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71.
A role for Src kinase in spontaneous epileptiform activity in the CA3 region of the hippocampus
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Sanna PP Berton F Cammalleri M Tallent MK Siggins GR Bloom FE Francesconi W 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(15):8653-8657
Members of the Src family of nonreceptor protein tyrosine kinases (PTKs) have been implicated in the regulation of cellular excitability and synaptic plasticity. We have investigated the role of these PTKs in in vitro models of epileptiform activity. Spontaneous epileptiform discharges were induced in vitro in the CA3 region of rat hippocampal slices by superfusion with the potassium channel blocker 4-aminopyridine in Mg(2+)-free medium. In hippocampal slices treated in this fashion, Src kinase activity was increased and the frequency of epileptiform discharges could be greatly reduced by inhibitor of the Src family of PTKs, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), but not by the inactive structural analog 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3). 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine also reduced epileptiform activity induced by either 4-aminopyridine or Mg(2+)-free medium alone. These observations demonstrate a role for Src family PTKs in the pathophysiology of epilepsy and suggest potential therapeutic targets for antiepileptic therapy. 相似文献
72.
Raivio T Dunkel L Wickman S Jänne OA 《The Journal of clinical endocrinology and metabolism》2004,89(3):1188-1192
We have examined the relationship between serum androgen bioactivity, as measured with a recombinant cell bioassay, and progression of puberty in 14 boys with constitutional delay of puberty. Six boys were followed up without treatment (control group), and eight boys received low-dose (1 mg/kg) testosterone enanthate im for 0-6 months together with an aromatase inhibitor, letrozole, 2.5 mg orally once a day for 0-12 months (treatment group). In the control group, serum androgen bioactivity increased during the course of puberty (P < 0.001). During 0-12 months of the study, the boys in the treatment group had higher androgen bioactivity levels (P < 0.05) and faster rate of pubic hair growth than the control boys (P < 0.05). Overall, the average serum androgen bioactivity during 12 months of follow-up correlated strongly with the concomitant changes in Tanner genital (r(S) = 0.89; n = 13; P < 0.005) and pubic hair stages (r(S) = 0.79; n = 13; P < 0.01). In conclusion, our results suggest that circulating androgen bioactivity mediates the tempo of pubertal maturation and that the combination of testosterone and letrozole given to boys with constitutional delay of puberty accelerates puberty. 相似文献
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74.
Tommaso Sanna Antonio Dello Russo Daniela Toniolo Michal Vytopil Gemma Pelargonio Giuseppe De Martino Enzo Ricci Gabriella Silvestri Vincenzo Giglio Loredana Messano Elisabetta Zachara Fulvio Bellocci 《European heart journal》2003,24(24):2227-2236
AIMS: Retrospective studies have identified a mutation in the lamin A/C (LMNA) gene in patients selected on the basis of a phenotype characterized by dilated cardiomyopathy, atrioventricular conduction disturbances and sudden death. However, the features of cardiac abnormalities in patients with an initial diagnosis of Emery-Dreifuss muscular dystrophy (EDMD) are poorly known. Aim of the present study was to investigate the spectrum of cardiac disease in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene. METHODS AND RESULTS: Ten consecutive patients with EDMD and a LMNA gene mutation were evaluated with structured medical interview, physical examination, ECG, echocardiogram and 24-h Holter monitoring. Electrophysiological testing and cardiac catheterization were performed if a class 1 or 2 American Heart Association guidelines indication was present. Cardiac disease was found in eight of 10 patients and consisted in the variable combination of supraventricular arrhythmias, disorders of atrioventricular conduction, ventricular arrhythmias, dilated cardiomyopathy, non-dilated cardiomyopathy, restrictive cardiomyopathy and sudden death despite pacemaker implant. CONCLUSIONS: Cardiac disease is common in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene and consists of arrhythmias, disorders of atrioventricular conduction, cardiomyopathies and sudden death despite pacemaker implant. 相似文献
75.
Mari Aikio Harri Elamaa David Vicente Valerio Izzi Inderjeet Kaur Lotta Seppinen Helen E. Speedy Dorota Kaminska Sanna Kuusisto Raija Sormunen Ritva Heljasvaara Emma L. Jones Mikko Muilu Matti Jauhiainen Jussi Pihlajam?ki Markku J. Savolainen Carol C. Shoulders Taina Pihlajaniemi 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(30):E3043-E3052
76.
