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131.
Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons 下载免费PDF全文
Cyr M Beaulieu JM Laakso A Sotnikova TD Yao WD Bohn LM Gainetdinov RR Caron MG 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(19):11035-11040
Dopamine is believed to contribute to the degeneration of dopamine-containing neurons in the brain. However, whether dopamine affects the survival of other neuronal populations has remained unclear. Here we document that mice with persistently elevated extracellular dopamine, resulting from inactivation of the dopamine transporter gene, sporadically develop severe symptoms of dyskinesia concomitant with apoptotic death of striatal dopamine-responsive gamma-aminobutyric acidergic neurons. Chronic inhibition of dopamine synthesis prevents the appearance of motor dysfunction. The neuronal death is associated with overactivation of dopaminergic signaling as evidenced by the robust up-regulation of striatal DeltaFosB, cyclin-dependent kinase 5, and p35. Moreover, hyperphosphorylation of the tau protein, a phenomenon associated with the activation of cyclin-dependent kinase 5 in several neurodegenerative disorders, is observed in symptomatic mice. These findings provide in vivo evidence that, in addition to its proposed role in the degeneration of dopamine neurons, dopamine can also contribute to the selective death of its target neurons via a previously unappreciated mechanism. 相似文献
132.
Raul Urrutia JohnR. Henley Tiffany Cook MarkA. McNiven 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(2):377-384
In the 7 years since dynamin was first isolated from bovine brain in search of novel microtubule-based motors, our understanding of this enzyme has expanded significantly. We now know that brain dynamin belongs to a family of large GTPases, which mediate vesicle trafficking. Furthermore, this enzymatic activity is markedly increased through association with microtubules, acidic phospholipids, and certain regulatory proteins that contain Src homology 3 (SH3) domains. From functional, genetic, and cellular manipulations, it is now generally accepted that dynamin participates in the endocytic uptake of receptors, associated ligands, and plasma membrane following an exocytic event. These observations have confirmed at least one function of dynamin that was predicted from seminal studies on a pleiotropic mutant, shibirets (shits) in Drosophila melanogaster. Of equal interest is the finding that there are multiple dynamin gene products, including two that are expressed in a tissue-specific manner, and they share marked homology with a larger family of distinct but related proteins. Therefore, it is attractive to speculate that the different dynamins may participate in related cellular functions, such as distinct endocytic processes and even secretion. In turn, dynamin could play an important role in cell growth, cell spreading, and neurite outgrowth. The purpose of this review is to enumerate on the expansive dynamin literature and to discuss the nomenclature, expression, and putative functions of this growing and interesting family of proteins. 相似文献
133.
Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia 总被引:9,自引:12,他引:9 下载免费PDF全文
134.
Raul I. Garcia D.M.D. Lawrence C. Perlmuter Ph.D. Dr. Howard H. Chauncey Ph.D. D.M.D. 《Dysphagia》1989,4(2):121-126
Missing natural teeth have been associated with a reduced acceptability for the taste and texture of hard foods as well as
with an increase in the perceived difficulty of chewing these foods. The present study examined the role of the personality
variables extroversion and anxiety in modulating the relationship between dentition status, masticatory performance, taste
preference, texture preference, and perceived ease of chewing of an easy-to-chew food (pot roast) and a more difficult-to-chew
food (raw carrots). Healthy adult men, participants in the Veterans Administration Dental Longitudinal Study, were examined.
Results indicated that with increased age there was a tendency for texture acceptability to increase for the easy-to-chew
food. Masticatory and swallowing performance were diminished in persons with artificial dentition, and these individuals also
perceived an increase in the difficulty of chewing raw carrots. There was a significant association of anxiety, but not extroversion,
with masticatory and swallowing performance. 相似文献
135.
