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排序方式: 共有81条查询结果,搜索用时 15 毫秒
1.
MRP8 and MRP14 are myeloic related proteins expressed by most circulating and emigrated neutrophils and monocytes. Their composite molecule MRP8/14 (27E10 antigen) was shown to exhibit striking antimicrobial properties. The aim of the present study was to assess the value of MRPs as markers for detection of the different stages of HIV infection (Centres for Disease Control and Prevention, 1993). By employing the ELISA technique we measured serum concentrations of these proteins in samples from 122 HIV patients at the various stages of disease, and the results were compared with those for healthy controls. Serum levels of the heterodimeric molecule 27E10 were significantly increased (P < 0.001) in patients with CDC stages II and III, with the highest levels being in patients with stage III and acute ongoing opportunistic infections. For the single component MRP14, significantly raised levels (P < 0.05) were only found in HIV stage III individuals with acute clinical events. Similar associations were not found for MRP8 alone. Increase was not related to CD4+ cell count. There was a significant correlation between 27E10 antigen serum concentrations and levels of neopterin in patients with HIV stages II and III without acute concurrent illness. Patients being treated with Zidovudine showed no statistically significant variation in levels of 27E10 and its single components MRP8 and MRP14 compared with untreated patients. These findings suggest that elevation of MRP14 levels occurs in HIV+ individuals at later stages post-HIV infection, after the onset of opportunistic infections. 27E10 antigen is concluded to be a potential marker for the different stages of HIV disease.  相似文献   
2.
We have previously demonstrated the loss of oral tolerance (OT) in lymphotoxinalpha-/- (LTalpha-/-) and TNFalpha / lymphotoxinalpha deficient (TNFalpha / LTalpha-/-) mice which have defective Peyer's patches (PP) and lymph node (LN) development. We have now studied OT in BALB / c mice with differential defects of the gut-associated lymphoid tissue (GALT) caused by inhibition of LTbetaR signaling during fetal development. Treatment of pregnant mice with LTbetaR-IgG (LTbetaRIgG) and TNFR I55-IgG (TNFR55IgG) abrogates the formation of PP (LTbetaRIgG) or of PP and mesenteric LN (MLN) (LTbetaRIgG / TNFRIgG) without genetically deleting the respective cytokine pathways. OT was readily induced in mice without PP but retaining MLN (PP null / LN +). In contrast, OTcould not be induced in mice lacking both MLN and PP (PP null / MLN null) as shown by the inability of these mice to suppress IFN-gamma secretion or DTH reactions. We next assessed OT in 129 x B6 LTalpha-/- mice with and without MLN. Timed treatment of pregnant LTalpha-/- mice with an agonist anti-LTbetaR mAb induces formation of MLN but not of PP in LTalpha-/- mice. LN + LTalpha-/- mice developed OT while LN LTalpha-/- mice were resistant to OT induction. Taken collectively, the data show that in the presence of MLN PP are not required for OT induction and that the presence of MLN is sufficient for OT induction in the LTalpha-/- model.  相似文献   
3.
AIM: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue. METHODS AND RESULTS: The authors developed a double transgenic mouse model with doxycycline induced human IL-8 expression restricted to intestinal epithelial cells. Doxycycline treatment of double transgenic mice for three days resulted in a 50-fold increase in the caecal IL-8 concentration and influx of neutrophils into the lamina propria. Although neutrophils entered the paracellular space between epithelial cells, complete transepithelial migration was not observed. Doxycycline treatment also increased the water content of the caecal and colonic stool, indicating dysfunctional water transport. However, the transmural electrical resistance was not decreased. Neutrophils recruited to the intestinal epithelium did not show evidence of degranulation and the epithelium remained intact as judged by histology. CONCLUSIONS: This conditional transgenic model of chemokine expression provides evidence that acute induction of IL-8 in the intestinal epithelium is sufficient to trigger neutrophil recruitment to the lamina propria, but additional activation signals are needed for full activation and degranulation of neutrophils, mucosal injury, and complete transepithelial migration.  相似文献   
4.
T Kucharzik  N Lugering  K Schmid  M Schmidt  R Stoll    W Domschke 《Gut》1998,42(1):54-62
Background—The derivation and ultrastructuralcomposition of M cells covering the lymphoid follicles of Peyer'spatches is still unknown. Results from different animal models haveshown that there are species specific differences in the composition ofintermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells.
Aims—To compare components of the cytoskeleton ofhuman M cells with those of adjacent absorptive enterocytes.
