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Androgens exert significant effects on the murine submandibular gland. Our objective in this study was to determine the nature and extent of testosterone regulation of gene expression in the female submandibular gland, and to explore the degree to which this control is the same as in male glands. Ovariectomized female BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 d. Glands were collected and total RNA was isolated. Samples were analyzed for differential expression of mRNA using CodeLink microarrays, and the data were evaluated using genesifter. Testosterone significantly influenced the expression of over 500 genes, and while many (n = 214) of the genes were similarly differentially expressed in androgen-treated males, there were also many that were unique. These findings support our hypotheses that testosterone extensively influences gene expression in the female submandibular gland, and that the nature of this influence is variable between sexes.

A verbenachalcone derivative was synthesized and shown to protect N2a cells from caspase induction caused by serum starvation and to enhance the effect of NGF on neurite outgrowth in PC12 cells. As an initial investigation of the compound's mechanism(s) of action, we performed differential gene expression profiling in PC12 cells using oligonucleotide ( approximately 10,000 gene probes) microarrays. Gene expression patterns were compared in the presence of NGF (2 and 50 ng/mL) and NGF (2 ng/mL) plus the verbenachalcone derivative. Ten genes were significantly (2-fold; p0.05) up-regulated and seven genes were significantly down-regulated in the presence of the compound. These results were independently validated by quantitative real-time PCR for a subset of genes (cathepsin L, sigma-1 receptor and protein tyrosine phosphatase receptor type R). These genes or their protein products may represent useful therapeutic targets for treating neurodegeneration, such as Alzheimer's disease.

Background Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. Methods We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed. Results We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida. Conclusions Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.

SUMMARYTravel is a risk factor for Legionnaires' disease. In 2008, two cases were reported in condominium guests where we investigated a 2001 outbreak. We reinvestigated to identify additional cases and determine whether ongoing transmission resulted from persistent colonization of potable water. Exposures were assessed by matched case-control analyses (2001) and case-series interviews (2008). We sampled potable water and other water sources. Isolates were compared using sequence-based typing. From 2001 to 2008, 35 cases were identified. Confirmed cases reported after the cluster in 2001–2002 were initially considered sporadic, but retrospective case-finding identified five additional cases. Cases were more likely than controls to stay in tower 2 of the condominium [matched odds ratio (mOR) 6·1, 95% confidence interval (CI) 1·6–22·9]; transmission was associated with showering duration (mOR 23·0, 95% CI 1·4–384). We characterized a clinical isolate as sequence type 35 (ST35) and detected ST35 in samples of tower 2's potable water in 2001, 2002, and 2008. This prolonged outbreak illustrates the importance of striving for permanent Legionella eradication from potable water.

A growing number of epidemiological studies conducted worldwide suggest an increase in the occurrence of adverse health effects in populations living, working, or going to school near major roadways. A study was designed to assess traffic emissions impacts on air quality and particle toxicity near a heavily traveled highway. In an attempt to describe the complex mixture of pollutants and atmospheric transport mechanisms affecting pollutant dispersion in this near-highway environment, several real-time and time-integrated sampling devices measured air quality concentrations at multiple distances and heights from the road. Pollutants analyzed included U.S. Environmental Protection Agency (EPA)-regulated gases, particulate matter (coarse, fine, and ultrafine), and air toxics. Pollutant measurements were synchronized with real-time traffic and meteorological monitoring devices to provide continuous and integrated assessments of the variation of near-road air pollutant concentrations and particle toxicity with changing traffic and environmental conditions, as well as distance from the road. Measurement results demonstrated the temporal and spatial impact of traffic emissions on near-road air quality. The distribution of mobile source emitted gas and particulate pollutants under all wind and traffic conditions indicated a higher proportion of elevated concentrations near the road, suggesting elevated exposures for populations spending significant amounts of time in this microenvironment. Diurnal variations in pollutant concentrations also demonstrated the impact of traffic activity and meteorology on near-road air quality. Time-resolved measurements of multiple pollutants demonstrated that traffic emissions produced a complex mixture of criteria and air toxic pollutants in this microenvironment. These results provide a foundation for future assessments of these data to identify the relationship of traffic activity and meteorology on air quality concentrations and population exposures.

Androgens exert significant effects on the murine submandibular gland. Our objective in this study was to determine the nature and extent of testosterone regulation of gene expression in the female submandibular gland, and to explore the degree to which this control is the same as in male glands. Ovariectomized female BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 d. Glands were collected and total RNA was isolated. Samples were analyzed for differential expression of mRNA using CodeLink microarrays, and the data were evaluated using genesifter. Testosterone significantly influenced the expression of over 500 genes, and while many (n = 214) of the genes were similarly differentially expressed in androgen-treated males, there were also many that were unique. These findings support our hypotheses that testosterone extensively influences gene expression in the female submandibular gland, and that the nature of this influence is variable between sexes.