Despite the significance of human touch, brain responses to interpersonal manual touch have been rarely investigated. We used functional magnetic resonance imaging to study brain activity in eight healthy adults whose left hand was touched by two individuals, in separate runs and in 20‐s blocks, either by holding, smoothing, or poking. Acceleration was measured from both the subject's and the touching person's hands for postimaging control of the stimuli. Independent component analysis of the functional magnetic resonance imaging data unraveled three functional networks involving the primary somatosensory cortex (SI). One network comprised the contralateral and another the ipsilateral Brodmann area 3. The third network included area 2 bilaterally, left‐hemisphere middle temporal gyrus and dorsolateral prefrontal regions, ventral prefrontal cortices bilaterally, and middle cingulate cortex. The response shapes and polarities varied between the three networks. The contralateral area 3 differentiated the responses between the three types of touch stimuli, and the response magnitudes depended on the variability of the touch within each block. However, the responses of the other two networks were strikingly similar to all stimuli. The subjects' reports on the pleasantness of the touch did not correlate with the characteristics of the SI responses. These findings imply area‐specific processing of the natural human touch in three networks including the SI cortex, with only area 2 connected to a functional network of brain areas that may support social interaction. 相似文献
77.
Ryan J. Wood-Bradley Sarah L. Henry Sanna Barrand Anais Giot Luke Eipper John F. Bertram Luise A. Cullen-McEwen James A. Armitage 《Anatomical record (Hoboken, N.J. : 2007)》2020,303(10):2657-2667
A maternal low protein (LP) diet in rodents often results in low nephron endowment and renal pathophysiology in adult life, with outcomes often differing between male and female offspring. Precisely how a maternal LP diet results in low nephron endowment is unknown. We conducted morphological and molecular studies of branching morphogenesis and nephrogenesis to identify mechanisms and timepoints that might give rise to low nephron endowment. Sprague–Dawley rats were fed a normal protein (19.4% protein, NP) or LP (9% protein) diet for 3 weeks prior to mating and throughout gestation. Embryonic day 14.25 (E14.25) kidneys from males and females were either cultured for 2 days after which branching morphogenesis was quantified, or frozen for gene expression analysis. Real-time PCR was used to quantify expression of key nephrogenesis and branching morphogenesis genes at E14.25 and 17.25. At E17.25, nephron number was determined in fixed tissue. There was no effect of either maternal diet or sex on branching morphogenesis. Nephron number at E17.25 was 14% lower in male and female LP offspring than in NP controls. At E14.25 expression levels of genes involved in branching morphogenesis (Gfrα1, Bmp4, Gdnf) and nephrogenesis (Hnf4a, Pax2, Wnt4) were similar in the dietary groups, but significant differences between sexes were identified. At E17.25, expression of Gfrα1, Gdnf, Bmp4, Pax2 and Six2 was lower in LP offspring than NP offspring, in both male and female offspring. These findings provide new insights into how a LP diet leads to low nephron endowment and renal sexual dimorphism. 相似文献
78.
Sanna Eriksson Titus Stuart Patterson Joanna Prince-Wright Akbar Dastjerdi Fieke Marije Molenaar 《Viruses》2022,14(2)
Haemorrhagic disease associated with elephant endotheliotropic herpesvirus (Elephantid herpesvirus, EEHV) infections is the leading cause of death for Asian elephant (Elephas maximus) calves. This study assessed the effect of captive herd management on EEHV shedding, as evidence of latent infection reactivation, focusing on: (1) the influence of social change on the odds of recrudescence; (2) the respective effects of between and within herd moves; and (3) characteristics of recrudescent viral shedding. Trunk and conjunctival swabs (n = 165) were obtained from six elephants at an EAZA-accredited zoo, collected during a period of social stability, and at times of social change. Longitudinal sampling took place at times of moving two bulls out of the collection and one new bull into an adjacent enclosure to the cow herd (between herd moves), and during a period of mixing this new bull with the cow herd to facilitate mating (within herd moves). Quantitative PCR was employed to detect EEHV 1a/b, 4a/b, and EF–1–α (housekeeping gene). Generalised estimating equations determined EEHV recrudescence odds ratios (OR) and relative viral DNA load. Sixteen EEHV 1a/b shedding events occurred, but no EEHV 4a/b was detected. All management-derived social changes promoted recrudescence (social change OR = 3.27, 95% CI = 0.412–26, p = 0.262; and between herd moves OR = 1.6, 95% CI = 0.178−14.4, p = 0.675), though within herd movements posed the most significant increase of EEHV reactivation odds (OR = 6.86, 95% CI = 0.823−57.1, p = 0.075) and demonstrated the strongest relative influence (post hoc Tukey test p = 0.0425). Shedding onset and magnitude ranged from six to 54 days and from 3.59 to 11.09 ΔCts. Differing challenges are associated with between and within herd movements, which can promote recrudescence and should be considered an exposure risk to naïve elephants. 相似文献
79.
Nicolas Farina Ben Hicks Kate Baxter Yvonne Birks Carol Brayne Margaret Dangoor Josie Dixon Peter R. Harris Bo Hu Martin Knapp Eleanor Miles Rotem Perach Sanna Read Louise Robinson Jennifer Rusted Rob Stewart Alan Thomas Raphael Wittenberg Sube Banerjee 《International journal of geriatric psychiatry》2020,35(3):290-301
80.