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51.
52.
Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors. 相似文献
53.
Inflammation of the central nervous system is an important but poorly understood part of neurological disease. After acute
brain injury or infection there is a complex inflammatory response that involves activation of microglia and astrocytes and
increased production of cytokines, chemokines, acute phase proteins, and complement factors. Antibodies and T lymphocytes
may be involved in the response as well. In neurodegenerative disease, where injury is more subtle but consistent, the inflammatory
response is continuous. The purpose of this prolonged response is unclear, but it is likely that some of its components are
beneficial and others are harmful. Animal models of neurological disease can be used to dissect the specific role of individual
mediators of the inflammatory response and assess their potential benefit. To illustrate this approach, we discuss how mutant
mice expressing different levels of the cytokine transforming growth factor β-1 (TGF-β1), a major modulator of inflammation,
produce important neuroinflammatory phenotypes. We then demonstrate how crosses of TGF-β1 mutant mice with mouse models of
Alzheimer's disease (AD) produced important new information on the role of inflammation in AD and on the expression of different
neuropathological phenotypes that characterize this disease. 相似文献
54.
Bersinger NA; Brandenberger A; Berger E; Baumann CK; Birkhauser MH 《Human reproduction (Oxford, England)》1998,13(7):1962-1967
We have previously observed the repeated presence of low but detectable
amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein
(SP1) in the serum of some women undergoing in-vitro fertilization (IVF)
treatment around the time of oocyte retrieval. The occurrence of these
signals seemed to be restricted to a defined group of patients which also
showed a lower pregnancy success rate in a preliminary study. To test our
hypothesis we have analysed 173 consecutive cycles leading to an embryo
transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1
ng/ml between days embryo transfer -5 and embryo transfer (group A). Five
pregnancies were obtained in this group (pregnancy rate = 9.3%), while in
group B, defined by the absence of detectable SP1 before embryo transfer
(119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41
pregnancies were achieved in 33 first-time non-pregnant patients undergoing
further attempts during the study period. Again the pregnancy rate was
higher in the first-time group B women (9/23 versus 1/10 for group A).
Patients tended to remain in their groups A or B, the latter being
associated with a better immediate as well as subsequent chance for
pregnancy. Group A cycles had a significantly lower endometrial thickness
two days before oocyte retrieval than group B (P = 0.0011). We postulate
that the presence of an unknown, maternal and progesterone- or follicle
stimulating hormone-independent factor in some patients could stimulate
tonic ectopic SP1 synthesis and at the same time negatively influence
endometrial development.
相似文献
55.
Polstra AM Van Den Burg R Goudsmit J Cornelissen M 《Journal of clinical microbiology》2003,41(12):5488-5491
Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma [KS]-associated herpesvirus) is associated with all forms of KS. HHV-8 DNA load in peripheral blood mononuclear cells (PBMCs) of KS patients has been shown to correlate with the clinical stage of the disease. Studies have been done to assess the HHV-8 viral load in different sample types from KS patients and its clinical relevance. This paper describes the design and evaluation of a quantitative real-time (TaqMan) PCR assay for routine diagnosis of HHV-8 infection. The linear dynamic range was 5 to 5 x 10(6) copies of HHV-8 DNA (r(2) > 0.99). The assay is very sensitive, specific, and easily reproducible (less than 2% variability) and can be used for different clinical samples, such as serum, plasma, and PBMCs. The question of which clinical sample, serum or plasma, is preferable for HHV8 DNA testing was addressed, using this newly developed real-time PCR assay. From 85 patients with diagnosed AIDS-KS, matched plasma and serum samples were collected. Of the 85 patients tested, 35 were positive for HHV-8 DNA in both plasma and serum (41%), 8 were positive in serum but not plasma, and 7 had detectable HHV-8 DNA only in plasma. The HHV-8 load was similar in both plasma and serum, and no significant difference was found. However, more inhibition was seen in the plasma samples with the use of a system quality control, seal herpesvirus type 1. Therefore, our results suggest that serum is the preferred material for HHV-8 load testing, since there is less possible hindrance in the amplification than with plasma. 相似文献
56.
