Isolation and characterization of anticomplementary beta-glucans from the shoots of bamboo Phyllostachys edulis

Bamboo, Phyllostachys edulis produces well known edible shoots in Asia. Immunostimulating anticomplementary (complement activating) substances have been recognized as a characteristic biological response modifier (BRM). In the present study, we isolated and characterized three anticomplementary beta-glucans (BS-BGA, BS-BGB, and BS-BGC) from bamboo shoots. Hot-water extraction, DEAE-Toyopearl 650M-column chromatography, amylase digestion and concanavalin A adsorption, and Sephacryl S-100 HR column chromatography were applied to isolate the beta-glucans. The average molecular masses of the beta-glucans were estimated to be from 14,500 to 85,300 Da by HPSEC-MALLS-RI. All three beta-glucans (0.1-1.0 mg/mL) activated the complement system via the alternative pathway, and could cleave human complement C3 under Ca 2+-free gelatin veronal buffered saline. Among them, the largest molecule, BS-BGA was the most potent complement activator. Methylation analysis and NMR spectroscopy were used to achieve their structural characterization. They are all water-soluble and composed mainly of backbone structures of beta-(1-->3)-glucan with beta-(1-->4)-linked side chains varying in degree of branching. BS-BGA consisted of a higher proportion of 3-linked glucopyranosyl residues and a lower degree of branching than BS-BGB and BS-BGC. In particular, BS-BGA contained a small amount of O-acetyl groups at C-6 of the 3-linked glucopyranosyl residues. These data demonstrate that the structural characteristics including molecular size, degree of branching, and O-acetyl substitution are involved, at least in part, in their different anticomplementary activities.     

Functional characterization of a neuropeptide F-like receptor from Drosophila melanogaster

A cDNA clone encoding a seven-transmembrane domain, G-protein-coupled receptor (NPFR76F, also called GPCR60), has been isolated from Drosophila melanogaster. Deletion mapping showed that the gene encoding this receptor is located on the left arm of the third chromosome at position 76F. Northern blotting and whole mount in situ hybridization have shown that this receptor is expressed in a limited number of neurons in the central and peripheral nervous systems of embryos and adults. Analysis of the deduced amino acid sequence suggests that this receptor is related to vertebrate neuropeptide Y receptors. This Drosophila receptor shows 62-66% similarity and 32-34% identity to type 2 neuropeptide Y receptors cloned from a variety of vertebrate sources. Coexpression in Xenopus oocytes of NPFR76F with the promiscuous G-protein Galpha16 showed that this receptor is activated by the vertebrate neuropeptide Y family to produce inward currents due to the activation of an endogenous oocyte calcium-dependent chloride current. Maximum receptor activation was achieved with short, putative Drosophila neuropeptide F peptides (Drm-sNPF-1, 2 and 2s). Neuropeptide F-like peptides in Drosophila have been implicated in a signalling system that modulates food response and social behaviour. The identification of this neuropeptide F-like receptor and its endogenous ligand by reverse pharmacology will facilitate genetic and behavioural studies of neuropeptide functions in Drosophila.     

急性淋巴细胞白血病最新治疗策略(下)

4分子治疗分析肿瘤细胞中的分子遗传性变异及后天变异的方法正在快速成熟起来。这些方法通常涉及基因组学、转录特征性识别及蛋白质组学,有利于更深入地了解ALL的发病机理,使用于临床评估的靶向治疗全面发展。最终,这些层出不穷的新技术将营造出一个全新的个性化分子医学时代,创造出效果更好而毒性更低的治疗方案。尽管治疗方案均显示了药物介入控制细胞周期进程、基因转录、细胞运动、凋亡及细胞代谢信号通路的可行性(图1),但针对ALL的分子治疗情况(表1)仍差强人意。我们将从众多正处于临床前期或早期临床研究的分子治疗方案中,选择出那…     

急性淋巴细胞白血病最新治疗策略(上)

