Several lines of evidence have suggested that decreases in postsynaptic inhibition may have a role in epileptogenesis in cortical structures. However, other studies have suggested that GABAergic inhibition is spared, or even augmented in some forms of post-lesional epilepsy. In the studies described here, inhibitory events were recorded in two models of post-lesional chronic epileptogenesis. (i) As previously reported (D.A. Prince and G.-F. Tseng. J. Neurophysiol. 69: 1276-1291. 1993), epileptiform activity develops in slices from partially isolated rat neocortical islands 2-3 weeks after the initial in vivo lesion. In this model of post-traumatic epilepsy, large amplitude polyphasic inhibitory postsynaptic currents (IPSCs) in layer V pyramidal neurons are associated with each interictal epileptiform field potential. The frequency of spontaneous IPSCs as well as miniature IPSCs was significantly increased in neocortical slices from the epileptogenic chronically injured cortex versus controls. Immunocytochemical reactions for parvalbumin and calbindin, calcium binding proteins present in subgroups of GABAergic neurons, showed an increased staining of both neuropil and somata within the epileptogenic tissue. Immunoreactivity for glutamic acid decarboxylase (GAD) and GABA also appeared to be increased in the neuropil. (ii) Cortical microgyri resembling human malformations were produced by freeze lesions made transcranially in P0 rat cortex (K.M. Jacobs, M.J. Gutnick, and D.A. Prince. Cereb. Cortex, 6: 514-523. 1996). The boundary between the four-layered microgyrus and surrounding cortex become epileptogenic within about 2 weeks, as judged by evoked extracellular field potentials and cellular activities. Epileptogenesis in the surrounding cortex is not altered when the microgyrus itself is isolated by transcortical cuts. Patch-clamp recordings from layer V neurons in the epileptogenic zone showed that spontaneous IPSCs are larger and more dependent on glutamatergic synapses than in control neurons. The amplitudes of polysynaptic IPSCs evoked by threshold stimulation were also larger than in control cells. Although evaluation of inhibitory events in these models is still incomplete, results to date suggest that GABAergic inhibition may be enhanced in epileptogenic areas associated with chronic cortical injury. Sprouting of axonal arborizations of pyramidal cells onto interneurons, upregulation of GABAergic neurons, and perhaps sprouting of inhibitory axons that make increased numbers of contacts onto pyramidal cells may all contribute to the increased inhibitory drive. Results in these models do not support the disinhibitory hypothesis of chronic epileptogenesis. 相似文献
The optimum conditions for the fluorine passivation of 316L stainless steel are described. The direct fluoridation products formed at temperatures of 320°C or lower are composed solely of FeF2 , while those which were formed at the temperatures of 330°C or higher have a compound-phase composition of FeF2 and FeF 3. At a critical temperature (400°C for 316L stainless steel) of the thermal modification process, FeF3 is converted to FeF2 and disappears completely as the temperature rises. Meanwhile, CrF3 is formed at a certain temperature (440°C for 316L stainless steel). The two-phase composition gets further crystallized as the thermal modification temperature rises. As the crystal growth induces the cracks on the fluoridated film, it is very difficult to form a satisfactory passivation film from the two-phase composition by thermal modification. It is confirmed that excellent passivation film has been obtained from the single-phase composition by the optimum fluoridation following the optimum thermal modification 相似文献
OBJECTIVE: To explore whether there are different disease patterns of rheumatoid arthritis (RA) in women and men. METHODS: We studied 55 male case patients and 110 female control patients who developed RA between 1970 and 1985 and who resided and received medical care in Olmsted County, Minnesota, for at least 10 years after the diagnosis of RA. Case and control patients were matched for the date of first diagnosis. The pattern and extent of joint involvement, the frequency of joint surgeries, and the presence and type of extraarticular manifestations were determined by retrospective chart review. RESULTS: Incidence rates in women were variable and age dependent, whereas the risk in men older than 36 years was constant over their lifetime. Erosive disease was more frequent in men than in women (72% versus 55%, respectively; P < 0.05) and tended to occur earlier (47% versus 31% for erosive disease within the first 4 years of RA). Although male sex was correlated with a higher risk of bony erosions and an accelerated course of RA, structural consequences of joint destruction were more pronounced in women. Joint surgery was performed more frequently in women (50%) than in men (27%) (P = 0.01). In particular, the frequencies of arthroplasties and arthrodeses of hand and foot joints were different (34 procedures in women versus 1 procedure in men; P < 0.001). Sex influenced the risk as well as the pattern of organ involvement in RA. Nodules and rheumatoid lung disease were typical manifestations in men (P = 0.001 and P < 0.001, respectively), whereas women typically developed sicca syndrome (P = 0.05). Despite differences in disease aggressiveness and disease pattern, there was little difference in the medical therapy in the men compared with the women. CONCLUSION: RA is a heterogeneous disease with variations in phenotype. Sex-associated factors influence disease severity as well as disease pattern. Because sex-related effects influence treatment goals, treatment responses, and side effects, they should be considered in clinical study design and analysis as well as in the treatment decisions for individual patients with RA. 相似文献
