一例遗传性蛋白C缺陷症家系的实验诊断

目的对1例遗传性蛋白C缺陷症家系进行临床表型诊断和基因突变检测。方法用发色底物法测定血浆蛋白C活性;用聚合酶链反应（PCR）法对先证者PC基因（PROC）的9个外显子及其侧翼序列进行扩增,PCR产物纯化后直接测序,检测其基因突变。家系成员DNA在先证者PROC基因突变区域扩增后测序,进行家系调查以期发现遗传规律。结果先证者蛋白C活性为38.6%,抗原为45.3%。直接基因测序分析发现先证者PROC基因外显子7区存在杂合错义突变c.565C〉T,该突变将引起编码的蛋白C 147位精氨酸被色氨酸替换（p.Arg147Trp）。家系分析发现先证者的c.565C〉T突变遗传于其父亲。结论 c.565C〉T杂合突变是导致该家系遗传性PC缺陷症的原因。     

Femtosecond lasing from a fluorescent protein in a one dimensional random cavity

We present evidence of random lasing from the fluorescent protein DsRed2 embedded in a random one-dimensional cavity. Lasing is achieved when a purified protein solution, placed inside a layered random medium, is optically excited with a femtosecond pump pulse in the direction perpendicular to the plane of random layers. We demonstrate that pumping with ultrashort pulses resulted in a lasing threshold two orders of magnitude lower than that found for nanosecond excitation.OCIS codes: (140.0140) Lasers and laser optics, (170.0170) Medical optics and biotechnology     

Treatment with recombinant human activated protein C: one size does not fit all

Protein C plays an important role in the coagulopathy associated with sepsis and probably also in the pathogenesis of sepsis-induced organ dysfunction. Plasma levels of protein C strongly correlate with clinical outcome in patients with severe sepsis. The RESPOND (Research Evaluating Serial Protein C Levels in Severe Sepsis Patients on Drotrecogin Alfa [Activated]) study shows that administration of recombinant human activated protein C in patients with severe sepsis with alternative dose regimens adjusted to plasma levels of protein C results in higher plasma levels of protein C. This may potentially translate to a better clinical outcome in patients with severe sepsis, although that was not directly shown in this trial.     

High mobility group box-1 protein – one step closer to the clinic?

High mobility group box (HMGB)1, originally described as a nuclear protein that binds to and modifies DNA, is now regarded as a central mediator of inflammation by acting as a cytokine. HMGB1 is postulated to be particularly important as a late acting mediator of lethal septicaemia in mice. Furthermore, it has been suggested that HMGB1 plays a role in clinical conditions such as autoimmunity, acute ischaemia-reperfusion injury, cardiovascular disease and cancer. HMGB1 has emerged as a candidate for therapeutic intervention in various disease conditions. However, further basic and clinical studies are warranted to confirm the roles played by HMGB1 in clinical medicine.     

DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis

Proteolytic cleavage of key substrates appears to be an important biochemical mechanism underlying the apoptotic process, and the centrality of interleukin 1 beta-converting enzyme (ICE)-like proteases as mediators of apoptosis has been suggested. The identification of the relevant substrates of the ICE protease family during apoptosis therefore constitutes a major challenge. Using human autoantibodies, we demonstrate here that a subset of autoantigens is specifically cleaved early during apoptosis. One of these cleaved molecules is identified as the catalytic subunit of the DNA-dependent protein kinase. The time courses of all proteolytic cleavages are identical and coincide with the onset of morphologic apoptosis. Furthermore, all cleavages share the same inhibition characteristics, which implicate an ICE-like activity(ies). We propose that cleavage of these autoantigens targets these molecules for an autoimmune response by revealing immunocryptic fragments in a proimmune apoptotic setting. Study of the immunogenicity of these fragments may yield insights into the autoimmune targeting of molecules. Moreover, the autoantibodies described will be valuable tools for the elucidation of mechanistically important proteolytic steps along the apoptotic pathway.     

Networks for research: the power of one plus one plus one.

Networks for emergency medicine research are both powerful and practical, and can be run on a very low budget. The keys to making them work are relevant questions, achievable goals, recognition of contributions, coordination, feedback and leadership. Many hands do really make the work light!     

High mobility group box-1 protein – one step closer to the clinic?

High mobility group box (HMGB)1, originally described as a nuclear protein that binds to and modifies DNA, is now regarded as a central mediator of inflammation by acting as a cytokine. HMGB1 is postulated to be particularly important as a late acting mediator of lethal septicaemia in mice. Furthermore, it has been suggested that HMGB1 plays a role in clinical conditions such as autoimmunity, acute ischaemia-reperfusion injury, cardiovascular disease and cancer. HMGB1 has emerged as a candidate for therapeutic intervention in various disease conditions. However, further basic and clinical studies are warranted to confirm the roles played by HMGB1 in clinical medicine.     

Murine tissue amyloid protein AA. NH2-terminal sequence identity with only one of two serum amyloid protein (ApoSAA) gene products

Amyloid protein AA is the presumptive fragment of an acute phase serum apolipoprotein, apoSAA. Two major murine apoSAA isotypes (apoSAA1 and apoSAA2) have been identified. The NH2-terminal amino acid sequences of purified murine apoSAA1 and apoSAA2 have been examined and compared with that of murine amyloid protein AA. Our results indicate that apoSAA1 and apoSAA2 are separate gene products and that amyloid protein AA has NH2-terminal amino acid sequence identity with only one of these isotypes, namely apoSAA2.