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1.
Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of
rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been
established.
Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological
milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium
thiomalate thus can exist in several different physical states which may have different biological activity. In addition the
pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action,
efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on
the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist
at different pH.
Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow
or a colourless solution. These have some similar but several different biological activities.
Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to
the wide variation in physical structure and biological activities exhibited by these compounds. 相似文献
2.
3.
N Bellamy W W Buchanan J M Esdaile A G Fam W F Kean J M Thompson G A Wells J Campbell 《The Journal of rheumatology》1991,18(11):1716-1722
Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for clinical trials in ankylosing spondylitis, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we have employed a Delphi technique to establish estimates for delta, and calculated the sample size requirements under 2 different conditions of Type I and Type II error probabilities. 相似文献
4.
Transplant Tolerance in Non-Human Primates: Progress, Current Challenges and Unmet Needs 总被引:1,自引:1,他引:0
L. S. Kean S. Gangappa T. C. Pearson C. P. Larsen 《American journal of transplantation》2006,6(5P1):884-893
Given the significant morbidity associated with current post-transplant immunosuppressive regimens, induction of immune tolerance continues to be an important goal of clinical organ transplantation. While many strategies for inducing tolerance have been successfully applied in murine models, significant barriers are faced when translating these approaches to the clinic. This has necessitated pre-clinical studies in the more closely related model system, the non-human primates (NHP). In this review, we will discuss the four most prominent strategies for inducing transplantation tolerance and highlight their relative success and shortcomings in NHP. These strategies are: (1) T-cell costimulation blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance induction through regulatory T-cells. After discussing the progress that has been made with each of these strategies, we will identify this field's most pressing unmet needs and discuss how we may best overcome the resulting barriers to tolerance induction. 相似文献
5.
6.
K. Hamby A. Trexler T. C. Pearson C. P. Larsen M. R. Rigby L. S. Kean 《American journal of transplantation》2007,7(8):1884-1896
We have used a sensitive and specific in vivo killing assay to monitor the kinetics, anatomic location and mechanisms controlling NK-mediated rejection of Balb/c bone marrow by C57BL/6 natural killer (NK) cells. We find that NK killing of fully allogeneic bone marrow is a rapid, highly efficient process, leading to substantial rejection of transplanted marrow within 6 h of transplant and elimination of 85% of the transplanted cells within 2 days. NK-mediated rejection occurred predominantly in the spleen, with sparing of rejection in the bone marrow and lymph nodes. Rejection was dependent on Perforin gene function, but was independent of interferon-gamma. Finally, rejection of Balb/c bone marrow by B6 NK cells required signaling through the Ly49D receptor, but occurred despite blockade of NKG2D, which distinguishes these results from previous studies using semiallogeneic transplant pairs. These results identify NK cells as highly active mediators of bone marrow rejection, and suggest that inhibiting NK function early during transplantation may increase the efficiency of engraftment and allow successful engraftment of limiting doses of donor bone marrow. 相似文献
7.
Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant. 相似文献
8.
Image-directed percutaneous biopsies with a biopsy gun 总被引:3,自引:0,他引:3
Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method. 相似文献
9.
10.
Substitution in the poliovirus replicase gene determines actinomycin D sensitivity of viral replication at elevated temperature 总被引:2,自引:0,他引:2
A series of ts+ revertants and recombinants derived from a temperature-sensitive plurimutant of poliovirus type 1 showed identical plaquing efficiencies at 37 degrees C and at 39 degrees C and exhibited similar yields and plaque morphology to wild-type virus. However, these viruses were characterized by clear inhibition of viral RNA synthesis at 39 degrees C, as measured by uridine incorporation in the presence of actinomycin D. Similarly, virus yields were decreased by one log in the presence of actinomycin D during infection at 39 degrees C. All the ts+ recombinants formed between temperature-sensitive mutants of poliovirus that were inhibited by actinomycin D carried a glutamine----histidine modification at residue 170 of their viral replicase (polypeptide 3D), due to a G----U substitution at nucleotide 6496. Inhibition of viral growth was increased by pretreatment of cells with actinomycin D for 3 h prior to infection, suggesting that actinomycin D sensitivity could reflect an increased dependence of viral RNA replication on host factor(s). 相似文献