The kinetics and distribution of C9 and SC5b-9 in vivo: effects of complement activation.

Many diseases associated with complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cell-regulating functions of the TCC. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of 125I-C9 (median and range) were: plasma half-life (t1/2) 25.9 (20.6-29.5) h, fractional catabolic rate (FCR) 5.7 (5.3-7.0)%/h, and extravascular/intravascular ratio (EV/IV) 0.7 (0.6-1.1). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation of the complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabeled in the spleen (exceeding the plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, 125I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0.7 (0.6-0.8) h, and less than 15% remaining after 4 h with accumulation of protein-bound label in the spleen and liver. These results demonstrate the complexity of C9 metabolism during complement activation.     

Fetal RhD genotyping: A more efficient use of anti-D immunoglobulin

The most important application of blood group genotyping by molecular genetics is the prediction of fetal RhD phenotype in pregnant women with anti-D, in order to assess the risk of haemolytic disease of the fetus and newborn. This diagnostic test performed on cell-free fetal DNA in the maternal plasma, is now a routine procedure in some countries. High-throughput modifications of this form of fetal D-typing would be valuable for testing fetuses of all D-negative pregnant women to avoid unnecessary antenatal treatment with anti-D immunoglobulin in the 40% of D-negative pregnant women with a D-negative fetus. The results of trials in Bristol and Amsterdam suggest that such routine testing is feasible and accurate.     

Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, -9, + DER(9)T(6:9)(p211:p24)

This report describes an adult male with a partial trisomy 6p(p211-pter) and a partial monosomy 9p(9p24-pter) resulting from a de novo unbalanced translocation. This patient does not show the classical featured of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs nor previously reported as part of the 9p monosomy or 6p trisomy syndromes.     

我院基于XML异构数据集成的开发应用及研究

基于XML的数据集成，Web Services中间件能够较容易地实现对各数据源的描述以及数据源之间的数据转换，它在应用程序和数据库之间起着接口的作用．本文结合实际医院信息工作，运用VFP9 COM模型，作了有效性的研究及应用，并对标准数据集的二次开发进行了讨论。结果表明，该方法用于医院跨网络平台、跨应用系统、异构信息集成是有效的和易于操作的。     

Inhibition of C5 or absence of C6 protects from sepsis mortality

Inhibiting complement anaphlytoxin C5a during sepsis may prevent sepsis mortality. Although human anti-C5 antibodies exist, their therapeutic use in microbial sepsis has been avoided because of the hypothesis that inhibiting C5b will prevent formation of the bactericidal membrane attack complex (MAC) and worsen clinical outcome. We wished to test the hypothesis that inhibition of C5 would improve outcomes in sepsis. Sepsis was induced in rats by laparotomy and cecal ligation and puncture (CLP) by an IACUC-approved protocol. Sham animals underwent laparotomy without CLP. Following CLP rats were randomized to receive a single IV dose of purified IgG ant-C5 antibody (Ab) or control IgG Ab. Anti-C5 Ab treated rats (n = 20) had significantly lower mortality vs. controls (n = 21), 20% vs. 52% (P = 0.019, log-rank). Analysis of bacterial load by culture of spleen and liver homogenates showed a reduction in colony forming units in anti-C5 Ab treated rats vs. control IgG (P = 0.003 and 0.009, respectively). Anti-C5 treatment reduced lung injury as measured by total MPO content of lung tissue (P = 0.024). Finally, rats genetically deficient in C6 production, unable to form MAC but capable of producing C5a and C5b, were protected from CLP-induced sepsis mortality. Our results show that in anti-C5 antibody therapy prevents CLP sepsis-induced mortality and improves lung injury. Inhibition of the complement MAC does not increase bacterial load or mortality, therefore, the use of anti-C5 therapy may be beneficial rather than detrimental in sepsis.     

