不同类型椎间融合器的材料学特征及其临床应用效果

目的:介绍各种不同椎间融合器在材料上的特点,以及不同椎间融合器的临床应用效果。方法:主要选择被Medline收录的外文文献和在国内核心杂志上发表的有关椎间融合器的文献,就其内容进行分析、分类、归纳及总结。结果:共检索到36篇文献,其中21篇从发展历史、材料等方面介绍了椎间融合器逐渐适应神经根、椎间隙、脊柱等压力的进程;证实了椎间融合器能够治愈多种脊椎疾病;15篇关于椎间融合器在使用后的效果及手术并发症。最后有10篇文章列为参考文献。结论:随着材料学发展和设计的进步,椎间融合器已能成功的缓解椎间隙、神经根、脊柱等的压迫,生物型、可吸收型椎间融合器将是未来发展的主流。但是,由于此类融合器的随访时间尚短,更多的相关研究还有待进行。     

Ganciclovir Treatment for Cytomegalovirus Infection in Immunocompromised Patients With Renal Disease

The safety and efficacy of a 10-day course of ganciclovir therapywas assessed in 17 consecutive patients with proven cytomegalovirusinfection. The patients were receiving immunosuppressive therapyfor a variety of non-malignant renal conditions, including renaltransplantation (seven patients), small vessel vasculitis (sixpatients), systemic lupus erythematosus (three patients) andGoodpasture's disease (one patient). Fifteen patients were pyrexialat the time of their cytomegalovirus infection. Twelve patientshad pneumonitis manifesting as a pulmonary parenchymal infiltrateor a reduction in gas transfer. Fourteen patients had a significantlymphopenia (lymphocyte count <1x10⁹/l), nine were leucopenic(white cell count <3.5xtimes 10⁹/l) and nine had abnormalliver biochemistry. One patient had an infection of the ileumand one an infection of the larynx. All these disease manifestationsresponded completely to a single course of ganciclovir therapy.There were no clinical relapses and no side effects were observed. Ganciclovir is a safe and effective therapy when administeredearly in the course of cytomegalovirus infection in immunosuppressedpatients with renal impairment.     

Detection of precursor Th cells in mesenteric lymph nodes after oral immunization with protein antigen and cholera toxin

We have characterized the earliest antigen-specific Th cells in murine mesenteric lymph nodes (MLN), following oral immunization with the hen egg lysozyme (HEL) as antigen and cholera toxin (CT) as adjuvant. We did this by analyzing in vitro proliferation and cytokine production in response to HEL by the MLN T cells. MLN cells taken 5 days after a single oral immunization with HEL and CT provided the earliest source of proliferating HEL-specific T cells. This proliferation was completely inhibited by anti-IL-2, but not inhibited by anti-IL-4 antibody. IL-2 protein was detected in culture supernatants but not IL- 4 using ELISA or bioassays. IL-4 mRNA was not found in responding cells using RT-PCR. Some of the day 5 MLN cultures produced IFN-gamma in response to HEL, but isolated T cells from the same MLN did not. Exogenous IL-4 alone did not stimulate day 5 MLN T cells, but IL-4 did synergize with HEL to induce a large proliferative response. The data indicate that the HEL-specific CD4 T cell pool in MLN 5 days after oral immunization is composed of undifferentiated precursor Th cells. These cells have the potential for IL-2 production and IL-4R expression upon re-stimulation in vitro.      

An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21

In our efforts to identify new loci responsible for non-syndromic autosomal recessive forms of deafness, DFNB loci, we have pursued the analysis of large consanguineous affected families living in geographically isolated areas. Here, we report on the study of a Lebanese family comprising nine members presenting with a pre-lingual severe to profound sensorineural isolated form of deafness. Linkage analysis led to the characterization of a new locus, DFNB21, which was assigned to chromosome 11q23-25. Already mapped to this chromosomal region was TECTA. This gene encodes alpha-tectorin, a 2155 amino acid protein which is a component of the tectorial membrane. This gene recently has been shown to be responsible for a dominant form of deafness, DFNA8/12. Sequence analysis of the TECTA gene in the DFNB21- affected family revealed a G to A transition in the donor splice site (GT) of intron 9, predicted to lead to a truncated protein of 971 amino acids. This establishes that alpha-tectorin mutations can be responsible for both dominant and recessive forms of deafness. Comparison of the phenotype of the DFNB21 heterozygous carriers with that of DFNA8/12-affected individuals supports the hypothesis that the TECTA mutations which cause the dominant form of deafness have a dominant-negative effect. The present results provide genetic evidence for alpha-tectorin forming homo- or heteromeric structures.      