利用目前的治疗手段,80%的急性淋巴细胞白血病(acute lymphoblastic leukem ia,ALL)患儿均能得到治愈,尚有部分患者需接受强化治疗,但治疗的副作用也带来了急性或远期的严重并发症。此外,成人ALL病人的生存率依然低于40%。因此,本病需要既可以提高治愈率又能改善生活质量的新治疗方案。本文讨论了新出现的可能会改善ALL病人预后的治疗方法,包括现有常规化疗药物的新剂型、新的抗代谢药和核苷衍生物、白血病相关抗原的单克隆抗体,针对白血病细胞的基因异常及相关信号通路的分子治疗。1常规化疗药物的新剂型化疗药物的脂质体剂型是将药物…     

DIABETES MELLITUS AND ADDISON'S DISEASE IN AN ADOLESCENT FEMALE

Abstract. Matsaniotis, N., Tzortzatou-Stathopoulou, F., Thomaidis, Th., Karakatsani-Kerasioti, Z., Theodoridis, Ch. and Dacou-Voutetakis, C. (First Department of Paediatrics of Athens University, "Aghia Sophia" Children's Hospital, Athens, Greece). Diabetes mellitus and Addison's disease in an adolescent female. Acta Paediatr Scand, 70: 949, 1981.-This short report describes a 16-year-old female who presented with Addison's disease 6 years after diabetes mellitus had been diagnosed. The possibility of both conditions being present should be borne in mind whenever an unexplained reduction of insulin requirements is noted, especially if this is accompanied by cutaneous pigmentation. The metabolic interrelationships of the two conditions are briefly discussed.     

Immunoglobulins in cerebrospinal fluid in central nervous system disorders

Immunoglobulins were estimated in the cerebrospinal fluid from 70 cases of nervous system diseases. Thirty childern with evidence of C.N.S. irritation without infection served as controls. The immunoglobulins were higher in cases with C.N. S infections. Within this group meningeal involvement (tubercular and pyogenic) resulted in a significant rise in IgG compared to viral encephalitis. The proportion of immunoglobulin in the CSF protein can be helpful in distinguishing TBM from PM.     

Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C virus-related liver cirrhosis

Background/Aims

Pegylated interferon (peginterferon) and ribavirin combination therapy is less effective and associated with a higher frequency of serious complications in chronic hepatitis C patients with cirrhosis than in noncirrhotic patients. This study evaluated the efficacy and tolerability of peginterferon and ribavirin treatment in patients with hepatitis C virus (HCV)-related cirrhosis.

Methods

Eighty-six patients with clinically diagnosed liver cirrhosis were treated with either peginterferon alpha-2a (n=51) or peginterferon alpha-2b (n=35) plus ribavirin. The sustained virologic response (SVR) and adverse effects were analyzed retrospectively.

Results

Of the 86 patients (55 males), 48 patients (55.8%) had HCV genotype 1 infection and 38 (44.2%) had genotype non-1 infection. The overall SVR rate was 34.9% (30/86), and the rates of SVR in the genotype 1 and non-1 patients were 20.8% (10/48) and 52.6% (20/38), respectively. The multivariate analysis revealed that having HCV genotype 1 (P=0.003) and high baseline viral load (>8.0×10⁵ IU/mL, P=0.012) were the independent predictive factors for SVR failure. In 20.9% (18/86) of the patients, treatment was not completed due to adverse events (27.8%), loss to follow-up (50.0%), and other reasons (22.2%).

Conclusions

Peginterferon and ribavirin combination therapy was relatively effective and feasible for clinically diagnosed HCV patients, especially in those with genotype non-1 infection and low baseline viral load.     

急性淋巴细胞白血病(上)

急性淋巴细胞白血病是淋巴前体细胞异常引起的恶性疾病,儿童与成人均可能发生。儿童发病高峰2～5岁。有效治疗的稳步进展使本病在儿童中的治愈率80％以上,同时为新的治疗方案提供了良机,新方案将保留我们在白血病无病生存病例中获得的治疗经验,同时减轻当前强化治疗方案中的毒副作用。     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

亮氨酸脑啡肽的电子结构及构效关系研究

对亮氨酸脑啡肽进行了量子化学(INDO)计算,研究其电子结构特征,讨论其活性部位、作用机理及构效关系。同吗啡和R31833进行了活性部位的电子结构与空间结构比较,推断它们的活性药效结构具有共同特点,与阿片受体相互作用时作用方式相同,作用部位有对应关系,因而具有相同的药理性质。