Role for macrophage migration inhibitory factor in acute respiratory distress syndrome

The critical role of macrophage migration inhibitory factor (MIF) in mediating inflammatory lung injury in acute respiratory distress syndrome (ARDS) has been raised recently. The present study has identified enhanced MIF protein expression in alveolar capillary endothelium and infiltrating macrophages in lung tissues from ARDS patients. The possibility that MIF up-regulates its synthesis in an autocrine fashion in ARDS was tested using cultured endothelial cells stimulated with MIF and a murine model of lipopolysaccharide (LPS)-induced acute lung injury. MIF induced significant MIF and tumour necrosis factor (TNF)-alpha synthesis in cultured endothelial cells and the effect was blocked by neutralizing anti-MIF antibody. A similar blocking effect was observed when MIF-stimulated endothelial cells were pretreated with neutralizing anti-TNF-alpha antibody or glucocorticoid, supporting the notion that MIF induced TNF-alpha production via an amplifying pro-inflammatory loop. Treatment with anti-MIF or glucocorticoid effectively attenuated pulmonary pathology and the synthesis of MIF or TNF-alpha in mice with LPS-induced acute lung injury. Mildly augmented expression of aquaporin 1 (AQP1) was also detected in alveolar capillary endothelium in ARDS. In vitro studies revealed that both MIF and TNF-alpha induced a small increase of AQP1 synthesis in cultured endothelial cells. These findings suggest that MIF plays a crucial pathological role leading to alveolar inflammation in ARDS. Anti-MIF and early glucocorticoid therapy may represent a novel therapeutic approach for reducing alveolar inflammation in ARDS.     

The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure.

The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.     

Identification of a new genotype H wild-type mumps virus strain and its molecular relatedness to other virulent and attenuated strains

A single clinical isolate of mumps virus designated 88-1961 was obtained from a patient hospitalized with a clinical history of upper respiratory tract infection, parotitis, severe headache, fever and lymphadenopathy. We have sequenced the full-length genome of 88-1961 and compared it against all available full-length sequences of mumps virus. Based upon its nucleotide sequence of the SH gene 88-1961 was identified as a genotype H mumps strain. The overall extent of nucleotide and amino acid differences between each individual gene and protein of 88-1961 and the full-length mumps samples showed that the missense to silent ratios were unevenly distributed. Upon evaluation of the consensus sequence of 88-1961, four positions were found to be clearly heterogeneous at the nucleotide level (NP 315C/T, NP 318C/T, F 271A/C, and HN 855C/T). Sequence analysis revealed that the amino acid sequences for the NP, M, and the L protein were the most conserved, whereas the SH protein exhibited the highest variability among the compared mumps genotypes A, B, and G. No identifying molecular patterns in the non-coding (intergenic) or coding regions of 88-1961 were found when we compared it against relatively virulent (Urabe AM9 B, Glouc1/UK96, 87-1004 and 87-1005) and non-virulent mumps strains (Jeryl Lynn and all Urabe Am9 A substrains).     

Cytopathologic analysis of paraspinal masses: a study of 59 cases with clinicoradiologic correlation

Paraspinal masses (PSM) are uncommon and present a wide spectrum of differential diagnoses on fine-needle aspiration (FNA). We analyzed 59 cases of PSM on FNA in a 15-yr period, in the context of clinicoradiologic correlation. Radiologic findings, clinical data, and tissue biopsies were reviewed. Patients were 14-83 yr of age (mean 54.7) with a M:F ratio of 1.36:1. Of the 59 cases, 39 (66%) were deemed diagnostic. Of these, 8 (21%) revealed nonneoplastic lesions and 31 (79%) yielded neoplasms: 2 (6%) benign and 29 (94%) malignant. Of the malignant cases, 22 (76%) were metastatic tumors from various sites, while 7 (24%) were cancers from local spread, which included non-Hodgkin's lymphoma (NHL, 5) and myeloma (2). Benign neoplasms were nerve sheath tumors. Metastatic tumors consisted of adenocarcinoma, 9; squamous-cell carcinoma, 3; renal-cell carcinoma, 1; and non-small-cell carcinoma/not otherwise specified (NOS), 9. Twenty-four (41%) cases received further studies: immunoperoxidase (IPOX) alone, 17 (71%); special stains for microorganisms, 2 (8%); IPOX/other special stains, 4 (17%); and flow cytometry analysis, 1 (4%). Eight (14%) cases received follow-up biopsies. Half of these biopsies added information to previously "nondiagnostic" FNAs. Of the previously "diagnostic" FNAs, tissue biopsy yielded no additional information. Cytopathologic diagnoses were consistent with the pre-FNA radiology analyses in 13 (39%) cases. In instances of radiologic and cytopathologic discrepancy (4 cases, 12%), diagnoses made by FNA reversed the initial radiologic impression of neoplasm to infection, and vice versa. PSMs are rare lesions (0.26% of total FNAs done in 15 yr at our institution). The most common lesion encountered is metastatic adenocarcinoma, followed by NHL. Ancillary studies are helpful in difficult cases. In cases of radiologic/cytopathologic discrepancy, FNA diagnoses are more accurate and decisive for patient management. The sensitivity and specificity of a PSM FNA are 88% and 75% respectively.     

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.     

