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21.
Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system. 总被引:10,自引:0,他引:10
Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were insensitive to alpha-bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental conditions exhibited different characteristics for single-channel conductance and agonist and antagonist sensitivity. The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of the FR produced a presynaptic afferent volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists decreased the amplitude of the afferent volley with different efficacies: nicotine greater than cytisine greater than ACh greater than DMPP. The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and DHBE, with IC50 values different from those reported for IPN postsynaptic nAChRs. This study thus demonstrates the functional diversity of nAChRs in the rat CNS. 相似文献
22.
Many people believe that euthanasia and assisted suicide are condoned carte blanche in the Netherlands. Not true. Both are formally forbidden by criminal law and can be administered only when certain procedures and criteria have been followed. Below, a look at the policies and practices regarding euthanasia and assisted suicide in The Netherlands and the role of nurses in this area. 相似文献
23.
Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule 下载免费PDF全文
Bianca LW Bendermacher Joep AW Teijink Edith M Willigendael Marie-Louise Bartelink Harry R Büller Ron JG Peters Jelis Boiten Machteld Langenberg Martin H Prins 《The British journal of general practice》2006,56(533):932-937
BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease. 相似文献
24.
Maarten E Witte Lars B Richard J Rodenburg Jeroen A Belien Rene Musters Thierry Hazes Liesbeth T Wintjes Jan A Smeitink Jeroen JG Geurts Helga E De Vries Paul van der Valk Jack van Horssen 《The Journal of pathology》2009,219(2):193-204
Mitochondrial dysfunction has been implicated in the development and progression of multiple sclerosis (MS) lesions. Mitochondrial alterations might occur as a response to demyelination and inflammation, since demyelination leads to an increased energy demand in axons and could thereby affect the number, distribution and activity of mitochondria. We have studied the expression of mitochondrial proteins and mitochondrial enzyme activity in active demyelinating and chronic inactive MS lesions. Mitochondrial protein expression and enzyme activity in active and chronic inactive MS lesions was investigated using (immuno)histochemical and biochemical techniques. The number of mitochondria and their co‐localization with axons and astrocytes within MS lesions and adjacent normal‐appearing white matter (NAWM) was quantitatively assessed. In both active and inactive lesions we observed an increase in mitochondrial protein expression as well as a significant increase in the number of mitochondria. Mitochondrial density in axons and astrocytes was significantly enhanced in active lesions compared to adjacent NAWM, whereas a trend was observed in inactive lesions. Complex IV activity was strikingly up‐regulated in MS lesions compared to control white matter and, to a lesser extent, NAWM. Finally, we demonstrated increased immunoreactivity of the mitochondrial stress protein mtHSP70 in MS lesions, particularly in astrocytes and axons. Our data indicate the occurrence of severe mitochondrial alterations in MS lesions, which coincides with enhanced mitochondrial oxidative stress. Together, these findings support a mechanism whereby enhanced density of mitochondria in MS lesions might contribute to the formation of free radicals and subsequent tissue damage. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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Postnatal maturation of mossy fibre excitatory transmission in mouse CA3 pyramidal cells: a potential role for kainate receptors 总被引:2,自引:1,他引:2
Kainate receptors (KARs) are abundantly expressed in the central nervous system at a period of intense synaptogenesis and might participate in the maturation of neural networks. We have described the postnatal development of mossy fibre excitatory synaptic transmission in CA3 pyramidal cells and we have explored the potential role of KARs in synaptic maturation. In CA3 pyramidal cells, mossy fibre stimulation evokes EPSCs as early as postnatal day 3 (P3). At this early stage, mossy fibre (MF)-EPSCs are fully blocked by GYKI 53655, an AMPA receptor (AMPAR) antagonist. A postsynaptic KAR component can only be detected from P6. Thus, AMPAR-EPSCs precede KAR-EPSCs during postnatal maturation at this synapse. All MF-EPSCs display a KAR component after P10. A key issue of the present work is that between P6 and P9, the presence of a postsynaptic KAR component tightly coincides with AMPAR-mediated EPSCs of large amplitude, and with the onset of low frequency facilitation (from 0.1 Hz to 1 Hz), a presynaptic form of short-term synaptic plasticity. In addition, mice lacking functional KARs throughout postnatal development display MF-EPSCs of significantly smaller amplitude at stages of maturation where synaptic KARs are normally present, due to both pre- and postsynaptic impairment of synaptic transmission. These data suggest a role for KARs in the maturation of mossy fibre synapses. 相似文献
28.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
29.
Romieu R; Lacabanne V; Kayibanda M; Antoine B; Bennoun M; Chouaib S; Guillet JG; Viguier M 《International immunology》1997,9(10):1405-1413
There is now good evidence that cytokines contribute to the regulation of
tumor growth. The cytokine-driven modulation of tumor growth was
investigated during the progression of a hepatocellular carcinoma (HCC) in
SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of
liver growth correlated with increased transforming growth factor
(TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis
factor (TNF)-alpha mRNA were detected earlier during tumor development.
Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2,
IL-4 and IFN-gamma mRNA production could be reported. In vitro,
hepatocyte-like tumor cell lines established at two stages, either before
or after HCC differentiation, were characterized. The early-stage-derived
cell line produced TNF-alpha mRNA, but had barely detectable expression of
TGF-beta 1 mRNA, while later-stage- derived cell lines showed the
reciprocal pattern. All cell lines displayed a lack of sensitivity to
TNF-alpha, although some degree of sensitivity to TNF-alpha could be
observed in the presence of actinomycin-D or after treatment with
IFN-gamma. The early-stage- derived cell line was sensitive to the growth
inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines
displayed a loss of sensitivity to TGF-beta 1 which correlated with the
increased expression of TGF-beta 1 mRNA. Altogether, this suggests that
tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression
patterns during HCC progression. This model of HCC could be of valuable
interest to assess the impact of various immunotherapeutic strategies on
modulation of tumor growth.
相似文献
30.