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71.
72.
Protection against virulent Mycobacterium avium infection following DNA vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting CD4(+) T cells
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Mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of M. avium varies from that of Mycobacterium tuberculosis, with the immunodominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this M. avium 35-kDa antigen (DNA-35) induces protective immunity against virulent M. avium infection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-gamma) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4(+) T-cell response, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and an increase in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vaccination with Mycobacterium bovis BCG and significantly greater than that for previous treated infection with M. avium. These results illustrate the importance of the 35-kDa protein in the protective response to M. avium infection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronic M. avium infection. 相似文献
73.
74.
Although CD4(+) T cells are essential for protective immunity against Mycobacterium tuberculosis infection, recent reports indicate that CD8(+) T cells may also play a critical role in the control of this infection. However, the epitope specificity and the mechanisms of activation of mycobacteria-reactive CD8(+) T cells are poorly characterized. In order to study the CD8(+) T cell responses to the model mycobacterial antigen, MPT64, we used recombinant vaccinia virus expressing MPT64 (VVWR-64) and a panel of MPT64-derived peptides to establish that the peptide MPT64(190-198) contains an H-2D(b)-restricted CD8(+) T cell epitope. A cytotoxic T lymphocyte response to this peptide could be demonstrated in M. bovis bacillus Calmette Guerin (BCG)-infected mice following repeated in vitro stimulation. When bone marrow-derived dendritic cells (DC) were infected with BCG, the expression of MHC class I molecules by DC was up-regulated in parallel with MHC class II and B7-2, whereas CD1d expression level was not modified. Moreover, BCG-infected DC activated MPT64(190-198)-specific CD8(+) T cells to secrete IFN-gamma, although with a lower efficacy than VVWR-64-infected DC. The production of IFN-gamma by MPT64(190-198)-specific CD8(+) T cells was inhibited by antibodies to MHC class I, but not to CD1d. These data suggest that mycobacteria-specific CD8(+) T cells are primed during infection. Therefore, anti-mycobacterial vaccine strategies targeting the activation of specific CD8(+) T cells by DC may have improved protective efficacy. 相似文献
75.
Identification of human T cell epitopes in the Mycobacterium leprae heat shock protein 70-kD antigen. 总被引:3,自引:0,他引:3
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E Adams W J Britton A Morgan A L Goodsall A Basten 《Clinical and experimental immunology》1993,94(3):500-506
In a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, which shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette-Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278-502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses. 相似文献
76.
Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle 总被引:1,自引:1,他引:1
Balasch J; Creus M; Fabregues F; Civico S; Reverter JC; Carmona F; Tassies D; Vanrell JA 《Human reproduction (Oxford, England)》1998,13(5):1180-1183
Increased antiphospholipid antibody prevalence has been demonstrated by a
number of recent studies in in-vitro fertilization (IVF) patients but the
potential effects of antiphospholipid antibodies on the different
components of the reproductive process and the consideration of whether to
test IVF patients for antiphospholipid antibodies are controversial. The
present study was undertaken to investigate the possible association
between the presence of circulating antiphospholipid antibodies (namely the
lupus anticoagulant and anticardiolipin antibodies), among a series of 21
consecutive IVF patients having a clinical spontaneous abortion after their
first embryo transfer. As a control group (n=42), the nearest IVF cycle
resulting in an ongoing pregnancy before and after each miscarried IVF
cycle (i.e. the closest cycles in temporal relationship to the index cycle)
was used. One patient (4.8%) in the study group and two women (4.8%) among
controls were seropositive for antiphospholipid antibodies. These low and
similar seropositivity rates found in the two groups studied lead us to
conclude that antiphospholipid antibodies testing in IVF patients should be
considered only in those women having repeated failures of
implantation/clinical abortion after embryo transfer but not in an
infertile general population reaching an IVF programme.
相似文献
77.
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
78.
Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? 总被引:4,自引:7,他引:4
Sowter MC; Akande VA; Williams JA; Hull MG 《Human reproduction (Oxford, England)》1997,12(10):2147-2150
A pilot study was designed to examine whether the outcome of embryo
transfer in women with a hydrosalpinx might be improved by surgical
drainage of the hydrosalpinx at the time of oocyte collection for in- vitro
fertilization treatment. A comparative, controlled but retrospective
analysis of the results was performed of all women with infective tubal
damage aged <40 years old, who had ovulatory cycles, a normal uterus and
a partner with normal spermatozoa. A standardized treatment regimen was
used. A maximum of three embryos were transferred. Hydrosalpinx was defined
by prior hysterosalpingography and/or laparoscopy with transcervical dye
injection. A total of 237 embryo transfer cycles in women with
hydrosalpinges (tubal distension not visible in 151, visible but not
drained in 30 and drained in 56) were compared with 705 embryo transfer
cycles in women with tubal disease but no hydrosalpinx. Results were
analysed in the first three cycles but also separately in the first cycle
to check for bias. Success rates were higher in the first cycle, but did
not significantly influence overall differences. Implantation rates were
significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2%
for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup
without evident tubal distension and 7.5% (not significant) in the drained
hydrosalpinx group. This study shows that tubal damage with distal
occlusion is associated with a marked reduction in embryo implantation,
even in the absence of obvious fluid distension. Surgical drainage of
distended hydrosalpinges appears to offer no benefit.
相似文献
79.
80.
KM Kanal NJ Hangiandreou AM Sykes HE Eklund PA Araoz JA Leon BJ Erickson 《Journal of digital imaging》2002,14(1):30-37
The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's
gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing
radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers,
and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed
with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant,
and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender
were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women
was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative
English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and
while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology
practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient
way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed
and sensitive manner. 相似文献