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1.
Treatment of patients diagnosed as schizophrenic with antipsychotic drugs (neuroleptics) is known to cause occasional unexplained depletion of white blood cells, especially neutrophil granulocytes. It has been known for many years that neuroleptics can interfere with the mitochondrial respiratory chain in vitro. Because there has been a growing interest recently in mitochondrial targeting of drugs, and since a quantitative structure-activity relationship (QSAR) model that predicts mitochondrial accumulation of neuroleptics has been published, we investigated the effects of neuroleptics on white blood cell mitochondria. Venous blood samples were collected from both patients undergoing treatment with neuroleptics and healthy volunteers. The samples were processed for transmission electron microscopy. The resulting images of white blood cells were analyzed using stereology to compare quantitatively mitochondrial morphology in the patient and control groups. We found that in patients, but not in controls, there was swelling of mitochondria and fragmentation of the mitochondrial cristae. There also were fewer mitochondria in patients than in controls, although due to the swelling of the organelles, the volume density of mitochondria in the two groups was not significantly different. Such changes are typical of a toxic insult. Consequently, it seems plausible that, since schizophrenia is not a disease considered to affect white blood cells per se, these changes probably are due to the medication. 相似文献
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Davidova VN Naberezhnykh GA Yermak IM Gorbach VI Solov'eva TF 《Biochemistry. Biokhimii?a》2006,71(3):332-339
The interaction of endotoxins--lipopolysaccharides (LPS) different in degree of the O-specific chain polymerization--with 20- and 130-kD chitosan was studied using the competitive binding of LPS with the complex of chitosan-anionic dye (tropaeolin 000-2) and the direct binding of (125)I-labeled LPS with chitosan immobilized on Sepharose 4B. The interaction of 20-kD chitosan with LPS was non-cooperative, and immobilization of the polycation on Sepharose resulted in its binding to (125)I-labeled LPS with a positive cooperativity. The interaction of LPS possessing a long O-specific chain with 130-kD chitosan was characterized by negative cooperativity. Binding constants of LPS with the polycation and the number of binding sites per amino group of chitosan were determined. The interaction affinity and stoichiometry of the LPS-chitosan complexes significantly depend on the LPS structure and concentration in the reaction mixture. The increase in the length of carbohydrate chains of LPS results in increase in the binding constants and decrease in the bound endotoxin amount. 相似文献
4.
I. M. Yermak V. N. Davydova 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2008,2(4):279-295
Lipopolysaccharides (LPS) are unique cell wall components of gram-negative bacteria. They represent amphiphilic biopolymeric compounds combining in a single molecule hydrophilic (O-specific chains, core oligosaccharide, etc.) and hydrophobic (lipid A) entities. LPS play a crucial role in various interactions between micro- and macroorganisms and display a broad range of biological activities including toxic activity and ability to activate immune cells. Biological activities of LPS are based on their ability to bind with high affinity to mammalian proteins, e.g., lipoproteins, bactericidal permeability-increasing proteins, lysozyme, etc., and thus to neutralize toxic effects of endotoxins. LPS are specific targets for antimicrobial polycationic compounds used in the therapy of bacterial infections. Studies of mechanisms of toxic effects of LPS culminated in the development of novel approaches to LPS neutralization. One of them is based on the use of compounds able to neutralize LPS toxicity at the expense of formation of macromolecular complexes with them. This approach is highly specific and has no effect on functional activity of antipathogenic defense mechanisms of the host. Interaction of LPS with various classes of cationic amphiphilic molecules including proteins, peptides, and polyamines was the subject of intensive studies in the past decade. Binding of cationic polymers is provided by electrostatic interactions between LPS and negatively charged phosphate and carboxylic groups of LPS localized in lipid A core. The present study is an overview of recently published data on different mechanisms of interactions of LPS with soluble proteins and polycations and modification of physiological activity of LPS. 相似文献
5.
Davydova VN Bratskaya SY Gorbach VI Solov'eva TF Kaca W Yermak IM 《Biophysical chemistry》2008,136(1):1-6
Electrokinetic properties of complexes of chitosan (Ch) with lipopolysaccharides (LPSs) from Escherichia coli O55:B5, Yersinia pseudotuberculosis 1B 598, and Proteus vulgaris O25 (48/57) and their size distribution were investigated using zeta-potential distribution assay and quasi-elastic light scattering. The interaction of LPS from different microorganisms with chitosan at the same w/w ratio of components (1:1) resulted in the formation of complexes in which the negative charge of LPS was neutralized (LPS from E. coli) or overcompensated (Y. pseudotuberculosis and P. vulgaris). The changing in size of the endotoxin aggregates during binding with chitosan was observed. The binding constants of chitosan with LPSs were determined by a method with using the anionic dye Orange II. The LPS from E. coli possess higher affinity to chitosan in comparison with the two others samples of endotoxin. 相似文献
6.
