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排序方式: 共有102条查询结果,搜索用时 15 毫秒
1.
Samir Jabari Alexandre B. M. da Silveira Enio C. de Oliveira Karl Quint André Wirries Winfried Neuhuber Axel Brehmer 《Cell and tissue research》2014,358(1):75-83
Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal neuron loss. Here, we examined changes of the innervation pattern of the lamina propria (LP) and muscularis mucosae (MM). Two alternating sets of cryosections were taken from seven non-chagasic colonic and seven chagasic megacolonic specimens (the latter included both the dilated megacolonic and the non-dilated transitional oral and anal zones) and were immunohistochemically triple-stained for smooth-muscle actin (SMA), synaptophysin (SYN) and glial acid protein S100 and, alternatively, for SMA, vasoactive intestinal peptide (VIP) and somatostatin (SOM). Subsequent image analysis and statistical evaluation of nervous tissue profile areas revealed that, in LP, the most extreme differences (i.e. increase in thickness or decrease in nerve, glia and muscle tissue profile area, respectively) compared with control values occurred in the dilated megacolonic zone itself. In contrast, the most extreme differences in the MM were in the anal-to-megacolonic zone (except the profile area of muscle tissue, which was lowest in the megacolonic zone). This parallels our previous results in the external muscle coat. A partial and selective survival of VIP-immunoreactive in contrast to SOM-immunoreactive nerve fibres was observed in both mucosal layers investigated. Thus, VIPergic nerve elements might be crucial for the maintenance of the mucosal barrier. The differential changes of neural tissue parameters in LP and MM might reflect a multifactorial rather than a pure neurogenic development of megacolon in chronic Chagas’ disease. 相似文献
2.
Immunization of mice by combinations of inactive fractions of Mycobacterium bovis strain BCG 总被引:4,自引:0,他引:4
3.
Ultrastructural differences between ganglia of the plexus submucosus internus (Meissner; PSI) and plexus submucosus externus (Schabadasch; PSE) are described. Comparison revealed a different glia index (ratio glia per neuron) between the PSE (3:1) and the PSI (1:1), the arrangement of PSI neurons in compartments and the appearance of broad membrane-to-membrane appositions inside the compartments of the PSI. Structural and immunohistochemical differences between the two plexuses are discussed. In general, PSE neurons show a wider variety in size and shape than most of the PSI neurons. 相似文献
4.
A. Brehmer Werner Stach Heinz-Jürgen Krammer Winfried Neuhuber 《Histochemistry and cell biology》1997,109(1):87-94
Sequential nitric oxide synthase immunohistochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)
histochemistry in pig small intestinal wholemounts revealed a complete colocalisation of the two nitrergic markers in submucous
neurons. The external submucous plexus (ESP) contained nitrergic neurons throughout. In the internal submucous plexus (ISP)
we found a moderate number of nitrergic neurons in the duodenum, while they were rare in the jejunum and nearly absent in
the ileum. Combined NADPHd histochemistry and silver impregnation showed morphological ESP type III and VI neurons to be NADPHd
positive whereas ESP type II, IV and V neurons were NADPHd negative. Axons of ESP type III, IV and VI neurons were often observed
to enter interconnecting strands directed abluminally. ESP type II neurons projected mainly to the ISP. In special silver-impregnated
wholemounts containing both external muscle layers and the abluminal part of the submucous layer, i.e. the myenteric plexus
and the ESP, the great majority of impregnated axons within the interconnecting strands were observed to run between both
plexuses and did not enter the circular muscle layer. We conclude that ESP type III and VI neurons are nitrergic while ESP
type II, IV and V neurons are non-nitrergic. Furthermore, we assume that ESP type III, IV and VI neurons may represent a submucosal
input to the myenteric plexus.
Accepted: 26 August 1997 相似文献
5.
J Rauterberg S Allam U Brehmer W Wirth W H Hauss 《Hoppe-Seyler's Zeitschrift für physiologische Chemie》1977,358(3):401-407
Smooth muscle cells were grown from explants of the tunica media of fetal and adult human aorta. Collagen was isolated after incubation with [14C]glycine and was characterized by ion-exchange chromatography. All cells investigated synthesized two types of collagen: Type I (chain composition [alpha1(I)]2alpha2) and type III (chain composition [alpha1(III)]3). The collagen made by cells from adult donors contained approximately 70% type I and 30% type III collagen. This corresponds to the collagen composition in teh original tissue. No age-relate change in the type I/type III ratio was found with cells from donors between 9 and 67 years of age. On the other hand, the type III portion of the collagen made by fetal cells was markedly less (about 15-20% of total collagen). 相似文献
6.
Wissing J Godl K Brehmer D Blencke S Weber M Habenberger P Stein-Gerlach M Missio A Cotten M Müller S Daub H 《Molecular & cellular proteomics : MCP》2004,3(12):1181-1193
Small molecule inhibitors belonging to the pyrido[2,3-d]pyrimidine class of compounds were developed as antagonists of protein tyrosine kinases implicated in cancer progression. Derivatives from this compound class are effective against most of the imatinib mesylate-resistant BCR-ABL mutants isolated from advanced chronic myeloid leukemia patients. Here, we established an efficient proteomics method employing an immobilized pyrido[2,3-d]pyrimidine ligand as an affinity probe and identified more than 30 human protein kinases affected by this class of compounds. Remarkably, in vitro kinase assays revealed that the serine/threonine kinases Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK) and p38alpha were among the most potently inhibited kinase targets. Thus, pyrido[2,3-d]pyrimidines did not discriminate between tyrosine and serine/threonine kinases. Instead, we found that these inhibitors are quite selective for protein kinases possessing a conserved small amino acid residue such as threonine at a critical site of the ATP binding pocket. We further demonstrated inhibition of both p38 and RICK kinase activities in intact cells upon pyrido[2,3-d]pyrimidine inhibitor treatment. Moreover, the established functions of these two kinases as signal transducers of inflammatory responses could be correlated with a potent in vivo inhibition of cytokine production by a pyrido[2,3-d]pyrimidine compound. Thus, our data demonstrate the utility of proteomic methods employing immobilized kinase inhibitors for identifying new targets linked to previously unrecognized therapeutic applications. 相似文献
7.
