Complement is a major component of innate immune system involved in defending against all the foreign pathogens through complement
fragments that participate in opsonization, chemotaxis, and activation of leukocytes and through cytolysis by C5b-9 membrane
attack complex. Bacterias and viruses have adapted in various ways to escape the complement activation, and they take advantage
of the complement system by using the host complement receptors to infect various cells. Complement activation also participates
in clearance of apoptotic cells and immune, complexes. Moreover at sublytic dose, C5b-9 was shown to promote cell survival.
Recently it was also recognized that complement plays a key role in adaptive immunity by modulating and modifying the T cell
responses. All these data suggest that complement activation constitutes a critical link between the innate and acquired immune
responses. 相似文献
Atherosclerosis is a chronic inflammatory disease in which dyslipidemia, inflammation, and the immune system play an important pathogenetic role. A role in atherogenesis was demonstrated for monocyte/macrophages, complement system, and T-lymphocytes. Complement activation and C5b-9 deposition occurs both in human and experimental atherosclerosis. Complement C6 deficiency has a protective effect on diet-induced atherosclerosis, indicating that C5b-9 assembly is required for the progression of atherosclerotic lesions. The maturation of atherosclerotic lesions beyond the foam cell stage was shown to be strongly dependent on an intact complement system. C5b-9 may be responsible for cell lysis, and sublytic assembly of C5b-9 induces smooth muscle cell (SMC) and endothelial cell (EC) activation and proliferation. All these data suggest that activation of the complement system plays an important role in atherogenesis. 相似文献
The cytopathogenic effect of partially purified toxin from Clostridium difficile on cultured human lung fibroblasts was studied. Conditions for determination of 50% tissue culture dose were standardized. The cytopathogenic effect of the toxin was dependent on toxin concentration, exposure time, and density of the cells. Transfer of the cells to 0 degrees C did not inhibit binding of toxin to the fibroblast surface, but prevented the development of the cytopathogenic effect. Both binding of toxin and some intracellular step(s) were prevented by 2,4-dinitrophenol. These preventative effects were reversible. Before and concomitantly with the appearance of the cytopathogenic effect, the cellular uptake of uridine and of amino acids was markedly stimulated. Protein synthesis was depressed when 100% of the cells showed the cytopathogenic effect, but the synthesis of nucleic acids was inhibited only several hours later. The primary cellular target for the toxin is still unknown. 相似文献
Crowding can substantially affect the transition of a protein between its native (N) and unfolded (U) states via volume exclusion
effects. Also, it influences considerably the aggregation (A) of unfolded proteins. To examine the details, we developed an
approach for computing the kinetic rates of the process N ↔ U → A in which the concentration of the protein is explicitly
taken into account. We then compute the relative change with temperature of the protein denaturation for various fractional
volume occupancies and partition of proteins in solution. The analysis indicates that, in protein solutions in which the average
distance between proteins is comparable with the radius of gyration of an unfolded protein, steric effects increase the stability
of the proteins which are in compact, native states. In heterogeneous protein solutions containing various types of proteins
with different thermal stabilities, the unfolding of the most thermolabile proteins will increase the stability of the other
proteins. The results shed light on the way proteins change the thermal stability of a cell as they unfold and aggregate.
This study may be valuable in questions related to the dynamics of thermal injuries. 相似文献
ABSTRACT Early detection of apoptotic cells on histological slides is of major importance for both diagnostic and research areas. In the current study, the aim was to propose a convenient method to stain the mitochondria and establish whether hepatocytes undergoing apoptosis can be identified in tissue sections using the proposed method. Liver tissue from five adult chinchillas was fixed with 10% neutral buffered formalin for Goldner’s trichrome (GT) and Groat’s iron hematoxylin and eosin (HE) stains and with Kolster’s fixative for the Heidenhain’s iron hematoxylin procedure. The HE and GT-stained sections showed the morphological features consistent with apoptosis i.e., homogenous intensely acidophilic cytoplasm, cell shrinkage with an irregular outline, nuclear shrinkage with cloudy karyoplasm, and karyopyknosis in the late stage. Sections stained with Heidenhain’s iron hematoxylin method was used to pinpoint mitochondria and revealed cells which were undergoing the first stages of the apoptosis process i.e., disappearance of mitochondria from the cell, chromatin condensation and margination, paracentral localization of nucleoli, and vacuolated nuclei. In more advanced stages of apoptosis, cells presented significant nuclear and cytoplasmic changes. It was concluded that this is the first report targeting the mitochondria, by performing inexpensive histological staining techniques, in order to assess dead cells in situ. 相似文献
The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup. 相似文献
We estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.
In order to assess the consequences of a concomitant blockade of P2X-receptors and ecto-nucleotidases, effects of 13 P2-receptor
antagonists were investigated on contractions of the rat vas deferens elicited by α,β-methylene ATP (α,β-MeATP) and ATP and
on the removal of ATP from the incubation medium by vas deferens tissue.
Increasing concentrations of all antagonists reduced and finally abolished contractions elicited by α,β-MeATP (3 μM), with
IC50-values ranging from 1.1 to 100 μM. Pyridoxalphosphate-6-azophenyl-2’,4’-disulphonate (PPADS), 6-azophenyl-4-amino-5-hydroxy-naphthalene-1,3-disulphonate
(NH02), 4,4’-diisothiocyanatostilbene-2,2’-disulphonate (DIDS) and uniblue A also progressively reduced and finally abolished
contractions elicited by ATP (1 mM). 8,8’-[Carbonylbis(imino-3,1-phenylenecarbonyl-imino)]-bis-(1,3,5-naphthalenetrisulphonate)
(NF023), sura- min, pyridoxalphosphate-6-azophenyl-2’,5’-disulphonate (iso-PPADS), trypan blue and reactive blue 19, in contrast,
caused only partial blockade, by 34–43% maximally; reactive blue 2 and reactive red 2 had no effect; and 6,6’-(1,1’-biphenyl-4,4’-diylbisazo)-bis-4-amino-5-hydroxy-naphtha-lene-1,3-disulphonate
(NH01) and Evans blue even enhan- ced the response to ATP. For antagonists causing full or partial inhibition, the IC50-values against ATP were close to those against α,β-MeATP. All antagonists attenuated the removal of ATP, with IC25%-values ranging from 0.8 μM to >320 μM.
The results confirm the frequent combination, in one antagonist molecule, of P2-receptor blockade and blockade of ecto-nucleotidases.
This dual action underlies the effect of such compounds on contractions of the vas deferens elicited by ATP which, for certain
substances (e.g., suramin, reactive blue 2), can be explained by a simple model in which the antagonist simultaneously blocks
the degradation of ATP and a single contraction-mediating receptor (P2X1). Several observations, however, do not conform with this model, and the existence of multiple contraction-mediating receptors
for ATP or multiple, pharmacologically distinct ecto-nucleotidases has to be considered.
Received: 23 October 1998 / Accepted: 11 January 1999 相似文献
Antibacterial activity of 1,1′-methylenedipyrazole (AM1), 1-hydroxymethylpyrazole (SAM1), 1,1′-methylenediimidazole (AM2), and 1-hydroxymethylimidazole (SAM2) has been tested against reference and clinical strains by both difusimetric and broth dilution methods. Overall, the minimal inhibitory concentrations of tested compounds ranged from 180 to 270?μg/ml, while the minimal bactericidal concentrations were between 360 and 720?μg/ml. Comparative assessment with phenol and formaldehyde shows that AM1, AM2, SAM1, and SAM2 have moderate to good antibacterial activity. 相似文献