Ontogeny of adenohypophyseal cells in the pituitary of the American shad (Alosa sapidissima) 总被引:1,自引:0,他引:1
Laiz-Carrión R del Mar Segura-Noguera M del Pilar Martín del Río M Mancera JM 《General and comparative endocrinology》2003,132(3):454-464
The distribution and ontogeny of adenohypophyseal cells have been studied in the pituitary gland of embryos, larvae, and juveniles of the clupeid American shad (Alosa sapidissima) using immunocytochemical techniques. In juvenile specimens, adenohypophysis was composed of rostral pars distalis (RPD), formed by cavities lined by prolactin (PRL), adrenocorticotropic hormone (ACTH), and gonadotropic hormone (GTH) cells; proximal pars distalis (PPD), containing growth hormone (GH), GTH, and putative thyroid stimulating hormone (TSH) cells; and pars intermedia (PI) with somatolactin (SL) and melanophore stimulating hormone (MSH) cells. At 3 days post-fertilization (3 days pre-hatching) the pituitary of embryos consisted of an oval mass of cells, close to the ventral margin of the diencephalon, divided in rostral and caudal regions. At this time PRL and ACTH cells appeared in the rostral region of the adenohypophysis, while SL cells were observed in the caudal region where MSH cells showed reactivity 1 day before hatching. At variance, GH cells showed a weak immunoreactivity in the rostral portion at hatching that increased 2 days latter. GTH cells also showed weak immunoreactivity in the rostral region of the adenohypophysis at hatching time. Two days later GTH cells were located in the rostral and central regions of the adenohypophysis. At hatching, the neurohypophysis was very small and no nerve processes were seen to penetrate the adenohypophysis tissue. After hatching, the pituitary gland elongated and in 7 days old larvae, the RPD showed a small lumen surrounded by a palisade of PRL, ACTH, and GHT cells; the PPD showed GH and GTH cells while the PI contained SL and MSH cells. The adenohypophysis and neural lobe increased in size with development and, in 42 days old larvae, they were similar to those of juvenile specimens. 相似文献
136.
Purified kinesin promotes vesicle motility and induces active sliding between microtubules in vitro. 总被引:7,自引:2,他引:7 下载免费PDF全文
R Urrutia M A McNiven J P Albanesi D B Murphy B Kachar 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(15):6701-6705
We examined the ability of kinesin to support the movement of adrenal medullary chromaffin granules on microtubules in a defined in vitro system. We found that kinesin and ATP are all that is required to support efficient (33% vesicle motility) and rapid (0.4-0.6 micron/s) translocation of secretory granule membranes on microtubules in the presence of a low-salt motility buffer. Kinesin also induced the formation of microtubule asters in this buffer, with the plus ends of microtubules located at the center of each aster. This observation indicates that kinesin is capable of promoting active sliding between microtubules toward their respective plus ends, a movement analogous to that of anaphase b in the mitotic spindle. The fact that vesicle translocation, microtubule sliding, and microtubule-dependent kinesin ATPase activities are all enhanced in low-salt buffer establishes a functional parallel between this translocator and other motility ATPases, myosin, and dynein. 相似文献
137.
Metzger ML Howard SC Fu LC Peña A Stefan R Hancock ML Zhang Z Pui CH Wilimas J Ribeiro RC 《Lancet》2003,362(9385):706-708
The causes of treatment failure in childhood acute lymphoblastic leukaemia are thought to differ between resource-rich and resource-poor countries. We assessed the records of 168 patients treated for this disease in Honduras. Abandonment of treatment (n=38), the main cause of failure, was associated with prolonged travel time to the treatment facility (2-5 h: hazard ratio 3.1, 95% CI 1.2-8.1 vs >5 h: 3.7, 1.3-10.9) and age younger than 4.5 years (2.6, 1.1-6.3). 35 patients died of treatment-related effects. Outcome could be substantially improved by interventions that help to prevent abandonment of therapy (such as funding for transport, satellite clinics, and support groups), and by prompt treatment of infection. 相似文献
138.
