Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLP_As).     

XbaI polymorphism of the apolipoprotein B gene and plasma lipid and lipoprotein response to dietary fat and cholesterol: a clinical trial

Friedlander Y, Kaufmann NA, Cedar H, Kark JD. XbaI polymorphism of the apolipoprotein B gene and plasma lipid and lipoprotein response to dietary fat and cholesterol: a clinical trial.
Clin Genet 1993: 43: 223–231. © Munksgaard, 1993
A dietary trial was carried out on a group of offspring whose parents were hospitalized for an acute myocardial infarction. The XbaI Restriction Fragment Length Polymorphism (RFLP) was used to examine the genetic contribution of variation at this apo B locus to the response of lipids and lipoproteins to dietary manipulations. Twenty participants were homozygotes for the 8.0 kb fragment (X1X1), two were homozygotes for the 5.0 kb fragment (X2X2), and 15 were heterozygotes (X1X2). Subjects were randomized to a 5-week crossover study. Half began on a low SFA - cholesterol (LSC) diet for 5 weeks and, after a washout period of 4 weeks, they were placed on a high SFA - cholesterol (HSC) diet for a second period of 5 weeks. This order was reversed in the second group of participants. Significant changes in total cholesterol, LDL-C, and apo B were observed when subjects were moved from the LSC to the HSF diet. The corresponding average change induced by the dietary manipulations in X1X1 subjects compared with subjects with X2 allele were: 18.1\pm17.6 mg/dl and 9.5\pm19.6 mg/dl for total cholesterol and 15.8\pm15.3 mg/dl and 4.8\pm20.9 mg/dl for LDL-C, respectively. Our observation indicated that variation at the apo B XbaI locus may interact with baseline levels to determine individual dietary response in LDL-C level. However, the differences between the genotypic classes were not statistically significant, suggesting that the apo B XbaI locus is not a major determinant of interindividual differences in lipid and lipoprotein response to diet in this population.     

Body weight regulation with a proportional hoarding response in the rat

Female rats hoarded food when their body weight was reduced by fasting. The amount hoarded (H) was proportional to body weight according to the equation: H=a (W_o ? W_b) with W_o: ad lib food-body weight and W_b: actual body weight. Body weights prior to starvation and after recovery were not statistically different from regression line thresholds for hoarding. These results show the existence of a proportional regulation of body weight with a hoarding response below the body weight set point.     

Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a critical regulator of adipogenesis. PPAR gamma+/- mice are resistant to high-fat diet-induced obesity and thus PPAR gamma may mediate physiological responses to dietary fat in other mammals. The aim of this study was to determine whether the human PPAR gamma proline to alanine substitution polymorphism (Pro12Ala) modifies the association between dietary fat and adiposity and plasma lipids. Subjects (n=2141) were controls selected for three case-control studies nested within the Nurses' Health Study, a large ongoing prospective cohort study. Associations between intake of total fat, fat subtypes and BMI were different in PPAR gamma 12Ala variant allele-carriers compared with non-carriers. Among homozygous wild-type Pro/Pro individuals, those in the highest quintile of total fat intake, had significantly higher mean body mass index (BMI) compared with those in the lowest quintile (27.3 versus 25.4 kg/m2, respectively; P-trend<0.0001) whereas among 12Ala variant allele-carriers there was no significant trend observed between dietary fat intake and BMI (P-trend=0.99; P-interaction=0.003). In contrast, intake of monounsaturated fat was not associated with BMI among homozygous wild-type women but was inversely associated with BMI among 12Ala variant allele-carriers (mean in lowest quintile=27.6 versus mean in highest quintile=25.5 kg/m2; P-trend=0.006; P-interaction=0.003). The relationship between dietary fat intake and plasma lipid concentrations also differed according to PPAR gamma genotype. These data suggest that PPAR gamma genotype is an important factor in physiological responses to dietary fat in humans.     

