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101.
CpG DNA functions via the toll-like receptor-9 (TLR-9) receptor, inducing B cell proliferation and promoting immunoglobulin production. B cell responses to CpG DNA-containing immune complexes could be important in chronic autoimmunity and immune responses to bacterial components. Therefore, we investigated the potential synergy of CpG DNA-stimulation with FcgammaR clustering (CFR) on splenic B cell activity. CFR-induced splenocyte proliferation was significantly increased compared to treatment with CpG DNA alone. While the levels of interleukin-10 (IL-10) were increased in CpG DNA-treated splenocyte cultures, particularly following FcgammaRII/III-clustering, CFR treatment reduced IL-6 levels. B-cell maturation in culture was enhanced by CFR. Indeed, the frequency of IgG expressing cells after stimulation with CpG DNA was increased and was even higher after CFR stimulation. Furthermore, the frequency of plasma cell precursors was markedly increased by stimulation with CFR. Late splenic B cell subsets, transitional type 2 (T2) and mature (M) B cells, responded strongly to CpG DNA with proliferation and the response was enhanced by FcgammaR-clustering. Immature transitional type 1 (T1) B cells showed distinctly lower proliferative response to CpG DNA and very small effects of FcgammaR-clustering, despite similar expression of Fcgamma-receptors by all B cell subsets. In conclusion, these data show synergistic impact of CpG DNA and simultaneous FcgammaR-clustering on B cell proliferation and differentiation. 相似文献
102.
103.
Van QN Klose JR Lucas DA Prieto DA Luke B Collins J Burt SK Chmurny GN Issaq HJ Conrads TP Veenstra TD Keay SK 《Disease markers》2003,19(4-5):169-183
The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%. 相似文献
104.
Ghosh D; Stewart DR; Nayak NR; Lasley BL; Overstreet JW; Hendrickx AG; Sengupta J 《Human reproduction (Oxford, England)》1997,12(5):914-920
The present study was undertaken to assess the temporal association between
the profiles of serum concentrations of oestradiol-17beta, progesterone,
chorionic gonadotrophin (CG) and relaxin in pregnancies established
naturally, and after embryo transfer, as well as in failed pregnancies in
rhesus monkeys. In naturally mated cycles (group 1) a conception rate of
75% was obtained. In group 1, the mean day of CG detection in serum was
11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day
post-ovulation. In group 2, embryo transfer to synchronous, non-mated
surrogate recipients was performed; seven embryo transfer cycles yielded
three pregnancies which were allowed to continue to term and normal infants
were delivered. In embryo transfer cycles the mean day of CG detection was
14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day
post-ovulation. A delay of about 3 days was observed in the appearance in
circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between
natural mated and embryo transfer conception cycles. Significant
differences (P < 0.05 for progesterone and P < 0.03 for oestradiol)
were obtained for the areas under the curves for progesterone and
oestradiol between days 12 and 16 in conception cycles compared with failed
pregnancies. These data provide the first observation of the normal
hormonal signals associated with maternal recognition of transferred
embryos during the peri- implantation period, and suggest that the use of
such an experimental primate embryo transfer model may help to elucidate
components of maternal and embryonic signal-response mechanisms during
embryo implantation.
相似文献
105.
J C York J B Cousar A D Glick J M Flexner R Stein R D Collins 《American journal of clinical pathology》1985,84(1):35-43
Composite lymphoma (CL) may be defined as two lymphomas, differing as to their cell of origin, that occur simultaneously in the same tissue specimen. While CL usually is indicated histopathologically by at least two morphologically distinct lymphomatous proliferations, the proof that these proliferations are separate and distinct neoplasms requires immunologic analysis. Many so-called cases of CL actually represent the well-known phenomenon of lymphoid transformation, in which there is a small cell and a large cell component in the same specimen. Immunologic studies in these cases have shown that the cytologically distinct neoplastic cells represent different stages in the same cell line. While studying a large series of follicular center cell (FCC) lymphomas, the authors recognized three cases in which there was both morphologic and immunologic evidence of a true CL. Following an initial diagnosis of a nodular FCC lymphoma, rebiopsies from 21 to 62 months later showed the coexistence of a nodular FCC (B-cell) component and a diffuse large cell (T-cell) component. 相似文献
106.
This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer. 相似文献
107.
108.
Newman JT Surman SR Riggs JM Hansen CT Collins PL Murphy BR Skiadopoulos MH 《Virus genes》2002,24(1):77-92
A complete consensus sequence was determined for the genomic RNA of human parainfluenza virus type 1 (HPIV1) strain Washington/20993/1964 (HPIV1 WASH/64), a clinical isolate that previously was shown to be virulent in adults. The sequence exhibited a high degree of relatedness to both Sendai virus, a PIV1 virus recovered from mice, and human PIV3 (HPIV3) with regard to cis-acting regulatory regions and protein-coding sequences. This consensus sequence was used to generate a full-length antigenomic cDNA and to recover a recombinant wild-type HPIV1 (rHPIV1). Interestingly, the rHPIV1 could be rescued from full-length antigenomic rHPIV1 cDNA using HPIV3 support plasmids, HPIV1 support plasmids, or a mixture thereof. The replication of rHPIV1 in vitro and in the respiratory tract of hamsters was similar to that of its biologically derived parent virus. The similar biological properties of rHPIV1 and HPIV1 WASH/64 in vitro and in vivo, together with the previous demonstration of the virulence of this specific isolate in humans, authenticates the rHPIV1 sequence as that of a wild-type virus. This rHPIV1 can now be used to study the biological properties of HPIV1 and as a substrate to introduce attenuating mutations for the generation of live-attenuated HPIV1 vaccine candidates.An erratum to this article can be found at 相似文献
109.
Ju He Guide Reifenberger Lu Liu V. Peter Collins C. David James 《Genes, chromosomes & cancer》1994,11(2):91-96
Recently, amplification of the gene encoding a p53 binding protein, MDM2, was determined in 8% of the cases constituting a large series of glioblastomas. Here we have utilized Southern blot analysis to examine 30 cell lines established from such tumors, and our investigation has revealed large increases in MDM2 gene dosage in two cases, one of which showed coamplification of the CDK4 gene that resides in close proximity to MDM2 in chromosomal region 12q13–14. Northern analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene amplification, and overexpression of MDM2 protein was evident in each of these by immunohistochemical and Western blot analysis. Analysis of TP53 cDNAs revealed normal TP53 sequences in the cell lines with MDM2 amplification; these results are consistent with those of previous studies suggesting that MDM2 amplification occurs only in tumors expressing wild-type p53. In total, these data suggest that MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%) comparable to that determined in primary tumors; occurs in cell lines expressing wild-type p53; and can involve the coamplification of additional genes. 相似文献
110.
Peebles RS Sheller JR Collins RD Jarzecka AK Mitchell DB Parker RA Graham BS 《Journal of medical virology》2001,63(2):178-188
Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines. 相似文献