Is Fast Food Making Us Fat?

This study looks at the contribution that consuming fast food may make to the rise in American obesity rates. One important goal of this study was to survey 500 U.S. adults in order to assess the frequency with which they consume fast food and dine in other restaurants. It also compares the BMI of survey participants with their reported frequency of eating fast food meals and snacks. An additional goal of the study was to assess the feasibility and effectiveness of gathering survey data via an online survey form. Study outcomes show that Americans report a notable amount of fast food consumption and that there is a correlation between BMI and the number of fast food meals consumed among survey participants. Results of this preliminary study may be used to assess the possibility of a more extensive project with a larger population. Findings may also be beneficial to individuals seeking to take steps toward a more healthful personal lifestyle and may provide useful data to health care professionals and community health organizations.

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE CS), it acts not as a proteinase, but as a receptor for a 1proteinase inhibitor (a 1PI, a 1antitrypsin, SerpinA1). Binding of a1PI to HLECS forms a motogenic complex. We previously demonstrated that a1PI deficiency attends HIV-1 disease and that a1PI augmentation produces increased numbers of immunocompetent circulating CD4 + lymphocytes. Herein we investigated the mechanism underlying the a 1PI deficiency that attends HIV-1 infection. Methods and Findings: Active a 1PI in HIV-1 subjects (median 17 mM, n = 35) was significantly below normal (median 36 mM, p,0.001, n = 30). In HIV-1 uninfected subjects, CD4 + lymphocytes were correlated with the combined factors a1PI, HLECS + lymphocytes, and CXCR4 + lymphocytes (r 2 = 0.91, p,0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with.220 CD4 cells/ml, CD4 + lymphocytes were correlated solely with active a 1PI (r 2 =0.93,p,0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human a 1PI. Chimpanzee a 1PI differs from human a1PI by a single amino acid within the 3F5-binding epitope. Unlike human a1PI, chimpanzee a1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-a 1PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 subjects

Binding of anti-gp120 to human, but not chimpanzee α₁PI.

<p>(<b>A</b>) Monoclonal antibody 3F5 (5 µg/ml) binding to α₁PI in sera from 18 HIV-1 uninfected humans and 20 HIV-1 uninfected chimpanzees was measured using ELISA. Antibody bound (A_{490 nm}) was normalized for the active α₁PI concentration in each specimen and is represented as A₄₉₀nm/[α₁PI (µM)]. Representative data from 6 measurements are depicted. Bars represent median values. Median 3F5 bound to human α₁PI was 0.12 and to chimpanzee α₁PI was 0.02. Negative control monoclonal antibody α70 (10 µg/ml) yielded A₄₉₀nm = 0.02 when incubated with α₁PI at concentrations varying between 3 µM and 540 µM. There was no difference in binding of α70 to human or chimpanzee sera (p>0.6). (<b>B</b>) IgG-α₁PI immune complexes (A_{490 nm}) were measured in sera from HIV-1 uninfected humans (n = 9), HIV-1 infected humans (n = 35), HIV-1 uninfected chimpanzees (n = 20), HIV-1 challenged chimpanzees (n = 2), rhesus monkeys pre-immunization and 2 time points post immunization (n = 12), and rhesus monkeys pre- and post-infection (n = 3). There was no significant difference in rhesus monkeys pre- and post-immunization, pre-and post-infection. Representative data of triplicate measurements are depicted. (<b>C</b>) Active α₁PI was measured in HIV-1 uninfected humans (26 µM, n = 20), HIV-1 infected humans (18 µM, n = 35), HIV-1 uninfected chimpanzees (35 µM, n = 20), HIV-1 challenged chimpanzees (39 µM, n = 2), rhesus monkeys pre-immunization and 2 time points post immunization (36 µM, n = 12), and rhesus monkeys pre- and post-infection (43 µM, n = 3). There was no significant difference in rhesus monkeys pre- and post-immunization, pre-and post-infection. Bars represent median values. (<b>D</b>) Inactive α₁PI was measured in HIV-1 uninfected (4 µM, n = 20) and HIV-1 infected humans (19 µM, n = 35). Bars represent median values. (<b>E</b>) Active α₁PI levels in sera from 5 HIV-1 infected subjects after incubation with either medium (control) or with monoclonal antibody 3F5.</p

Regression analysis of CD4⁺ and absolute lymphocyte numbers in HIV-1 uninfected subjects.

