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31.
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
32.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
33.
M Niewald W Lehmann H J Tkocz B Scharding U Uhlmann K Schnabel H K Leetz 《Strahlentherapie und Onkologie》1986,162(10):605-612
Irradiation of the thoracic wall with high-speed electrons is one of the standard methods of prophylaxis and therapy of local recurrences and cutaneous metastases of an operated mammary carcinoma. The surface dose, however, is only 85% of the maximum dose, due to the depth dose curve of the electron beams with the preponderantly applied energy of 7MeV. This is a poor value, since most of all recurrences appear near to the surface and so the risk of giving an insufficient dose is involved. The dose distribution could be essentially improved by the use of moulages on the chest. These moulages were made of different materials which were tested and compared with respect to their suitability for radiotherapeutic purposes. The best materials proved to be "Urgo-Plastan" (manufacturer: Holphar, Sulzbach) and "Orthoplast" (manufacturer: Johnson & Johnson, Düsseldorf). Both materials are synthetic substances which after heating can easily be adapted to the body shape and which offer a good stability, little inconvenience for the patient and a relative easy handling. With these moulage materials, the surface dose is increased to 98% ("Urgo-Plastan") and 99% ("Orthoplast") of the maximum dose. 相似文献
34.
M Niewald W Lehmann B Scharding W Berberich K Schnabel H K Leetz 《Strahlentherapie und Onkologie》1986,162(7):448-454
A most precise immobilisation of the patient's head is indispensable in order to reach a high degree of exactness and reproducibility in radiotherapy of malignant head and neck tumors. Face masks made of different synthetic materials have proved to be a simple and economical solution for this problem. Based on our own experiences with "Baycast Longuettes" (manufacturing firm: Johnson & Johnson, Düsseldorf), eleven substances have been tested in the phantom (compound of plaster and synthetic resin, thermoplast, polyurethane foam, compounds of cotton and synthetic resin, and fibre glass compounds). An appropriate material was "Hexcelite" (manufacturing firm: Medimex, Hamburg), a reticulated thermoplast which after warming up can be easily adapted to the patient's face and which guarantees a very good fixation of the head. As compared to solid masks, there is only a slight superposition of the depth dose of Co-60 gamma radiation by secondary electrons from the mask material, so that an increased rate of radiogenic dermatitides is not to be expected. 相似文献
35.
Carlos R Ferreira Kristina Kintzinger Mary E Hackbarth Ulrike Botschen Yvonne Nitschke M Zulf Mughal Genevieve Baujat Dirk Schnabel Eric Yuen William A Gahl Rachel I Gafni Qing Liu Pedro Huertas Gus Khursigara Frank Rutsch 《Journal of bone and mineral research》2021,36(11):2193-2202
Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA. 相似文献
36.
J Davies B Srinivasan PA Brennan 《Annals of the Royal College of Surgeons of England》2021,103(1):e42
Lipomas are common benign tumours that can occur in most parts of the body. Lipomas arising from the deep temporal fat pad, found between the two layers of the deep temporal fascia, are rare, however; there has been only one documented case report to our knowledge. We describe a second case arising from the temporal fat pad in a patient treated at our unit, having previously reported the first one, and discuss the relevant anatomy and management. 相似文献
37.
Joshua R Lewis Trudy Voortman John PA Ioannidis 《Journal of bone and mineral research》2021,36(2):219-226
A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
38.
Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fibres. For example, nerve fibres are usually assumed to be perfectly straight. Such idealizations can cause discrepancies between theoretical predictions and experimental results. One well-known discrepancy is that the currently used models predict (contradictory to experimental findings) that an activation of nerve fibres is not possible with a pure transverse electric field. This situation occurs when a magnetic coil is placed symmetrically above a straight nerve fibre for magnetic nerve stimulation, or when an anode and a cathode are placed equidistantly on a line perpendicular to the fibre in the case of electrical stimulation. It is shown that this discrepancy does not occur if the physiological undulation of peripheral nerve fibres is included in the models. Even for small undulation amplitudes (e.g. 0.02 mm), it is possible to activate the fibre in these positions. For physiological undulations, as found in the literature, and favourable (off-centre) positions, the typical reduction of the thresholds is in a range between one and five, compared with perfectly straight fibres. 相似文献
39.
Patterns of structural deterioration due to ischemia in Purkinje fibres and different layers of the working myocardium 总被引:1,自引:0,他引:1
P A Schnabel J Richter A Schmiedl F Bach U Bartels B Ramsauer M M Gebhard H J Bretschneider 《The Thoracic and cardiovascular surgeon》1991,39(4):174-182
Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion. 相似文献
40.
Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. 总被引:1,自引:0,他引:1