Optimizing the efficiency of high-field multivoxel spectroscopic imaging by multiplexing in space and time.

A new strategy to yield information from the maximum number of voxels, each at the optimum signal-to-noise ratio (SNR) per unit time, in MR spectroscopic imaging (MRSI) is introduced. In the past, maximum acquisition duty-cycle was obtained by multiplexing in time several single slices each repetition time (TR), while optimal SNR was achieved by encoding the entire volume of interest (VOI) each TR. We show that optimal SNR and acquisition efficiency can both be achieved simultaneously by multiplexing in space and time several slabs of several slices, each. Since coverage of common VOIs in 3D proton MRSI in the human brain typically requires eight or more slices, at 3 T or higher magnetic fields, two or more slabs can fit into the optimum TR (approximately 1.6 s). Since typically four or less slices would then fit into each slab, Hadamard encoding is favored in that direction for slice profile reasons. It is demonstrated that per fixed examination length, the new method gives, at 3 T, twice as many voxels, each of the same SNR and size, compared with current 3D chemical shift imaging techniques. It is shown that this gain will increase for more extensive spatial coverage or higher fields.     

Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck

BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25.     

Ocular autonomic function in progressive autonomic failure

Ocular autonomic function was assessed in 4 patients with progressive autonomic failure (PAF) and age-matched control subjects, by measurement of the pupil cycle time, and determination of autonomic denervation hypersensitivity of the iris. Pupil cycle time was abnormal in all patients with PAF; sustained pupil cycling was absent in 5 of the 8 eyes tested of the PAF patients, compared with only 16 eyes from 70 control subjects. Pupil constriction in response to 2.5% methacholine, indicative of parasympathetic denervation hypersensitivity, was significantly increased in patients with PAF (p < 0.001), whilst pupil dilation in response to 0.5% phenylephrine, indicative of sympathetic denervation hypersensitivity, was also significantly higher in the PAF patients (p < 0.001). The results suggest that ocular autonomic function may provide a sensitive early indicator of generalised autonomic dysfunction.     

Acoustic rhinometry in pre-school children

Acoustic rhinometry was performed in 35 normal nose-breathing children between 3 and 6 years. The average cross-sectional areas at the nasal valve, at the anterior end of the turbinates, and in the nasopharynx were 0.34±0.06 cm², 0.35±0.08 cm² and 1.37±0.48 cm² respectively. The average minimal cross-sectional area was 0.29±0.06 cm². The minimal cross-sectional area was located at the nasal valve in 14 and at the anterior end of nasal tubinates in 21 of the 35 children. As would be expected, the cross-sectional areas at different sites of the nasal cavity increased with increasing age of the children. But, whereas the minimal cross-sectional area increased by 0.024 cm² per year, the nasopharyngeal cross-sectional area increased by 0.20 cm² per year. No significant differences were found between boys and girls. Measurements of the posterior nasal and nasopharyngeal cross-sectional areas were unreliable, whenever the minimal cross-sectional area was less than 0.2 cm². Furthermore, assessment of the nasopharynx may be difficult because of involuntary movements of the soft palate.     

Motivated behavior and the estrous cycle in rats

(1) The estrous cycle in the rat may be used to study recurrent changes in motor behaviors and motivation which are strongly related to cyclic hormonal and CNS changes. (2) The peak in motivated behaviors occurs during a sharply defined period on the night between proestrus and estrus and is evident in facilitated wheel-running, lordosis, and intracranial self-stimulation. (3) Behaviors without a clearly motivated character do not show an estrous cyclicity. (4) The estrous cyclic variation in intracranial self-stimulation was observed at a specific locus — the pars campacta of the substantia nigra. (5) A neurochemical link between sexually motivated behavior, wheel running and intracranial self-stimulation is suggested. This link is in part dopaminergic but is probably also activated by many other systems.     

