注射用Rtnf的全身过敏性和血管局部刺激性作用研究

目的:观察Rtnf是否具有血管刺激作用、全身过敏反应,评价其注射用药的安全性。方法:通过家兔耳缘静脉刺激实验、豚鼠全身主动过敏实验(ASA)观察注射用药Rtnf的安全性。结果:注射用Rtnf对家兔血管内皮无损伤和刺激作用,病理切片观察,耳廓皮肤的表皮和真皮各结构完好,未见变性、坏死、缺失,表皮下乳头层及网织层无炎细胞渗出、无出血,血管内无血栓形成,附件结构正常;豚鼠未出现过敏现象。结论:在本次实验条件下,注射用Rtnf溶血性试验符合注射用药安全性要求;无血管刺激作用;对豚鼠不致敏。     

细胞块技术在淋巴造血组织肿瘤诊断及鉴别诊断中的意义

传统细胞学涂片诊断方法有微创、简便、迅速的优点,但其对于淋巴造血组织肿瘤的诊断有一定的缺陷,不仅易误诊为其他恶性肿瘤,而且还难以进一步分型.在临床难以实施骨髓或淋巴结活检的情况下,应用细胞块技术及免疫组织化学检测能弥补这一不足,不仅可以明确肿瘤来源,还可进一步分型,细胞学诊断对于以浆膜腔积液及淋巴结肿大为首发症状的病例尤为重要.我们收集了由细胞学首先诊断为淋巴造血组织肿瘤的病例进行分析,探讨细胞块技术在淋巴造血组织肿瘤诊断及鉴别诊断中的意义.     

Co-infection with influenza A/H1N1 and A/H3N2 viruses in a patient with influenza-like illness during the winter/spring of 2008 in Shanghai, China

Co-infection with different influenza viruses occurs naturally and plays an important role in epidemiology and pathogenicity. To monitor the prevalence of influenza viruses in humans during seasonal influenza epidemics in Shanghai, China, and to analyze the genetic characteristics of the viruses, 365 nasopharyngeal swabs collected from patients with influenza-like illness between January and April 2008, were tested by a colloidal gold assay, viral isolation in Madin-Darby canine kidney (MDCK) cells, direct immunofluorescence assay and multiplex RT-PCR. The genetic characteristics of the viruses were analyzed by full-length PCR amplification of the HA segment. One case of co-infection with influenza A/H1N1 and A/H3N2 viruses was detected among the 7 cases of A/H1N1, 84 cases of A/H3N2 and 48 cases of influenza B virus during the winter/spring of 2008. All influenza A/H1N1 and A/H3N2 isolates were similar, including the co-infecting isolates. The present study demonstrates the possibility of natural co-infection with different types of influenza viruses in humans, which could provide the opportunity for the occurrence of viral genetic reassortment within the human respiratory tract.     

High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as an early endogenous alarmin of inflammation following injury and as a late mediator of lethality in sepsis. Although HMGB1 has been implicated in acute lung injury, rheumatoid arthritis, and allograft rejection, its role in T-cell mediated hepatitis remains obscure. Here, we investigated the role and the underlying mechanisms of HMGB1 in concanavalin A (Con A) induced hepatic injury. We demonstrate that high levels of HMGB1 were detected in the necrotic area and in the cytoplasm of hepatocytes after Con A treatment. Administration of exogenous recombinant HMGB1 enhanced Con A-induced hepatitis, while blockade of HMGB1 protected animals from T cell-mediated hepatitis as evidenced by decreased serum transaminase, associated with reduced hepatic necrosis and mortality. Blockade of HMGB1 by a neutralizing antibody inhibited proinflammatory cytokine production, NFκB activity, and the late stage of T/NKT cell activation. These finding thus suggest a pivotal factor of HMGB1 in Con A-induced hepatitis. Blockage of extracellular HMGB1 may represent a novel therapeutic strategy to prevent hepatic injury in T cell-mediated hepatitis.     

Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I_Na) during phase 0 of the cardiac action potential. The importance of I_Na for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which I_Na dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase I_Na delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce I_Na decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced I_Na dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies.     

