Inactivation of Friend erythroleukemia virus and Friend virus- transformed cells by merocyanine 540-mediated photosensitization

The Friend virus complex was used as a model to study the effects of merocyanine 540 (MC 540)-mediated photosensitization on enveloped viruses. Simultaneous exposure to the lipophilic dye MC 540 and white light inactivated cell-free virus, cell-associated virus, and virus- transformed cells. When used under experimental conditions that are known to preserve most mature blood cells, at least some coagulation factors, and a significant portion of the pluripotent hematopoietic stem cell compartment, MC 540-mediated photosensitization reduced virus titers by greater than or equal to 4 log and the concentration of in vitro clonogenic erythroleukemia cells by greater than or equal to 5 log. Animals that received a single intravenous injection of photosensitized virus were resistant to a subsequent challenge with live virus. High sensitivity to MC 540-mediated photosensitization appears to be a property that is shared by other enveloped viruses. Thus, photosensitization mediated by MC 540 may be of benefit in the sterilization of blood products (in particular, cellular products), the production of vaccines, and selected areas of antiviral therapy.     

计算机辅助的EBRA-FCA法分析半髋表面置换治疗股骨头缺血性坏死假体生物力学变化

背景:对于中晚期(FicatⅢ,Ⅳ期)股骨头缺血性坏死且髋臼基本完好的患者,单纯股骨头表面置换是一种较好的治疗方法。股骨假体位置、下沉影响全髋关节置换术的治疗效果,但假体位置、下沉对半髋表面置换术疗效的影响尚需进一步研究。目的:观察钴铬合金半髋表面置换对中晚期(FicatⅢ,Ⅳ期)股骨头缺血性坏死且髋臼基本完好患者髋关节功能的影响,并分析疗效与股骨假体柄干角、下沉的关系,评估计算机辅助X射平片分析对假体失败的预测价值。设计:病例分析。单位:广西医科大学第一附属医院脊柱骨病科。对象:选择1997-06/2002-07广西医科大学第一附属医院脊柱骨病科收治的中晚期(FicatⅢ,Ⅳ期)股骨头缺血性坏死行半髋表面置换患者41例(48髋),患者手术时的年龄29～49岁,平均(37±9)岁,其中男30例,女11例。其中FicatⅢ期35髋,FicatⅣ期13髋,髋臼均相对正常。所有患者病变部位病理检查均为股骨头缺血性坏死;且均签署知情同意书。方法:①于术前和随访时采用UCLA(UniversityofCaliforniaLosAnge-les)髋关节功能评分标准对患者手术前后疼痛、步行、功能、活动进行评分,每一项记分为1～10分,10分为最佳。优,35～40分,好29～34分,一般22～28分,差<22分。术后评分为随访时评分平均值。②运用计算机辅助的EBRA-FCA法,在术后骨盆的X射线平片上测量股骨假体的柄干角、下沉,并对半髋表面置换术治疗股骨头缺血性坏死的疗效与股骨假体的柄干角、下沉的关系进行分析。③采用复诊的方式进行随访,于术后2个月开始第1次随访,每年随访1次,共随访8年。④两组样本间均数比较采用独立样本t检验(并做方差齐性检验)。在对临床结果的析因分析(posthocanalysis)基础上,比值比(oddsratio)分析用来确定假体早期失败的相对危险性。主要观察指标:①纳入患者半髋表面置换术前后UCLA评分比较。②FicatⅢ期和Ⅳ期患者术后疗效比较。③不同疗效患者随访期间股骨假体柄干角和下沉程度比较。结果:全部病例均获随访,其中8例随访3年,8例随访4年,8例随访5年,7例随访6年,6例随访7年,4例8年。①UCLA髋关节功能评分:疼痛、步行、功能、活动评分别由术前的(3.1±1.2),(4.4±1.7),(5.8±2.3),(5.5±2.7)分提高到术后的(9.1±2.5),(9.2±2.9),(9.1±3.4),(7.1±3.1)分,差异明显(P<0.01)。②疗效:FicatⅢ期35髋术后的满意率为89%与FicatⅣ期13髋术后的满意率相近(69%,P>0.05),其中疗效差8髋为失败组,其余40髋为成功组。③计算机辅助的X射线平片检查结果:失败组6个髋的股骨假体有明显下沉(其柄干角小于130°),2个髋的髋臼有破坏(1个柄干角为128°,1个柄干角为136°)。成功组平均柄干角明显大于失败组,分别为139°±6.2°,127°±5.3°,差异明显(P<0.01)。失败组中,6髋假体头中心和假体柄尖的下沉分别为(5.02±1.3)mm和(4.85±1.1)mm明显大于成功组[(1.48±0.2)和(1.04±0.2)mm,P<0.05];小于130°的柄干角其发生不良后果的机会增加了7.1倍。④股骨假体下沉时间:计算机辅助的X线片分析显示股骨假体下沉超过2mm的时间为(19.5±3.2)个月,明显早于临床出现症状的时间和X射线平片异常的时间[(35.6±4.2),(24.8±2.5)个月,P<0.01]。结论:①钴铬合金半髋表面置换是一种可供选择的向全髋关节置换术过渡的较好的治疗方法,可以恢复中晚期(FicatⅢ,Ⅳ期)股骨头缺血性坏死的且髋臼基本完好的患者的髋关节功能。②假体的松动下沉与假体的位置有关。③用来评估假体柄在骨盆平片上的下沉程度的计算机辅助的平片分析可以预测假体的失败。     