二甲基亚砜诱导人肝癌细胞BEL-7402凋亡的研究

目的 :研究二甲基亚砜 (DMSO)对人肝癌细胞凋亡的诱导作用。方法 :用不同浓度的DMSO处理体外培养的人肝癌细胞BEL 74 0 2 ,应用普通光镜、荧光显微镜、MTT分析方法和流式细胞技术 (FCM )检测肝癌细胞凋亡的形态学变化、细胞存活率、凋亡百分率和细胞周期分布的变化。结果 :DMSO诱导BEL 74 0 2细胞核DNA凝缩和核片段化 ,最后形成凋亡小体 ;随着DMSO浓度的增加和处理时间的延长 ,细胞存活率明显下降 ,其IC50 为 1.9% ;2 %的DMSO处理细胞 12h ,凋亡率达 17.2 1% ,同时S期细胞明显增加 ,G2 M期细胞明显下降。结论 :DMSO可诱导人肝癌细胞凋亡 ,并使细胞受阻于S期而进入凋亡程序。     

On the Role of Proteasomes in Cell Biology and Proteasome Inhibition as a Novel Frontier in the Development of Immunosuppressants

The proteasome, a large protease complex in cells, is the major machinery for protein degradation. It was previously considered a humble garbage collector, performing housekeeping duties to remove misfolded or spent proteins. Until recently, the interests of immunologists in proteasomes were focused largely on its role in antigen processing. Its real importance in cell biology has only been revealed contemporarily due to the availability of relatively specific inhibitors. It has now become increasingly clear that many aspects of immune responses highly depend on proper proteasome activity. Recently, a proteasome inhibitor has been successfully used to prevent acute as well as ongoing heart allograft rejection in mice. Such inhibitors are also efficacious in treating several autoimmune diseases, such as arthritis, psoriasis, and probably type I diabetes, in animal models. Phase II and III clinical trials of proteasome inhibitors in treating various tumors have shown promising results, and the side-effects of these drugs are tolerable. Therefore, proteasome inhibition represents a new and promising frontier in immunosuppressant development.     

二乙酰二脱水卫矛醇对小鼠白血病L1210细胞增殖的影响

目的　研究二乙酰二脱水卫矛醇 (1 ,2 :5 ,6 dianhydro 3 ,4 diacetylgalactitol,DADAG)的抗脑白血病作用及机制。方法　用小鼠脑内移植瘤模型、MTT法、DNA掺入法、流式细胞仪和Westernblot法 ,观察DADAG对小鼠脑内移植瘤和体外白血病L1 2 1 0 细胞的作用 ,并探讨作用机制。结果　DADAG对DBA/ 2小鼠脑内移植白血病L1 2 1 0 有明显的抑制作用 ;对体外白血病L1 2 1 0 细胞同样有很强的抗增殖作用 ,其IC50 值为 2 4 6mg·L- 1 。DADAG不可逆地抑制L1 2 1 0 细胞内DNA的生物合成。DADAG 2 4mg·L- 1 处理L1 2 1 0 细胞 6h后 ,细胞发生G2 /M周期阻滞 ,2 4h后达最高峰。细胞周期素B1 蛋白水平在DADAG处理 2 4h后开始下降 ,而磷酸化的细胞周期依赖性激酶CDK1在DADAG处理 6h后开始上调 ,并呈时间依赖性。结论　DADAG的抗脑白血病作用与其抑制白血病细胞的增殖密切相关     

不同情期大鼠血浆神经降压素含量的变化

本文试图阐明不同情期大鼠血浆神经降压素含量的变化。血浆神经降压素以无水乙醇提取后采用放射免疫分析法测定。间情期、动情前期和动情期大鼠血浆内神经降压素样免疫活性物质的含量依次分别为92.1±7.7ng/L,118.0±9.4ng/L 和144.3±10.2ng/L。动情期大鼠血浆神经降压素样免疲活性物质的含量较间情期大鼠有极显著差异(P<0.01)。