a<p>Values for independent and dependent variables represent mean ± standard deviation. HLE_CS⁺ lymphocytes and CXCR4⁺ lymphocytes in the lymphocyte gate (Ly) were quantitated using flow cytometry. Active α₁PI and CXCL12 were quantitated in serum as described.</p>b<p>Multilinear regression was performed to determine the relationship of the dependent variables to the independent variables using power of test α = 0.05. Dependent variables were considered to be significantly related to the independent variable if they contributed significantly to the multilinear regression (p<0.05). In this population sample, variables were found to have constant variance and normality.</p

HIV-1 patient serum antibodies that bind the 3F5-recognized gp120 epitope are the same antibodies that bind and inactivate α₁PI.

a<p>Sera were selected from HIV-1 infected subjects with undetectable HIV RNA (n = 13) or from HIV-1 uninfected subjects (n = 9). Of the 22 sera tested, only 5 exhibited increased α₁PI activity in the presence of SHIV, and these 5 were the only specimens that were also positive for IgG-α₁PI immune complexes (A₄₉₀nm>0.5). Immune complexes were undetectable in the other 17 sera and none of those sera exhibited a difference in α₁PI activity in the presence of SHIV (Mean difference = 0.7 µM±1 µM).</p

Correlation between α₁PI, IgG-α₁PI immune complexes, and CD4⁺ lymphocytes in HIV-1 infected subjects.

<p>(<b>A</b>) In subjects with >220 CD4 cells/µl, CD4⁺ lymphocyte levels correlate with active α₁PI (r² = 0.927, p<0.0001, n = 26). CD4⁺ lymphocyte levels also correlate with inactive α₁PI, (r² = 0.906, p<0.0001, n = 26). Subjects receiving protease inhibitor therapy are depicted by red squares. All other subjects are depicted by black circles. In the 9 subjects with <220 CD4 cells/µl, no correlation was found to exist between CD4⁺ lymphocyte levels and active α₁PI. Non-linear regression was performed using a 3 parameter Sigmoid curve with power of test α = 0.05. In this population, all variables were found to have normality and constant variation. (<b>B</b>) In 8 of 35 subjects, IgG-α₁PI immune complexes were detected and were correlated with CD4⁺ lymphocyte levels (r² = 0.822, p = 0.05) and with inactive α₁PI (r² = 0.988, p<0.0001).</p

Regression analysis of CD4⁺ and absolute lymphocyte numbers in HIV-1 infected subjects.

a<p>Values for independent and dependent variables represent mean ± standard deviation. HLE_CS⁺ lymphocytes and CXCR4⁺ lymphocytes in the lymphocyte gate (Ly) were quantitated using flow cytometry. Active α₁PI and CXCL12 were quantitated in serum as described.</p>b<p>Multilinear regression was performed to determine the relationship of the dependent variables to the independent variables using power of test α = 0.05. Dependent variables were considered to be significantly related to the independent variable if they contributed significantly to the multilinear regression (p<0.05). In this population sample, variables were found to have constant variance and normality.</p

Corresponding conformation at the 3F5-recognized epitope in α₁PI and CD4-complexed HIV-1 gp120.

<p>HIV-1 gp120 is depicted from two perspectives (<b>A,B</b>) with green representing two α-helices (aa 100–115 and 476–484). The gp120 peptide immunogen used to raise 1C1 and 3F5 (aa 471–490) is located at the C-terminus of gp120, and the linear segment ⁴⁸⁶YKVV⁴⁸⁹ is depicted in red along with Met95 and the oligosaccharide-linked segment ²³⁴NGT²³⁶, all of which are within 8 Å of the conformational epitope. The gp120-homologous domain in α₁PI is also located at the C-terminus of the protein, and is depicted from two perspectives (<b>C,D</b>) with violet representing the antiparallel β-sheet strand at the base of the cleft (aa 369–389), and green representing the α-helices that form the mouth of the cleft (aa 27–44 and 259–277). Met-385, which distinguishes human from chimpanzee α₁PI, is depicted in red along with the segment ³⁸⁶GKVV³⁸⁹, the oligosaccharide, and oligosaccharide-linked segment ⁴⁶NST⁴⁸. The HLE_G-reactive site Met-358, is depicted in yellow for orientation. Structures for human α₁PI (1HP7) and CD4-complexed HIV-1 gp120 (1RZJ) from the NCBI Molecular Modeling Database (MMDB) were analyzed using Cn3D software. Small carbohydrate structures, depicted in multiple colors, were associated with 1RZJ in MMDB, and the three associated with 1HP7 were added using Adobe Photoshop.</p