knockout mice are protected against lithogenic diet-induced gallstones.

The scavenger receptor and multiligand transporter CD36 functions to promote cellular free fatty acid uptake and regulates aspects of both hepatic and intestinal cholesterol metabolism. However, the role of CD36 in regulating canalicular and biliary cholesterol transport and secretion is unknown. Here, we show that germline knockout (KO) mice are protected against lithogenic diet (LD)-induced gallstones compared with congenic (C57BL6/J) controls.

Prevention of hepatic fibrosis with liver microsomal triglyceride transfer protein deletion in liver fatty acid binding protein null mice.

Unlabelled: Blocking hepatic very low-density lipoprotein secretion through genetic or pharmacologic inhibition of microsomal triglyceride transfer protein (Mttp) causes hepatic steatosis, yet the risks for developing hepatic fibrosis are poorly understood. We report that liver-specific Mttp knockout mice (Mttp-LKO) exhibit both steatosis and fibrosis, which is exacerbated by a high-transfat/fructose diet. When crossed into germline liver fatty acid (FA) binding protein null mice (Mttp-LKO, i.

Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families.

Background: The overwhelming majority (approximately 80%) of individuals with classic familial adenomatous polyposis (FAP) exhibit mutations in the coding sequence of the adenomatous polyposis coli (APC) tumor suppressor gene. Families without detectable APC mutations are unable to benefit from the use of genetic testing for clinical management of this autosomal dominant syndrome.

Methods: We used exome sequencing and linkage analysis, coupled with second-generation sequencing of the APC locus including non-coding regions to investigate three APC mutation-negative classical FAP families.

Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease.

Unlabelled: Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes, also modulates HSC FA utilization and in turn regulates the fibrogenic program.

Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L-Fabp -/- mice.

The tissue-specific sources and regulated production of physiological signals that modulate food intake are incompletely understood. Previous work showed that L-Fabp(-/-) mice are protected against obesity and hepatic steatosis induced by a high-fat diet, findings at odds with an apparent obesity phenotype in a distinct line of aged L-Fabp(-/-) mice. Here we show that the lean phenotype in L-Fabp(-/-) mice is recapitulated in aged, chow-fed mice and correlates with alterations in hepatic, but not intestinal, fatty acid amide metabolism.

Occupational exposure influences on gender differences in respiratory health.

Background: The aim of this study was to evaluate gender differences in the respiratory health of workers exposed to organic and inorganic dusts.

Methods: Meta-analysis techniques incorporating logistic regression were applied to a combined file of 12 occupational health studies.

Results: Meta-analysis of data on 1,367 women and 4,240 men showed that women had higher odds of shortness of breath whether exposed to inorganic dust or having no occupational exposure, with an overall odds ratio (OR) of 2.

Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome.

Introduction: In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome.

Methods: Male NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21.

Three measures of forest fire smoke exposure and their associations with respiratory and cardiovascular health outcomes in a population-based cohort.

Background: During the summer of 2003 numerous fires burned in British Columbia, Canada.

Objectives: We examined the associations between respiratory and cardiovascular physician visits and hospital admissions, and three measures of smoke exposure over a 92-day study period (1 July to 30 September 2003).

Methods: A population-based cohort of 281,711 residents was identified from administrative data.

Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function.

Abetalipoproteinemia (ABL) is a rare Mendelian disorder of lipid metabolism due to genetic deficiency in microsomal triglyceride transfer protein (MTP). It is associated with defects in MTP-mediated lipid transfer onto apolipoprotein B (APOB) and impaired secretion of APOB-containing lipoproteins. Recently, MTP was shown to regulate the CD1 family of lipid antigen-presenting molecules, but little is known about immune function in ABL patients.

Myoepithelial carcinoma of the orbit: a clinicopathological and histopathological study.

