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951.
Manganelli F Iodice V Provitera V Pisciotta C Nolano M Perretti A Santoro L 《Muscle & nerve》2007,36(6):816-820
We assessed the involvement of cutaneous innervation in two subjects with a molecularly confirmed diagnosis of spinobulbar muscular atrophy (SBMA) using antidromic nerve conduction studies, quantitative sensory testing, and sweat tests, as well as immunohistochemical techniques and confocal microscopy of glabrous and hairy skin biopsy. Both patients showed a marked reduction in amplitude of sensory action potentials and moderate or severe abnormalities of tactile thresholds and mechanical pain perception. A severe reduction of sweat drops on the Silastic imprint test and a widespread loss of small myelinated and unmyelinated fibers in hairy skin were also observed. Fiber loss involved either somatic or autonomic fibers and did not show any distal-proximal gradient. These results, together with loss of Meissner corpuscles and their large myelinated afferent fibers in glabrous skin, confirmed the extensive involvement of sensory neurons of large and small size and revealed an autonomic skin denervation in SBMA. 相似文献
952.
We used immunohistochemical techniques and confocal microscopy to study the morphometry of myelinated nerve endings in glabrous and hairy skin. A total of 30 healthy volunteers took part in this study designed to assess the possibility of obtaining reliable information on myelinated fibers using samples of hairy skin and to determine whether differences exist between myelinated terminations from different sites. We obtained consistent information on cutaneous myelinated terminations using hairy as well as glabrous skin samples. Myelinated endings from hairy and glabrous skin differ in density and distribution. However, from a comparison of our findings with data from nerve biopsy studies, we conclude that all cutaneous myelinated terminations are thinner terminal branches of large myelinated A beta fibers, whereas cutaneous terminations of small myelinated A delta fibers lose their myelin before entering the dermis and become indistinguishable from C-fiber terminations. The classic criteria, based on fiber size, used to distinguish myelinated fiber subgroups in sensory nerves are therefore not suitable for identifying myelinated terminations in the skin. 相似文献
953.
Adult bone marrow and peripheral blood contain sub-populations of vascular precursor cells, which can differentiate into mature endothelial cells and have therefore been commonly termed endothelial progenitor cells (EPCs). Although EPCs encompass rather heterogeneous cell sub-populations of multiple origins and localization, these cells were basically characterized by expression of progenitor markers and by the development of colony-forming units and late endothelial outgrowth with terminal differentiation into mature endothelial cells. Notably, functional studies in vivo have implied the contribution of EPCs to therapeutic reendothelialization and inhibition of neointimal growth following endothelial injury. In the context of this regenerative arterial remodeling, an adequate homing of EPCs plays a central role. This multi-step process of EPC mobilization, recruitment and firm adhesion is regulated by key angiogenic chemokines (CCL2, CXCL1, CXCL7, CXCL12) and their respective receptors (CCR2, CXCR2, CXCR4). Furthermore, the recruitment of circulating EPCs to sites of arterial injury is synchronized by activated platelets and adhesion molecules of the selectin and integrin family. Thus, translating this molecular knowledge to interventional cardiovascular medicine, such a detailed understanding in the complex regulation of EPC homing may be helpful for more effectively preventing "in-stent" stenosis by facilitating stent endothelialization. 相似文献
954.
Wang JY Gualco E Peruzzi F Sawaya BE Passiatore G Marcinkiewicz C Staniszewska I Ferrante P Amini S Khalili K Reiss K 《Journal of neuroscience research》2007,85(11):2360-2373
Tumor necrosis factor-alpha (TNFalpha) released in the brain by HIV-activated macrophages/microglia is suspected to compromise neuronal survival. Previously, we have demonstrated that activated receptor for insulin-like growth factor I (IGF-IR) protects neurons from TNFalpha-induced neuronal damage (Wang et al. [ 2006] J. Neurosci. Res. 83:7-18). Because TNFalpha triggers phosphorylation of insulin receptor substrate 1 (IRS-1) on serine residues (pS-IRS-1; Rui et al. [ 2001] J. Clin. Invest. 107:181-189), and pS-IRS-1 binds integrins (Reiss et al. [ 2001] Oncogene 20:490-500), we asked how these events affect neuronal processes. We show that beta1-integrin and pS-IRS-1 colocalize in PC12 cells and in primary cortical neurons. TNFalpha treatment elevated membrane-associated pS-IRS-1, enhanced pS-IRS-1 interaction with beta1-integrin, and attenuated cell attachment to collagen IV. In contrast, IGF-I inhibited pS-IRS-1-beta1-integrin complexes and improved cell attachment. The domain of IRS-1 involved in beta1-integrin binding mapped between amino acids 426 and 740, and the expression of 426-740/IRS-1 mutant attenuated neuronal outgrowth. Our results indicate that TNFalpha facilitates the interaction of pS-IRS-1 and beta1-integrin and destabilizes neuronal processes. IGF-I counteracts TNFalpha-mediated accumulation of pS-IRS-1-beta1-integrin complexes supporting the stability of neuronal processes. 相似文献
955.