Juliana C. Vinagre Carmen C. G. Vinagre Fernanda S. Pozzi Cristiane Z. Zácari Raul C. Maranhão 《European journal of nutrition》2014,53(3):981-987
Purpose
Previously, it was showed that vegan diet improves the metabolism of triglyceride-rich lipoproteins by increasing the plasma clearance of atherogenic remnants. The aim of the current study was to investigate this metabolism in lacto-ovo vegetarians whose diet is less strict, allowing the ingestion of eggs and milk. Transfer of lipids to HDL, an important step in HDL metabolism, was tested in vitro.Methods
Eighteen lacto-ovo vegetarians and 29 omnivorous subjects, all eutrophic and normolipidemic, were intravenously injected with triglyceride-rich emulsions labeled with 14C-cholesterol oleate and 3H-triolein. Fractional clearance rates (FCR, in min?1) were calculated from samples collected during 60 min. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids.Results
LDL cholesterol was lower in vegetarians than in omnivores (2.1 ± 0.8 and 2.7 ± 0.7 mmol/L, respectively, p < 0.05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegetarians than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal. Cholesteryl ester transfer to HDL was lower in vegetarians than in omnivores (2.7 ± 0.6, 3.5 ± 1.5 %, p < 0.05), but free cholesterol, triglyceride and phospholipid transfers and HDL size were equal.Conclusion
Similarly to vegans, lacto-ovo vegetarian diet increases remnant removal, as indicated by cholesteryl oleate FCR, which may favor atherosclerosis prevention, and has the ability to change lipid transfer to HDL. 相似文献139.
Samuel W. Hawes Elisa M. Trucco Jacqueline C. Duperrouzel Stefany Coxe Raul Gonzalez 《Substance use & misuse》2019,54(2):271-281
Background: Characterizing patterns of adolescent cannabis use (CU), as well as risk factors and outcomes uniquely associated with these pathways is essential for informing treatment and prevention efforts. Yet, few studies have examined these issues among youth at-risk of engaging in problematic cannabis use. Further, research accounting for use of other substances or sex differences in patterns of CU remains exceedingly sparse. Methods: Trajectory-based modeling was used to identify underlying CU pathways among a predominantly Hispanic (90%) sample of at-risk youth (n?=?401; 46% female) across adolescence (ages~14–18), controlling for baseline substance use and participant demographics. Adolescent psychopathology (i.e., conduct disorder, attention deficit hyperactivity disorder, anxiety, and depression) was examined as a predictor and outcome of CU. Results: Three trajectories of adolescent CU were identified, with most youth (74%) engaging in relatively “low” levels of use, followed by ~12% exhibiting an early-initiating “chronic” course, and 14% “escalating” in use. Although boys and girls both experienced increased levels of CU across adolescence, boys were more likely to exhibit escalating and chronic patterns of use. Findings revealed unique associations between adolescent CU pathways and facets of psychopathology; most notably, the relatively robust and bidirectional association between CU trajectories and conduct problem symptoms. Conclusions: Specific facets of psychopathology may confer unique associations with CU across development, including the initiation and exacerbation of CU during adolescence. 相似文献
140.
Pau Abrisqueta Julio Delgado Miguel Alcoceba Ana Carla Oliveira Javier Loscertales Jose A. Hernández-Rivas Christelle Ferrà Raul Cordoba Lucrecia Yáñez Angeles Medina Cristina Motlló Gloria Iacoboni Guillermo Villacampa Marcos González Francesc Bosch 《British journal of haematology》2020,190(6):854-863
Richter syndrome (RS) is an uncommon evolution of chronic lymphocytic leukaemia (CLL) with a dismal prognosis. Clinical-biological features predicting outcome and best therapeutic approach for these patients remain to be established. In this study, 128 patients with RS, including 112 diffuse large B-cell lymphoma (DLBCL)-type RS, 15 Hodgkin lymphoma (HL)-type RS, and one plasmablastic lymphoma, were identified in 11 centres of the Spanish CLL Study Group (GELLC). The median overall survival (OS) was 5·9 months for DLBCL-type RS and 30·8 months for HL-type RS. Eastern Cooperative Oncology Group Performance Status, haemoglobin level, platelet count, serum lactate dehydrogenase and β2-microglobulin levels, tumour protein p53 (TP53) abnormalities in the CLL clone concomitant to RS, number of prior therapies, and clonal relationship between CLL and RS, were associated with OS in patients with DLBCL-type RS. A platelet count of <100 × 109/l, prior CLL therapy (0 vs. ≥1), and presence of TP53 alterations maintained an independent prognostic impact in the multivariate analysis. Patients without any of these factors had a better clinical outcome, with a median OS of 75·3 months, while patients with one or two or more of these factors presented a median OS of 25·5 and 3 months, respectively. Although OS of patients with RS is generally poor, a proportion of patients achieved prolonged survival. Treatment of RS remains a medical need, and further therapeutic approaches with novel therapies are warranted. 相似文献