全自动红细胞沉降率分析仪Monitor-100测定结果的评价

目的评价全自动血沉仪Monitor-100测定红细胞沉降率(ESR)结果的可靠性和准确性。方法随机选取住院和门诊患者146例,采用自动ESR分析仪Monitor-100的30min和1h及魏氏法测定ESR,并对3种方法进行比较并进行重复性检测。结果 (1)仪器法30min、仪器法1h、魏氏法检测ESR值分别为37.8±34.1、38.1±33.7和36.4±32.9,两两比较其差异均无统计学意义(P0.05)。(2)仪器法30min、仪器法1h、魏氏法的阳性结果检出率依次为43.2%、44.5%和45.2%,未发现有统计学差异(P0.05)。(3)仪器法30min、仪器法1h、仪器法30min与魏氏法、仪器法1h与魏氏法之间比较,Kapper值依次为0.944、0.875、0.903。(4)重复性检测CV值均较小,均在可接受范围内。结论全自动ESR分析仪Monitor-100与魏氏法相比,假阳性率和假阴性率均较低,且一致性、重复性极好,方便快速且安全,应在临床上大量推广。     

Finding the elusive and causative autoantibody: An atypical case of autoimmune hemolytic anemia

An isolated IgA‐mediated autoimmune hemolytic anemia can present a diagnostic challenge. When a routine direct antiglobulin test (DAT) is negative but clinical suspicion remains high, further testing with monospecific antisera should be performed. As with IgG‐mediated WAIHA, steroids are first‐line treatment, though splenectomy is often required to achieve a durable treatment response.     

Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium,cartilage, and bone in the LITHE study

Objective

We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.

Methods

The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early response was evaluated at week 16 as ±20% improvement in swollen/tender joint counts; and ACR50 was evaluated at week 52. Biomarkers (tissue inflammation: C3M, CRPM, and VICM; cartilage degradation: C2M; and bone turnover: CTx and osteocalcin) were tested in serum from baseline, week 4, 16, 24, and 52, and dose-dependent effect was investigated. Patients were divided into the following three groups: early non-responders (ENR), ACR50 responders, and non-responders; their biomarker profiles were compared.

Results

At week 52, CRP was inhibited to 4% and 40% of baseline by TCZ8 and TCZ4, respectively. CRPM (63%), C2M (84%), C3M (69%), and VICM (42%) were significantly (p < 0.05) reduced by TCZ8, but not by TCZ4. MMP3 and osteocalcin changed to <58% and >111%, respectively, in response to TCZ. CTx was not changed significantly. ENRs had significantly less inhibition of CRPM (p < 0.05), C2M (p < 0.01), and C3M (p < 0.01) compared to early responders. There was a significant difference in the C2M, C3M, and CRPM profiles of the ENRs, non-responders, and responders. ACR50 responders had significantly inhibited levels (p < 0.001), irrespective of dose.

Conclusions

TCZ8 strongly inhibited the biomarkers of joint tissue remodeling suggesting that TCZ actively suppresses key pathobiological processes at the site of inflammation in RA patients. The differences in biomarkers' profiles of responders and non-responders indicate that specific responder profiles exist.     

Full dynamics of a red blood cell in shear flow

At the cellular scale, blood fluidity and mass transport depend on the dynamics of red blood cells in blood flow, specifically on their deformation and orientation. These dynamics are governed by cellular rheological properties, such as internal viscosity and cytoskeleton elasticity. In diseases in which cell rheology is altered genetically or by parasitic invasion or by changes in the microenvironment, blood flow may be severely impaired. The nonlinear interplay between cell rheology and flow may generate complex dynamics, which remain largely unexplored experimentally. Under simple shear flow, only two motions, “tumbling” and “tank-treading,” have been described experimentally and relate to cell mechanics. Here, we elucidate the full dynamics of red blood cells in shear flow by coupling two videomicroscopy approaches providing multidirectional pictures of cells, and we analyze the mechanical origin of the observed dynamics. We show that contrary to common belief, when red blood cells flip into the flow, their orientation is determined by the shear rate. We discuss the “rolling” motion, similar to a rolling wheel. This motion, which permits the cells to avoid energetically costly deformations, is a true signature of the cytoskeleton elasticity. We highlight a hysteresis cycle and two transient dynamics driven by the shear rate: an intermittent regime during the “tank-treading-to-flipping” transition and a Frisbee-like “spinning” regime during the “rolling-to-tank-treading” transition. Finally, we reveal that the biconcave red cell shape is highly stable under moderate shear stresses, and we interpret this result in terms of stress-free shape and elastic buckling.     

