Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease

We sought to identify the molecular basis of the autosomal dominant form of Kufs disease, an adult onset form of neuronal ceroid lipofuscinosis. We used a combination of classic linkage analysis and Next Generation Sequencing to map and identify mutations in DNAJC5 in a total of three families. We analyzed the clinical manifestations in 20 individuals with mutation in DNAJC5. We report here the mapping and the identification of a p.L116del mutation in DNAJC5 segregating with the disease in two distinct American families, as well as a p.L115R mutation in an additional family. The age of onset and clinical manifestations were very homogeneous among mutation positive individuals, including generalized tonic–clonic seizures, myoclonus, ataxia, speech deterioration, dementia, and premature death. A few individuals also exhibited parkinsonism. DNAJC5, which encodes the cysteine string protein (CSPα), a presynaptic protein implicated in neurodegeneration, causes autosomal dominant Kufs disease. The leucine residues at positions 115 and 116 are hotspots for mutations and result in a homogeneous phenotype of progressive myoclonus epilepsy with onset around 30 years old.     

Recovery and viability of Orientia tsutsugamushi from packed red cells and the danger of acquiring scrub typhus from blood transfusion

BACKGROUND: The purpose of this study was to determine whether infective Orientia tsutsugamushi, the etiologic agent of scrub typhus, could survive normal blood banking processing and storage procedures. STUDY DESIGN AND METHODS: Mononuclear cells isolated from whole blood by density gradient centrifugation were inoculated with O. tsutsugamushi, Karp strain. Infection of the mononuclear cells was confirmed by Giemsa stain, direct fluorescent antibody assay, and polymerase chain reaction using primers specific for the groESL operon of O. tsutsugamushi. The quantity of rickettsial particles in each preparation was determined by direct counts from the Giemsa-stained preparations. Infected mononuclear cells were returned to their respective aliquots of packed red blood cells, which were then either stored at 4 degrees C or glycerolized and frozen at -70 degrees C. RESULTS: Rickettsiae survived up to 10 days (but not 30 days) of refrigerated storage and 45 days of frozen storage, as determined by inoculation of mice with 0.5-mL aliquots of the blood components. Infection of the mice was determined by illness, death, direct fluorescent antibody assay of peritoneal smears, polymerase chain reaction of blood, and enzyme-linked immunosorbent assay detection of antibodies in plasma. CONCLUSION: Because the quantity of rickettsiae injected into the mice was comparable to the quantity reported in the literature for human blood during natural infections, scrub typhus could present a risk in blood collected from donors in endemic areas. This may especially be true, because people can be rickettsemic before illness, after successful antibiotic treatment, and chronically after resolution of disease.     

Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase

Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolated Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolated     

我国髌骨骨折经镍钛记忆合金聚髌器与AO张力带治疗的系统评价

目的：系统评价我国镍钛记忆合金聚髌器与AO张力带治疗髌骨骨折的疗效与安全性.方法：计算机检索中国知网（CNKI：2003～2013.6）、万方数据库（2003～2013.6）、维普数据库（2003～2013.6）,中国生物医学数据库及超星电子图书.手工检索国内近五年来发表于中国矫形外科杂志、临床骨科杂志、中国骨与关节杂志及当代医学等杂志上的文献.收集所有相关镍钛记忆合金聚髌器与AO张力带治疗髌骨骨折的随机对照试验及半随机对照试验,采用RevMan5.0软件进行系统评价.结果：共纳入11篇随机对照试验及半随机对照试验,共735例患者,纳入研究质量评价结果为B级9篇,C级2篇.系统评价结果显示,与AO张力带组相比,镍钛记忆合金聚髌器组手术时间短,[SMD=-1.91,95％CI（-3.23,-0.58）,P=0.005＜0.05];术后并发症少,[RR=0.20,95％CI（0.09,0.43）,P＜0.05];术后优良率高RR=1.11,95％CI（1.00,1.23）,P=0.05],但在术后骨折愈合时间方面差异无统计学意义.结论：镍钛记忆合金聚髌器在治疗髌骨骨折时优于AO张力带组,值得临床推广.但由于本文尚存在一定的局限性,故需要更严格的、大样本量的、多中心性的,并且采用正确的随机、盲法、分配隐藏等的文献研究来进一步论证.