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11.
Summary Lung fragments from 10 human fetuses aged 10 to 14 weeks of gestation were implanted into athymic nude mice. Cytodifferentiation of the transplants was studied by both scanning and transmission electron microscopy.Two weeks after implantation mitotic figures of epithelial and stroma cells were observed. In five week old transplants ciliated as well as endocrine cells were found dispersed among undifferentiated bronchial epithelium. During further experimental period epithelial differentiation in the transplants proceeded. Thus, eight week old implants assumed the morphologic appearance of fetal lungs in the canalicular stage displaying prospective type I and II pneumocytes. In addition stroma cells also differentiated forming mature fibroblasts and myofibroblasts.Our study indicates that human fetal lung tissue transplanted into nude mice not only grow but even differentiate. Xenogeneic transplantation of human fetal cells and tissues, therefore, offers additional opportunities to investigate the prenatal development of human tissues.Supported by EMDO and by Hartmann Müller Foundation 相似文献
12.
Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson’s disease 总被引:12,自引:0,他引:12
Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of this form and the rapidly expanding knowledge about the structure and biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction might lead to neurodegeneration, and the implications of this novel piece of information for the pathogenesis of the common PD forms. Although much work remains to be done to clarify the biology of DJ-1, its proposed activity as a molecular chaperone and/or as oxidative sensor appear intriguing in the light of the current theories on the pathogenesis of PD. 相似文献
13.
The activity of 5-deoxy-5-fluorouridine (dFUR) depends on its activation to 5-fluorouracil (FU) by pyrimidine nucleoside phosphorylases. These enzymes are found in tumors and normal tissues, with the highest activity in the small intestines. The present study examined the inhibition of dFUR phosphorolysis in intestinal tissues. dFUR metabolism in intestinal homogenates was inhibited by uracil (U), uridine (UR), and thymidine (TdR), which are the normal substrates for the phosphorylases. Conversely dFUR reduced the metabolism of these inhibitors. A good agreement was found between the observed data and the computer-fitted data using the equations for competitive inhibition between dFUR and the inhibitors. In the absence of inhibitors, the V
max of dFUR phosphorolysis was 47.1 ± 4.9 µM/min and the apparent K
m was 910 ± 167 µM. The V
max was unaltered by the inhibitors, while the K
m was increased with increasing inhibitor concentrations. The maximal inhibition of dFUR metabolism by UR and TdR was about 80%. The K
i,'s were 372 µM for U, 87.2 µM for UR, and 112 µM for TdR and are orders of magnitude higher than their reported endogenous serum concentrations. The rate of dFUR phosphorolysis to FU in the intact intestinal epithelial crypt cells, indicated by the ratio of FU to dFUR in the intracellular fluid, was reduced by UR in a concentration-dependent fashion. These data indicate that the naturally occurring pyrimidines inhibit competitively the dFUR metabolism by the intestinal phosphorylases, that this inhibition occurs at concentrations much higher than the circulating endogenous levels, and that phosphorolysis is the major route of dFUR metabolism. 相似文献
14.
A. N. Aleksandrov V. I. Ovsyannikov 《Bulletin of experimental biology and medicine》1993,116(4):1186-1188
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N
o
10, pp. 341–343. October, 1993 相似文献
15.
Summary A possible interaction between the tetracyclic antidepressant mianserin and a coumarin derivative has been investigated. Sixty-three subjects, 61 of whom required anticoagulant therapy for a variety of medical conditions, were treated for 5 consecutive weeks with phenprocoumon, in a dose adjusted to reduce the prothrombin time to 15%–25%. After an initial control period of one week, subjects were randomly treated under double-blind conditions with mianserin 3×10 mg daily or 3×20 mg daily, or with a matching placebo. The dose of mianserin was gradually increased to reach the maximum by the 6th day. Three subjects dropped out and 60 completed the trial.The dose of phenprocoumon and the prothrombin, bleeding, and coagulation times were not significantly affected by administration of mianserin. It can be concluded that there is no clinically important interaction between phenprocoumon and doses of mianserin effective in depression. Sedation was more frequent in patients taking mianserin than in those given placebo. 相似文献
16.
