New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles

The PKD1 gene, which is responsible for the most common form of autosomal dominant polycystic kidney disease, has recently been cloned and sequenced. Many disease-causing mutations have been characterized in this gene, most of them resulting in premature protein termination. However, mutation analysis not routinely implemented for family investigations in a clinical setting, because of the large size and complexity of the gene. Instead, genetic linkage analysis using highly polymorphic CA dinucleotide repeats that map around the gene is still the method of choice. Recently, a few intragenic polymorphisms have been described that are also useful for linkage studies. Here, a new diallelic polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091-A/G, which has previously been described in Caucasians, were not detected in DNA from 44 Japanese samples tested. This is particularly important when allelic frequencies in a particular population are used for linkage analysis of families of different ethnic origin. Also, observation of the two polymorphisms together as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently than the establishment of the Ala4091-A/G polymorphism, and specifically on the G allele.     

Oral absorption improvement of poorly soluble drug using solid dispersion technique

A new triazol antifungal agent, (+)-2-(2,4-difluorophenyl)-3-methyl-1-(1H-1, 2,4-triazol-1-yl)-3-[6-(1H-1,2,4-triazol-1-yl)pyridazin++ +-3-ylthio]butan-2-ol (MFB-1041), shows poor oral absorption and is practically insoluble in water (1.2 micrograms/ml). Solid dispersion systems with an enteric polymer such as hydroxypropylmethylcellulose phthalate (HP-55) and carboxymethylethylcellulose (CMEC), and a nonenteric polymer, hydroxypropylmethylcellulose (Metolose) were evaluated to improve drug absorption and solubility. The oral bioavailabilities of these solid dispersions in beagle dogs were over 6 times higher than that of a suspension system with increasing drug solubility in an alkaline medium. X-Ray powder diffraction measurement of the solid dispersion showed a complete drug phase change from a crystal to an amorphous state. Further, from the results of a stability test, the preparations were stable in a desiccated condition and the absorption profiles also showed no change. From the results, it was suggested that the oral administrative preparation of MFB-1041 having a superior absorption profile and a high stability could be obtained by a drug phase change from a crystal to an amorphous state, especially in the spray-drying method using enteric polymers.     

Autonomic nervous function of the patients with neurally mediated syncope

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.     

铝合金局部加压凝固及流动数值模拟的研究

局部加压方法是压铸中用于消除铸件厚壁处缩孔缺陷的一种新工艺.本研究通过实验模型测量了不同加压条件下铸件的冷却曲线,分析了局部加压引起的凝固变化.考虑局部加压引起的补缩流动,通过适时修改网格文件、初始和边界条件的方法,模拟了局部加压过程中铝合金的凝固及流动变化,并与实验结果进行了对比,二者基本吻合.     

Use of electron microscopy on microstructure characterization of high chromium cast irons

The physical metallurgy underlying the development of cast microstructures in abrasion resistant high chromium cast irons, and their structural modification by thermal treatments is relatively complex. Structural characterisation via electron microscopy therefore has a key role to play in furthering our understanding of the phase transformations that control the microstructures and hence the service performances of these irons as wear parts. This paper shows how both scanning and especially transmission electron microscopy can provide valuable information on the nature of eutectic and secondary carbides and on the matrix structures in these irons. Particular attention is given to current characterisation research on conventionally cast 30%Cr irons that are used for applications involving corrosive wear e.g. slurry pumps and on a semi-solid cast 27%Cr iron that has a potential for applications in industry.     

Continuous emulsion polymerization of vinyl acetate. II Operation in a single Couette–Taylor vortex flow reactor using sodium lauryl sulfate as emulsifier

Continuous emulsion polymerizations of vinyl acetate were conducted at 50°C in a single continuous Couette–Taylor vortex flow reactor (CCTVFR) using sodium lauryl sulfate as emulsifier and potassium persulfate as initiator. The polymerization can be carried out very smoothly and stably, but the steady‐state monomer conversion attained in a CCTVFR is not as high as that in a plug flow reactor (PFR), but only slightly higher than that in a continuous stirred tank reactor (CSTR), even if the Taylor number is adjusted to an optimum value. Also, the effects of operating variables, such as the emulsifier, initiator, and monomer concentrations in the feed and the mean residence time on the kinetic behaviors were almost the same as those observed in a CSTR. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2755–2762, 2002     

Comparison of selective cytotoxicity of alkyl lysophospholipids

Alkyl lysophospholipids have been shown to be cytooxic to a number of neoplastic tissues. One, ET-18-OCH₃, has been used to selectively purge leukemic cells from mixtures with normal marrow progenitor cells,in vitro andin vivo. We have measured the 50% inhibitory (IC₅₀) effect of a series of ether, lipids (EL) on leukemic cells (HL60, K562, Daudi, KG-1, KG-1a) and normal marrow progenitor cells. Cells were incubated with varying concentrations of EL for 4 hr and assayed for viability, [³H]thymidine incorporation and clonogenicity in semi-solid media. The effect on protein kinase C (PKC) activity was assayed for each compound. Compounds tested included three glycerophosphocholine analogs-ET-18-OCH₃, ET-16-NHCOCH₃, and BM 41.440. In addition, a lipoidal amine, CP 46665, an ethyleneglycolphospholipid, AEPL, and four single chain alkylphosphocholine analogs, HePC₂, HePC₃, HePC₄ and HePC₆ were also tested. During the period of incubation, the cells remained viable (>70%) as judged by trypan blue dye exclusion. The glycerophosphocholines were the most active and showed the highest therapeutic index. The lipoidal amine was active, but toxic to normal marrow progenitor cells. The ethyleneglycolphospholipid was active against HL60, but not against the other cell lines. The single chain alkylphosphocholine analogs were less active. All of the compounds inhibited PKC activity; however, the glycerophosphocholines were the most inhibitory. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Comparison of coal hydroliquefaction catalysed by ZnCl2-MCln (CuCl,CrCl3 and MoCl5) and ZnCl2 melts

Hydrogenation of four bituminous coals impregnated with 5 wt% of either mixtures of ZnCl₂-MCl_n (CuCl, CrCl₃ and MoCl₅) systems or ZnCl₂ was carried out using a batch autoclave system at 400° for 3 h at 9.8 MPa of initial hydrogen pressure. The ZnCl₂-MoCl₅ system showed the highest yield of the hexane-soluble (HS) fraction compared with the other systems irrespective of the coal used. The difference between the yields of HS fractions using the ZnCl₂-MoCl₅ and other systems was most marked for coals of fairly low volatile matter content, though the conversion was relatively low (47–66%), whilst for coals of high volatile matter content HS yields with the binary melt systems were high (86–91% conversion). Elemental analyses of the HS fractions indicated that the ZnCl₂-MoCl₅ system is most favourable in decreasing the average molecular weight and the heteroatom content of HS, this characteristic trend being confirmed also with five HS fractions separated by Chromatographic techniques. Both elemental analyses and molecular weights of asphaltene (benzene-soluble materials, BS) indicated that the ZnCl₂-MoCl₅ system is also most effective in cracking coal structure.