Post-mortem analysis for two prevalent β-oxidation mutations in sudden infant death

BACKGROUND: Fatty acid oxidation disorders may cause sudden and unexpected infant death and are associated with the histological hallmark of hepatic steatosis. The goal of the present study was to assess the value of post-mortem molecular analysis for medium-chain acyl-coenzyme A dehydrogenase (MCAD) and mitochondrial trifunctional protein (MTP) defects in unexplained sudden infant death (SID) associated with fatty infiltration of the liver. MCAD catalyzes the first step of medium-chain fatty acid oxidation while MTP catalyzes the last three steps of long-chain fatty acid oxidation. METHODS: In a retrospective study, 220 consecutive cases of sudden and unexplained infant death certified by medical examiners at Wake Forest University Medical Center were assessed for hepatic steatosis. Subjects with evidence of hepatic steatosis were screened for mutations in MCAD and MTPalpha-subunit using DNA isolated from paraffin-embedded liver tissue, single-strand conformation variance, and nucleotide sequence analyses. RESULTS: Sixteen cases (7.3%) were associated with diffuse micro-vesicular or mixed micro- and macro-vesicular hepatic steatosis. Two of these 16 cases (12.5%) had disease-causing mutations. One was homozygous for the prevalent MCAD A985G mutation. The second was a compound heterozygous for the prevalent MTP G1528C mutation and a novel 1 bp deletion in exon 18 of the MTPalpha-subunit gene. CONCLUSIONS: A significant proportion (7.3%) of SID is associated with hepatic steatosis. The present data support post-mortem molecular analysis for the MCAD A985G and MTP G1528C prevalent mutations in cases of sudden and unexplained infant death associated with hepatic steatosis.     

IL-6对人精子顶体反应影响机制的初步探讨

目的:探讨IL-6对人精子顶体反应(AR)的影响机制。方法:采用BAEE/ADH法测定精子顶体酶的活性,以及通过FITC-PSA法检测精子顶体反应。结果:IL-6可诱导精子顶体酶及超氧化物歧化酶(SOD)的活性,促进精子顶体反应;胞外Ca2+单独不能诱导精子顶体反应,且没有胞外Ca2+的参与,IL-6也不能诱导精子顶体反应;蛋白激酶C(PKC)抑制剂calphC能逆转IL-6诱导的精子顶体反应。结论:IL-6对精子顶体反应有一定的促进作用,可能通过诱导精子的顶体酶和SOD活性等途径来实现,在此作用中,也涉及了PKC的激活,且还需要外源性Ca2+的参与。     

Reversed siderophores act as antimalarial agents.

We describe here a family of biomimetic iron carriers that display high binding efficiency for ferric ions and favorable permeation properties across erythrocytic membranes. These carriers inhibit in vitro growth of Plasmodium falciparum by scavenging intracellular iron. The chemical features were realized by reproducing the iron-binding cavities of natural iron carriers (siderophores) and by systematic substitutions of their hydrophilic envelopes for more hydrophobic ones. In contrast to natural carriers, which participate in receptor-mediated iron uptake in cells and act as growth promoters, our synthetic carriers were designed to penetrate cellular membranes by diffusion, scavenge intracellular iron, and thereby act as growth inhibitors. Based on these properties we designate the compounds reversed siderophores and refer to the specific analogs of the natural ferrichrome as synthetic ferrichromes. The antimalarial activity of the synthetic ferrichromes correlated with their lipophilicity, and this antimalarial activity was averted when the chelators were applied as iron (III) complexes. The sites of synthetic ferrichrome action reside in the intraerythrocytic parasite and not in serum or on normal erythrocyte components. The agents were effective against all stages of parasite growth and against a variety of multidrug-resistant strains of P. falciparum. The most potent agent of this synthetic ferrichrome series, SF1-ileu, was not toxic to mammalian cells in culture and was 15-fold more potent and 20-fold faster acting than desferrioxamine. Taken in toto, these agents constitute a series of promising candidates for future use in malaria chemotherapy.     

5992例孕产妇梅毒筛查与分析

目的 了解妊娠期梅毒的流行情况及对围产结局的影响。方法 对5992例孕产妇进行甲苯胺红不加热血清试验（TRUST）筛查，对TRUST阳性病例再进行梅毒螺旋体血清颗粒凝集试验（TPPA）确诊。并对围产结局进行观察分析。结果 5992例孕产妇，检出梅毒患者43例（0．72％），其中30例经青霉素治疗的患者其新产儿经半年以上随访无1例感染梅毒，在未治疗的13例患者中有10例分娩的新生儿TPPA滴度均≥1：40，其中2例为先天性梅毒。1例为死亡梅毒婴儿。结论 开展妊娠期梅毒血清学的产前筛查，加强对妊娠期梅毒的治疗，对减少先天性梅毒的发生尤为重要。     

Hydrophobic interactions in Plasmodium falciparum invasion into human erythrocytes