W. Weber 《International journal of legal medicine》1980,85(1):63-71
Zusammenfassung Nach § 19 StGB sind Kinder unter 14 Jahren schuldunfähig. Ihr Anteil an Tötungsdelikten und gefährlichen bzw. schweren Körperverletzungen betrug für das Jahr 1978 in der Bundesrepublik Deutschland je 0,7%. Eine quantitative Untersuchung über die physische Fähigkeit der Kinder, Intensivtaten zu begehen, ist bisher nicht bekannt geworden. Deshalb wurden die manuell erreichbaren Stoßintensitäten von einem Kollektiv 12- und 13jähriger Knaben quantitativ für drei Stoßrichtungen untersucht und mit den von Männern (21 bis 70 Jahre) erreichten Ergebnissen verglichen. Nach den von den Kindern erzielten Resultaten ist die Vorstellung der Erwachsenen zu korrigieren. Für 12- und 13jährige Knaben sind nicht per se mangelnde physische Kräfte bei Gewaltdelikten zu unterstellen.Vortrag auf der 58. Jahrestagung der Deutschen Gesellschaft für Rechtsmedizin, Mülnster (Westfalen) 18. 22.9.1979 相似文献
17.
Ph. Cornu J. Benavides B. Scatton J. -J. Hauw J. Philippon' 《Acta neurochirurgica》1992,119(1-4):146-152
Summary The density of 3 (peripheral type benzodiazepine) binding sites, a marker of reactive and tumoural cells, has been measured in different types of human brain tumours; 3 sites were quantified autoradiographically in sections from biopsy or autopsy specimens labelled with the specific radioligand3H-PK 11195. Compared to normal brain parenchyma, up to 12-fold increase in 3 site densities were found in appparently viable areas of high grade astrocytoma and glioblastoma specimens, whereas more limited increases (2 to 3-fold) in this marker were observed in areas of necrosis. Low grade gliomas (astrocytomas) and meningiomas exhibited only moderate increases (2 to 3-fold) in this autoradiographic marker. Metastases of lung or kidney origin were characterized by greatly elevated (up to 20-fold) 3 site densities as compared to normal brain parenchyma. In every case, there was a good spatial correspondence between the histopathological limits of the tumour and the anatomical location of the increase in 3 site densities. These results suggest that 3 site densities in human brain tumours reflect their proliferative activity and point to a possible future usefulness of positron or gamma-ray emitting 3 site ligands for the clinical investigation and detection of human brain proliferative diseases. 相似文献
18.
Marc Rosenbaum Virginia Andreani Tanya Kapoor Simone Herp Henrik Flach Marlena Duchniewicz Rudolf Grosschedl 《Genes & development》2014,28(11):1165-1178
MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1−/− mice. A similar developmental block was observed in Mzb1fl/flmb1Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin µ heavy chains (µHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with µHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of µHCs under conditions of ER stress. 相似文献
19.
Yangyang Wang Xinhui Wang Cristina R. Ferrone Joseph H. Schwab Soldano Ferrone 《Molecular oncology》2015,9(10):1982-1993
This review discusses the potential use of intracellular tumor antigens as targets of antibody‐based immunotherapy for the treatment of solid tumors. In addition, it describes the characteristics of the intracellular tumor antigens targeted with antibodies which have been described in the literature and have been identified in the authors'' laboratory. Finally, the mechanism underlying the trafficking of the intracellular tumor antigens to the plasma membrane of tumor cells are reviewed. 相似文献
20.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by abnormal proliferation of synoviocytes, leukocyte infiltration, and angiogenesis. The endoplasmic reticulum (ER) is the site of biosynthesis for all secreted and membrane proteins. The accumulation of unfolded proteins in the ER leads to a condition known as ER stress. Failure of the ER''s adaptive capacity results in abnormal activation of the unfolded protein response. Recently, we have demonstrated that ER stress-associated gene signatures are highly expressed in RA synovium and synovial cells. Mice with Grp78 haploinsufficiency exhibit the suppression of experimentally induced arthritis, suggesting that the ER chaperone GRP78 is crucial for RA pathogenesis. Moreover, increasing evidence has suggested that GRP78 participates in antibody generation, T cell proliferation, and pro-inflammatory cytokine production, and is therefore one of the potential therapeutic targets for RA. In this review, we discuss the putative, pathophysiological roles of ER stress and GRP78 in RA pathogenesis. 相似文献