Methods—The expression and localisation ofdifferent cytokeratins, vimentin, and desmin in M cells was determinedon follicle associated epithelia of human appendix usingimmunohistochemistry and immunogold electron microscopy.
Results—Cytokeratins specific for humanintestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 wereexpressed in both absorptive enterocytes and M cells with nodifferences in intensity and cellular distribution between both celltypes. Vimentin and desmin, tissue specific markers of eithermesenchymal or myogenic cells, as well as other cytokeratins were notdetectable in enterocytes or M cells.
Conclusion—This is the first study on thestructure of intermediate filaments in human intestinal M cells. Ourresults show that in contrast to several animal models, human M cellsapparently do not differ from adjacent enterocytes in the compositionof their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as ofvimentin and desmin supports the hypothesis of an epithelial origin ofhuman intestinal M cells and suggests that M cells may derive fromdifferentiated enterocytes.

Keywords:human intestinal M cells; appendix; cytokeratin; intermediate filaments; follicle associated epithelium

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6.
BACKGROUND AND STUDY AIMS: In patients with low-grade gastric MALT lymphoma, conventional endoscopic ultrasonography (EUS) is considered to be the most accurate modality for locoregional staging. The aim of this study was to evaluate the diagnostic role of ultrasonic miniprobes as part of routine clinical staging. PATIENTS AND METHODS: A total of 39 patients who were histologically diagnosed with low-grade MALT lymphoma were reviewed retrospectively before treatment (n = 15) and during follow-up (n = 24). Assessment of tumor penetration into the gastric wall was based on the TNM system. Pathological lymph-node involvement was suggested by the presence of inhomogeneous hypoechoic echo patterns, with clearly demarcated borders. All examinations were carried out using a mechanical miniprobe (Olympus; diameter 2.4 mm, 12 MHz) introduced through the working channel of the endoscope. Ultrasonic miniprobe findings were compared with conventional EUS data and histology. RESULTS: Using pretreatment endoscopic ultrasonography, gastric lymphomas presented endoscopically with an ulcer (in five of 15 patients) or a diffuse infiltrative pattern (ten of 15 patients). The ultrasonic miniprobe identified a T1 lesion in 53 % (T2, 33 %) and EUS in 60 % (T2, 20 %) of cases. Pathological lymph-node involvement in T1-T2 lesions was diagnosed with the ultrasonic miniprobe in 53 % of cases and with EUS in 60 %. Using endoscopic ultrasonography during the follow-up period, in patients with normal miniprobe ultrasonography (n = 15), the histological examination confirmed a complete remission in all patients. Hypoechoic thickening of the mucosa or submucosa, or both, was seen in nine patients. Endoscopic biopsies in four of these nine patients revealed recurrent lymphoma. CONCLUSIONS: The ultrasonic miniprobe can be recommended as part of routine care in patients with gastric MALT lymphoma, both initially and during the follow-up period. The clinical significance of ultrasonic miniprobe examinations is that they can be performed as a single-step procedure during diagnostic endoscopy.  相似文献   
7.
Treatment options for inflammatory bowel disease (IBD) are incompletely helpful, and surgery is often needed. One promising class of future therapeutic agents for IBD is melanocortin-related peptides, which exhibit potent immunomodulatory effects. We investigated KdPT, a tripeptide derivative of the C-terminus of α-melanocyte-stimulating hormone, as an anti-inflammatory small molecule in vivo and in vitro. Intestinal inflammation was studied after oral administration of dextran sodium sulfate and in IL-10 gene-deficient mice. The effects of KdPT on key colonic epithelial cell functions were studied in vitro and in vivo by evaluating proliferation, wound healing, transepithelial resistance, and expression of tight junction proteins. Melanin assays were performed to determine the melanotropic effects of KdPT. KdPT-treated animals showed markedly reduced severity of inflammation in both colitis models. In colonic epithelial cells, KdPT increased proliferation, accelerated closure of wounds, and improved transepithelial electrical resistance after stimulation with interferon-γ/tumor necrosis factor-α. Moreover, treatment with KdPT also prevented the loss of tight junction protein expression and improved barrier function in vivo. KdPT acted independently of IL-1 receptor type I in vivo and did not affect melanogenesis in vitro. KdPT is capable of attenuating the course of experimental colitis in different models and maintains epithelial cell function. Furthermore, KdPT does not induce pigmentation, emphasizing the potential of this small molecule for the future treatment of IBD.  相似文献   
8.