Human glycophorins block in vitro invasion of Plasmodium falciparum merozoites into human erythrocytes. A segment of glycophorin A which appears to be involved in the inhibition, is at, or adjacent to, the membrane-spanning domain of the molecule. To study the role of hydrophobic interactions in the inhibition, a series of proteins were derivatized with lipophilic side groups, and tested for inhibitory activity. Glycophorin A became five times more inhibitory after derivatization with nitrobenzylfurazan groups. Bovine serum albumin was derivatized to different degrees with nitrobenzylfurazan, dinitrobenzyl, trinitrobenzyl, dansyl, disulfonic stilbene, and fluorescein groups. The presence of hydrophobic side groups on the protein rendered it highly inhibitory to invasion, whereas the presence of hydrophilic substitutes such as disulfonic stilbenes did not. Other soluble proteins such as human serum albumin, transferrin, ovalbumin, fetuin and casein derivatized with dinitrobenzyl groups, were also found to block invasion. Inhibition was not a result of toxic effects of the protein derivatives on parasite metabolism or development. A minimum of ten hydrophobic side groups per bovine serum albumin was required in order to elicit appreciable inhibition. The invasion blocking activity was highly correlated with the rate and affinity of binding of the derivatized macromolecules to heptyl-Sepharose. The latter provided a quantitative measure for the capacity of amphiphiles to undergo hydrophobic interactions with insoluble matrices. The results of the present study indicate that hydrophobic interactions may be an essential component in the invasion of P. falciparum merozoites into human erythrocytes.     

Piretanide-dextran and piretanide-polyethylene glycol interact with high affinity with the Na+ 2 Cl− K+ cotransporter in the thick ascending limb of the loop of Henle

Piretanide blocks the Na⁺ 2Cl^– K⁺ cotransporter protein in the thick ascending limb (TAL) of the loop of Henle reversibly. When tested from the luminal side in isolated perfused cTAL segments it leads to a half maximal inhibition (IC₅₀) of the equivalent short circuit current (I_sc) at a concentration of 10^–6 mol/l. From the basolateral side it has no effect on I_sc up to 10^–4 mol/l. The present study was designed to search for high affinity blockers of the Na⁺ 2Cl^– K⁺ cotransporter with large molecular weight in an attempt to use these macromolecules for antibody-labelling or affinity separation of this transport-protein. Amino-ethyl-dextran or amino-ethyl-polyethylene glycol (M.W. 5kd) were coupled to isothiocyanato-piretanide (ISO-PIR) at room temperature in DMSO. The resulting compounds dextran-sulfonylurea-piretanide (PIR-DEX) and polyethylene glycol-sulfonylurea-piretanide (PIR-PEG) (M.W. 5.38kd) were purified and tested in isolated perfused cTAL segments. IC₅₀ values for ISO-PIR, PIR-DEX and PIR-PEG were estimated from dose response curves after their addition to the lumen or bath perfusate, respectively. ISO-PIR, PIR-DEX and PIR-PEG acted from the lumen side at 3·10^–6, 6·10^–6 and 2·10^–6 mol/l. The inhibitory effect was easily reversible. From the basolateral side no effect for any compound was seen at up to 10^–4 mol/l. In clearance experiments PIR-DEX was given to female Wistar rats as an i.v. bolus (25 mol/kg) and the diuretic urine was collected. After dialysis (exclusion limit 2.5kd) the dialysed urine and the dialysate were tested in isolated perfused cTAL segments. The dialysates had no effect on I_sc, but the dialysed urine inhibited I_sc by 35% from the luminal side. The present data show: High molecular derivatives of piretanide with dextran or polyethylene glycol moieties block the Na⁺ 2Cl^– K⁺ cotransporter in cTAL segments at roughly the same low concentration as piretanide itself. Our data exclude a metabolism of these piretanide compounds in the kidney. Since these macromolecular probes can probably not enter the cell their inhibitory effect indicates that the binding site for piretanide diuretics on the Na⁺ 2Cl^– K⁺ cotransporter is exposed on the surface of the luminal cell membrane.This study was supported by Deutsche Forschungsgemeinschaft Gr 480/9     

中文Frost多维度完美主义问卷的信效度检验

目的：检验中文Frost多维度完美主义问卷（FMPS）信效度。方法：共有1280名大学本科生作为被试填写了FMPS问卷，其1000名被试的数据用于探索性因素分析，另外280名被试的数据用于验证性因素分析。部分被试被要求填写测量焦虑、抑郁、强迫等心理困扰的问卷，作为效标效度检验。结果：中文版Frost多维度完美主义问卷由五个维度组成。各维度的项目载荷在0．45—0．78之间。五个因素（担心错误、条理性、父母期望、个人标准和行动的疑虑）可以解释总方差的53．7％。各维度的内部一致性系数为0．64-0．81。重测信度为0．63-0．82。中文FMPS与焦虑、抑郁、强迫等心理困扰也有屉著的相关，其中“担心错误”和“行动的疑虑”与各种心理困扰的相关系数在0．30—0．70之间。结论：中文FMPS的维度结构与其英文原问卷相似，且具有令人满意的信效度。适合在中国文化环境下使用。     

孕妇妊娠晚期和妊高征患者血小板参数的分析

目的观察正常孕妇妊娠晚期和妊高征患者血小板参数的变化及临床意义。方法采用日本Sysmex KX-21型血液细胞分析仪分别对正常孕妇（118例）、妊高征患者（59例）及对照组（正常婚检妇女59例）的血液标本进行血小板（PLT）计数、平均血小板体积（MPV）、血小板分布宽度（PDW）的测定。结果妊高征组和正常孕妇组的MPV、PDW显著高于对照组（P〈0.01）;妊高征组MPV、PDW明显高于正常孕妇组（P〈0.05）;妊高征组的PLT显著低于对照组（P〈0.01）。结论妊高征患者由于血小板消耗和破坏增加,导致血小板减少,MPV、PDW明显增高,因此,检测血小板参数对预测妊高征的发生有一定的参考意义。     

神经病学临床见习的教学方法

本文从多方面介绍了神经病学临床见习的教学方法,认为临床见习的重点是理论联系实际,促进医学生向医生的转变.