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61.
Evolutionary silencing of the human elastase I gene (ELA1) 总被引:6,自引:0,他引:6
62.
Mauro S. Sandrin Ian F. C. McKenzie Roger W. Melvold Günter J. Hmmerling 《European journal of immunology》1982,12(3):205-209
The B6.C-H-2bm12 has been examined serologically with a new set of reagents and several complementation studies were performed to determine the extent of the mutation. The results show that: (a) the mutation has also affected the site(s) bound by xenogeneic anti-Ia antibodies; (b) the IJb region was not affected; (c) complementation studies with stains bearing a, b, d, k and s haplotypes did not complement bm12 for the expression of the lost I-Ab specificities, suggesting a structural (rather than regulatory) gene alteration in bm12; (d) H-2 haplotypes b and bm12 could complement d to establish the Ia.22 specificity, indicating that Ia-1 and Ae are separate genes in the I-A subregion. In addition, an antibody to the gained specificity on bm12 is described. 相似文献
63.
McKenzie BS Corbett AJ Brady JL Dyer CM Strugnell RA Kent SJ Kramer DR Boyle JS Lew AM 《Immunologic research》2001,24(3):225-244
There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require
strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by
current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great
interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization.
We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting
delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial,
replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines
or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use
of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this
review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying
mechanisms that might argue for or against these strategies. 相似文献
64.
Huisman JA; Paulussen RJ; Geurts TB; Odink J; Rekers H 《Human reproduction (Oxford, England)》1997,12(1):34-38
The objective was to demonstrate bioequivalence between s.c. and i.m.
administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio
3:1). In two randomized, single-centre, cross-over studies, 18 healthy
volunteers on each formulation were assigned to one of the two
administration sequences. Subjects were given single doses of one of the
above gonadotrophins after endogenous gonadotrophin production had first
been suppressed using high-dose oral contraceptive. Subsequently, rate
(Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone
(FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax
and AUC, analysis of variance (ANOVA) was performed on log-transformed data
and for tmax ANOVA was performed on ranks. Intramuscular and s.c.
injections of Humegon were bioequivalent with respect to the main
pharmacokinetic parameters, being AUC and Cmax of FSH absorption.
Intramuscular and s.c. injections of Normegon were bioequivalent with
respect to the AUC of FSH and not bioequivalent with respect to the Cmax of
FSH. For tmax of FSH as well as for most LH variables of both preparations,
bioequivalence could not be proven due to the high intra- and
interindividual variability and/or concentrations being close to the
detection limit. Thus, the main pharmacokinetic FSH variables after i.m.
and s.c. administration of Humegon and Normegon were bioequivalent.
相似文献
65.
Interleukin-9 is a cytokine produced by Th2 cells and is a candidate gene for asthma and atopy. We have generated IL-9-deficient mice to delineate the specific roles of IL-9 in Th2 responses. Using a pulmonary granuloma model, we have demonstrated a distinct requirement for IL-9 in the rapid and robust generation of pulmonary goblet cell hyperplasia and mastocytosis in response to lung challenge. In contrast, eosinophilia and granuloma formation were not affected. IL-9 was not required for T cell development or differentiation, the generation of naive or antigen-driven antibody responses, or the expulsion of the intestinal parasitic nematode Nippostrongylus brasiliensis. Thus, deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation. 相似文献
66.
Intrafractional motion during proton beam scanning 总被引:2,自引:0,他引:2
Lambert J Suchowerska N McKenzie DR Jackson M 《Physics in medicine and biology》2005,50(20):4853-4862
Patient and internal organ motion during treatment with a scanned proton beam can introduce unplanned heterogeneities in the dose distribution throughout the irradiated volume. With static beam techniques, a margin around the target volume is added to compensate for patient and organ motion. This margin may not provide the solution with dynamic beam scanning. Intrafractional motion parallel and perpendicular to the beam axis is studied using two different scanning methods on a cubic water phantom. The direction of motion relative to the beam scanning direction as well as the method of scanning the proton beam across the target has a significant effect on the resulting dose distribution within the target volume. In the extreme cases studied here up to 100% of the target receives a dose outside the recommended limits, with a minimum dose as low as 34% of the prescribed dose. 相似文献
67.