NPI‐2358 ( 1 ) is a potent antimicrotubule agent that was developed from a natural diketopiperazine, phenylahistin, which is currently in Phase I clinical trials as an anticancer drug. To understand the precise recognition mechanism of tubulin by this agent, we focused on its potent derivative, KPU‐244 ( 2 ), which has been modified with a photoreactive benzophenone structure, and biotin‐tagged KPU‐244 derivatives ( 3 and 4 ), which were designed and synthesized for tubulin photoaffinity labeling. Introduction of the biotin structure at the p′‐position of the benzophenone ring in 2 exhibited reduced, but significant biological activities with tubulin binding, tubulin depolymerization and cytotoxicity in comparison to the parent KPU‐244. Therefore, tubulin photoaffinity labeling studies of biotin‐derivatives 3 and 4 were performed by using Western blotting analysis after photoirradiation with 365 nm UV light. The results indicated that tubulin was covalently labeled by these biotin‐tagged photoprobes. The labeling of compound 4 was competitively inhibited by the addition of diketopiperazine 1 or colchicine, and weakly inhibited by the addition of vinblastine. The results suggest that photoaffinity probe 4 specifically recognizes tubulin at the same binding site as anticancer drug candidate 1 , and this leads to the disruption of microtubules. Probe 4 serves well as a useful chemical probe for potent antimicrotubule diketopiperazines, much like phenylahistin, and it also competes for the colchicine‐binding site. 相似文献
Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was reported. We performed molecular studies of the BCL6 gene in 54 patients with NHL. Twelve patients (22%) with rearranged BCL6 genes were selected for histological, clinical, molecular, and cytogenetic studies. Ten of these cases were diffuse, large cell type lymphoma, one a follicular lymphoma, and one a mantle cell lymphoma (MCL). All cases were of the B-cell type and this is the first time a rearranged BCL6 gene has been found in an MCL. Cytogenetic data for 10 cases were available and the partner sites of the 3q27 translocation were determined in 7 of 10 patients. These locations were variable, including 6p21.3, 9p22, and 14q11 in addition to the immunoglobulin loci 14q32 (IGH), 2p12 (IGK), and 22q11 (IGL). The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements. 相似文献
A new scaling technique was developed in the present work to investigate the image integration of consumers, taking advantage of the recent visual and object-oriented programming technology. Employed visual stimuli were the logos (and the accompanying symbolic marks, if any) of the four leading cosmetic makers, the logos of their brands and the photos of their product packages of skincare items targeted at young females. 19 females subjects evaluated the stimuli with respect to four, five and eight items for the corporate (Clmg), the brand (Blmg) and the package (Plmg) images. The image inheritance was analyzed on the internally anchored items. In addition, external anchores were employed to facilitate the Kansei processing in part of the Bimg evaluations. The major findings included the contrasting patterns exhibited by two makers both in the maker/brand discrepancies and in the image inheritances. Among the important issues to be considered in the future work are the mediation effect of the matching task and the class structure of evaluative items like those employed in AHP.
Argatroban has selective antithrombin activity and widely used for treatment of ASO. In this study we investigated vasodilating activity of Argatroban besides antithrombin activity in ASO patients. Three patients who have undergone F-P bypasses previously which were all occluded received 10 mg or 20 mg of Argatroban per day intravenously for 4 weeks. Skin temperature were measured before and after administration of Argatroban at the point of 1, 2, 4 weeks which increased 2.3-6.0 degrees C after administration of Argatroban. Subjective symptoms were also improved and these patients became to be able to walk 1.5-3.3 km. These patients were also given PGE, intravenously, however, temperature increase was less than 1.1 degrees C. These results showed that Argatroban has not only antithrombin activity but also significant vasodilating activity resulting in increase of skeletal muscle blood flow. 相似文献