非霍奇金淋巴瘤与p53蛋白表达的关系

目的 :探讨非霍奇金淋巴瘤 (NHL)与 p5 3蛋白表达的关系。 方法 :用免疫组化S P法检测 10 2例 (低度恶性 2 3例 ,中度恶性 36例 ,高度恶性 4 3例 )NHLp5 3蛋白表达 ,根据 p5 3蛋白阳性细胞百分率将其表达水平分为 4级 :0级 (阴性 ) ,1级 (1%～ 2 5 % ) ,2级 (2 6 %～ 5 0 % ) ,3级 (>5 0 % )。结果 :低度恶性组 2 0 / 2 3(87% )p5 3表达为 0级 ,中度恶性组 31/ 36 (86 1% )表达为 1级 ,高度恶性组 33/ 4 3(76 7% )表达为 2～ 3级。 2 5例随访 7～ 6 8个月 ,p5 30～ 1级NHL完全缓解率 (CRR ,11/ 14 )高于p5 32～ 3级NHLCRR (1/ 11,P <0 0 1) ,前者生存率 (13/ 14 )高于后者 (3/ 11,P <0 0 1)。NHLp5 3蛋白表达水平与其恶性度密切相关 (P <0 0 1)。结论 :p5 3蛋白表达阳性细胞百分率是判断NHL恶性度、疗效及预后较可靠的参数。肿瘤性p5 3蛋白表达检测对中高度恶性NHL的诊断有参考价值     

肺癌组织3号染色体短臂上抑癌基因异常改变的初步分析

目的 探讨3号染色体短臂上的抑制基因Fhit,hMLH1及VHL在肺癌发展中的可能作用。方法 选取上述基因内含子或附近的微卫星多态位点对45例肺癌组织进行杂合性缺失（LOH）分析,并对其中17例进行了Fhit蛋白的免疫组化染色。结果 Fhit基因内含子3个位点D3S1234、D3S1300及D3S4103的杂合率分别为77．8％（35／45）、73．3％（33／45）和82．2％（37／45）,LOH阳性率分别为62．9％（22／35）、63．6％（21／33）和59．5％（22／37）。与hMLH1基因连锁的两个位点D3S1561、D3S1612杂合率分别为48．9％（22／45）、42．2％（19／45）,LOH阳性率分别为54．5％（12／22）和63．2％（12／19）。与VHL基因连锁的两个位点D3S1038、D3S1283的杂合率分别为62．2％（28／45）和80．0％（36／45）,LOH阳性率分别为64．3％（18／28）和41．7％（15／36）。17例肺癌组织有64．7％（11／17）Fhit蛋白表达缺失。在Fhit蛋白缺失的11个病例中,有10例存在一个或多个Fhit基因位点的LOH。结论 上述3个抑癌基因存在的高频率LOH可为肺癌的早期诊断提供新的途径和依据。Fhit基因的杂合性缺失可能是Fhit蛋白表达下调的机理之一。     

CD44v3、CD44v6在非小细胞肺癌中的表达及其与淋巴结转移的关系

目的　研究CD44v3、CD44v6在肺癌中的表达及其与肺癌淋巴结转移的关系。方法　采用免疫组化、流式细胞术测定5 2例非小细胞肺癌 (NSCLC)和 1 2例正常肺组织的CD44v3、CD44v6的表达水平 ,并分析其与肺癌淋巴结转移之间的关系。结果　肺癌组织CD44v3、CD44v6水平明显高于正常肺组织 (P <0 .0 5 )。CD44v3、CD44v6在淋巴结转移组中的阳性表达率显著高于无淋巴结转移组 (P <0 .0 5 )。结论　CD44v3、CD44v6在非小细胞肺癌中有不同程度的表达 ,CD44v6与肺癌淋巴结转移的关系更密切 ,表达CD44v6的肺癌更易向周围淋巴结转移。检测CD44v6在肺癌中的表达 ,可能作为判断肺癌淋巴结转移潜能的一个辅助指标。     

血管紧张素转换酶基因多态性与2型糖尿病颈动脉硬化性病变的关系

目的 :探讨血管紧张素转换酶 (angiotensinconvertingenzyme ,ACE)基因多态性与 2型糖尿病合并颈动脉硬化性病变之间的关系。方法 :应用聚合酶链反应技术检测 176名 2型糖尿病患者ACE基因 16内含子插入 /缺失(insertion/deletion ,I/D)型多态性 ,利用B型超声检测糖尿病患者颈动脉硬化性病变的情况 ,通过Logistic多元回归分析 ,筛选 2型糖尿病患者颈动脉硬化性病变的危险因素。结果 :(1)糖尿病颈动脉硬化性病变组ACE基因DD型和D等位基因频率显著高于无颈动脉硬化性病变组 (DD基因型频率 :0 .5 0vs 0 .18;D等位基因频率 :0 .71vs0 .38;P <0 .0 1)。 (2 )Logistic回归分析显示 ,ACE基因DD型、年龄、合并高血压及男性是糖尿病颈动脉硬化性病变的危险因素 (OR分别为 3 .86 9,1.0 81,2 .44 7,2 .173,P <0 .0 5 )。 (3)在控制了年龄、性别、高血压后的危险性分层分析显示 ,ACE基因DD型是颈动脉硬化性病变的独立危险因素。结论 :ACE基因I/D多态性与 2型糖尿病颈动脉硬化性病变的发病相关 ,且其作用独立于年龄、性别及高血压病史