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71.
Dr. David Lo Christina R. Reilly Linda C. Burkly Jenefer DeKoning Terri M. Laufer Laurie H. Glimcher 《Immunologic research》1997,16(1):3-14
Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting
major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are
responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection
of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that
with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire:
Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium
is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial
and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the
function of the thymic medulla is discussed. 相似文献
72.
Hohe A Egener T Lucht JM Holtorf H Reinhard C Schween G Reski R 《Current genetics》2004,44(6):339-347
The moss Physcomitrella patens is the only land plant known to date with highly efficient homologous recombination in its nuclear DNA, making it a unique model for plant functional genomics approaches. For high-throughput production of knockout plants, a robust transformation system based on polyethylene glycol-mediated transfection of protoplasts was developed and optimised. Both the DNA conformation and pre-culture of plants used for protoplast isolation significantly affected transformation efficiencies. Employing a newly developed PCR high-throughput method, the gene-targeting efficiency in more than 1,000 plants transformed with different cDNA-based knockout constructs was determined and analysed with regard to the length and intron/exon structure of the homologous gene locus. Different targeting constructs, each containing an identical selectable marker gene, were applied as batch DNA in a single transformation experiment and resulted in double-knockout plants. Thus, the fast and efficient generation of multiple targeted gene-knockouts is now feasible in Physcomitrella.Communicated by U. Kück 相似文献
73.
Mira Karrasch Matti Laine Juha O Rinne Pekka Rapinoja Eija Sinerv? Christina M Krause 《International journal of psychophysiology》2006,59(2):168-178
We report preliminary findings on EEG oscillatory correlates of working memory in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related desynchronization (ERD) and synchronization (ERS) of the 1-20 Hz EEG frequencies were studied using wavelet transforms in elderly controls, MCI patients and mild probable AD patients performing an auditory-verbal Sternberg memory task. Behaviourally, the AD patients made more errors than the controls and the MCI group. Statistically significant differences during the encoding of the memory set were found between the controls and the MCI group, such that the latter group showed ERD in the approximately 10-20 Hz frequencies. The findings may reflect different, compensatory encoding strategies in MCI. During retrieval, the most obvious differences were observed between the controls and the AD group: the ERD in the approximately 7-17 Hz frequencies was absent in the AD group particularly in anterior and left temporal electrode locations. This finding might indicate that AD is associated with deficient lexical-semantic processing during the retrieval phase in working memory tasks. Future studies with larger patient groups are needed to establish the diagnostic value of ERD/ERS patterns in MCI and AD. 相似文献
74.
75.
In-vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium 总被引:21,自引:6,他引:21
Goud PT; Goud AP; Qian C; Laverge H; Van der Elst J; De Sutter P; Dhont M 《Human reproduction (Oxford, England)》1998,13(6):1638-1644
In-vitro maturation (IVM) of oocytes is a promising technique to reduce the
costs and avert the side-effects of gonadotrophin stimulation for in-vitro
fertilization (IVF). The pregnancy rates from oocytes matured in vitro are
much lower than those of in-vivo stimulation cycles indicating that
optimization of IVM remains a challenge. Therefore, we investigated the
effect of supplementation of the medium with gonadotrophins, oestradiol and
epidermal growth factor (EGF) and the effect of retaining or removing the
cumulus cells on nuclear and cytoplasmic maturation of immature oocytes.
Human germinal vesicle (GV) oocytes obtained after gonadotrophin
stimulation for intracytoplasmic sperm injection (ICSI) were cultured in a
complex defined medium either supplemented with gonadotrophins, oestradiol
and physiological concentrations of EGF (2 ng/ml) or gonadotrophins and
oestradiol alone. The cumulus cells were either removed or kept intact. In
GV stage oocytes cultured without cumulus (group I) significantly more
oocytes reached the metaphase II (MII) stage at 30 h in media supplemented
with EGF (64.3 versus 33.9%, P < 0.003). For oocytes cultured with
intact cumulus (group II), more oocytes reached MII at 30 h than in group
I, but there was no difference in medium with or without EGF
supplementation (81.8 and 79.8% respectively). Cytoplasmic maturation of
MII oocytes was judged from their capability to activate and fertilize
after ICSI. In group I, the rates of activation and normal fertilization
were similar. However, in group II, significantly more oocytes underwent
normal fertilization in the EGF-supplemented than the unsupplemented group
(71.7 versus 45.6%, P < 0.05). The cleavage rates of the fertilized
oocytes were similar in the sibling oocyte subgroups cultured with or
without EGF supplementation, but the overall cleavage rates were higher in
cumulus-intact compared to cumulus-denuded oocytes (88.9 versus 47.8%, P
< 0.001). Thus, supplementation of the maturation medium with EGF and
maintenance of the cumulus during culture improve the nuclear and
cytoplasmic maturation of human oocytes in vitro.
相似文献
76.
