Pegylated Interferon-α Plus Ribavirin Therapy Improves Left Ventricular Diastolic Dysfunction in Patients With Chronic Hepatitis C Attaining Sustained Virological Response

Background

Pegylated interferon (pegIFN) in combination with ribavirin (RBV) has successfully improved the rate of sustained virological response (SVR) in chronic hepatitis C virus (HCV) infected individuals, which reduces the progression of the chronic liver disease. However, the influence of combination therapy (pegIFN/RBV) on cardiac function has yielded ambiguous results. The present study aimed to evaluate the effects of combination therapy with pegIFN/RBV on cardiac function of HCV-infected individuals with SVR.

The clinical value of Fibulin-1 for prognosis and its prospective mechanism in intrahepatic cholangiocarcinoma

Background

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. Fibulin-1 has been demonstrated to be involved in various cancers, however, its role in ICC remains unclear.

Inhibition of CD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo.

The common acute lymphoblastic leukemia antigen [(CALLA) CD10, neutral endopeptidase 24.11 (NEP)] is a cell-surface zinc metalloprotease expressed by a subpopulation of early murine B-lymphoid progenitors and by bone marrow stromal cells that support the earliest stages of B lymphopoiesis. In previous in vitro studies in which uncommitted murine hematopoietic progenitors plated on a stromal cell layer differentiate into immature B cells, the inhibition of CD10/NEP increased early lymphoid colony numbers. To further characterize CD10/NEP function during lymphoid ontogeny in vivo, we utilized a Ly5 congenic mouse model in which the lymphoid differentiation of uncommitted hematopoietic progenitors from Ly5.1 donors was followed in sublethally irradiated Ly5.2 recipients treated with a specific long-acting CD10/NEP inhibitor (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta- alanine (SCH32615)). The expression of Ly5.1, B220, and surface IgM (sIgM) was utilized to characterize donor-derived hematopoietic cells (Ly5.1+), B lymphocytes (B220+), and mature B cells (B220+ sIgM+) from the lymphoid organs of recipient animals treated with SCH32615 or vehicle alone. SCH32615-treated animals had higher percentages of Ly5.1+ donor splenocytes than animals treated with vehicle alone (16.9% vs. 10.4%, 63% increase, P = 0.013). Animals treated with the CD10/NEP inhibitor also had relatively more Ly5.1+ splenic B (B220+) cells than vehicle-treated animals (14.4% vs. 8.2%, 75% increase, P = 0.018). To more specifically characterize the effects of CD10/NEP inhibition on B-cell differentiation, Ly5.1+ splenocytes from animals treated with SCH32615 or vehicle alone were analyzed for coexpression of B220 and sIgM. Animals treated with the CD10/NEP inhibitor had a significantly higher percentage of mature donor B cells (Ly5.1+ B220+ sIgM+, 10.2% vs. 5.2%, 90% increase, P = 0.006) and a more modest relative increase in immature donor B cells (Ly5.1+ B220+ sIgM-, 4.7% vs. 3.4%, 38% increase, P = not significant). Taken together, these results suggest that CD10/NEP inhibition promotes the reconstitution and maturation of splenic B cells. Therefore, CD10/NEP may function to regulate B-cell ontogeny in vivo by hydrolyzing a peptide substrate that stimulates B-cell proliferation and/or differentiation.     

Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation

The balance between pro- and anti-inflammatory cytokines modulates inflammation. Intracellular inhibitors of signaling, in turn, contribute to the negative regulation of cytokines. One of these inhibitors is suppressor of cytokine signaling-1 (SOCS-1). Socs1(-/-) mice die by 3 weeks of age with inflammation and fatty necrosis of the liver. Here, cre/loxP deletion of Socs1 was used to investigate the contribution of specific cells/tissues to inflammatory disease. Mice with SOCS-1 deficiency in myeloid and lymphoid cells, but not lymphoid alone, became ill at 50 to 250 days of age. These mice developed splenomegaly and T-cell/macrophage infiltration of many organs, including liver, lung, pancreas, and muscle. There were also abnormally high levels of the proinflammatory cytokines interferon gamma (IFN-gamma), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and activated T cells circulating in these mice. Socs1(null) T cells were found to be hypersensitive to multiple cytokines, including IL-1, IL-2, and IL-12, resulting in IFN-gamma production without requiring T-cell receptor (TCR) ligation. Additionally, Socs1(null) macrophages produced excessive amounts of IL-12 and TNF in response to other cytokines, including IFN-gamma. A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation.     