Two cases of invasive myoepithelial carcinoma arising from the paranasal sinuses and invading the orbit are presented. Patient 1, a 53-year-old man, had a 3-month history of proptosis, pain and epiphora of the right eye. The second patient, a 24-year-old man, had for a week been complaining of protrusion of his left eye and of orbital pain.

Sex differences in emphysema and airway disease in smokers.

Background: The authors of previous reports have suggested that women are more susceptible to cigarette smoke and to an airway-predominant COPD phenotype rather than an emphysema-predominant COPD phenotype. The purpose of this study was to test for sex differences in COPD phenotypes by using high-resolution CT (HRCT) scanning in male and female smokers with and without COPD.

Methods: All subjects completed spirometry and answered an epidemiologic respiratory questionnaire.

Longitudinal analysis of respiratory symptoms in population studies with a focus on dyspnea in marine transportation workers.

Purpose: Longitudinal respiratory symptoms are rarely studied in occupational epidemiology. We investigated dyspnea change over time and predictors of change over time using two longitudinal modeling techniques, a semi-parametric group-based approach (SAS® Proc Traj) and a generalized linear mixed model (SAS® Proc Glimmix), and compared the two techniques for use in longitudinal studies of respiratory symptoms.

Methods: Data were previously collected from a lung health surveillance study of marine transportation workers.

Increased susceptibility to diet-induced gallstones in liver fatty acid binding protein knockout mice.

Quantitative trait mapping identified a locus colocalizing with L-Fabp, encoding liver fatty acid binding protein, as a positional candidate for murine gallstone susceptibility. When fed a lithogenic diet (LD) for 2 weeks, L-Fabp(-/-) mice became hypercholesterolemic with increased hepatic VLDL cholesterol secretion. Seventy-five percent of L-Fabp(-/-) mice developed solid gallstones compared with 6% of wild-type mice with an increased gallstone score (3.

Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice.

Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp (-/-) mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol "Western" diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption between the genotypes, and fatty acid (FA) oxidation was reduced, rather than increased, in SF-fed L-fabp (-/-) mice as evidenced by decreased heat production and serum ketones.

Occupational noise exposure and hearing protector use in Canadian lumber mills.

Noise exposure is probably the most ubiquitous of all occupational hazards, and there is evidence for causal links between noise and both auditory and nonauditory health effects. Noise control at source is rarely considered, resulting in reliance on hearing protection devices to reduce exposure. A comprehensive noise survey of four lumber mills using a randomized sampling strategy was undertaken, resulting in 350 full-shift personal dosimetry measurements.

Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice.

FA transport protein 4 (FATP4), one member of a multigene family of FA transporters, was proposed as a major FA transporter in intestinal lipid absorption. Due to the fact that Fatp4(-/-) mice die because of a perinatal skin defect, we rescued the skin phenotype using an FATP4 transgene driven by a keratinocyte-specific promoter (Fatp4(-/-);Ivl-Fatp4(tg/+) mice) to elucidate the role of intestinal FATP4 in dietary lipid absorption. Fatp4(-/-);Ivl-Fatp4(tg/+) mice and wild-type littermates displayed indistinguishable food consumption, growth, and weight gain on either low or high fat (Western) diets, with no differences in intestinal triglyceride (TG) absorption or fecal fat losses.

Biomarkers of airway acidity and oxidative stress in exhaled breath condensate from grain workers.

Rationale: Grain workers report adverse respiratory symptoms due to exposures to grain dust and endotoxin. Studies have shown that biomarkers in exhaled breath condensate (EBC) vary with the severity of airway inflammation.

Objectives: The purpose of the study was to evaluate biomarkers of airway acidity (pH and ammonium [NH(4)(+)]) and oxidative stress (8-isoprostane) in the EBC of grain workers.

Altered hepatic triglyceride content after partial hepatectomy without impaired liver regeneration in multiple murine genetic models.