Polymorphic nucleotide within the promoter of nitrate reductase (NarGHJI) is specific for Mycobacterium tuberculosis
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Stermann M Bohrssen A Diephaus C Maass S Bange FC 《Journal of clinical microbiology》2003,41(7):3252-3259
Mycobacterium tuberculosis rapidly reduces nitrate, leading to the accumulation of nitrite. This characteristic served for the past 40 years to differentiate M. tuberculosis from other members of the Mycobacterium tuberculosis complex (MTBC), such as Mycobacterium bovis (non-BCG [referred to here as simply "M. bovis"]), Mycobacterium bovis BCG, Mycobacterium africanum, or Mycobacterium microti. Here, a narG deletion in M. tuberculosis showed that rapid nitrite accumulation of M. tuberculosis is mediated by narGHJI. Analysis of narG mutants of M. bovis and M. bovis BCG showed that, as in M. tuberculosis, nitrite accumulation was mediated by narGHJI, and no other nitrate reductase was involved. However, in contrast to M. tuberculosis, accumulation was delayed for several days. Comparison of the narGHJI promoter revealed that, at nucleotide -215 prior to the start codon of narG, M. tuberculosis carried a thymine residue, whereas the bovine mycobacteria carried a cytosine residue. Using LightCycler technology we examined 62 strains of M. tuberculosis, M. bovis, M. bovis BCG, M. microti, and M. africanum and demonstrated that this single nucleotide polymorphism was specific for M. tuberculosis. For further differentiation within the MTBC, we included, by using LightCycler technology, the previously described analysis of oxyR polymorphism, which is specific for the bovine mycobacteria, and the RD1 polymorphism, which is specific for M. bovis BCG. Based on these results, we suggest a LightCycler format for rapid and unambiguous diagnosis of M. tuberculosis, M. bovis, and M. bovis BCG. 相似文献
57.
Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme 总被引:10,自引:0,他引:10
Gerris J De Neubourg D Mangelschots K Van Royen E Vercruyssen M Barudy-Vasquez J Valkenburg M Ryckaert G 《Human reproduction (Oxford, England)》2002,17(10):2626-2631
BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate. 相似文献
58.
Marion Imbert-Bouteille Frédéric Tran Mau Them Julien Thevenon Thomas Guignard Vincent Gatinois Jean-Baptiste Riviere Anne Boland Vincent Meyer Jean-François Deleuze Elodie Sanchez Florence Apparailly David Geneviève Marjolaine Willems 《European journal of medical genetics》2019,62(3):161-166
Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features. 相似文献
59.
Marion Dorsch Hanno Hock Ulrich Kunzendorf Tibor Diamantstein Thomas Blankenstein 《European journal of immunology》1993,23(1):186-190
In order to analyze the effect of a high local concentration of macrophage colony-stimulating factor (M-CSF; CSF-1) on tumor growth, the plasmacytoma cell line J558L was transfected with the human M-CSF gene and injected into syngeneic BALB/c mice. In contrast to the parental tumors, M-CSF transfectants were heavily infiltrated by macrophages as evidenced by immunohistochemistry with antibodies to Mac-1 and Mac-3 and by isolation of the macrophages from the tumor. Nevertheless, tumor growth was only slightly affected by M-CSF and M-CSF-producing cells grew as tumor in all cases. The growth retardation of M-CSF-producing cells varied depending on the experiment and seemed to be due to an indirect effect because the growth rate of the cells in vitro had not changed upon gene transfer. Attempts to activate the tumor-infiltrating macrophages for tumor suppression by systemic application of interferon-γ and/or lipopolysaccharide were not successful. Altogether, our results suggest that M-CSF is a potent chemoattractant for macrophages in vivo but alone is not sufficient to activate these macrophages for tumoricidal activity. 相似文献
60.
Studies of the association of the A, B and Lewis blood group antigens with carcinoembryonic antigen (CEA) 总被引:1,自引:0,他引:1
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Carcinoembryonic antigen (CEA) was purified from primary tumour or from hepatic metastases obtained from ten cases of carcinoma of the colon. In nine cases the blood group antigens A, B, Lea or Leb were detected in CEA preparations by the binding of 125I-labelled CEA by blood group antibodies. The extent of binding appeared to preclude simple contamination of CEA preparations by blood group glycoprotein. In all cases the blood group antigens detected were consistent with the patients' known blood groups. Blood group I and i activities were not detected.
It is concluded that the determinants of A, B and Lewis antigens and of CEA share the same glycoprotein carrier molecules.
相似文献