The seroprevalence of Helicobacter pylori in a referral population of children in the United States

OBJECTIVES: The purpose of this study was to determine the prevalence of serum antibodies directed against Helicobacter pylori (H. pylori) in children referred to children's hospitals or medical centers throughout the United States. METHODS: This multisite cross-sectional prospective study involved 992 children from 12 states using a validated anti-H. pylori IgG enzyme immunoassay. The children were recruited into two groups: those without any GI complaints (non-GI referral, n = 619) and those who were referred for endoscopy because of abdominal pain (GI referral, n = 373). RESULTS: GI referral children had a higher rate of seropositivity (22.5%) than non-GI referral children (14.1%) from the same geographic regions. In both groups, older children were more likely to be seropositive for H. pylori, as were nonwhite children and those with lower socioeconomic status. H. pylori seropositivity rates were higher in GI referral children with four or more household members (relative risk [RR] = 1.47; CI 1.01-2.14). Multivariate analysis controlling for age, ethnicity, and household income, showed that presence of GI symptoms were associated with a nearly 2-fold risk for H. pylori seropositivity (odds ratio = 1.77, CI 1.27-2.47). Epigastric pain (RR = 2.21; CI = 1.33-3.66) and having three or more episodes of abdominal pain in the last 3 months (RR = 0.59, CI = 0.35-0.99) were the only specific symptoms significantly associated with H. pylori seropositivity. CONCLUSIONS: The H. pylori seropositivity rate of GI referral children with symptoms of abdominal pain was significantly higher. H. pylori infection in early childhood was found to be associated primarily with the child's household size and socioeconomic status.     

补碘对缺碘大鼠甲状腺功能及形态的影响

目的研究不同剂量补碘对缺碘Wistar大鼠甲状腺的影响。方法于2003—03～2004—03取中国医科大学实验动物部4周龄Wistar大鼠经低碘饲料喂养3个月建立缺碘大鼠模型，对其进行8个月的1倍、3倍和6倍补碘，3个补碘量分别对应于前期流行病调查所见的3个农村社区的碘摄入水平。观察缺碘大鼠经不同剂量补碘后甲状腺功能、形态的变化。结果在补充1倍、3倍和6倍碘后，缺碘甲状腺质量分数未能恢复，仍然为甲状腺肿，甲状腺内碘潴留。电镜下缺碘引起的内质网扩张和线粒体肿大在补碘后未见恢复，且随补碘剂量的增加，超微结构损伤呈现加重的趋势。结论对缺碘动物单纯补碘可能难以纠正起初缺碘引起的甲状腺损伤，甲状腺可能处于亚临床病理状态。     

sFasL检测对结核性与恶性胸腔积液鉴别诊断价值的探讨

目的探讨sFasL对恶性胸腔积液与结核性胸腔积液鉴别诊断价值。方法应用ELISA法分别检测32例恶性胸腔积液和43例结核性胸腔积液中sFasL的含量，对结果进行统计学处理。结果结核性胸腔积液组sFasL（13．56±5．38ng／m1）显著高于恶性胸腔积液组（5．72±2．59ng／m1），二者具显著性差异（P〈0．001）。以10ng／ml为临界值，胸腔积液中sFasL〉10ng／ml诊断为结核性胸腔积液的敏感性为81．4％（35／43），特异性为81．3％（26／32），临床诊断符合率为81．4％（61／75）。结论sFasL对结核性、恶性胸腔积液的鉴别诊断有临床实用价值。     

Estrogen increases galanin immunoreactivity in hyperplastic prolactin-secreting cells in Fisher 344 rats.

Galanin is a widely distributed regulatory peptide which modulates the pituitary secretion of PRL and GH. Estrogen administration strongly stimulates galanin gene expression in the rat anterior pituitary. In adult female Fischer 344 rats, estrogen also induces hyperplasia of lactotropes. We used immunocytochemical analysis to assess the effects of estrogen on galanin-like immunoreactivity (Gal-IR) in the rat pituitary and hypothalamus during sc diethylstilbestrol (DES) implantation and after its removal at 30 days. In the anterior pituitary, DES implantation increased the portion of Gal-IR-containing cells from less than 2% in the control rats to 18.3% after 3 days of DES and 36% after 30 days. These changes paralleled the lactotrope hyperplasia exhibited in response to DES exposure. Ten and 30 days after removal of the DES capsules, the percentage of Gal-IR-containing cells in the anterior pituitary decreased to 6.3% and 1.5%, respectively. Colocalization studies revealed that Gal-IR-containing cells were predominantly lactotropes. Immunoelectron microscopy demonstrated that Gal-IR was concentrated in the Golgi region of these hyperplastic lactotropes and suggests that little of the synthesized galanin is secreted. The distribution of Gal-IR in the hypothalamus, median eminence, and neurohypophysis was unaffected by DES treatment. These data demonstrate that galanin is synthesized by hyperplastic pituitary lactotropes of Fischer 344 rats and that peptide accumulation is dependent on the presence of circulating estrogens. In contrast, neuronal galanin synthesis in the hypothalamus does not appear to be regulated by estrogen.