Unlabelled: Liver regeneration is impaired following partial hepatectomy (PH) in mice with genetic obesity and hepatic steatosis and also in wild-type mice fed a high-fat diet. These findings contrast with other data showing that liver regeneration is impaired in mice in which hepatic lipid accumulation is suppressed by either pharmacologic leptin administration or by disrupted glucocorticoid signaling. These latter findings suggest that hepatic steatosis may actually be required for normal liver regeneration.

Examining adversarial growth in illness: the factor structure of the Silver Lining Questionnaire (SLQ-38).

The Silver Lining Questionnaire (SLQ-38) is purported to measure 10 aspects of adversarial growth in illness. To date however, no empirical evidence exists to support this claim. Hence the aim of this study was to investigate the factor structure of the SLQ-38 in a sample of 560 individuals with multiple sclerosis (MS), cancer, cardiac, and renal disease.

ApoB100 is required for increased VLDL-triglyceride secretion by microsomal triglyceride transfer protein in ob/ob mice.

Microsomal triglyceride transfer protein (Mttp) is a key player in the assembly and secretion of hepatic very low density lipoproteins (VLDL). Here we determined the effects of Mttp overexpression on hepatic triglyceride (TG) and VLDL secretion in leptin-deficient (ob/ob) mice, specifically in relation to apolipoproteinB (apoB) isoforms. We crossed Apobec1(-/-) mice with congenic ob/ob mice to generate apoB100-only ob/ob mice (A-ob/ob).

Assessment of pesticide exposure control practices among men and women on fruit-growing farms in British Columbia.

Exposure to pesticides can be reduced by wearing personal protective equipment (PPE) or by implementing alternative pest control techniques, such as Integrated Pest Management (IPM). A cross-sectional telephone survey was conducted to explore the prevalence of these practices and the factors that may be associated with them among men and women involved in fruit growing in British Columbia (BC), Canada. Survey variables were developed using a framework that incorporated aspects of farm structure, health promotion, and risk perception theories.

Environmental and occupational exposures: do they affect chronic obstructive pulmonary disease differently in women and men?

This workshop summary examines current research that addresses the question: Are women more susceptible than men to the effects of inhaled pollutants, namely those found in work or residential environments? A systematic literature review was performed in preparation for the workshop. A total of 73 recent (since 2000) articles were retrieved reporting on occupational and environmental exposures and their impact on chronic obstructive pulmonary disease, of which only nine provided gender-stratified results. In two mortality studies, results were contrary (one finding increased chronic obstructive pulmonary disease mortality in relation to traffic among elderly women compared with men, the other finding no gender difference).

Diet-induced obesity and hepatic steatosis in L-Fabp / mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation.

Liver fatty acid (FA)-binding protein (L-Fabp), a cytoplasmic protein expressed in liver and small intestine, regulates FA trafficking in vitro and plays an important role in diet-induced obesity. We observed that L-Fabp(-/-) mice are protected against Western diet-induced obesity and hepatic steatosis. These findings are in conflict, however, with another report of exaggerated obesity and increased hepatic steatosis in female L-Fabp(-/-) mice fed a cholesterol-supplemented diet.

Within- and between-person variability of exhaled breath condensate pH and NH4+ in never and current smokers.

Recent studies have suggested that the collection of exhaled breath condensate (EBC) may be a viable method in occupational field studies to sample secretions of the lower airway because it is simple to perform and non-invasive. However, there are unresolved questions about whether certain laboratory conditions may influence the analysis of EBC biomarker measurements. A total of 12 subjects performed 116 EBC tests.

The healthy worker effect in asthma: work may cause asthma, but asthma may also influence work.

Despite the increasing attention to the relationship between asthma and work exposures, occupational asthma remains underrecognized and its population burden underestimated. This may be due, in part, to the fact that traditional approaches to studying asthma in populations cannot adequately take into account the healthy worker effect (HWE). The HWE is the potential bias caused by the phenomenon that sicker individuals may choose work environments in which exposures are low; they may be excluded from being hired; or once hired, they may seek transfer to less exposed jobs or leave work.