Comparison of real-time PCR and culture for detection of Porphyromonas gingivalis in subgingival plaque samples 总被引:6,自引:0,他引:6 下载免费PDF全文
Boutaga K van Winkelhoff AJ Vandenbroucke-Grauls CM Savelkoul PH 《Journal of clinical microbiology》2003,41(11):4950-4954
Porphyromonas gingivalis is a major pathogen in destructive periodontal disease in humans. Detection and quantification of this microorganism are relevant for diagnosis and treatment planning. The prevalence and quantity of P. gingivalis in subgingival plaque samples of periodontitis patients were determined by anaerobic culture and real-time PCR amplification of the 16S small-subunit rRNA gene. The PCR was performed with primers and a fluorescently labeled probe specific for the P. gingivalis 16S rRNA gene. By the real-time PCR assay, as few as 1 CFU of P. gingivalis could be detected. Subgingival plaque samples from 259 adult patients with severe periodontitis were analyzed. P. gingivalis was detected in 111 (43%) of the 259 subgingival plaque samples by culture and in 138 (53%) samples by PCR. The sensitivity, specificity, and positive and negative predictive values of the real-time PCR were 100, 94, 94, and 100%, respectively. We conclude that real-time PCR confirms the results of quantitative culture of P. gingivalis and offers significant advantages with respect to the rapidity and sensitivity of detection of P. gingivalis in subgingival plaque samples. 相似文献
77.
Regulatory role of interleukin-10 in experimental group B streptococcal arthritis 总被引:4,自引:0,他引:4 下载免费PDF全文
Puliti M Von Hunolstein C Verwaerde C Bistoni F Orefici G Tissi L 《Infection and immunity》2002,70(6):2862-2868
Intravenous inoculation of CD-1 mice with 10(7) CFU of type IV group B Streptococcus (GBS) results in a high incidence of diffuse septic arthritis, associated with high levels of systemic and local production of interleukin-1beta (IL-1beta) and IL-6. In this study, the role of the anti-inflammatory cytokine IL-10 in the evolution of GBS systemic infection and arthritis was evaluated. IL-10 production was evident in sera and joints of GBS-infected mice. Neutralization of endogenous IL-10 by administration of anti-IL-10 antibodies (1 mg/mouse) at the time of infection resulted in worsening of articular lesions and 60% mortality associated with early sustained production of IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha). The effect of IL-10 supplementation was assessed by administering IL-10 (100, 200, or 400 ng/mouse) once a day for 5 days, starting 1 h after infection. Treatment with IL-10 had a beneficial effect on GBS arthritis, and there was a clear-cut dose dependence. The decrease in pathology was associated with a significant reduction in IL-6, IL-1beta, and TNF-alpha production. Histological findings showed limited periarticular inflammation and a few-cell influx in the articular cavity of IL-10-treated mice, confirming clinical observations. In conclusion, this study provides further information concerning the role of IL-10 in regulating the immune response and inflammation and calls attention to the potential therapeutic use of IL-10 in GBS arthritis. 相似文献
78.
Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21) 总被引:3,自引:0,他引:3
Shimizu S Suzukawa K Kodera T Nagasawa T Abe T Taniwaki M Yagasaki F Tanaka H Fujisawa S Johansson B Ahlgren T Yokota J Morishita K 《Genes, chromosomes & cancer》2000,27(3):229-238
The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. Genes Chromosomes Cancer 27:229-238, 2000. 相似文献
79.
Sturm G Kränke B Rudolph C Aberer W 《The Journal of allergy and clinical immunology》2002,110(6):928-933
BACKGROUND: Hymenoptera venom immunotherapy in allergic patients is a well-established treatment modality for the prevention of systemic anaphylactic reactions caused by insect stings. A variety of therapy regimens exists, from conventional to rush and ultrarush modalities that operate on continuous or intermittent schedules. OBJECTIVE: The aim of this study was to report the 8-year experience with our rush venom immunotherapy regimen in predominantly high-risk patients and to compare data on safety and convenience with the results of 26 studies published from 1978 to 2001. METHODS: One hundred one patients allergic to bee, yellow jacket, or hornet venom were treated with rush Hymenoptera venom immunotherapy. Diagnosis and selection of patients for venom immunotherapy were carried out according to the recommendations of the European Academy of Allergology and Clinical Immunology. We used a 4-day regimen, and the incidence and nature of systemic reactions (SRs) were documented. Fifty-two patients were treated with honeybee venom, and 49 were treated with yellow jacket venom. RESULTS: One hundred (99%) patients reached the maintenance dose. We observed 8 injection-related SRs (0.47% of all injections given) in 7 (6.9%) patients. The number of SRs was higher in patients treated with bee venom extract (12%) compared with in patients receiving yellow jacket venom extract (2%). There was no significant difference in the risk of SRs between female and male patients. The incidence of SRs was considerably lower than the average of 17.8% reported in the literature. CONCLUSION: With a rush immunotherapy regimen over a time period of 8 years in predominantly high-risk patients, the incidence of SRs was low, despite the high number of patients with bee venom allergy, who are more likely to have side effects. Epinephrine as rescue medication was never necessary, and the regimen proved to be safe and convenient for both the patients and the medical staff. 相似文献
80.
Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours 总被引:5,自引:0,他引:5
Gunawan B Schulten HJ von Heydebreck A Schmidt B Enders C Höer J Langer C Schüler P Schindler CG Kuhlgatz J Füzesi L 《The Journal of pathology》2004,202(4):421-429
Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003). 相似文献