Comparison of the interaction of agmatine and crude methanolic extracts of bovine lung and brain with alpha 2-adrenoceptor binding sites.

1. In the present study we have evaluated whether alpha 2-adrenoceptor binding sites on bovine cerebral cortex membranes labelled by [3H]-clonidine, [3H]-idazoxan and [3H]-RX-821002 can distinguish between known agonists and antagonists. This model has then been used to compare the binding profiles of the putative non-catecholamine, clonidine-displacing substance (CDS), agmatine and crude methanolic extracts of bovine lung and brain. 2. Saturation studies carried out in the presence and absence of noradrenaline, 10 mumol 1(-1), revealed that the maximum number of binding sites on bovine cerebral cortex membranes for [3H]-idazoxan and [3H]-RX-821002 were approximately 60-80% greater than those for [3H]-clonidine (62.6 fmol mg-1 protein). Rauwolscine, the selective alpha 2-adrenoceptor antagonist, was approximately 100 fold more potent against each of the ligands than the selective alpha 1-adrenoceptor diastereoisomer, corynanthine. Also, the pKi value for the selective alpha 1-adrenoceptor prazosin against each ligand was less than 6. 3. Adrenaline, UK-14034, rauwolscine, corynanthine, RX-811059 and prazosin produced concentration-dependent inhibition of binding of all three 3H-ligands. The agonists, adrenaline and UK-14304, were approximately 5 and 10 fold less potent against [3H]-idazoxan and [3H]-RX-821002, respectively, than against [3H]-clonidine. In marked contrast, the antagonists, rauwolscine, corynanthine, RX-811059 and prazosin exhibited a different profile, being approximately 2-3 fold more potent against sites labelled by [3H]-RX-821002 and [3H]-idazoxan compared to sites labelled by [3H]-clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

HIV疫苗

尽管经过了 2 0年的努力 ,对预防HIV/AIDS感染的疫苗开发仍然没有确切的结果。本文分析了开发HIV疫苗如此艰难的原因 ,提出了通过免疫学途径研究针对发达国家感染者的最佳候选疫苗 ,然后再将最有希望的疫苗引入发展中国家 ,以努力预防感染和发病的工作计划。     

Pelizaeus-Merzbacher disease: classical or connatal?

The clinical features and investigation results of 7 patients with Pelizaeus-Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD. Our findings support the view that the more severe connatal form shows rapid neurological deterioration from an early age leading to death usually in the first decade. In younger patients in whom the evolution is still unclear, severe feeding problems and extrapyramidal features may suggest the connatal form. By contrast, in the classical form of PMD, cerebellar signs and cognitive deterioration are more prominent with a more slowly progressive course. Nuclear magnetic resonance imaging and brainstem auditory evoked potentials were very helpful in supporting the diagnosis of PMD either in a known affected family or in sporadic cases, but were not useful in distinguishing between the two types of PMD. Genetic counseling in this condition is difficult, particularly in the connatal form in which inheritance may be either X-linked or autosomal recessive.     

Effective and organ doses from thoron decay products at different ages.

The dosimetry of radon-220, often known as thoron, and its decay products has received less attention than has that of radon-222. Dose coefficients used by international bodies such as UNSCEAR and ICRP and by the UK's former National Radiological Protection Board are based on calculations from the 1980s. We present calculations for thoron decay products using the most recent ICRP models. These indicate that the effective dose is dominated by the doses to lung and that, under the present models, these doses are somewhat higher than under the previous consensus. Conversely, the present models give doses to organs outside the respiratory tract that are somewhat lower than those previously calculated. Dose coefficients for children are somewhat higher than those for adults. However, breathing rates for children are lower than those for adults and there are no great differences in annual doses.     

Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats.

PURPOSE: Transforming growth factor beta (TGF-beta), which generally stimulates the growth of mesenchymally derived cells but inhibits the growth of epithelial cells, has been proposed as a possible target for cancer therapy. However, concerns have been raised that whereas inhibition of TGF-beta signaling could be efficacious for lesions in which TGF-beta promotes tumor development and/or progression, systemic pharmacologic blockade of this signaling pathway could also promote the growth of epithelial lesions. EXPERIMENTAL DESIGN: We examined the effect of a TGF-beta inhibitor on mesenchymal (leiomyoma) and epithelial (renal cell carcinoma) tumors in Eker rats, which are genetically predisposed to develop these tumors with a high frequency. RESULTS: Blockade of TGF-beta signaling with the ALK5/type I TGF-beta R kinase inhibitor, SB-525334, was efficacious for uterine leiomyoma; significantly decreasing tumor incidence and multiplicity, and reducing the size of these mesenchymal tumors. However, SB-525334 was also mitogenic and antiapoptotic for epithelial cells in the kidney and exacerbated the growth of epithelial lesions present in the kidneys of these animals. CONCLUSION: Although pharmacologic inhibition of TGF-beta signaling with SB-525334 may be efficacious for mesenchymal tumors, inhibition of this signaling pathway seems to promote the development of epithelial tumors.