In vivo measurements of blood flow and bone metabolism in osteoarthritis

With increasing age, there may be a decrease in femoral blood flow. In some patients, this may result in local ischaemia, which subsequently may lead to local degenerative changes. Consequently, bone blood flow may play an important role in the aetiology of osteoarthritis of the hip. Little is known about bone blood flow in the femoral head of patients with advanced hip osteoarthritis. The purpose of this study was to evaluate bone blood flow and metabolism in vivo in patients with osteoarthritis of the hip. Ten patients with symptomatic osteoarthritis of the hip were enrolled prospectively. Femoral bone blood flow and metabolism were measured using positron emission tomography together with H ₂ ¹⁵ O and [¹⁸F]fluoride, respectively. Blood flow was 0.054 ± 0.032 mL cm^?3 min^?1 and 0.041 ± 0.012 mL cm^?3 min^?1 in symptomatic and contralateral femoral heads, respectively (p = 0.435). The net flux of fluoride from plasma to bone mineral (K _i ) was significantly (p = 0.027) higher in the femoral head of the osteoarthritic hip (0.022 ± 0.012 mL cm^?3 min^?1) than in that of the contralateral hip (0.007 ± 0.005 mL cm^?3 min^?1). This study showed significant increase in bone metabolism in the proximal femur of patients with symptomatic osteoarthritis of the hip joint. There was no evidence of decreased blood flow.     

Macrophage tropism of feline leukemia virus (FeLV) of subgroup-C and increased production of tumor necrosis factor-alpha by FeLV-infected macrophages

Erythroid aplasia is induced in cats by feline leukemia virus (FeLV) of subgroup C but not by FeLV of subgroup A. In an investigation of the role of macrophages in FeLV-C-induced diseases, the concentrations of FeLV and tumor necrosis factor-alpha (TNF-alpha) were compared between feline peritoneal macrophages incubated with FeLV of subgroup A or C. FeLV of both subgroups infected macrophages, but expression of FeLV-C was 21-fold higher than FeLV-A in peritoneal macrophages (P = .004). The supernatants of FeLV-C-inoculated macrophage cultures contained significantly higher levels of TNF-alpha (70 +/- 14 U/mL) at 72 hours postincubation compared with FeLV-A-inoculated (38 +/- 8 U/mL) and uninoculated (31 +/- 8 U/mL) cultures. Moreover, a positive correlation was shown between cell-associated FeLV surface glycoprotein gp70 and TNF-alpha expression in FeLV-C-infected macrophages by immunofluorescence (r = .6; P = .001), measured with a computer- assisted, laser-based digital imaging system. The addition of TNF-alpha to a uniform population of FeLV-infected cells (feline embryonic fibroblasts) caused an enhancement of viral expression (P < .05). These results indicate that FeLV-C has tropism for macrophages, FeLV expression is positively correlated with TNF-alpha expression in macrophages, and TNF-alpha enhances FeLV replication in fibroblasts. We suggest that FeLV-C infection of macrophages and secretion of TNF-alpha may be important in hematopoietic suppression in FeLV-C-infected cats.     

Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation

Factor XI (FXI) may be activated in a purified system by thrombin and by autoactivation in the presence of negatively charged substances such as dextran sulfate or sulfatides. The current studies were performed to determine if these processes occur during the coagulation of plasma. FXII--deficient plasma was supplemented with 125I-FXI and clot formation was induced with tissue factor and/or sulfatides. Cleavage of FXI was studied by standard polyacrylamide gel electrophoresis and autoradiography. Activated FXI (FXIa) was detected after 20 minutes of incubation with sulfatides alone and this process was markedly accelerated by the addition of tissue factor (TF). The enhancing effect of TF was blocked by hirudin, which indicated thrombin involvement in FXI activation. The contribution of FXIa to FIX activation in this system was studied using a 3H-FIX activation peptide release assay. Sulfatides increased FIX activation about twofold in plasma induced to clot with TF but had no effect if the plasma was immunodepleted of FXI. FIX activation was also increased in plasma induced to clot with FXa if sulfatides were present. The enhanced generation of FIXa was dependent on FXI and was blocked by hirudin. Some activation was seen in the reactions with sulfatides and hirudin and is likely solely caused by FXI autoactivation. The data indicate that during the coagulation of plasma in the presence of sulfatides, FXI is activated by a mechanism that is thrombin dependent and does not require FXII.