Purpose The hypothesis tested in the study was that the effect of estrogen and progesterone on the lacrimal gland is mediated through specific receptors and that hormonal effects involve the regulation of gene expression and protein synthesis. Methods Lacrimal glands were collected from young adult, ovariectomized mice, that were treated with 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone or vehicle for 2 weeks. Glands were pooled according to treatment, processed for the isolation of RNA, and evaluated for differentially expressed mRNAs by using gene microarrays. Bioarray data were analyzed with sophisticated bioinformatics and statistical programs. The expression of selected genes was verified by using gene chips and quantitative real-time PCR methods. Results The results demonstrate that 17beta-estradiol, progesterone, or both hormones together significantly influences the expression of hundreds of genes in the mouse lacrimal gland. Sex steroid treatment led to numerous alterations in gene activities related to transcriptional control, cell growth and/or maintenance, cell communication, signal transduction, enzyme catalysis, immune expression, and the binding and metabolism of nucleic acids and proteins. A number of the 17beta-estradiol, progesterone or 17beta-estradiol plus progesterone effects on gene expression were similar, but most were unique to each treatment. Of particular interest was the finding that these hormones seem to contribute little to the known sex-related differences in gene expression of the lacrimal gland. Conclusions These results support the hypothesis that estrogen's and progesterone's action on the lacrimal gland involves the regulation of numerous genes. However, these hormone effects do not appear to represent a major factor underlying the sexual dimorphism of gene expression in lacrimal tissue.

Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P < 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.

The objective of this study was to determine the nature and extent of androgen influence on gene expression in the lacrimal gland. Lacrimal glands were obtained from orchiectomized mice that had been treated with testosterone or vehicle for 2 weeks, as well as from testicular feminized mice and their Tabby controls. Samples were pooled according to experiment, processed for the isolation of RNA, and analyzed for differentially expressed mRNAs by using primarily CodeLink Bioarrays, GEM 1 and 2 gene chips and quantitative real-time PCR (qPCR) procedures. Gene chip data were analyzed with GeneSifter.Net software. Our results demonstrate that testosterone regulates the expression of over 2000 genes in the lacrimal gland. Gene ontologies most affected by androgen treatment included those related to cell growth, proliferation and metabolism, cell communication and transport, nucleic acid binding, signal transduction and receptor activities. Our findings also indicate that androgen action may be mediated, at least in part, through classical androgen receptors, and may contribute to the sex-related differences in gene expression of lacrimal tissue. Overall, these results support our working hypothesis that androgen action on the lacrimal gland is mediated primarily through a receptor-associated regulation of gene transcription.

Significant, sex-associated differences exist in the physiology and pathophysiology of the lacrimal gland. We hypothesize that many of these differences are due to fundamental variations in gene expression. The purpose of this study was to determine the extent to which sex-related differences in gene expression are present in the lacrimal gland. Lacrimal glands were obtained from adult male and female BALB/c mice (n=5-10mice/sex/experiment), pooled according to sex and processed for the isolation of RNA. Samples were analyzed for differentially expressed mRNAs by using Atlas Mouse cDNA Expression Arrays, cDNA amplification techniques, GEM 1 and 2 gene chips, CodeLink bioarrays and quantitative real-time PCR (qPCR) procedures. Quantitative evaluation of Atlas Array gene expression was performed with an image analysis system developed in our laboratory, whereas gene chip data were analyzed with Rosetta Resolver and GeneSifter.Net software. Statistical significance was determined by using Student's t-test. Our results with CodeLink bioarrays show that sex has a significant influence on the expression of over 490 genes in the mouse lacrimal gland. These genes are involved in a wide range of biological processes, molecular functions and cellular components, including such activities as development, growth, transcription, metabolism, signal transduction, transport, receptor activity and protein and nucleic acid binding. The expression of selected genes was confirmed by the use of GEM gene chips and qPCR. Our findings also demonstrate that certain methodological approaches are less useful in attempting to assess the magnitude of sex-associated differences in the lacrimal gland. These results support our hypothesis that sex-related differences in gene expression play a role in the sexual dimorphism of the lacrimal gland.

Christine A. Kohler, MD, Albert Einstein school of Medicine, Bronx, New York, Emilio Gonzalez-Ayala, MD, Baylor University College of Medicine, Houston, Texas, Patricia Rowley, MD, Texas Tech University Health Sciences Center, El Paso, Texas, Fernando Malamud, MD, University of Mississippi School of Medicine, Jackson, Mississippi, Abraham Verghese, MD, FRCP(C), FACP, Texas Tech University Health Sciences Center, El Paso, Texas

PURPOSE. In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study’s purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression. METHODS. Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA). RESULTS. The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes. CONCLUSIONS. These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways. (Invest Ophthalmol Vis Sci. 2005;46: 3666‐3675) DOI:10.1167/iovs.05-0426