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81.
Postsynaptic density antigens: preparation and characterization of an antiserum against postsynaptic densities 总被引:6,自引:3,他引:3
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Long-term immunization of rabbits with postsynaptic densities (PSD) from bovine brain produced an antiserum specific for PSD as judged by binding to subcellular fractions and immunohistochemical location at the light and electron microscope levels. (a) The major antigens of bovine PSD preparations were three polypeptides of molecular weight 95,000 (PSD-95), 82,000 (PSD-82), and 72,000 (PSD-72), respectively. Antigen PSD-95, also present in mouse and rat PSDs was virtually absent from cytoplasm, myelin, mitochondria, and microsomes from rodent or bovine brain. Antigens PSD-82 and PSD-72 were present in all subcellular fractions from bovine brain, especially in mitochondria, but were almost absent from rodent brain. The antiserum also contained low-affinity antibodies against tubulin. (b)Immunohistochemical studies were performed in mouse and rat brain, where antigen PSD-95 accounted for 90 percent of the antiserum binding after adsorption with purified brain tubulin. At the light microscope level, antibody binding was observed only in those regions of the brain where synapses are known to be present. No reaction was observed in myelinated tracts, in the neuronal cytoplasm, or in nonneuronal cells. Strong reactivity was observed in the molecular layer of the dentate gyrus, stratum oriens and stratum radiatum of the hippocampus, and the molecular layer of the cerebellum. Experimental lesions, such as ablation of the rat entorhinal cortex or intraventricular injection of kainic acid, which led to a major loss of PSD in well- defined areas of the hippocampal formation, caused a correlative decrease in immunoreactivity in these areas. Abnormal patterns of immunohistochemical staining correlated with abnormal synaptic patterns in the cerebella of reeler and staggerer mouse mutants. (c) At the electron microscopic level, immunoreactivity was detectable only in PSD. The antibody did not bind to myelin, mitochondria or plasma membranes. (d) The results indicate that antigen PSD-95 is located predominantly or exclusively in PSD and can be used as a marker during subcellular fractionation. Other potential uses include the study of synaptogenesis, and the detection of changes in synapse number after experimental perturbations of the nervous system. 相似文献
82.
Inactivation of sodium conductance has been studied in squid axons with voltage clamp techniques and with the enzyme pronase which selectively destroys inactivation. Comparison of the sodium current before and after pronase treatment shows a lag of several hundred microseconds in the onset of inactivation after depolarization. This lag can of several hundred microseconds in the onset of inactivation after polarization. This lag can also be demonstrated with double-pulse experiments. When the membrane potential is hyperpolarized to -140 mV before depolarization, both activation and inactivation are delayed. These findings suggest that inactivation occurs only after activation are delayed. These findings suggest that inactivation occurs only after activation; i.e. that the channels must open before they can inactivate. The time constant of inactivation measured with two pulses (τ(c)) is the same as the one measured from the decay of the sodium current during a single pulse (τ(h)). For large depolarizations, steady-state inactivation becomes more incomplete as voltage increases; but it is relatively complete and appears independent of voltage when determined with a two- pulse method. This result confirms the existence of a second open state for Na channels, as proposed by Chandler and Meves (1970. J. Physiol. [Lond.]. 211:653-678). The time constant of recovery from inactivation is voltage dependent and decreases as the membrane potential is made more negative. A model for Na channels is presented which has voltage-dependent transitions between the closed and open states, and a voltage-independent transition between the open and the inactivated state. In this model the voltage dependence of inactivation is a consequence of coupling to the activation process. 相似文献
83.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
84.
Flendrie M Vissers WH Creemers MC de Jong EM van de Kerkhof PC van Riel PL 《Arthritis research & therapy》2005,7(3):R666-R676
Various dermatological conditions have been reported during tumor necrosis factor (TNF)-α-blocking therapy, but until now
no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature
of clinically important dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis (RA).
RA patients starting on TNF-α-blocking therapy were prospectively followed up. The numbers and natures of dermatological events
giving rise to a dermatological consultation were recorded. The patients with a dermatological event were compared with a
group of prospectively followed up RA control patients, naive to TNF-α-blocking therapy and matched for follow-up period.
289 RA patients started TNF-α-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years
of follow-up. TNF-α-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More
of the RA patients given TNF-α-blocking therapy (25%) than of the anti-TNF-α-naive patients (13%) visited a dermatologist
during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period
of withdrawal of TNF-α-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic
lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective
study focusing on dermatological conditions during TNF-α-blocking therapy. It shows that dermatological conditions are a significant
and clinically important problem in RA patients receiving TNF-α-blocking therapy. 相似文献
85.
