Body Mass Index, Neighborhood Fast Food and Restaurant Concentration, and Car Ownership

Eating away from home and particularly fast food consumption have been shown to contribute to weight gain. Increased geographic access to fast food outlets and other restaurants may contribute to higher levels of obesity, especially in individuals who rely largely on the local environment for their food purchases. We examined whether fast food and restaurant concentrations are associated with body mass index and whether car ownership might moderate this association. We linked the 2000 US Census data and information on locations of fast food and other restaurants with the Los Angeles Family and Neighborhood Study database, which consists of 2,156 adults sampled from 63 neighborhoods in Los Angeles County. Multilevel modeling was used to estimate associations between body mass index (BMI), fast food and restaurant concentration, and car ownership after adjustment for individual-level factors and socioeconomic characteristics of residential neighborhoods. A high concentration of local restaurants is associated with BMI. Car owners have higher BMIs than non-car owners; however, individuals who do not own cars and reside in areas with a high concentration of fast food outlets have higher BMIs than non-car owners who live in areas with no fast food outlets, approximately 12 lb more (p = 0.02) for an individual with a height of 5 ft. 5 in. Higher restaurant density is associated with higher BMI among local residents. The local fast food environment has a stronger association with BMI for local residents who do not have access to cars

Seismic performance of group pile foundation with ground improvement during liquefaction

A pile foundation with ground improvement under the footing is a composite foundation with the objectives of enhancing the seismic performance and rationalizing the substructure by combining the pile foundation with ground improvement. Although the effectiveness of this method has been confirmed in previous studies for application to soft grounds, the applicability of this method to liquefiable grounds has yet to be fully investigated. In this study, therefore, centrifuge model tests and finite element analyses were conducted to clarify the effectiveness of this method and to ascertain the improvement in strength (stiffness) when the method is applied to a liquefiable ground. Firstly, in order to investigate the effect of an improved ground on the behavior of the pile foundation during liquefaction, dynamic centrifuge model tests were conducted for three cases with different strengths of the improved ground. Then, three-dimensional soil–water coupled finite element analyses of the centrifuge model experiments were performed to validate the applicability of the analytical method. After that, parametric studies, in which the strength of the improved ground and the input ground motion were changed, were conducted using the same analytical model. The results confirmed that the horizontal displacement of the pile heads was reduced by the improved ground even in the liquefiable ground, and that the effect of this reduction was more remarkable in cases of high stiffness of the improved ground. Furthermore, it was possible to reduce the bending moments at the pile heads by applying the ground improvement. However, since the bending moment at the boundary between the improved ground and the natural ground became the local maximum, there was an optimum stiffness of the ground improvement at which the maximum bending moment of the piles was reduced. This is because improving the ground around the pile heads has the same effect as extending the footing. It was thus concluded that the behavior of the pile foundation is similar to that of a composite foundation comprised of a caisson and group piles

Efficacy of a combination therapy targeting CDK4/6 and autophagy in a mouse xenograft model of t(8;21) acute myeloid leukemia

One of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML) is t(8;21). Although patients with t(8;21) AML have a more favorable prognosis than other cytogenetic subgroups, relapse is still common and novel therapeutic approaches are needed. A recent study showed that t(8;21) AML is characterized by CCND2 deregulation and that co-inhibition of CDK4/6 and autophagy induces apoptosis in t(8;21) AML cells. In this study, we examined the in vivo effects of co-inhibiting CDK4/6 and autophagy. We used a mouse model in which t(8;21)-positive Kasumi-1 cells were subcutaneously inoculated into NOD/Shi-scid IL2Rgnull mice. The mice were treated with the autophagy inhibitor chloroquine (CQ), a CDK4/6 inhibitor (either abemaciclib or palbociclib), or a CDK4/6 inhibitor plus CQ. After 20 days of treatment, tumor volume was measured, and immunostaining and transmission electron microscopy observations were performed. There was no change in tumor growth in CQ-treated mice. However, mice treated with a CDK4/6 inhibitor plus CQ had significantly less tumor growth than mice treated with a CDK4/6 inhibitor alone. CDK4/6 inhibitor treatment increased the formation of autophagosomes. The number of single-strand DNA-positive (apoptotic) cells was significantly higher in the tumors of mice treated with a CDK4/6 inhibitor plus CQ than in mice treated with either CQ or a CDK4/6 inhibitor. These results show that CDK4/6 inhibition induces autophagy, and that co-inhibition of CDK4/6 and autophagy induces apoptosis in t(8;21) AML cells in vivo. The results suggest that inhibiting CDK4/6 and autophagy could be a novel and promising therapeutic strategy in t(8;21) AML

Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat

Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial natriuretic factor was investigated in male Sprague-Dawley rats. Plasma concentrations (mean ± S.E.M.) of C-terminal atrial natriuretic factor were 55.0 ± 6.1 fmol/ml, 31.2 ± 4.0 fmol/ml and 23.5 ± 3.3 fmol/ml (n = 12) in the abdominal aorta, the portal vein and the hepatic vein, respectively. N-terminal atrial natriuretic factor plasma levels in these vessels were 3031 ± 756 fmol/ml, 2264 ± 661 fmol/ml and 1618 ± 496 fmol/ml (n = 6), respectively. Although the mesenteric extraction ratio was higher (p < 0.05) for C-terminal atrial natriuretic factor (42% ± 6%) than for N-terminal atrial natriuretic factor (28% ± 4%), there were no significant differences in the hepatic extraction ratio (41% ± 5% vs. 39% ± 6%) and the splanchnic extraction ratio (56% ± 5% vs. 50% ± 7%). These data suggest a major role of the liver in the splanchnic extraction of C-terminal and of N-terminal atrial natriuretic factor in the rat. (HEPATOLOGY 1992;16:790-793

Increased AT 1 receptor expression and mRNA in kidney glomeruli of AT 2 receptor gene-disrupted mice

The proposed feedback between angiotensin II AT2 and AT1 receptors prompted us to study AT1 receptor expression in kidneys of male AT2 receptor-gene disrupted mice (agtr2 −/y). In wild-type (agtr2 +/y) mice, AT1 receptor binding and mRNA is abundant in glomeruli, and AT1 receptor binding is also high in the inner stripe of the outer medulla. AT2 receptors are scarce, primarily associated to cortical vascular structures. In agtr2 −/y mice, AT1 receptor binding and mRNA were increased in the kidney glomeruli, and AT1 receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT2 receptor expression is very low in male agtr 2 +/y mice, their gene disruption alters AT1 receptor expression. AT1 upregulation alone may explain the AT2 gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT1/AT2 receptor feedback could have clinical significance because AT1antagonists are widely used in medical practice.Fil: Saavedra, Juan M.. National Institute of Mental Health; Estados UnidosFil: Häuser, Walter. National Institute of Mental Health; Estados UnidosFil: Ciuffo, Gladys Maria. National Institute of Mental Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Egidy, Giorgia. National Institute of Mental Health; Estados UnidosFil: Hoe, Kwang Lae. National Institute of Mental Health; Estados UnidosFil: Jöhren, Olaf. National Institute of Mental Health; Estados UnidosFil: Sembonmatsu, Takaaki. Vanderbilt University; Estados UnidosFil: Inagami, Tadashi. Vanderbilt University; Estados UnidosFil: Armando, Inés. National Institute of Mental Health; Estados Unido

Promyelocytic Leukemia Zinc Finger Protein Activates GATA4 Transcription and Mediates Cardiac Hypertrophic Signaling from Angiotensin II Receptor 2

Background: Pressure overload and prolonged angiotensin II (Ang II) infusion elicit cardiac hypertrophy in Ang II receptor 1 (AT1) null mouse, whereas Ang II receptor 2 (AT2) gene deletion abolishes the hypertrophic response. The roles and signals of the cardiac AT2 receptor still remain unsettled. Promyelocytic leukemia zinc finger protein (PLZF) was shown to bind to the AT2 receptor and transmit the hypertrophic signal. Using PLZF knockout mice we directed our studies on the function of PLZF concerning the cardiac specific transcription factor GATA4, and GATA4 targets. Methodology and Principal Findings: PLZF knockout and age-matched wild-type (WT) mice were treated with Ang II, infused at a rate of 4.2 ng?kg 21?min 21 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in PLZF knockout and WT mice (140 mmHg). WT mice developed prominent cardiac hypertrophy and fibrosis after Ang II infusion. In contrast, there was no obvious cardiac hypertrophy or fibrosis in PLZF knockout mice. An AT 2 receptor blocker given to Ang II-infused wild type mice prevented hypertrophy, verifying the role of AT2 receptor for cardiac hypertrophy. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that PLZF bound to the GATA4 gene regulatory region. A Luciferase assay verified that PLZF up-regulated GATA4 gene expression and the absence of PLZF expression in vivo produced a corresponding repression of GATA4 protein. Conclusions: PLZF is an important AT2 receptor binding protein in mediating Ang II induced cardiac hypertrophy throug

Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells

Introduction: The nuclear factor-κB (NF-κB) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-κB pathway linked to renal inflammation. Although both AT1 and AT2 receptors are involved in Ang II-mediated NF-κB activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1β (IL-1β) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-κB. Materials and methods: In vitro studies were done in primary cultured rat mesangial cells. NF-κB pathway was evaluated by phosphorylated levels of p65/IκB and DNA binding activity. The Ang II receptor subtype was determined by pretreatment with AT1 and AT2 antagonists. Results: In mesangial cells the simultaneous presence of Ang II and IL-1β caused a synergistic activation of the NF-κB pathway and a marked upregulation of proinflammatory factors under NF-κB control, including monocyte chemoattractant protein-1. The AT1, but not AT2, antagonist abolished the synergistic effect on NF-κB activation and proinflammatory genes caused by coincubation of Ang II and IL-1β. Conclusions: These data indicates that Ang II, via AT1/NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cellsThis work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDinREN RD06/0016, RD12/0021, PI11/01854), Comunidad de Madrid (Fibroteam S2010/BMD- 2321, S2010/BMD-2378), and Research Institute Queen Sophia (IRSIN). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO. MA and ESL are supported by a ‘Sara Borrell’ postdoctoral contract from Instituto de Salud Carlos III (CD10/00347 and CD09/00066, respectively