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21.
Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation 总被引:3,自引:0,他引:3
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Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells. 相似文献
22.
阮强 《中华微生物学和免疫学杂志》1994,(5)
研究资料表明,人巨细胞病毒(HCMv)单一蛋白的单一抗原决定簇只能被部分患者阳性血清识别。组建在血清学诊断中能够替代全病毒抗原的基因工程抗原,需要含有病毒多种主要抗原蛋白的抗原决定簇。为搞清在表达载体中重复插入某一抗原决定簇基因是否能表达出更高抗原效价的融会蛋白,我们用点突变的方法,在表达载体中分别插入了人HCMv的ppUL32蛋白羧基端一个抗原决定簇基因的1个、2个和3个拷贝。在免疫转印检测中,这些克隆表达的融合蛋白与特异性阳性血清的反应性差别不明显。这表明,插入表达载体中目的基因的多寡对表达蛋白的抗原效价没有显著影响。 相似文献
23.
24.
Bhattacharya S; MacLennan F; Hamilton MP; Templeton A 《Human reproduction (Oxford, England)》1997,12(7):1440-1442
Although the conventional method of pain relief during outpatient oocyte
recovery involves physician-administered drugs, patient- controlled
analgesia (PCA) offers an alternative technique with the potential to give
women more control over peroperative analgesia. We conducted a prospective
randomized study to compare the effect of fentanyl administered either
through a PCA delivery system or by a physician. Thirty-nine women were
randomized to PCA during egg collection while 42 were allocated to receive
intermittent doses administered by a physician. Pain was evaluated by means
of a 100 mm linear analogue scale. The mean (SD) pain score in the PCA
group was 38.5 (19.8) while in the other group it was 46.1 (21.3) (P =
0.1). In the PCA group, 64% of women felt very satisfied with their
analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the
PCA users, 39% of demands were successful. Significantly more fentanyl
(97.5 microg) was used in the PCA group than in the other group (84.6
microg) (P = 0.03). Though intraoperative PCA with fentanyl is an effective
alternative to physician-administered techniques, many women still feel the
need for more analgesia during the procedure.
相似文献
25.
AIMS--To classify lesions discovered at colectomy in patients with ulcerative colitis; to assess the importance of histological findings by correlating them with biochemical parameters. METHODS--Liver tissue specimens taken at colectomy from 59 patients with chronic ulcerative colitis were studied using light microscopy. The findings were compared with results of biochemical liver function tests. RESULTS--Abnormal laboratory findings were found in 12 patients with liver histology consistent with primary sclerosing cholangitis. Non-specific reactive hepatitis was observed in six patients, eight had fatty liver, and three minor non-specific parenchymal changes. Twenty nine patients had normal liver histology. The highest cholestatic serum enzyme activities were seen in two patients with sclerosing cholangitis. Cholangiography in these patients also revealed changes in the extrahepatic bile ducts. However, identical histological changes were also present in patients with only slightly abnormal or even normal liver enzyme activities. CONCLUSION--Biochemical tests of liver function do not reliably indicate the extent or severity of bile duct damage in ulcerative colitis, the assessment of which requires liver biopsy. 相似文献
26.
Morphological studies have shown that macrophages and microglia undergo
apoptosis in the central nervous system (CNS) in acute experimental
autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative
levels of macrophage and microglial apoptosis, and the molecular mechanisms
involved in this process, we used three-colour flow cytometry to identify
CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the
inflammatory cells isolated from the spinal cords of Lewis rats 13 days
after immunization with myelin basic protein (MBP) and complete Freund's
adjuvant. Simultaneously, we analyzed the DNA content of these cell
populations to assess the proportions of cells undergoing apoptosis and in
different stages of the cell cycle or examined their expression of three
apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and
Bcl-2. Microglia were highly vulnerable to apoptosis and were
over-represented in the apoptotic population. Macrophages were less
susceptible to apoptosis than microglia and underwent mitosis more
frequently than microglia. The different susceptibilities of microglia and
macrophages to apoptosis did not appear to be due to variations in Fas,
FasL or Bcl- 2 expression, as the proportions of microglia and macrophages
expressing these proteins were similar, and were relatively high.
Furthermore, in contrast to T cell apoptosis, apoptosis of
microglia/macrophages did not occur more frequently in cells expressing Fas
or FasL, or less frequently in cells expressing Bcl-2. These results
indicate that the apoptosis of microglia and CNS macrophages in EAE is not
mediated through the Fas pathway, and that Bcl-2 expression does not
protect them from apoptosis. Expression of FasL by macrophages and
microglia may contribute to the pathogenesis and immunoregulation of EAE
through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high
level of microglial apoptosis in EAE indicates that microglial apoptosis
may be an important homeostatic mechanism for controlling the number of
microglia in the CNS following microglial activation and proliferation.
相似文献
27.
OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation. 相似文献
28.
Iron-overload diseases frequently develop hepatocellular carcinoma. The
genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might
involve an oxidative process via the intermediate production of reactive
oxygen species. This was presently investigated by examining kinetics of
formation and repair of DNA base lesions in primary rat hepatocyte cultures
supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and
100 microM). Seven DNA base oxidation products have been identified in DNA
extracts by gas chromatography- mass spectrometry, which showed a
predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine,
2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil,
5-OH-cytosine) in control cultures. All these DNA oxidation products
revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA
supplementation, among which fapy-adenine showed the highest increase and
5-OH-cytosine was the least prominent. Involvement of iron in this
oxidative process was established by a correlation between extent in DNA
oxidation and intracellular level of toxic low molecular weight iron. DNA
excision- repair activity was estimated by release of DNA oxidation
products in culture medium. All the seven DNA oxidation products were
detected in the medium of control cultures and showed basal repair
activity. This DNA repair activity was increased in a time- and
dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was
5-OHMe-Uracil, were preferentially repaired, which explains the low levels
detected in oxidized DNA. Since oxidized bases substantially differed from
one another in terms of excision rates from cellular DNA, specific
excision- repair enzymes might be involved. Our findings, however,
demonstrate that even though DNA repair pathways were activated in
iron-loaded hepatocyte cultures, these processes were not stimulated enough
to prevent an accumulation of highly mutagenic DNA oxidative products in
genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in
understanding the hepatocarcinogenic evolution of iron-overload diseases.
相似文献
29.
30.
Yuli R Tak Rinka MP Van Zundert Rowella CWM Kuijpers Boukje S Van Vlokhoven Hettie FW Rensink Rutger CME Engels 《BMC public health》2012,12(1):21