Increased levels of interleukin-18 in patients with pulmonary sarcoidosis

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.     

Associations between cytokines,endocrine stress response,and gastrointestinal symptoms in autism spectrum disorder

Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.     

嗜麦芽窄食单胞菌噬菌体SM1生物学特征及其在感染动物模型中的疗效

目的：通过分离嗜麦芽窄食单胞菌(Sm)噬菌体,研究噬菌体SM1的生物学特征及其在感染动物模型中的疗效,为噬菌体治疗Sm感染提供实验依据。方法：利用噬菌斑法从医院污水中分离噬菌体SM1,电镜观察其形态特征,并提取基因组行酶切电泳;测定噬菌体SM1最佳感染复数、耐受突变率、一步生长曲线及其在感染动物模型中的作用。结果：筛选出1株具有较宽裂解谱的双链DNA肌尾噬菌体SM1,基因组大小约50 kb;其感染宿主菌的潜伏期为15 min,爆发期为50 min,裂解量为187,耐受突变率为6×10^-10;噬菌体SM1治疗组小鼠7 d后全部存活。结论：噬菌体SM1具有裂解谱较宽、潜伏期短、裂解量大及耐受突变率低的特点,而且可有效治疗Sm感染的小鼠。     

Hyperphosphorylation of retinoblastoma protein and stimulation of growth by okadaic acid in human pancreatic cancer

Phosphorylation/dephosphorylation of intracellular proteins are important steps in the regulation of cell growth. Okadaic acid, an inhibitor of the serine/threonine protein phosphatases 1 and 2A, is a potent tumor promoter. This effect may be through the inhibition of dephosphorylation (termed hyperphosphorylation) and subsequent inactivation of tumor-suppressor proteins. We examined whether okadaic acid regulates growth of human pancreatic cancer cells (MIA PaCa-2 and Panc-1) or alters the phosphorylation of the retinoblastoma tumor-suppressor protein. Growth studies, nuclear labeling analyses, and Western blotting for retinoblastoma protein were performed. Okadaic acid stimulated cell growth and induced hyperphosphorylation of the retinoblastoma protein. The growth-stimulatory effect of okadaic acid on these human pancreatic cancer cells may be mediated by inactivation of the growth suppressive effect of the retinoblastoma protein by hyperphosphorylation. These studies suggest that the growth of these human pancreatic cancer cells is still regulated by tumor-suppressor proteins.This work was supported by grants from the National Institutes of Health (5P01 DK35608, 2R01 DK15241, T32 DK07639), the American Cancer Society (CB-571), and the John Sealy Memorial Endowment Fund.     

New Research on Kidney Cancer: Highlights from Urologic and Oncologic Congresses in 2006

ObjectivesThis paper communicates the major new findings on renal cell cancer (RCC) that were presented at the 2006 annual meetings of the European Association of Urology (EAU), American Urological Association (AUA), and American Society of Clinical Oncology (ASCO), and discussed during a closed meeting in September 2006.MethodsThe most relevant new findings were selected by urologic experts in the field of RCC.ResultsOne basic research study suggested that there might be pathways other than the von Hippel-Lindau/hypoxia-inducible factor-α pathway involved in RCC tumour angiogenesis. Partial nephrectomy is still relatively uncommon compared with radical nephrectomy, even in small tumours. Overall and cancer-specific 5-yr survival for laparascopic cryoablation was high, suggesting that it might be suitable for small renal masses. Radiofrequency ablation appears feasible and safe in healthy American Society of Anesthesiologists I and II patients. There were major contributions on angiogenesis inhibitors for metastatic RCC. Sorafenib significantly prolonged progression-free survival (PFS) compared with placebo in patients who failed prior systemic therapy. Sunitinib significantly prolonged PFS compared with interferon (IFN)-α as first-line treatment of low- and intermediate-risk patients. Temsirolimus significantly increased overall survival compared with IFN-α as first-line treatment in poor-risk patients.ConclusionsRelevant new data on partial nephrectomy, cryoablation, and radiofrequency ablation are discussed in this paper. New standards are emerging for the treatment of metastatic RCC, which is now based on antiangiogenic drugs.