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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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Carlo Paribello Leeping Tao Anthony Folino Elizabeth Berry-Kravis Michael Tranfaglia Iryna M Ethell Douglas W Ethell 《BMC neurology》2010,10(1):91
Background
Fragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in fmr1 knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS. 相似文献4.
Dendritic spines are dynamic structures that accommodate the majority of excitatory synapses in the brain and are influenced by extracellular signals from presynaptic neurons, glial cells, and the extracellular matrix (ECM). The ECM surrounds dendritic spines and extends into the synaptic cleft, maintaining synapse integrity as well as mediating trans-synaptic communications between neurons. Several scaffolding proteins and glycans that compose the ECM form a lattice-like network, which serves as an attractive ground for various secreted glycoproteins, lectins, growth factors, and enzymes. ECM components can control dendritic spines through the interactions with their specific receptors or by influencing the functions of other synaptic proteins. In this review, we focus on ECM components and their receptors that regulate dendritic spine development and plasticity in the normal and diseased brain. 相似文献
5.
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
6.
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
7.
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8.
Several studies have reported the up-regulation of EphB receptor-tyrosine kinases and ephrin-B ligands in a variety of tumors, suggesting a functional relation between EphB/ephrin-B signaling and tumor progression. The ability of the EphB receptors to regulate cell migration and promote angiogenesis likely contributes to tumor progression and metastasis. Here we show that EphB receptors, and especially EphB4, regulate the migration of murine melanoma cells. Highly malignant melanoma cells express the highest levels of EphB4 receptor and migrate faster than less malignant melanoma cells. Furthermore, inhibition of EphB receptor forward signaling by overexpression of a form of EphB4 lacking the cytoplasmic portion or by treatment with competitively acting soluble EphB2-Fc results in slower melanoma cell migration. In contrast, overexpression of active EphB4 significantly enhances cell migration. The effects of EphB4 receptor on cell migration and cell morphology require its kinase activity because the inhibition of EphB4 kinase activity by overexpression of kinase dead EphB4 inhibits cell migration and affects the organization of actin cytoskeleton. Activation of EphB4 receptor with its ligand ephrin-B2-Fc enhances the migratory ability of melanoma cells and increases RhoA activity, whereas inhibiting EphB receptor forward signaling decreases RhoA activity. Moreover, expression of dominant negative RhoA blocks the effects of active EphB4 on cell migration and actin organization. These data suggest that EphB4 forward signaling contributes to the high migratory ability of invasive melanoma cells by influencing RhoA-mediated actin cytoskeleton reorganization. 相似文献
9.
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
10.
Early evolution of metazoan serine/threonine and tyrosine kinases: identification of selected kinases in marine sponges 总被引:14,自引:1,他引:13
The phylum Porifera (sponges) was the first to diverge from the common
ancestor of the Metazoa. In this study, six cDNAs coding for protein-
serine/threonine kinases (PS/TKs) are presented; they have been isolated
from libraries obtained from the demosponges Geodia cydonium and Suberites
domuncula and from the calcareous sponge Sycon raphanus. Sequence
alignments of the catalytic domains revealed that two major families of
PS/TK, the "conventional" (Ca(2+)-dependent) protein kinase C (PKC), the
cPKC subfamily, as well as the "novel" (Ca(2+)- independent) PKC (nPKC),
form two separate clusters. In each cluster, the sequence from S. raphanus
diverges first. To approach the question about the origin of
protein-tyrosine kinases (PTK), which are found only in Metazoa, we
analyzed two additional PS/TKs which have been cloned from S. domuncula:
the stress-responsive protein kinase (KRSvSD) and the
protein-kinase-C-related kinase (PRKvSD). The construction of the
phylogenetic tree, comprising the eight PS/TKs and the PTK cloned
previously from G. cydonium, revealed that the PTK derived from the branch
including the KRSvSD kinase. These data facilitate the first molecular
approach to elucidate the origin of metazoan PTK within the PS/TK
superfamily.
相似文献