Effects of a dietary fibre supplement to a weight reduction programme on blood pressure. A randomized, double-blind, placebo-controlled study

Sixty-two moderately obese (body mass index = 34.8), but normotensive females were treated with a balanced hypocaloric diet providing 1,600 kcal/day and either a 6.5 g dietary fibre supplement or placebo in a randomized, double-blind, parallel group design. During a 12-week treatment programme, weight loss was similar in both groups (4.1 and 4.4 kg, respectively). Initially the blood pressure was 123/76 mmHg in the fibre group compared with 124/74 mmHg in the placebo group (p less than 0.05). In the fibre-treated group a significant fall in diastolic blood pressure by 4 mmHg was found (p less than 0.05). No significant change was seen in the placebo group. It is suggested that dietary fibre may affect blood pressure independently of weight change.     

A novel adenoviral vector-mediated neuronal selective gene expression in neonatal mouse brain in response to hypoxia

Selective gene expression targeting neurons is a challenge, which, if successfully overcome, carries an enormous potential for clinical applications in therapeutics against neurodegenerative diseases. We have reported previously the construction of a series of adenoviral vectors capable of selectively expressing a reporter gene luciferase in cultured neurons [D. Huang, A. Desbois, S.T. Hou, A novel adenoviral vector which mediates hypoxia-inducible gene expression selectively in neurons, Gene Ther. 12 (2005) 1369-1376]. A combination of neuron restrictive silencer elements (NRSEs), hypoxia responsive elements (HREs) and CMV minimal promoter (CMVmp) was packaged into replication defective adenovirus to target gene expression selectively in neurons in a hypoxia-regulated manner. In the present study, we injected the adenoviral vectors into the neonatal mouse brain followed by treatment with hypoxia. The expression of the reporter luciferase gene was examined by luciferase assay and fluorescent immunostaining. Neurons and glial cells were identified by staining with antibodies against NeuN and GFAP, respectively. Remarkably, in response to hypoxia, Ad/5HRE-3NRSE showed strong hypoxia-inducible gene expression of the reporter luciferase selectively in neurons but not in glial cells. In contrast, brains infected with the control vector Ad/5HRE showed no selectivity in luciferase expression (in both neurons and glial cells) under the hypoxic condition. Taken together, these studies demonstrated that this vector (Ad/5HRE-3NRSE) can mediate gene expression selectively in neurons both in vitro and in vivo, supporting the suggestion that further refinement of this vector may lead to the development of a useful tool to investigate mechanisms of neuronal damage following cerebral ischemia and a possible effective gene therapy vector to stroke.     

Body fat and fat distribution in relation to sex differences in blood pressure

The extent to which the relationship between body fat and blood pressure either differs by sex or explains sex differences in blood pressure is examined. Estimates of the relationship of blood pressure to several measures of adiposity in men and women were obtained from a systematic review of the literature and tests of whether these relationships differ by sex were performed. Analysis of covariance (controlling for age and race) was used for both casual and ambulatory blood pressure in the Cornell Worksite Blood Pressure Study (N = 276). In general, most adiposity measures were significantly related to casual and ambulatory blood pressure in men and women. Subscapular skinfold thickness and body mass index exhibited the strongest associations. The vast majority of adiposity/blood pressure associations were not significantly different for men and women. Finally, sex differences in adiposity did not account for much of the sex difference observed in blood pressure. © 1995 Wiley-Liss, Inc.     

Per1 and Per2 gene expression in the rat suprachiasmatic nucleus: circadian profile and the compartment-specific response to light