Partial trisomy 3q syndrome inherited from familial t(3;9)(q26.1; p23)

A five-year-old girl was referred to prometaphase chromosome analysis because of mental retardation, facial dysmorphic features suggestive of Cornelia de Lange syndrome, cleft palate and additional minor congenital malformations of the cardiac system and fingers and toes. A familial balanced translocation (3;9)(q26.1; p23) was found. The karyotype of the proposita was 46,XX,der(9),t(3;9)(q26.1;p23). Thus the patient was trisomic for 3q26.1-qter and monosomic for 9p23-pter. The unbalanced chromosome constitution was not detected by standard Q-banding analysis shortly after birth. The karyotype was misdiagnosed as 46,XX,9(p+) in the proposita and her mother, and thought to be a normal variant of chromosome 9. The repeated cytogenetic study led to the diagnosis of the translocation and to the possibility of prenatal diagnosis in the translocation carriers. A survey of 22 published cases of dup(3q) showed that nearly 60% were secondary to familial balanced rearrangements with an excess of maternally derived abnormal chromosomes 3. Red blood cell galactose-1-phosphate-uridyltransferase (GALT) activity was normal in the patient, consistent with previous assignment of the gene locus for GALT to 9p13 (Shih et al. 1982).     

Pharmacodynamic relationship between PCSK9, alirocumab,and LDL-C lowering in the ODYSSEY CHOICE I trial

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Regionally defective colonization of the terminal bowel by the precursors of enteric neurons in lethal spotted mutant mice

In order to gain insight into the process of colonization of the bowel by the neural crest-derived precursors of enteric neurons, the development of the enteric nervous system was examined in lethal spotted mutant mice, a strain in which a segment of bowel is congenitally aganglionic. In addition, nerve fibers within the ganglionic and aganglionic zones of the gut of adult mutant mice were investigated with respect to their content of acetylcholinesterase, immunoreactive substance P, vasoactive intestinal polypeptide and serotonin, and their ability to take up [³Hserotonin. In both the fetal gut of developing mutant mice and in the mature bowel of adult animals abnormalities were limited to the terminal 2 mm of colon. The enteric nervous system in the proximal alimentary tract was indistinguishable from that of control animals for all of the parameters examined. In the terminal bowel, the normal plexiform pattern of the innervation and ganglion cell bodies were replaced by a coarse reticulum of nerve fibers that stained for acetylcholineserase and were continuous with extrinsic nerves running between the colon and the pelvic plexus. These coarse nerve bundles contained greatly reduced numbers of fibers that displayed substance P- and vasoactive intestinal polypeptide-like immunoreactivity, but a serotonergic innervation was totally missing from the aganglionic bowel. During development, acetylcholineserase and uptake of [³Hserotonin appeared in neural elements in the foregut of mutant mice on the 12th day of embryonic life (E12), about the same time these markers appeared in the forgut in normal mice. By day E14, neurons expressing one or the other marker were recognizable as far distally as about 2 mm from the anus. The appearance of neurons in segments of gut grown for 2 weeks as expiants in culture was used as an assay for the presence of neuronal progenitor cells in the segments of fetal bowel at the time of explantation. Both acetyl- cholinesterase activity and uptake of [³Hserotonin developed in neuronsin vitro in expiants of proximal bowel between days E10 and E17. At all times, however, the terminal 2mm of mutant but not normal fetal gut gave rise to aneuronal cultures. In some mutant mice rare, small, ectopically-situated pelvic ganglia were found just outside aganglionic segments of fetal colon. Uptake of [³Hserotonin, normally a marker for intrinsic enteric neurites, was found in these ganglia.The experiments suppport the hypothesis that the terminal 2 mm of the gut in lethal spotted mutant mice is intrinsically abnormal and thus cannot be colonized by the precursors of enteric neurons. The defect seems to be specific in that both cells and processes of intrinsic enteric neurons, including all serotonergic and most peptidergic neurites, seem to be excluded from the abnormal region while extrinsic nerve fibers, including sympathetic and sensory axons, are able to enter the aganglionic zones. Since examination of neural progenitor cells has failed to reveal a significant proximo-distal displacement of these cells through the enteric tube during development of the murine bowel, a defect in the migration of precursor cells down the alimentary tract to the terminal gut seems unlikely to be substantially involved in the pathogenesis of aganglionosis. This conclusion is supported by the normal enteric nervous system in proximal regions of the mutant gut and the presence of enteric type neurons outside of, but at the same level as the aganglionic region.