Effect of calcium phosphate coating crystallinity and implant surface roughness on differentiation of rat bone marrow cells

In this study, we examined the effect of calcium phosphate (Ca-P) coating crystallinity and of surface roughness on growth and differentiation of osteogenic cells. Grit-blasted titanium substrates were provided with Ca-P coatings of different crystallinities. Rat bone marrow (RBM) cells were cultured on these substrates and on noncoated rough and smooth titanium substrates. After specific culture times, expression of osteogenic markers by the cells was studied. Cells cultured on crystalline coatings and on titanium substrates proliferate, express alkaline phosphatase, osteocalcin (OC), and show mineralization of the extracellular matrix. Rough titanium substrates only express low OC levels. Significantly higher OC levels were expressed on smooth titanium, and even higher levels on the crystalline Ca-P coating. No difference was found in calcification between smooth and rough titanium. The crystalline coating showed more calcification than the titanium substrates. When substrates without cells were incubated in medium, precipitation of calcium was found. On the titanium substrates, this precipitate disappeared after prolonged incubation. The precipitate on the crystalline coating was stable and increased with longer incubation times. On the amorphous coatings, no proliferation and differentiation of RBM cells were found. After longer culture periods, substrates showed extensive dissolution. Cells on the amorphous coatings did express high levels of prostaglandin E2. In contrast, prostaglandin E2 expression was low for the other substrates. We conclude that crystalline Ca-P coatings stimulate differentiation of RBM cells, to a higher extent than titanium substrates. Surface roughness only has a limited effect on phenotype expression of the cells. In contrast, thin amorphous coatings show negative effects on the growth and differentiation of cultured RBM cells.     

The gene for schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36

Schnyder's crystalline corneal dystrophy (SCCD) is an autosomal dominant eye disease characterized by a bilateral clouding of the central cornea, arcus lipoides and/or visible crystalline deposits of cholesterol in the stroma. There is accumulation of phospholipid, unesterified cholesterol and cholesterol ester in the corneal stroma; this is believed to be due to an imbalance in the local factors affecting lipid/cholesterol transport or metabolism. The cellular mechanism of abnormal lipid transport and metabolism in SCCD is of interest due to its potential involvement in atherosclerosis, and its implications for the pathogenesis of cerebrovascular, coronary and peripheral vascular disease as well as corneal opacification. To determine the chromosomal location of the SCCD locus, genome-wide linkage analysis has been performed in two large Swede-Finn kindreds recently identified in central Massachusetts. After analysing 300 microsatellite markers > 90% of the genome was excluded from linkage to the SCCD locus. We now report the chromosomal assignment of the gene for SCCD in both families to be 1p34.1-p36; the maximum multipoint lod- score was 8.48 in the interval between D1S214 and D1S503. From haplotype analysis, the SCCD locus lies in the 16 cM interval between markers D1S2663 and D1S228. Several candidate genes for SCCD have been localized to the 1p34.1-p36 interval.      

Encapsidated adenovirus minichromosomes allow delivery and expression of a 14 kb dystrophin cDNA to muscle cells

Adenovirus-mediated gene transfer to muscle is a promising technology for gene therapy of Duchenne muscular dystrophy (DMD). However, currently available recombinant adenovirus vectors have several limitations, including a limited cloning capacity of approximately 8.5 kb, and the induction of a host immune response that leads to transient gene expression of 3-4 weeks in immunocompetent animals. Gene therapy for DMD could benefit from the development of adenoviral vectors with an increased cloning capacity to accommodate a full-length (approximately 14 kb) dystrophin cDNA. This increased capacity should also accommodate gene regulatory elements to achieve expression of transduced genes in a tissue-specific manner. Additional vector modifications that eliminate adenoviral genes, expression of which is associated with development of a host immune response, might greatly increase long-term expression of virally delivered genes in vivo. We have constructed encapsidated adenovirus minichromosomes theoretically capable of delivering up to 35 kb of non-viral exogenous DNA. These minichromosomes are derived from bacterial plasmids containing two fused inverted adenovirus origins of replication embedded in a circular genome, the adenovirus packaging signals, a beta-galactosidase reporter gene and a full-length dystrophin cDNA regulated by a muscle-specific enhancer/promoter. The encapsidated minichromosomes are propagated in vitro by trans-complementation with a replication-defective (E1 + E3 deleted) helper virus. We show that the minichromosomes can be propagated to high titer (> 10(8)/ml) and purified on CsCl gradients due to their buoyancy difference relative to helper virus. These vectors are able to transduce myogenic cell cultures and express dystrophin in myotubes. These results suggest that encapsidated adenovirus minichromosomes may be useful for gene transfer to muscle and other tissues.