sclera is specific for insulin since it has a high affinity for insulin and a lower affinity for IGF-1 (IC50 for unlabeled insulin = 0.4 nM; unlabeled IGF-1 = 5.0 nM). The embryonic chick sclera also contains two high-affinity IGF-1 binding sites. One of these sites exhibits poor binding specificity since it has an equal affinity for insulin and IGF-1. However, the specificity of this site increases in the young adult. The second IGF-1 binding site exhibits a more conventional specificity in that it has a higher affinity for IGF-1 than for insulin. The specificity of this binding site also improves in the young adult. The presence of insulin and IGF-1 receptor binding site subtypes is not correlated with structurally different receptor binding subunits since only a single population of binding subunits is observed (apparent molecular weight of 125 +/- 2.7 kD) in embryonic and adult sclera.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
73.
J. C. Arnold J. G. O'Grady J. M. Tredger R. Williams 《European journal of clinical pharmacology》1990,39(3):257-260
The following study of cyclosporine pharmacokinetics was performed to investigate the effects of withdrawal of low-dose maintenance prednisolone (0.3-0.6 mg/kg body weight) from the routine immunosuppressive regimen given to 10 liver transplant recipients with stable liver function tests. After oral administration of cyclosporine (6.4-10.3 mg/kg) whole blood concentrations were measured by radioimmunoassay (RIA) with both a specific monoclonal antibody detecting parent drug and a non-specific antibody additionally detecting a cross-section of metabolites. Withdrawal of prednisolone produced no significant change in the mean time and concentration of maximum blood cyclosporine (3.3 h and 1160 micrograms/l, respectively), the initial and terminal elimination half-life (3.5 h and 18.4 h, respectively) and the area under the blood concentration versus time curve (AUC) measured with either the specific or non-specific monoclonal antibody. Measurements with these two antibodies indicated that the terminal elimination of cyclosporine metabolites was more rapid than for the parent drug (half-life: 14.5 vs 18.4, respectively). 相似文献
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76.
T cell responses to orbital antigens in thyroid-associated ophthalmopathy. 总被引:3,自引:1,他引:2 下载免费PDF全文
K Arnold N Tandon R S McIntosh R Elisei M Ludgate A P Weetman 《Clinical and experimental immunology》1994,96(2):329-334
Thyroid-associated ophthalmopathy (TAO) is most likely to be a T cell-mediated disease, in which cytokines released in the extraocular muscles activate fibroblasts, increasing glycosaminoglycan production. The nature of the orbital antigen recognized by the infiltrating T cells is unclear, although it is possible that there is cross-reactivity between this and a thyroid autoantigen to explain the close association with thyroid autoimmunity. We have tested the ability of human and porcine eye muscle antigen preparations to stimulate proliferation of circulating T cells from healthy subjects and patients with TAO or Graves' disease without clinical TAO. Occasional responses were seen, particularly after depletion of CD8+ T cells, and two out of 10 TAO patients responded to eye muscle proteins of 25-50 kD after fractionation of antigens on gels and subsequent elution. There was no disease-specific response of T cells to R1, R14, D1 and 1D3, recombinant proteins identified from screening an eye muscle cDNA library with sera from patients with autoimmune thyroid disease. We have also found that interferon-gamma (IFN-gamma) production by T cells from TAO patients was not stimulated by eye muscle membrane antigens or by 1D3. These results suggest that the frequency of circulating T cells responding to eye muscle antigens in TAO is low, and that several candidate orbital antigens, including the 64-kD protein 1D3, are unlikely to be important T cell autoantigens in this condition. 相似文献
77.
A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications. 总被引:6,自引:0,他引:6 下载免费PDF全文
D C Chung A P Smith D N Louis F Graeme-Cook A L Warshaw A Arnold 《The Journal of clinical investigation》1997,100(2):404-410
The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease. 相似文献
78.
S K Brantley S F Davidson M B Johnson P A St Arnold S K Das 《Annals of plastic surgery》1990,25(1):44-47
Investigations into the effects of prior silicone exposure on subsequent capsule formation around silicone implants assume particular relevance in light of the exponential increase in the medical application of polymers such as silicone. The inert nature of silicone has been in question with regard to its effects on the immune system, specifically whether or not it may act as a hapten or antigen. The present study analyzes the effects of prior silicone exposure on subsequent capsule formation, histological consistency, and pressures when an animal is reexposed to a silicone implant. Twelve female Lewis rats (body weight 250 g) were randomly divided into two groups. Group 1 (n = 6) rats were subcutaneously injected with 2.5 ml of Freund's Complete Adjuvant, Group 2 (n = 6) rats were injected with an equal volume of adjuvant sonicated with silicone gel. At 4 weeks a gel-filled silicone implant was placed subcutaneously in each animal. Capsule pressures were obtained at 4 months and the capsules from 3 rats from Group 2 were excised and examined microscopically. Pressures were measured again at 8 months and all remaining capsules were excised and examined. No statistically significant differences were noted when comparing two profiles over time between silicone-exposed and nonexposed animals in regard to capsule thickness or capsule pressure. However, capsule pressures were significantly lower at 8 months than at 4 months in both groups (p less than 0.034). In this model, significant reductions in capsule pressure were noted in both groups over time, but prior exposure to silicone did not appear to alter capsule histology, thickness, or pressure. 相似文献
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