Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

PCR检测结核分枝杆菌DNA中不同细菌裂解方法结果观察

目的：寻找适合于临床ＰＣＲ检测结核杆菌ＤＮＡ简单、快速、有效、经济的细菌裂解方法。方法：采用１１种细菌裂解剂对相同数量的结核分枝杆菌进行裂解，裂解上清液直接用于ＰＣＲ扩增，结果：１％ＴｒｉｔｏｎＸ－１００，１％ＮＰ４０，１％Ｔｅｗｅｅｎ２０、和１％ＯＰ四种裂解剂的裂解液可直接扩增出结核分枝杆菌ＤＮＡ；ＳＤＳ，ＮａＯＨ，十二烷基肌酸钠等裂解剂的裂解液直接用于ＰＣＲ扩增均为阴性。结论：１％的Ｔｒｉｔｏｎｘ－１００，ＮＰ４０、Ｔｅｗｅｅｎ２０和乳化剂ＯＰ裂解细菌效果好，又不抑制ＰＣＲ反应，适合于作为临床ＰＣＲ检测结核杆菌的裂解剂。     

Synthesis and post-translational modification of the androgen receptor in LNCaP cells

Androgen receptor synthesis and modification were studied in the human LNCaP cell line. Immunoblotting with a specific polyclonal antibody showed that the androgen receptor migrated as a closely spaced 110–112 kDa doublet on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Most of the receptor protein is present in the higher molecular mass form. Pulse labelling experiments with [³⁵S]methionine showed that the androgen receptor is synthesized as a single 110 kDa protein which is rapidly converted to a 112 kDa protein. Alkaline phosphatase treatment of cytosols from [³⁵S]methionine pulse labelled cells caused a gradual elimination of the 112 kDa isoform with a concomitant increase of the 110 kDa isoform. This indicates that the observed 110 to 112 kDa upshift of the newly synthesized androgen receptor reflects receptor phosphorylation. Both isoforms can bind hormone and can undergo a hormone dependent transformation to a tight nuclear binding form, indicating that the 110 to 112 kDa conversion is not an obligatory step for hormone binding or receptor transformation.     

长效重组人超氧化物歧化酶的研制及其辐射防护作用

选用无毒、无免疫原性的高分子化合物聚乙二醇(PEG)为修饰剂,以活性酯法制备出PEG- 重组人超氧化物歧化酶(PEG-rh SOD)共价结合物.修饰酶的生物半衰期为15h,比修饰前延长了90倍,对酸、碱、热的耐受力明显高于修饰前.用照射小鼠的活存率评价了PEG-rhSOD的辐射防护作用.小鼠受8.5Gy γ射线照射前1h腹腔注射30万U/kg PEG-rh SOD,可提高活存率42%,与未修饰的rhSOD相比,活存率提高14%.实验仍在进行中.     

Differential effect of pancuronium at the adductor pollicis, the first dorsal interosseous and the hypothenar muscles. An electromyographic and mechanomyographic dose-response study

Cumulative dose-response curves were constructed from evoked compound electromyographic (EMG) recordings in man to compare the sensitivity to pancuronium of the adductor pollicis, the hypothenar and the first dorsal interosseous muscles. Also, the EMG and mechanomyography-based sensitivity of the adductor pollicis muscle were compared. The EMG and the mechanomyogram were evaluated in random sequence in each of 21 adult thiopental, fentanyl and diazepam anesthetized patients. The EMG-based ED50 were 36-38 micrograms.kg-1 with no differences between muscles. The EMG-based ED90 of the adductor pollicis and the hypothenar muscles were 62-65 micrograms.kg-1 compared to the 60 micrograms.kg-1 of the first dorsal interosseous muscle (P < 0.05). ED50 (34 micrograms.kg-1), and ED90 (56 micrograms.kg-1) obtained from the adductor pollicis mechanomyogram were significantly lower than those based on the EMG (P < 0.05). It is concluded that differences in sensitivity to pancuronium exist between the three muscles when evaluated from the EMG, and that the apparent sensitivity of a given muscle to a muscle relaxant may depend upon whether the response is evaluated using EMG or mechanomyography.     

广东省中山市头癣现状及其病原体分离结果分析

目的:了解广东省中山地区头癣现状及其病原体分布、流行情况。方法:对107例镜检阳性病发进行真菌培养、鉴定和临床分析。结果:107例患者中白癣81例(占75.7％),脓癣24例(22.4％),黑癣2例(1.9％),未发现黄癣。107例病发分离出5种共101个菌株,其中犬小孢子菌90株(占89.1％),须癣毛癣菌5株(4.9％),红色毛癣菌3株(2.79％),断发毛癣菌2株(1.98％),紫色毛癣菌1株(0.99％)。结论:广东省中山地区头癣种类以白癣为主,脓癣次之,黑癣少见,黄癣基本消失,流行的病原菌以亲动物性的犬小孢子菌占绝对多数。发病年龄以1岁～15岁的少年儿童为主,成年人少见。     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

变换型煤用于制造低含量CO水煤气气化的研究

在小型单管气化反应炉内进行了本题的研究。用粉煤和变换剂制成的型煤进行了水煤气气化反应试验，考察了变换剂种类添加量，气化反应温度，反应时间，蒸汽流量对煤气组成的产气率的影响。结果表明，Ｃａ基变换剂可使煤气ＣＯ含量ψ降低０．１０左右，Ｃａ－Ｎａ复合变换剂还可显著提高煤气产率。     

Oxidative modification of high density lipoprotein induced by cultured human arterial smooth muscle cells

Objective: To observe the oxidative modification of high density lipoprotein (HDL) induced by culturedhuman arterial smooth muscle cells (SMCs). Methods: HDL cocultured with SMCs at 37℃ in 48 h was subjected,and native HDL (N-HDL) served as control. Oxidative modification of HDL was identified by using agarose gel electro-phoresis. Absorbances of conjugated diene (CD) and lipid hydroperoxide (LOOH) were measured with ultravioletspectrophotometry at 234 and 560 nm respectively, and fluorescence intensity of thiobarbuturic acid reaction substance     

Synthesis of JTT‐501 and its metabolite JTP‐20604 labelled with 13C

JTT‐501 specifically labelled with ¹³C was obtained via a four‐step synthesis at an isotopic enrichment level of 99% and in 14% overall chemical yield starting from 4‐hydroxy‐[ring‐U‐¹³C₆]benzaldehyde (3) . The hydrogenation of [¹³C₆]JTT‐501 over Pd/C gave [¹³C₆]JTP‐20604 in 90% chemical yield. Copyright © 2003 John Wiley & Sons, Ltd.