Tissue injury and inflammation in inflammatorybowel disease (IBD) are associated with enhancedmonocytic lysosomal enzyme release. In this study,peripheral monocytes and lamina propria mononuclearcells (LPMNC) were isolated from IBD patients andnormal controls. Cells were stimulated withlipopolysaccharide after treatment with IL-13, IL-4, andIL-10, and enzyme secretion was assessed by using thecorresponding p-nitrophenyl glycosides as substrates.Molecular forms of cathepsin D were examined to describethe mode of enzyme release. IL-10 and IL-4 stronglydown-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness tothe inhibitory effect of IL-13. Impaired monocyteresponse was not found with combinations of IL-13 andIL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretioncompared with LPMNC from noninvolved IBD mucosa butresponded inefficiently to either IL-4, IL-13, or IL-10alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressedenzyme release by these cells. Both the precursor andmature forms of cathepsin D were elevated in IBDpatients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both theprecursor and mature form of cathepsin D. Our resultsfavor the potent clinical utility of combined treatment,thus improving chances of developing effective treatments for human IBD.  相似文献   
9.
BACKGROUND: Little is known about the function of T cells in the inflammatory infiltrate in Helicobacter pylori-associated gastritis and B-cell lymphoma of mucosa-associated lymphoid tissue (MALT type). Previous studies have proposed a dominant Th1-type response in low-grade MALT lymphoma consistent with the Th1 response observed in H. pylori-associated gastritis. METHODS: We performed a novel flow cytometric approach in which CD3 panning for enrichment and activation of small numbers of T cells and intracellular cytokine analysis were combined to selectively characterize the cytokine profile of T cells (IFN-gamma for Th1) derived from the gastric mucosa of 23 patients with low-grade MALT lymphoma stage IEI1 (lymphoma infiltration of mucosa/submucosa sparing the muscularis). Endosonography was performed in each case to control the depth of lymphoma infiltration. For comparison, 19 patients with H. pylori-positive gastritis were also analysed. RESULTS: There was a CD4/CD8 ratio of 4 in patients with MALT lymphoma and of 2 in chronic gastritis. The proportion of IFN-gamma producing cells within the CD4-positive T-cell population in MALT lymphoma was 22%; in chronic gastritis it was 13% while no such difference could be encountered in CD8-positive T cells. CONCLUSIONS: The data point towards a dominant intratumoral IFN-gamma dominated T-cell response associated with early low-grade MALT lymphoma. A polarized IFN-gamma dominated Th1-type response may either contribute to the inability of the immune system to eradicate H. pylori infection, thereby promoting the activation status of the lymphocytic infiltrate in low-grade MALT lymphoma, or may mirror a concomitant tumor-specific T-cell response accompanying early stages of tumor progression.  相似文献   
10.
Vascular cell adhesion molecule-1 (VCAM-1), a key receptor for the leukocyte-associated integrin (VLA4), is a crucial mediator of leukocyte adhesion and has co-stimulatory functions in inflammation at various organ sites. Specifically, VCAM-1/VLA4 interactions have been shown to play important roles in the setting of cutaneous immune responses, such as psoriatic lesions in humans and acute Graft-versus-Host-Disease in mice. VCAM-1 is generally expressed on activated endothelial cells in inflamed tissues, mediating endothelium-leukocyte interactions, leading to leukocyte diapedesis to the site of inflammation. We report novel and unexpected membrane expression of VCAM-1 in the basal squamous epithelial strata of the normal human esophagus and distinct patterns of epithelial expression in esophageal pathology. To further delineate the differential expression patterns of VCAM-1 in the esophageal epithelium, we examined specimens from squamous cell carcinoma (SCC), adenocarcinoma, and Barrett's columnar cell metaplasia. VCAM-1 was strongly expressed in squamous cell carcinoma, but not adenocarcinoma nor columnar epithelia in Barrett's esophagus. VCAM-1 expression was focally accentuated at sites characteristic of microscopic tumor invasion in SCC, pointing to a potential role of VCAM-1 in the development of metastasis. In addition, in vitro immunofluorescence studies using OE21 cells, an esophageal squamous epithelial cell line, displayed distinct VCAM-1 immunoreactivity confined to mitotic and dividing cells. Cell cycle arrest caused a significant decrease in VCAM-1 immunoreactivity in OE21 cells. These data suggest a previously unappreciated role for VCAM-1 in esophageal squamous epithelial homeostasis and pathology.  相似文献   
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