Cleavage of RNA hairpins mediated by a developmentally regulated CCCH zinc finger protein. 总被引:8,自引:1,他引:7
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Control of RNA turnover is a major, but poorly understood, aspect of gene regulation. In multicellular organisms, progress toward dissecting RNA turnover pathways has been made by defining some cis-acting sequences that function as either regulatory or cleavage targets (J. G. Belasco and G. Brawerman, Control of Messenger RNA Stability, 1993). However, the identification of genes encoding proteins that regulate or cleave target RNAs has been elusive (C. A. Beelman and R. Parker, Cell 81:79-183, 1995); this gap in knowledge has made it difficult to identify additional components of RNA turnover pathways. We have utilized a modified expression cloning strategy to identify a developmentally regulated gene from Drosophila melanogaster that encodes a RNase that we refer to as Clipper (CLP). Significant sequence matches to open reading frames encoding unknown functions identified from the Caenorhabditis elegans and Saccharomyces cerevisiae genome sequencing projects suggest that all three proteins are members of a new protein family conserved from lower eukaryotes to invertebrates. We demonstrate that a member of this new protein family specifically cleaves RNA hairpins and that this activity resides in a region containing five copies of a previously uncharacterized CCCH zinc finger motif. CLP's endoribonucleolytic activity is distinct from that associated with RNase A (P. Blackburn and S. Moore, p. 317-433, in P. D. Boyer, ed., The Enzymes, vol. XV, part B, 1982) and is unrelated to RNase III processing of rRNAs and tRNAs (J. G. Belasco and G. Brawerman, Control of Messenger RNA Stability, 1993, and S. A. Elela, H. Igel, and M. Ares, Cell 85:115-124, 1995). Our results suggest that CLP may function directly in RNA metabolism. 相似文献
86.
The chorion genes of the medfly, Ceratitis capitata, I: Structural and regulatory conservation of the s36 gene relative to two Drosophila species. 总被引:6,自引:2,他引:4
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M Konsolaki K Komitopoulou P P Tolias D L King C Swimmer F C Kafatos 《Nucleic acids research》1990,18(7):1731-1737
We have used low stringency screening with the Drosophila melanogaster s36 chorion gene to recover its homologue from genomic and cDNA libraries of the medfly, Ceratitis capitata. The same gene has also been recovered from a genomic library of D. virilis. The medfly s36 gene shows similar developmental specificity as in Drosophila (early choriogenesis). It is also specifically amplified in ovarian follicles; this is the first report of chorion gene amplification outside the genus Drosophila. Alignments of s36 sequences from three species show that, in addition to its regulatory conservation, the s36 gene is extensively conserved in sequence, in a region corresponding to a central protein domain, and in short regions of 5' flanking DNA that might correspond to cis-regulatory elements. 相似文献
87.
A Wellington S Emmons B James J Calley M Grover P Tolias L Manseau 《Development (Cambridge, England)》1999,126(23):5267-5274
Spire is a maternal effect locus that affects both the dorsal-ventral and anterior-posterior axes of the Drosophila egg and embryo. It is required for localization of determinants within the developing oocyte to the posterior pole and to the dorsal anterior corner. During mid-oogenesis, spire mutants display premature microtubule-dependent cytoplasmic streaming, a phenotype that can be mimicked by pharmacological disruption of the actin cytoskeleton with cytochalasin D. Spire has been cloned by transposon tagging and is related to posterior end mark-5, a gene from sea squirts that encodes a posteriorly localized mRNA. Spire mRNA is not, however, localized to the posterior pole. SPIRE also contains two domains with similarity to the actin monomer-binding WH2 domain, and we demonstrate that SPIRE binds to actin in the interaction trap system and in vitro. In addition, SPIRE interacts with the rho family GTPases RHOA, RAC1 and CDC42 in the interaction trap system. Thus, our evidence supports the model that SPIRE links rho family signaling to the actin cytoskeleton. 相似文献
88.
We investigated the cytotoxic, neurotoxic, apoptotic and antiproliferative effects of extracts from Petalonia fascia, Jania longifurca and Halimeda tuna on the MCF-7 breast cancer cell line. J. longifurca extracts were more toxic than those of P. fascia and H. tuna. The algal extracts showed significant toxic effects at different dilutions. The toxic effects were due to increased oxidative stress and resulted in apoptosis. Algal toxicity may exert negative effects through the food chain or by direct interaction. Algal toxicity also has potential for cancer therapy. The toxic effects that we observed may be especially important for therapy for breast tumors. 相似文献
89.
Konstantinos Doris Sophia P Karabela Chrysoula A Kairi Davina CM Simoes Charis Roussos Spyros G Zakynthinos Ioannis Kalomenidis Timothy S Blackwell Georgios T Stathopoulos 《Respiratory research》2010,11(1):118
Background
Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.Methods
Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.Results
Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.Conclusions
Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer. 相似文献90.
Angela CM Luyf Barbera DC van Schaik Michel de Vries Frank Baas Antoine HC van Kampen Silvia D Olabarriaga 《BMC bioinformatics》2010,11(1):598