Wang Y Greenwood JS Calcagnotto ME Kirsch HE Barbaro NM Baraban SC 《Annals of neurology》2007,61(2):139-152
OBJECTIVE: To identify brain regions, cell types, or both that generate abnormal electrical discharge in tuberous sclerosis complex (TSC). Here we examined excitatory and inhibitory synaptic currents in human tissue samples obtained from a TSC patient with no discernible cortical tubers and acute neocortical brain slices from a mouse featuring synapsin-driven conditional deletion of a TSC1 gene. These studies were designed to assess whether TSC gene inactivation alters excitability. METHODS: We used visualized patch-clamp (human and mouse) and extracellular field (mouse) recordings. Additional mice were processed for immunohistochemistry or Western blot analysis. RESULTS: Detailed anatomic studies in brain tissue sections from synapsin-TSC1 conditional knock-out mice failed to uncover gross anatomic defects, loss of lamination, or frank tuber formation. However, regions of abnormal and potentially activated neocortex were shown using antibodies to nonphosphorylated neurofilaments (SMI-311) and immediate early genes (c-Fos). Extracellular recordings from neocortical slices, examining synaptic activity in these regions, demonstrated clear differences in excitability between conditional knock-out and age-matched control mice. Whole-cell patch-clamp recordings demonstrated excitatory synaptic currents with strikingly long duration and epileptiform discharge patterns, similar to waveforms observed in our human tissue samples. These events were 1-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor mediated and were most prominent in neocortex. Normal-appearing inhibitory postsynaptic currents (human) and intrinsic neuronal firing patterns (mouse) were also recorded. INTERPRETATION: This combination of human and mouse tissue studies suggests, for the first time, that synaptic excitation is altered in a direction that favors seizure generation in TSC brain tissue regardless of cortical tubers. 相似文献
956.
Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in rat hippocampal slices and cerebrospinal fluid 总被引:1,自引:0,他引:1
Oses JP Viola GG de Paula Cognato G Júnior VH Hansel G Böhmer AE Leke R Bruno AN Bonan CD Bogo MR Portela LV Souza DO Sarkis JJ 《Epilepsy research》2007,75(2-3):104-111
Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced seizure susceptibility induced by kindling is probably attributable to plastic changes in the synaptic efficacy. Adenosine and guanosine act both as important neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal activity. Adenosine and guanosine can be released per se or generated from released nucleotides (ATP, ADP, AMP, GTP, GDP, and GMP) that are metabolized and rapidly converted to adenosine and guanosine. The aim of this study was to evaluate nucleotide hydrolysis by ecto- and soluble nucleotidases (hippocampal slices and CSF, respectively) after PTZ-kindling (stages 3, 4, or 5 seizures) or saline treatment in rats. Additionally, the levels of purines in rat cerebrospinal fluid (CSF), as well as ecto-NTPDases (1, 2, 3, 5, 6 and 8) and ecto- 5'-nucleotidase expression were determined. Ecto-enzyme assays demonstrated that ATP, AMP, GDP, and GMP hydrolysis enhanced when compared with controls. In addition, there was an increase of ADP, GDP, and GMP hydrolysis by soluble nucleotidases in PTZ-kindling rats compared to control group. The HPLC analysis showed a marked increase in PTZ-kindled CSF concentrations of GTP, ADP, and uric acid, but GDP, AMP, and hypoxanthine concentrations were decreased. Such alterations indicate that the modulatory role of purines in CNS could be affected by PTZ-kindling. However, the physiological significance of these findings remains to be elucidated. 相似文献
957.
958.
Sjogren MH Sjogren R Lyons MF Ryan M Santoro J Smith C Reddy KR Bonkovsky H Huntley B Faris-Young S 《Digestive diseases and sciences》2007,52(6):1540-1547
Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C.
A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV)
genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon
α-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response
in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with
response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability
of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response.
It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could
be achieved in a larger proportion of patients infected with HCV genotype 1. 相似文献
959.
960.