Silencing the Metallothionein‐2A Gene Induces Entosis in Adherent MCF‐7 Breast Cancer Cells

The presence of a live cell cohabiting within another cell has fascinated scientists for many decades. Far from being a spurious event, many have attempted to uncover the molecular mechanism underlying this phenomenon. In this study, we observed anchorage‐dependent MCF‐7 cells internalizing neighboring epithelial cells (entosis) after siRNA‐mediated silencing of the Metallothionein‐2A (MT‐2A) gene. MTs belong to a family of low‐molecular weight proteins, which bind metal ions endogenously and its over‐expression has been reported in a variety of cancers that include breast, prostate, and colon. We provide microscopic evidence at light and ultrastructural levels of the occurrence of entosis after altering MT expression in a subpopulation of MCF‐7 breast cancer cells by silencing the MT‐2A gene. Our results demonstrate that adheren junctions may play important roles in the formation of cell‐in‐cell cytostructure after MT‐2A gene downregulation and the entotic process does not appear to involve genes associated with autophagy. Interiorized cells often underwent lysosomal degradation within the cytoplasmic body of the engulfing cell. It would appear that a subset of breast cancer cells could die via entosis after MT‐2A gene silencing. Anat Rec 293:1685–1691, 2010. © 2010 Wiley‐Liss, Inc.     

FAK is involved in invasion and metastasis of hepatocellular carcinoma

Studies have shown that focal adhesion kinase (FAK) is overexpressed in several human tumors and plays an important role in tumor progression. However, the role and underlying mechanisms of FAK in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we examined FAK and phosphorylated FAK Tyr397 expression in a large series of HCCs. We found that both FAK and phosphorylated FAK Tyr397 were overexpressed in HCC samples and HCC cell lines. Increased FAK and phosphorylated FAK Tyr397 expressions were correlated with tumor stage, vascular invasion and intrahepatic metastasis in HCC. Furthermore, HCC cell adhesion, migration and invasion were substantially impaired by siRNA-mediated knockdown of FAK expression, whereas cell growth, apoptosis and cell cycle distribution were not affected. In addition, depletion of FAK induced a significant reduction in expressions and activities of both MMP-2 and MMP-9. Taken together, FAK contributes to invasion and metastasis of HCC partly through regulating expressions and activations of both MMP-2 and MMP-9, suggesting FAK could be a promising therapeutic target for HCC.     

Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood

BACKGROUND: This marmoset study addresses concerns about feeding human male infants with soy formula milk (SFM). METHODS: From age 4 to 5 days, seven male co-twin sets were fed standard formula milk (SMA) or SFM for 5-6 weeks; blood samples were subsequently collected at 10-week intervals. Testes from co-twins killed at 120-138 weeks were fixed for cell counts. RESULTS: SFM- and SMA-fed twins showed normal weight gain; puberty started and progressed normally, based on blood testosterone measurements. Body weight, organ weights (prostate, seminal vesicles, pituitary, thymus and spleen) and penis length were comparable in co-twins. All SMA- and 6/7 SFM-fed males were fertile. Unexpectedly, testis weight (P = 0.041), Sertoli (P = 0.025) and Leydig cell (P = 0.026) numbers per testis were consistently increased in SFM-fed co-twins; the increase in Leydig cell numbers was most marked in males with consistently low-normal testosterone levels. Seminiferous epithelium volume per tubule showed a less consistent, non-significant increase in SFM-fed males; raised germ cell numbers per testis, probably due to increased Sertoli cells, conceivably resulted in larger testes. Average lumen size, although greater in SFM-fed group, was inconsistent between co-twins and the difference was not significant. CONCLUSIONS: Infant feeding with SFM has no gross adverse reproductive effects in male marmosets, though it alters testis size and cell composition, and there is consistent, if indirect, evidence for possible 'compensated Leydig cell failure'. Similar and perhaps larger changes likely occur in adult men who were fed SFM as infants.     

Decreased phosphatidylethanolamine binding protein expression correlates with Abeta accumulation in the Tg2576 mouse model of Alzheimer's disease

Phosphatidylethanolamine binding protein (PEBP) is a multifunctional protein, with proposed roles as the precursor protein of hippocampal cholinergic neurostimulating peptide (HCNP), and as the Raf kinase inhibitor protein (RKIP). Previous studies have demonstrated a decrease in PEBP mRNA in CA1 region of AD hippocampus. The current study demonstrates that PEBP is decreased in the hippocampus of 11 month Tg2576 mice, in the absence of change in mRNA levels compared to non-transgenic littermates. The level of PEBP in transgenic mouse hippocampus significantly decreases at 11 months (a time point when Abeta begins accumulating) and 15 months (when Abeta plaques have formed). There was a significant correlation between decreased PEBP expression and accumulation of Abeta. Immunohistochemical studies on Tg2576 and AD brain sections demonstrate that PEBP immunoreactivities are present at the periphery of dense multicore Abeta plaques, and in selective astrocytes, primarily surrounding plaques. These findings suggest that PEBP expression may be influenced by accumulation of Abeta. Down-regulation of PEBP may result in lower levels of HCNP or altered coordination of signal transduction pathways that may contribute to neuronal dysfunction and pathogenesis in AD.