Molecular architecture of the ribosome‐bound Hepatitis C Virus internal ribosomal entry site RNA
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Justus Loerke Jochen Ismer Andrea Schmidt Tarek Hilal Thiemo Sprink Kaori Yamamoto Thorsten Mielke Jörg Bürger Tanvir R Shaikh Marylena Dabrowski Peter W Hildebrand Patrick Scheerer Christian MT Spahn 《The EMBO journal》2015,34(24):3042-3058
Internal ribosomal entry sites (IRESs) are structured cis‐acting RNAs that drive an alternative, cap‐independent translation initiation pathway. They are used by many viruses to hijack the translational machinery of the host cell. IRESs facilitate translation initiation by recruiting and actively manipulating the eukaryotic ribosome using only a subset of canonical initiation factor and IRES transacting factors. Here we present cryo‐EM reconstructions of the ribosome 80S‐ and 40S‐bound Hepatitis C Virus (HCV) IRES. The presence of four subpopulations for the 80S•HCV IRES complex reveals dynamic conformational modes of the complex. At a global resolution of 3.9 Å for the most stable complex, a derived atomic model reveals a complex fold of the IRES RNA and molecular details of its interaction with the ribosome. The comparison of obtained structures explains how a modular architecture facilitates mRNA loading and tRNA binding to the P‐site. This information provides the structural foundation for understanding the mechanism of HCV IRES RNA‐driven translation initiation. 相似文献
8.
Jennifer MP Woo Zhuofeng Lin Mohamad Navab Casey Van Dyck Yvette Trejo-Lopez Krystal MT Woo Hongyun Li Lawrence W Castellani Xuping Wang Noriko Iikuni Ornella J Rullo Hui Wu Antonio La Cava Alan M Fogelman Aldons J Lusis Betty P Tsao 《Arthritis research & therapy》2010,12(3):R93
Introduction
The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.Methods
Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.Results
In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL, LP < 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL < 0.05) and oxidized phospholipids (oxPLs) (PL, LP < 0.005), and elevated total and vertebral bone mineral density (PL, LP < 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+ macrophages (PLP < 0.01), significantly increased mean α-actin stained area (PLP < 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (PL, LP < 0.0005) and VCAM-1 (PL < 0.0002).Conclusions
L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis. 相似文献9.
Jabari S da Silveira AB de Oliveira EC Neto SG Quint K Neuhuber W Brehmer A 《Histochemistry and cell biology》2011,135(1):47-57
One frequent chronic syndrome of Chagas’ disease is megacolon, an irreversible dilation of a colonic segment. Extensive enteric
neuron loss in the affected segment is regarded as key factor for deficient motility. Here, we assessed the quantitative balance
between cholinergic and nitrergic neurons representing the main limbs of excitatory and inhibitory colonic motor innervation,
respectively. From surgically removed megacolonic segments of four patients, each three myenteric wholemounts (from non-dilated
oral, megacolonic and non-dilated anal parts) was immunohistochemically triple-stained for choline acetyltransferase, neuronal
nitric oxide synthase (NOS) and the panneuronal human neuronal protein Hu C/D. Degenerative changes were most pronounced in
the megacolonic and anal regions, e.g. bulked, honeycomb-like ganglia with few neurons which were partly enlarged or atrophic
or vacuolated. Neuron counts from each 15 ganglia of 12 megacolonic wholemounts were compared with those of 12 age- and region-matched
controls. Extensive neuron loss, mainly in megacolonic and anal wholemounts, was obvious. In all three regions derived from
megacolonic samples, the proportion of NOS-positive neurons (control: 55%) was significantly increased: in non-dilated oral
parts to 61% (p = 0.003), in megacolonic regions to 72% (p < 0.001) and in non-dilated anal regions to 78% (p < 0.001). We suggest the chronic dilation of megacolonic specimens to be due to the preponderance of the nitrergic, inhibitory
input to the intestinal muscle. However, the observed neuronal imbalance was not restricted to the dilated regions: the non-dilated
anal parts may be innervated by ascending, cholinergic axons emerging from less affected, more anally located regions. 相似文献
10.
Brehmer D Gässler C Rist W Mayer MP Bukau B 《The Journal of biological chemistry》2004,279(27):27957-27964
The DnaK chaperone of Escherichia coli assists protein folding by an ATP-dependent interaction with short peptide stretches within substrate polypeptides. This interaction is regulated by the DnaJ and GrpE co-chaperones, which stimulate ATP hydrolysis and nucleotide exchange by DnaK, respectively. Furthermore, GrpE has been claimed to trigger substrate release independent of its role as a nucleotide exchange factor. However, we show here that GrpE can accelerate substrate release from DnaK exclusively in the presence of ATP. In addition, GrpE prevented the association of peptide substrates with DnaK through an activity of its N-terminal 33 amino acids. A ternary complex of GrpE, DnaK, and a peptide substrate could be observed only when the peptide binding to DnaK precedes GrpE binding. Furthermore, we demonstrate that GrpE slows down the release of a protein substrate, sigma(32), from DnaK in the absence of ATP. These findings suggest that the ATP-triggered dissociation of GrpE and substrates from DnaK occurs in a concerted fashion. 相似文献