CD47 functions as a removal marker on aged erythrocytes

CD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor signal regulatory protein alpha (SIRPα) expressed by macrophages. Thus, the CD47-SIRPα interaction constitutes a negative signal for erythrocyte phagocytosis. However, we recently reported that CD47 does not only function as a ‘don't eat me’ signal for uptake but can also act as an ‘eat me’ signal. In particular, a subset of old erythrocytes present in whole blood was shown to bind and to be phagocytosed via CD47- SIRPα interactions. Furthermore, we provide evidence that experimental ageing of erythrocytes induces a conformational change in CD47 that switches the molecule from an inhibitory signal into an activating one. We also demonstrate that aged erythrocytes have the capacity to bind the CD47-binding partner thrombospondin-1 (TSP-1) and that treatment of aged erythrocytes with a TSP-1-derived peptide enabled their phagocytosis by human red pulp macrophages. Finally, CD47 on erythrocytes that had been stored for prolonged time was shown to undergo a conformational change and bind TSP-1. These findings reveal a more complex role for CD47- SIRPα interactions in erythrocyte removal, with CD47 acting as a molecular switch for controlling erythrocyte phagocytosis.     

Effects of Heat on Fragility and Morphology of Human and Calf Erythrocytes

It is important to know the species differences when data from animal experiments are interpreted for human application. This in vitro study focused on the effects of heat, a major concern in mechanically actuated artificial heart development, on the physiology of human and calf erythrocytes (RBC). RBC from calves and healthy human donors were incubated at 25, 37, 46, 48, 50, or 52°C for 1 h. Osmotic fragility was tested and morphological changes were then observed by scanning electron microscopy. The osmotic fragility of human and calf RBC increased at and above 50°C. After incubation at 50°C, 6% of human and 1 % of calf RBC hemolyzed. Changes in surface morphology, which included spherocytic or echinocytic for MS, were observed in 97% of human and 19% of calf RBC after incubation at 50°C. In conclusion, human RBC showed greater changes in osmotic fragility and morphology at and above 50°C. These changes, however, were not observed in either species after 1 h incubation at 46°C.     

Dose-related cellular effects of platelet-derived growth factor-BB differ in various types of rabbit tendons in vitro

Cellular responsiveness to growth factors that can affect tendon healing may be site-specific. We have compared the dose-response effects of platelet-derived growth factor-BB (PDGF-BB) on proteoglycan, collagen, noncollagen protein and DNA synthesis between intrasynovial intermediate and proximal segments of deep flexor tendons, and extrasynovial peroneal tendons of rabbits during short-term cultures. PDGF-BB stimulated matrix and DNA synthesis of the three types of tendon segments in a dose-dependent manner in the range from 0.1 to 100 ng/mL. PDGF-BB stimulated collagen synthesis and noncollagen protein synthesis (calculated from LogED 50 ) in proximal intrasynovial tendon segments more than in extrasynovial peroneal tendon segments, and DNA synthesis less in proximal than in intermediate intrasynovial tendons. However, the estimated maximal stimulations (E max ) by PDGF-BB were similar in the three types of tendon segments. These findings show that PDGF-BB stimulates DNA and matrix synthesis differently in various types and regions of tendons during short term explant culture and suggests that there may be differences in cellular responsiveness during tendon healing.