A. O. Barabanova A. S. Shashkov V. P. Glazunov V. V. Isakov T. B. Nebylovskaya W. Helbert T. F. Solov’eva I. M. Yermak 《Journal of applied phycology》2008,20(6):1013-1020
Sulfated polysaccharides occurring in the red algae Tichocarpus crinitus cell wall were fractionated and purified. NMR and FT-IR spectroscopy analyses revealed that the non-gelling fraction contained
a sulfated galactans having a new carrageenan-like structure. It is built with alternatively linked 1,3-linked β-D-galactopyranosyl-2,4-disulphates
and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl residues. Minor amounts of its biosynthetic precursor were detected in a water-extracted
specimen. Brief analysis of rheological and biological properties of the non-gelling fraction was carried out. The carrageenan-like
polysaccharide from T. crinitus displayed the properties of “random coil” polymer at high temperature, and possesses high anticoagulant activity at low concentration. 相似文献
7.
Treatment of patients diagnosed as schizophrenic with antipsychotic drugs (neuroleptics) is known to cause occasional unexplained depletion of white blood cells, especially neutrophil granulocytes. It has been known for many years that neuroleptics can interfere with the mitochondrial respiratory chain in vitro. Because there has been a growing interest recently in mitochondrial targeting of drugs, and since a quantitative structure-activity relationship (QSAR) model that predicts mitochondrial accumulation of neuroleptics has been published, we investigated the effects of neuroleptics on white blood cell mitochondria. Venous blood samples were collected from both patients undergoing treatment with neuroleptics and healthy volunteers. The samples were processed for transmission electron microscopy. The resulting images of white blood cells were analyzed using stereology to compare quantitatively mitochondrial morphology in the patient and control groups. We found that in patients, but not in controls, there was swelling of mitochondria and fragmentation of the mitochondrial cristae. There also were fewer mitochondria in patients than in controls, although due to the swelling of the organelles, the volume density of mitochondria in the two groups was not significantly different. Such changes are typical of a toxic insult. Consequently, it seems plausible that, since schizophrenia is not a disease considered to affect white blood cells per se, these changes probably are due to the medication. 相似文献
8.
S.P. NG Z.G. LI B.W. CHEN Z.K. QIN M.M. GARCIA S.W.K. IM M.H. NG 《Journal of Rapid Methods and Automation in Microbiology》1997,5(4):285-294
We previously described an enrichment-immunoassay utilizing a T6 monoclonal antibody capture enzyme-linked immunosorbent assay. Here we evaluated it for the rapid screening for Salmonella in fishmeal obtained from the national Animal and Plant Quarantine service in the People's Republic of China. In this method, the number of Salmonella present is first expanded by appropriate enrichment cultures, and the pathogens are then directly detected by the T6 immunoassay. In a total of 94 enrichment cultures of fishmeal, we obtained an overall concordance of 98% between the results obtained in parallel by this method and by conventional test method. The positive prediction by this method was 92% and the negative prediction was 100%. The turn around time for the new test was 27 h which is a significant improvement from the turn around time exceeding 96 h required for the conventional test method. This test proved to be compatible with the routine work flow in the practical setting of a quarantine laboratory. 相似文献
9.
Eveline C van Asbeck Andy IM Hoepelman Jelle Scharringa Bjorn L Herpers Jan Verhoef 《BMC microbiology》2008,8(1):229
Background
Mannose binding lectin (MBL) is an important host defence protein against opportunistic fungal pathogens. This carbohydrate-binding protein, an opsonin and lectin pathway activator, binds through multiple lectin domains to the repeating sugar arrays displayed on the surface of a wide range of clinically relevant microbial species. We investigated the contribution of MBL to antifungal innate immunity towards C. parapsilosis in vitro. 相似文献10.
The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet
been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors
is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer,
a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite.
Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance.
A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal
mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the
highest incidence, we concluded that in this model the immune system constituted a ‘tumor-suppressive factor’ delaying and
sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation
back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic
than tumors from normal mice, resulting in a high rejection rate. CD8+cytotoxic T cells were found to be indispensable for
this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating
immunogenic tumor cell variants in the incipient tumor.
In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations
and hypotheses. 相似文献