The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation. 相似文献
Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). The pressure application of α,β-methylene ATP (α,β-meATP) caused reproducible depolarizations which were depressed by suramin (30 μM) and abolished by suramin (100 μM). Pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10, 30 μM) also concentration-dependently inhibited the α,β-meATP-induced depolarization, although with a much slower time-course than suramin. Almost complete inhibition developed with 30 μM PPADS. Reactive blue 2 (30 μM) did not alter the effect of α,β-meATP, while reactive blue 2 (100 μM) slightly depressed it.
Pressure-applied (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) also depolarized LC neurones. Kynurenic acid (500 μM) depressed and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 μM) abolished the response to AMPA. Suramin (100 μM) potentiated the AMPA effect.
Pressure-applied noradrenaline hyperpolarized LC neurones. Suramin (100 μM) did not alter the effect of noradrenaline.
Focal electrical stimulation evoked biphasic synaptic potentials consisting of a fast depolarization (p.s.p.) followed by a slow hyperpolarization (i.p.s.p.). A mixture of D(−)-2-amino-5-phosphonopentanoic acid (AP-5; 50 μM), CNQX (50 μM) and picrotoxin (100 μM) depressed both the p.s.p. and the i.p.s.p. Under these conditions suramin (100 μM) markedly inhibited the p.s.p., but did not alter the i.p.s.p. In the combined presence of AP-5 (50 μM), CNQX (50 μM), picrotoxin (100 μM), strychnine (0.1 μM), tropisetron (0.5 μM) and hexamethonium (100 μM), a high concentration of suramin (300 μM) almost abolished the p.s.p. without changing the i.p.s.p.
In the presence of kynurenic acid (500 μM) and picrotoxin (100 μM), PPADS (30 μM) depressed the p.s.p. Moreover, the application of suramin (100 μM) to the PPADS (30 μM)-containing medium failed to cause any further inhibition. Neither PPADS (30 μM) nor suramin (100 μM) altered the i.p.s.p.
It was concluded that the cell somata of LC neurones are endowed with excitatory P2-purinoceptors. ATP may be released either as the sole transmitter from purinergic neurones terminating at the LC or as a co-transmitter of noradrenaline from recurrent axon collaterals or dendrites of the LC neurones themselves.
Objective. To compare health locus of control scores in women from different ethnic backgrounds.
Method. One‐hundred and twenty‐eight Caucasian, South Asian and Afro‐Caribbean women completed written or orally presented versions of the multidimensional health locus of control scale, as well as ratings of religiousness, health status and occupational status.
Results. South Asian women scored higher on ‘chance’ and ‘powerful others’ locus of control as predicted. They also had higher scores on internality. The ethnic differences persisted after controlling for occupation and health status. High religiousness among the South Asians appeared to explain some, but not all, of their higher scores.
Conclusion. South Asians may differ from British Caucasians in relation to their beliefs about internal and external influences on health. 相似文献
We observed that peripheral T cells activated in vivo or invitro by superantigens are susceptible to cell death when theirantigen receptor is cross-linked with the appropriate anti-ßTCR mAb. TCR ligation by mAbs specifically drove the T cellclonal deletion in both CD4+ and CD8+ cell subsets. An IL-2/1L-2Rinteraction seems to be a critical step In predisposing superantigenactivated cells to death; In fact, in vivo IL-2R bockade reversedT cell deletion In superantlgen plus anti-ß TCR mAbtreated mice. TCR ligatlon by mAbs also produced cell deathof the relevant targets in in vitro IL-2 activated T cells.Surprisingly, no T cell deletion was demonstrable in IL-2 activatedcells following staphylococcal enterotoxin B - TCR Interaction,ruling out the possibility that superantigen in Itself can inducecell death. Thus, while superantigen activation opens the celldeath program, a subsequent TCR-antigen (self) Interaction appearsnecessary to produce clonal deletion in mature T lymphocytes. 相似文献
The present study was undertaken to investigate the effects of modulation of the (NMDA) receptor on learning and memory. Thus, the performance of rats treated with d-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. d-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, d-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg d-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations. 相似文献
The tetrameric STRs, HUMTH01, HUMVWA31A and HUMFES/FPS, were studied in a population from the Basque Country (northern Spain) for their frequency distribution and applicability to identity and paternity testing. All systems conformed to Hardy-Weinberg equilibrium; pairwise comparisons demonstrated the allelic independence between loci, and furthermore, all systems seemed to be in agreement with expectations from the Stepwise Mutation Model (SMM) of the mutation-drift theory, which indicates the homogeneity of the population and suggests a replication slippage mechanism as a possible model for generating alleles. A comparison with other population groups appeared to indicate that frequencies are well conserved in Caucasians, but differ from other racial groups. The calculated parameters a priori probability of exclusion (PEX) and index of discrimination (ID), show the informativeness of these loci for the determination of identity and relatedness of individuals. 相似文献