The metallothioneins induced in HeLa cells by dexamethasone and Zn2+ were labeled with [3H]cysteine and [35S]cysteine respectively. These labeled metallothioneins were compared to one another and to metallothioneins from human liver by (a) gel permeation chromatography on Sephadex G-75 columsn, (b) ion-exchange chromatograhy on DEAE-Sephadex A-25 columns, (c) electrophoresis on non-denaturing polyacrylamide gels, and (d) electrophoresis of reduced and alkylated proteins on dodecylsulfate/polyacrylamide gels. The dexamethasone-induced metallothioneins of HeLa cells, the Zn2+-induced metallothioneins of HeLa cells, and the metallothioneins of human liver were indistinguishable by these four criteria.
Nader, Philip R. MD; Sallis, James F. PhD; Abramson, Ian S. PhD; Broyles, Shelia L. PhD; Patterson, Thomas L. PhD; Senn, Karen EdD; Rupp, Joan W. MS, RD; Nelson, Julie A. BS Author Information
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer provides the prototypical example of an obesity-related cancer. The obesity epidemic gave rise to an enormous increase in the incidence of non-alcoholic fatty liver disease (NAFLD), a condition that affects one third of American adults. In about 20% of these individuals, simple liver steatosis (hepatosteatosis) progresses to non-alcoholic steatohepatitis (NASH) characterized by chronic liver injury, inflammation, and fibrosis. In addition to liver failure, NASH greatly increases the risk of HCC. Here we discuss the metabolic processes that control the progression from NAFLD to NASH and from NASH to HCC, with a special emphasis on the role of free-non-esterified cholesterol in the process.
McKenzie, T. L.; Sallis, J. F. FACSM; Alcaraz, J.; Roby, J.; Kolody, B. Author Information
This study evaluated a new tool, “The Audit of Physical Activity Resources for Seniors” (APARS), which assesses the physical activity environment in Senior Living Residences (SLRs). Audits were conducted in 29 SLRs and inter-rater reliability was assessed. Pearson correlations were examined between APARS items and objectively measured physical activity and sedentary time, and self-rated health, collected from residents at a subset of 12 SLRs (N=147). Eighty-nine of the 90 items (98.9%) demonstrated Kappa or ICC values above .70 and/or percent agreement above 80%. The 90 items were summarized into nine scales. Two scales (outside supportive physical activity features/functionality and outside exercise facilities) were related to greater physical activity and less sedentary time. Four scales (inside social facilities, onsite services, exercise programs, and social activities) were related to greater sedentary time and better self-rated health. APARS items demonstrated adequate inter-rater reliability and some evidence for construct validity to assess health-related environments in retirement facilities. Social activities in SLRs could benefit residents by incorporating more physical activity. Use of APARS could inform more health-promoting designs of senior living facilities.
Metallothioneins are induced by both Zn2+ and dexamethasone in HeLa cells grown in serum-free medium. Dexamethasone is able to induce metallothionein synthesis in HeLa cells in virtually zinc-free medium ([Zn2+] = .01 microM). The presence of dexamethasone does not shift the dose/response curve for metallothionein induction by Zn2+, further indicating that the two inducers work through independent mechanisms. Dexamethasone stimulates Zn2+ uptake 1.7-fold over 24 h. However, there is no increase in Zn2+ uptake during the first 4 h. In contrast, metallothionein synthesis in response to either Zn2+ or dexamethasone is clearly observable within 4 h of exposure to either inducer. The increased intracellular 65Zn2+ content observed at 24 h is completely accounted for by the increased level of metal bound to metallothionein. In a continuous labeling experiment the rate of synthesis of metallothionein reached a steady state after about 4 h, in response to either inducer. The lag period was identical for both dexamethasone and Zn2+, with similarly shaped induction curves. Induction by dexamethasone, but not by Zn2+, was inhibited by progesterone. Zn2+ and dexamethasone appear to induce metallothionein synthesis in HeLa cells by mechanisms independent of one another.
Two inflammatory cytokines, IL-23 and IL-17A, produced by myeloid cells and different lymphocyte subsets, were found to play important pathogenic functions in several inflammation-related cancers. In colorectal cancer, elevated expression of IL-23, IL-23 receptor and IL-17A has been linked to adverse prognostic outcome and rapid progression to metastatic disease. In mouse models of colorectal tumourigenesis genetic or pharmacological inhibition of these cytokines attenuates tumour development and malignant progression. Collectively, such findings suggest that IL-23 and/or IL-17A inhibitors should be evaluated for their therapeutic and preventative potential in human cancers, especially in colorectal cancer.
Physically inactive lifestyles are a major public health challenge, and research in the transportation field on influences on the choice to walk and bike may provide guidance toward solutions. In the interests of promoting effective collaboration among the transportation, planning, and health fields, the current paper was written to fulfill three purposes. The first purpose was to summarize the transportation and planning studies on the relation between community design and non-motorized (“active”) transport and to interpret these studies from a health perspective. The second purpose was to summarize studies from the health literature that examine the relation between physical environmental variables and leisure-time physical activity that have relevance for transportation research. The third purpose was to promote more collaboration among transportation, planning, and health investigators by identifying opportunities for transdisciplinary research.
<div>Abstract<p>T cells can inhibit tumor growth, but their function in the tumor microenvironment is often suppressed. Many solid tumors exhibit abundant macrophage infiltration and low oxygen tension, yet how hypoxic conditions may affect innate immune cells and their role in tumor progression is poorly understood. Targeted deletion of the hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages in a progressive murine model of breast cancer resulted in reduced tumor growth, although vascular endothelial growth factor-A levels and vascularization were unchanged. Tumor-associated macrophages can suppress tumor-infiltrating T cells by several mechanisms, and we found that hypoxia powerfully augmented macrophage-mediated T-cell suppression <i>in vitro</i> in a manner dependent on macrophage expression of HIF-1α. Our findings link the innate immune hypoxic response to tumor progression through induction of T-cell suppression in the tumor microenvironment. Cancer Res; 70(19); 7465–75. ©2010 AACR.</p></div>
