Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes

Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin- based cytoskeleton.     

Leukemia of non-T lineage natural killer cells

An unusual case of an aggressive leukemia of natural killer (NK) cells occurred in a 65-year-old male. Clinical characteristics of this case included hepatosplenomegaly, ascites, marrow infiltrate with leukemic cells, and a WBC up to 82.8 X 10(9) before therapy. One year before his presentation he had been noted to have a WBC of 12.1 X 10(9) with 78% lymphocytes, and 6 months before had noted intermittent fever and weight loss. He and his brother had well documented hereditary cold urticaria. The patient was treated with a modification of ProMACE CYTABOM regimen and had prompt regression of the leukemia with associated acute tumor lysis. Renal, hepatic, and marrow failure predominated during a terminal course that ended 22 days after therapy was commenced, and at autopsy there was no evidence for leukemic cell infiltrate in the liver, spleen or marrow. The leukemic cells were large granular lymphocytes by light and electron microscopic criteria, and had the following immunophenotype: CD2+, DR+, Leu7+, NKH1+, CD11+, CD3-, CD5-, CD4-, CD8-, CD16-. The cells displayed high antibody- dependent cell-mediated cytotoxicity (ADCC) and NK activity, and had a high rate of spontaneous proliferation in vitro that was not augmented by phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). Southern analysis of DNA from leukemic cells revealed normal germline arrangements for the beta and gamma chains of the T cell antigen receptor and immunoglobulin heavy chain genes. The majority of metaphases were clonally abnormal revealing consistent rearrangements involving extra material attached to the long arms of chromosomes 5 and 11.     

磁共振扩散张量成像评价肌萎缩侧索硬化症非锥体束的扩散特征

目的:应用磁共振扩散张量成像初步评价肌萎缩侧索硬化症非锥体束的扩散特征。方法:于2004-10/2006-10选择武汉大学人民医院神经科收治的肌萎缩侧索硬化症患者16例,为病例组。纳入标准:①符合ElEscorial诊断标准诊断和分型。②为散发性病例。③患者知情同意。排除标准:①糖尿病、原发性高血压、脑血管疾病病史。②服用神经系统活性药物史。③颅脑和颈髓MRI扫描显示有其他神经系统疾病。同期选择与病例组年龄和性别相匹配的健康体检者15例,为对照组。两组间性别、年龄比较差异无显著性意义(P>0.05)。所有受试者行轴位扩散张量成像扫描,选取左右侧非锥体束走行区各5个感兴趣区(中央后回皮质下白质、额叶白质、胼胝体压部、膝部、丘脑)测量各向异性分数和平均扩散系数。结果:所有受试者均完成实验,图像质量符合实验要求,未见明显变形。双侧感兴趣区的各向异性分数和平均扩散系数差异无显著性意义,故左右侧合并取均值分析。在中央后回皮质下白质、额叶白质、胼胝体压部、膝部、丘脑非锥体束走行区,肌萎缩侧索硬化症组和对照组均以胼胝体压部的各向异性程度最高(分别为0.825±0.021,0.833±0.023),两组间各向异性分数和平均扩散系数差异无显著性意义。结论:在病程早期,肌萎缩侧索硬化症患者非锥体束损害征象不明显,随访研究有可能阐明肌萎缩侧索硬化症患者运动系统以外部位是否受累和受累的程度。     

A comparative trial of granulocyte-colony-stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers

BACKGROUND: The clinical utility of polymorphonuclear neutrophil (PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. To define the optimal conditions for mobilization of PMNs in granulocyte donors, the effects of granulocyte-colony-stimulating factor (G-CSF) and dexamethasone, separately and in combination, on PMN counts in normal volunteers were compared. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens in 5 consecutive weeks: 1) G-CSF, 300 micrograms given subcutaneously; 2) G-CSF, 600 micrograms subcutaneously: 3) dexamethasone, 8 mg given orally; 4) G-CSF, 300 micrograms subcutaneously, plus dexamethasone, 8 mg orally; and 5) G-CSF, 600 micrograms subcutaneously, plus dexamethasone 8 mg orally. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for the determination of absolute neutrophil counts (ANCs). RESULTS: Maximal ANC was achieved at 12 hours after each regimen, except dexamethasone alone (maximum, 24 hours). Dexamethasone significantly increased the maximal ANC induced by either dose of G-CSF alone (p < 0.05). The greatest mobilization of PMNs occurred after the administration of G-CSF (600 micrograms) and dexamethasone (8 mg); the ANC increased from a mean baseline value of 3,594 per microL to 43,017 per microL at 12 hours. All of the drug regimens were well tolerated. CONCLUSION: Dexamethasone significantly increases the level of neutrophilia induced in normal subjects by G-CSF. The combination of dexamethasone and G-CSF (at the dosages used in this study) is a convenient, well-tolerated regimen for the mobilization of PMNs in the peripheral blood of granulocyte donors. Moreover, the optimal quantitative yield of PMNs is likely to be achieved by leukapheresis 12 hours after drug administration.     

隐神经-大隐静脉营养血管远端蒂复合瓣移植修复小腿、踝足部创伤

目的:在显微解剖学基础上,观察隐神经-大隐静脉营养血管远端蒂复合瓣移植修复小腿、踝足部创伤的临床效果。方法:选择2004-05/2007-04由解放军南京军区福州总医院骨科、解放军第97医院骨科、解放军第107医院骨科采用隐神经-大隐静脉营养血管远端蒂复合瓣移植修复小腿、踝足部组织缺损48例,患者对治疗均知情同意。其中皮瓣修复小腿、踝周及足部的创面感染、缺损23例;肌皮瓣修复小腿上段、下段的溃疡、骨髓炎和骨钢板外露12例,跟骨内侧骨髓炎5例;骨皮瓣修复伴有胫骨缺损和跟骨骨不连的创面8例。术后定期随访,观察隐神经-大隐静脉营养血管远端蒂皮瓣移植修复术后的存活情况及骨皮瓣的骨愈合、功能情况。结果:48例患者术后均有程度不同的皮瓣肿胀,其中3例皮瓣远侧边缘少量坏死,经换药愈合;皮瓣部分坏死植皮1例。伤口Ⅰ期愈合44例,Ⅱ期愈合4例。所有病例经5￣15个月随访,创面及骨不连修复,外形满意。结论:隐神经-大隐静脉营养血管远端蒂皮瓣、复合瓣用于外伤造成的小腿远端骨缺损、骨不连、大的死腔以及踝足部的缺损创面修复,具有快捷方便,抗感染力强,成活率高和愈合快的优点。     

Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone

BACKGROUND: The collection of adequate numbers of neutrophils (polymorphonuclear leukocytes, PMNs) from normal donors has long hampered the development of neutrophil transfusion therapy. The stimulation of donors with granulocyte-colony-stimulating factor (G- CSF) plus dexamethasone is a promising way of improving PMN collections. STUDY DESIGN AND METHODS: Sixteen normal subjects received G-CSF (600 micrograms subcutaneously) and dexamethasone (8 mg by mouth) 12 hours before leukapheresis. Measurements included PMN morphology, immunophenotype analysis, chemiluminescence, bactericidal activity, in vivo kinetics, and adverse effects. RESULTS: A mean of 77.4 +/− 6.4 × 10(9) PMNs was collected with each leukapheresis; 14 percent were bands. PMNs had increased surface expression of CD11b, CD18, CD14, CD32, and CD64. Bactericidal capacity against Staphylococcus aureus was normal. Inducible respiratory burst was maintained, although the responses to some agonists were diminished. Returned leukapheresis cells labeled with 3H-diisopropylfluorophosphate had a modestly decreased percentage of recovery and circulated with a prolonged half- life. Migration of these cells to skin chambers was approximately equal to that of the subjects' own blood PMNs. Adverse effects included transient bone pain, headache, hunger, and insomnia. CONCLUSIONS: Precollection treatment of leukapheresis donors with G-CSF plus dexamethasone is an effective way to enhance the collection of PMNs with normal or near-normal functional properties for PMN transfusion therapy.