DXA‐derived Abdominal Fat Mass,Waist Circumference,and Blood Lipids in Postmenopausal Women

The purpose of this study was to determine the utility of dual‐energy X‐ray absorptiometry (DXA)‐derived fat mass indices for predicting blood lipid profile in postmenopausal women. A secondary purpose was to determine whether waist circumference is comparable with DXA‐derived measurements in predicting blood lipid profile. Subjects were 423 postmenopausal women (age 58.1 ± 6.3 years). Fat mass was assessed at abdomen, trunk, and total body using DXA. Anthropometric measurements included BMI and waist circumference. Blood samples were analyzed for total cholesterol (TC), triglyceride (TAG), high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and cholesterol/HDL ratio. Of the DXA‐derived measures, abdominal‐fat mass was the best predictor of blood lipid profiles. DXA‐derived abdominal fat mass and waist girth explained 20 and 16.5% of variation in TC/HDL ratio, respectively, in univariate analysis, with no difference between the slopes of the regression coefficients. Eighty‐four percent of subjects were common to the top quartiles of waist circumference and abdominal fat mass, and blood lipid profiles generally worsened across increasing quartiles. DXA‐derived abdominal fat mass and waist circumference are of equivalent utility for predicting alterations in blood lipids. Waist circumference is, therefore, ideal as an inexpensive means in primary health‐care services for predicting risk of cardiovascular diseases in postmenopausal women.     

Impact of Cigarette Smoke Exposure on Innate Immunity: A Caenorhabditis elegans Model

Background

Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and lung cancer. Respiratory bacterial infections have been shown to be involved in the development of COPD along with impaired airway innate immunity.

Methodology/Principal Findings

To address the in vivo impact of cigarette smoke (CS) exclusively on host innate defense mechanisms, we took advantage of Caenorhabditis elegans (C. elegans), which has an innate immune system but lacks adaptive immune function. Pseudomonas aeruginosa (PA) clearance from intestines of C. elegans was dampened by CS. Microarray analysis identified 6 candidate genes with a 2-fold or greater reduction after CS exposure, that have a human orthologue, and that may participate in innate immunity. To confirm a role of CS-down-regulated genes in the innate immune response to PA, RNA interference (RNAi) by feeding was carried out in C. elegans to inhibit the gene of interest, followed by PA infection to determine if the gene affected innate immunity. Inhibition of lbp-7, which encodes a lipid binding protein, resulted in increased levels of intestinal PA. Primary human bronchial epithelial cells were shown to express mRNA of human Fatty Acid Binding Protein 5 (FABP-5), the human orthologue of lpb-7. Interestingly, FABP-5 mRNA levels from human smokers with COPD were significantly lower (p = 0.036) than those from smokers without COPD. Furthermore, FABP-5 mRNA levels were up-regulated (7-fold) after bacterial (i.e., Mycoplasma pneumoniae) infection in primary human bronchial epithelial cell culture (air-liquid interface culture).

Conclusions

Our results suggest that the C. elegans model offers a novel in vivo approach to specifically study innate immune deficiencies resulting from exposure to cigarette smoke, and that results from the nematode may provide insight into human airway epithelial cell biology and cigarette smoke exposure.     

Major groove width variations in RNA structures determined by NMR and impact of <Superscript>13</Superscript>C residual chemical shift anisotropy and <Superscript>1</Superscript>H–<Superscript>13</Superscript>C residual dipolar coupling on refinement

Ribonucleic acid structure determination by NMR spectroscopy relies primarily on local structural restraints provided by ¹H– ¹H NOEs and J-couplings. When employed loosely, these restraints are broadly compatible with A- and B-like helical geometries and give rise to calculated structures that are highly sensitive to the force fields employed during refinement. A survey of recently reported NMR structures reveals significant variations in helical parameters, particularly the major groove width. Although helical parameters observed in high-resolution X-ray crystal structures of isolated A-form RNA helices are sensitive to crystal packing effects, variations among the published X-ray structures are significantly smaller than those observed in NMR structures. Here we show that restraints derived from aromatic ¹H– ¹³C residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) can overcome NMR restraint and force field deficiencies and afford structures with helical properties similar to those observed in high-resolution X-ray structures.     

Semiautomated enzymic micro methods for blood glucose and lactic acid on a single filtrate

Methods have been modified and adapted to permit enzymic automated micro analysis of glucose on 0.021 ml of blood, and of lactic acid on 0.0115 ml of blood. By means of a single 1:20 Somogyi filtrate with a final volume of 1–1.4 ml prepared from 0.1–0.15 ml blood, both determinations can be accomplished individually on the autoanalyzer.The range of concentrations of each method has been extended so that glucose may be determined between 5 and $\text{200 mg}\text{100 ml}$ (or higher depending on dilution) and lactic acid between 5 and $\text{125 mg}\text{100 ml}$.The methods are sensitive, reproducible, and stable. The recoveries and the comparison studies with manual methods are well within the limits of clinical investigation procdures.     

Five Hundred Sixty-Five Triples of Chicken,Human, and Mouse Candidate Orthologs

The Human Genome Project has provided abundant gene sequence information on human and important model organisms. The chicken is well positioned from an evolutionary standpoint to serve as a link between higher and lower organisms, particularly mammals, and amphibia and fish. In this study we used stringent criteria to select 565 triples of chicken, human, and mouse candidate orthologs. We analyze the sequences with respect to nucleotide and amino acid similarities. This analysis also allows measurement of evolutionary distances of different proteins. We found that chicken-human and chicken-mouse sequence identities are highly correlated; similarly for chicken-human and chicken-mouse evolutionary distances. With chicken as the out-group, we found that mouse has a higher substitution rate than human, supporting the generation-time effect hypothesis. We also described the transversion bias, which is the preference for some transversions than others in nucleotide substitutions. We demonstrated that there are statistically significant properties in the differences of orthologous sequences. The differential patterns, in combination with sequence similarity analysis, may lead to the identification of genes that are very divergent from the mammalian orthologs.     

Protection against recurrent ocular herpes simplex virus type 1 disease after therapeutic vaccination of latently infected mice

The potential of therapeutic vaccination of animals latently infected with herpes simplex virus type 1 (HSV-1) to enhance protective immunity to the virus and thereby reduce the incidence and severity of recurrent ocular disease was assessed in a mouse model. Mice latently infected with HSV-1 were vaccinated intranasally with a mixture of HSV-1 glycoproteins and recombinant Escherichia coli heat-labile enterotoxin B subunit (rEtxB) as an adjuvant. The systemic immune response induced was characterized by high levels of virus-specific immunoglobulin G1 (IgG1) in serum and very low levels of IgG2a. Mucosal immunity was demonstrated by high levels of IgA in eye and vaginal secretions. Proliferating T cells from lymph nodes of vaccinated animals produced higher levels of interleukin-10 (IL-10) than were produced by such cells from mock-vaccinated animals. This profile suggests that vaccination of latently infected mice modulates the Th1-dominated proinflammatory response usually induced upon infection. After reactivation of latent virus by UV irradiation, vaccinated mice showed reduced viral shedding in tears as well as a reduction in the incidence of recurrent herpetic corneal epithelial disease and stromal disease compared with mock-vaccinated mice. Moreover, vaccinated mice developing recurrent ocular disease showed less severe signs and a quicker recovery rate. Spread of virus to other areas close to the eye, such as the eyelid, was also significantly reduced. Encephalitis occurred in a small percentage (11%) of mock-vaccinated mice, but vaccinated animals were completely protected from such disease. The possible immune mechanisms involved in protection against recurrent ocular herpetic disease in therapeutically vaccinated animals are discussed.