Expression profiles of rPer1 and rPer2 messenger RNAs, rat homologues of the Drosophila clock gene period, were examined in the rat suprachiasmatic nucleus, a main locus of circadian oscillation, with special reference to the topographical compartmentation of the suprachiasmatic nucleus. Quantitative in situ hybridization of rPer1 and rPer2 messenger RNAs showed a robust circadian rhythm in the suprachiasmatic nucleus, with a characteristic peak/trough profile in each gene: the peak of rPer1 messenger RNA was in the daytime and that of rPer2 messenger RNA was at the transition time of day to night in both light-dark and constant dark conditions. Light exposure at circadian time 16 increased both rPer1 and rPer2 messenger RNAs in the suprachiasmatic nucleus. In a detailed histological analysis, we found that light exposure at circadian time 16 induced the expression of rPer1 and rPer2 genes in neurons limited to the ventrolateral part of the suprachiasmatic nucleus, although the usual circadian rPer1 and rPer2 messenger RNA oscillation in light-dark and constant dark conditions occurred strongly in neurons in the dorsomedial part but weakly in neurons in the ventrolateral part of the suprachiasmatic nucleus. These rPer expression profiles indicate that the two major subpopulations of neurons in the suprachiasmatic nucleus play different roles in the generation of circadian rhythm: a strong autonomous expression ability with no light response in dorsomedial neurons and a strong light responsiveness with a weak autonomous expression in ventrolateral neurons.     

Pasteurella multocida gene expression in response to iron limitation

Pasteurella multocida is the causative agent of a wide range of diseases in avian and mammalian hosts. Gene expression in response to low iron conditions was analyzed in P. multocida using whole-genome microarrays. The analysis shows that the expression of genes involved in energy metabolism and electron transport generally decreased 2.1- to 6-fold while that of genes used for iron binding and transport increased 2.1- to 7.7-fold in P. multocida during the first 2 h of growth under iron-limiting conditions compared with controls. Notably, 27% of the genes with significantly altered expression had no known function, illustrating the limitations of using publicly available databases to identify genes involved in microbial metabolism and pathogenesis. Taken together, the results of our investigations demonstrate the utility of whole-genome microarray analyses for the identification of genes with altered expression profiles during varying growth conditions and provide a framework for the detailed analysis of the molecular mechanisms of iron acquisition and metabolism in P. multocida and other gram-negative bacteria.     

Design and methods for testing a simple dietary message to improve weight loss and dietary quality

Background  

The current food pyramid guidelines have been criticized because of their complexity and the knowledge required for users to understand the recommendations. Simplification of a dietary message to focus on a single key aspect of dietary quality, e.g., fiber intake, may make the message much easier to comprehend and adhere, such that respondents can achieve greater weight loss, better dietary quality and overall metabolic health.     

Design and methods for testing a simple dietary message to improve weight loss and dietary quality

Background  

It can be challenging for patients and clinicians to properly interpret a change in the clinical condition after a treatment has been given. It is not known to which extent spontaneous improvement, effect of placebo and effect of active interventions contribute to the observed change from baseline, and we aimed at quantifying these contributions.     

Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile

BACKGROUND AND AIMS: Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both are positive for neural crest-derived markers including HMB-45 antigen. METHODS: To further explore the similarities between hepatic AMLs and stellate cells, gene expression of a hepatic AML was studied by cDNA microarray. Real-time polymerase chain reaction was used to confirm gene expression. Hepatic stellate cells can be quiescent, activated, or have a myofibroblastic phenotype depending on their state of activation. Expression of known markers of activated stellate cells was compared between the AML, activated primary mouse stellate cells, and stellate cell lines with activated and myofibroblastic phenotypes. Next, 5 novel genes from the AML were selected because they were not previously known to be markers of stellate cells and mRNA expression measured in the activated mouse stellate cells and in myofibroblastic stellate cell lines. Finally, expression levels of 10 novel genes were determined in 5 cirrhotic and 5 noncirrhotic human livers. RESULTS: Overexpression of known markers of activated stellate cells including transforming growth factor beta (TGF- beta ), smooth muscle actin, and collagen was found in the hepatic AML. Three of 5 novel markers that were identified in the AML, RRAD (Ras-related associated with diabetes), CTSK (cathepsin K), and NIBAN were also found to be overexpressed in activated stellate cells compared with quiescent or myofibroblastic stellate cells. In addition, 9 of 10 novel genes overexpressed in AML were also overexpressed in cirrhotic human livers versus noncirrhotic livers. CONCLUSIONS: Hepatic AMLs share a similar gene expression profile and may differentiate toward activated stellate cells.