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61.
Human hepatic lipase mutations and polymorphisms. 总被引:2,自引:0,他引:2
Human hepatic lipase (HL) is a 477 residue glycoprotein that hydrolyzes triglycerides from plasma lipoproteins. Familial HL deficiency is a rare recessive disorder that is characterized by premature atherosclerosis and abnormal circulating lipoproteins. While studying the HL gene from the world's index family with HL deficiency, we identified four coding sequence variants of HL, one in each of exons 4, 5, 6, and 8. In this report we present the genetic basis for two new HL gene variants, one in each of exons 3 and 5. All six HL DNA variants are single base pair changes. Two variants (at codons 133 and 202) are diallelic DNA polymorphisms that are silent at the amino acid level. One variant (V73M) is an allele that defines an uncommon HL isoprotein. One variant (N193S) has two alleles of approximately equal frequency in the population that specify two common HL isoproteins. Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia. 相似文献
62.
Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2 总被引:2,自引:0,他引:2
Campbell KA; Studer EJ; Kilmon MA; Lees A; Finkelman F; Conrad DH 《International immunology》1997,9(8):1131-1140
A novel system to study the effects of co-cross-linking CD23/FceRII and sIg
on murine B lymphocytes utilizes a highly multivalent form of anti- Ig
prepared by covalently linking anti-Ig antibodies to a DNP-dextran
backbone. CD23-sIg co-cross-linking is accomplished by the addition of
DNP-specific monoclonal IgE. Previous studies demonstrated that co-
cross-linking CD23 and sIg significantly inhibited mouse B cell
proliferation, especially at high doses of the multivalent anti-Ig.
Interestingly, examination of early activation signals reveals no
difference in B cells subjected to co-cross-linking conditions as compared
to B cells activated with anti-Ig alone. Total cellular protein tyrosine
phosphorylation levels are unchanged by co-cross- linking. Analysis of B
cell mRNA reveals that co-cross-linking the receptors does not alter the
expression levels of ornithine decarboxylase 8 h after stimulation as
compared to the controls. In contrast, levels of the proto-oncogene c-myc
were significantly elevated 1 h after inducing B cell activation under
co-cross-linking conditions. However, it remains unclear whether this
aberrant c-myc regulation plays any role in inducing apoptosis. In
addition, on day 3 after stimulation, the co-cross-linking of CD23 and sIg
resulted in the formation of apoptotic B cells, determined by both
photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei.
B cells obtained from bcl-2 transgenic mice proliferated as well as
controls, and failed to undergo apoptosis when CD23 and sIg were
co-cross-linked on their surface. These studies indicate that
co-cross-linking of CD23 with B cell sIg inhibits B cell proliferation by a
mechanism that is distinct from that seen by co-cross-linking of the Fc
gamma RII and sIg. In addition, these results suggest a means by which
antigen- specific IgE can down-regulate additional B cell activation and
IgE synthesis.
相似文献
63.
腕关节关节囊内韧带的解剖观察及其创伤学意义 总被引:4,自引:2,他引:4
本文描绘了腕关节关节囊内韧带的解剖,其中首次描述了中腕关节的韧带连结,即大、小多角骨,头状骨至舟状骨的韧带和钩骨至三角骨的韧带.本文还论述了与这些韧带连结方式密切相关的腕骨生理运动特点及维持腕关节稳定性的因素.文章还讨论了与腕关节关节囊内韧带有关的腕部创伤学特点. 相似文献
64.
An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus 总被引:16,自引:0,他引:16
Qin C Wang J Wei Q She M Marasco WA Jiang H Tu X Zhu H Ren L Gao H Guo L Huang L Yang R Cong Z Guo L Wang Y Liu Y Sun Y Duan S Qu J Chen L Tong W Ruan L Liu P Zhang H Zhang J Zhang H Liu D Liu Q Hong T He W 《The Journal of pathology》2005,206(3):251-259
A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS. 相似文献
65.
de Jong MD Bach VC Phan TQ Vo MH Tran TT Nguyen BH Beld M Le TP Truong HK Nguyen VV Tran TH Do QH Farrar J 《The New England journal of medicine》2005,352(7):686-691
In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. The cerebrospinal fluid contained 1 white cell per cubic millimeter, normal glucose levels, and increased levels of protein (0.81 g per liter). The diagnosis of avian influenza A (H5N1) was established by isolation of the virus from cerebrospinal fluid, fecal, throat, and serum specimens. The patient's nine-year-old sister had died from a similar syndrome two weeks earlier. In both siblings, the clinical diagnosis was acute encephalitis. Neither patient had respiratory symptoms at presentation. These cases suggest that the spectrum of influenza H5N1 is wider than previously thought. 相似文献
66.