W A Sadler G M Shanks C P Wright J S Emanuel J L McKenzie S E Anderson D N Hart 《Pathology》1987,19(1):71-76
A monoclonal antibody, CMRF1, to human beta 2-microglobulin (beta 2m) was used to purify antigen to develop an in-house beta 2m radioimmunoassay. This immunoadsorption purified material was used to prepare a rabbit anti-beta 2m serum and was radiolabelled for the radioimmunoassay. The assay compared favourably with a widely used commercial radioimmunoassay but the immunological potency of the in-house standard was lower than that of the commercial reagent. This potency difference was not accounted for by antigenic denaturation. Subsequent two-dimensional gel electrophoresis revealed a second 12,000 dalton protein with a higher isoelectric point than beta 2m in the immunoadsorption purified material, which was also present, although in lesser amounts, in the commercial product. The different relative content of the additional 12,000 dalton protein appeared to explain the immunological potency difference between the in-house and the commercial standard. These results strengthen suggestions that there may be some heterogeneity or polymorphism in human beta 2m. 相似文献
68.
Cholera toxin has been shown to modulate immune responses, generally producing enhancement when administered simultaneously with antigen and suppression when administered a day or more earlier. In a previous study using chronically isolated ileal loops in rabbits, we found that two subcutaneous (s.c.) "priming" and "boosting" doses of biologically active cholera toxin suppressed the local intestinal immunoglobulin A response to intraloop doses of cholera toxin. In the study reported here, two different biologically inactive but antigenically intact cholera toxoids, glutaraldehyde toxoid and choleragenoid, where administered s.c. by the same immunization schedule as for toxin in the earlier experiment. Suppression of local immune response to intraloop cholera toxin as compared with animals receiving no s.c. inoculations was again found. The results suggest that in this model suppression was immunological (mediated by an immunological mechanism) rather than toxigenic (mediated by biological activity of cholera toxin). In addition, the occurrence of suppression of local intestinal immune response after systemic immunization suggests that suboptimal protection against enteric infections could occur after s.c. vaccination. 相似文献
69.
Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee. 相似文献
70.
Mark D. Hulett Ian F. C. McKenzie P. Mark Hogarth 《European journal of immunology》1993,23(3):640-645
FcγRII and Fc?RI are functionally distinct cell surface receptors for immunoglobulin (Ig); FcγRII binds IgG with low affinity, whereas Fc?RI binds IgE with high affinity, yet they are homologous in structure and sequence having extracellular regions containing two Ig-like domains with 38% amino acid identity. Chimeric receptors derived from human FcγRII and FcγRI were produced by exchanging homologous regions of the two receptors to define binding region(s) for IgG in FcγRII and IgE in Fc?RI. Firstly, a chimeric form of the Fc?RI α chain was produced by replacing the transmembrane region and cytoplasmic tail with that of FcγRII. This mutant α chain could be expressed on the cell surface independently of associated β and γ subunits, and retained high-affinity IgE binding, indicating that the extracellular region of the FcγRI α chain is sufficient for high-affinity IgE binding. Secondly, to identify the role of the individual domains in Fc binding of both FcγRII and FcγRI, chimeric receptors were generated by exchanging the first extracellular domains between FcγRII and the α chain mutant and used to demonstrate that the second extracellular domain of both receptors contains region(s) directly involved in Ig binding. Additional chimeric receptors were constructed to localize the Ig interactive regions in domain two of FcγRII and FcγRI; these identified a single region of IgG binding in FcγRII located between residues Ser136 to Val169, and at least three independent IgE binding regions in the FcγRI α chain, between residues Trp87 to Lys128, Tyr129 to Asp145, and Ser146 to Val169. 相似文献