Oxygen-dependent up-regulation of mucoid exopolysaccharide (alginate) production in Pseudomonas aeruginosa. 总被引:9,自引:2,他引:9
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We previously showed substantial differences in Pseudomonas aeruginosa exopolysaccharide production in vitro at oxygen tensions reflective of the right versus left cardiac circuits in vivo (40 versus 80 mm Hg, respectively; A. S. Bayer, T. O'Brien, D. C. Norman, and C. C. Nast, J. Antimicrob. Chemother. 23:21-35, 1989). However, those studies did not specifically confirm this exopolysaccharide to be the characteristic P. aeruginosa mucoid alginate seen in patients with cystic fibrosis. With a murine monoclonal antibody prepared against P. aeruginosa alginate, strongly positive immunofluorescence (IF) staining of a nonmucoid P. aeruginosa strain (PA-96) was seen after its exposure in vitro to oxygen tensions (pO2) of approximately 80 mm Hg; the intensity of the IF staining under these conditions was similar to that observed with a phenotypically mucoid P. aeruginosa strain (C1712M) from a cystic fibrosis patient. In contrast, the same nonmucoid strain (PA-96), after exposure to pO2 of approximately 40 mm Hg, showed little IF staining for alginate. Following enzyme treatment with alginase, PA-96 cells previously exposed to the higher pO2 and exhibiting enhanced alginate production, as determined by IF staining, now showed no IF staining. Moreover, treatment of the oxygen-up-regulated PA-96 cells with alginase released amounts of unsaturated alginate breakdown products (uronic acids) quantitatively similar to those released by typically mucoid strains treated with the same enzyme. These data indicated that the P. aeruginosa exopolysaccharide in our studies was, indeed, mucoid alginate and that variations in oxygen tensions represent one of the trigger mechanisms for the up-regulation of mucoid exopolysaccharide production. 相似文献
67.
Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
68.
一种新型的脱细胞组织工程血管支架的构建和评价 总被引:3,自引:0,他引:3
本研究的目的是制备一种免疫原性较小、生物相容性较好、力学性能优良的组织工程血管支架。新鲜获得的犬主动脉,置于三蒸水中4℃过夜,使血管细胞由于渗透压差较大而破裂;随后经过多聚环氧化合物家族的乙二醇缩水甘油醚(EX-810)的作用。进一步促进细胞破裂的同时。对血管支架的纤维结构起交联作用;最后应用物理超声的方法清除支架内的细胞碎片残留。用这种方法处理的犬主动脉内几乎没有可见的核染,基本消除了血管支架的免疫原性。同新鲜的血管相比较。这种组织工程血管支架的各种力学指标与新鲜的犬主动脉没有显著差异。说明处理后的支架仍然保持新鲜血管的力学特征。同时它还表现出极低的细胞毒性。分别在支架上种植内皮细胞和平滑肌细胞,扫描电镜检测结果表明,两种细胞在支架上生长良好,且局部已经融合成片。 相容性 相似文献
69.
杂种犬11只,由股动脉放血使平均动脉压(MAP)维持在6.0kPa90min后回输全部血液,继续观察150min。在休克30min后,对照组和维拉帕米处理组(Ver组)分别静脉滴注生理盐水和Ver溶液[(10μg/kg·min)15min],液体总量为3ml/kg。对照组犬在失血后心率(HR)加快,左室dp/dtmax显著降低,回输血液后MAP虽有回升,但仍低于基础值,左室dp/dtmax无明显改善;Ver使休克犬HR减慢,血液回输后MAP缓慢恢复至基础值,左室dp/dtmax显著高于对照组;电镜观察可见对照组心肌肌原纤维和线粒体等有明显的损伤,而Ver组心肌超微结构基本正常。结果还显示:Ver组犬心肌中丙二醛含量、黄嘌呤氧化酶活性低于对照组,而超氧化物歧化酶活性高于对照组。结果表明:Ver对失血性休克犬的心脏具有保护作用,其机制可能与其阻滞膜Ca2+内流、抑制脂质过氧化有关。 相似文献
70.
实验用大鼠76只,用辐射热-甩尾法测痛,以电针后痛阈变化的百分率评价镇痛效应;用放射免疫分析法测定脑内L-Enk含量。发现脑室注入三肽-促甲状腺素释放激素(TRH)后,能显著降低电针镇痛效果;提高丘脑内L-Enk含量,但痛阈与脑内L-Enk含量的变化无相关关系。本文证明,TRH在电针镇痛过程中是对抗作用。已知针刺镇痛与脑内多种神经质和肽类有关,在不利于针刺镇痛的因素中,TRH是新添的“一员”。 相似文献