Analysis of lactation defects in transgenic mice.

Although lactation is the only physiological function of the mammary gland, little is known about the molecular events required for secretory activation and milk production. Genetically altered mice have been used extensively to study mammary gland development during puberty and pregnancy, as well as mammary tumorigenesis. A number of approaches have been used to produce genetic modifications in mammary glands of mice, including transgenic mice utilizing mammary specific promoters, traditional knockout mice, mammary-specific gene deletion, and conditionally-regulated transgenes.

Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine.

The mammary gland of the lactating mouse synthesizes and secretes milk lipid equivalent to its entire body weight in a single 20-day lactation cycle, making it one of the most active lipid synthetic organs known. We test the hypothesis that multiple control points and potential regulatory mechanisms regulate milk lipid synthesis at the level of gene expression. The mammary transcriptome of 130 genes involved in glucose metabolism was examined at late pregnancy and early lactation, utilizing data obtained from microarray analysis of mammary glands from quadruplicate FVB mice at pregnancy day 17 and lactation day 2.

Status of carotenoids, vitamin A, and vitamin E in the mother-infant dyad and anthropometric status of infants in Malawi.

This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.

Effect of antibiotic treatment of subclinical mastitis on human immunodeficiency virus type 1 RNA in human milk.

Although subclinical mastitis is associated with increased HIV load in breast milk, it is not known whether empirical treatment with antibiotics will reduce breast milk HIV load. We examined the effect of antibiotic treatment for subclinical mastitis on HIV load in breast milk. Seventy-five HIV-infected post-partum women in Malawi with subclinical mastitis were treated with oral amoxicillin/clavulanic acid and were followed between 1 and 24 weeks later.

The in vivo effects of the Pro12Ala PPARgamma2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank.

Aims/hypothesis: To investigate the phenotypic effects of common polymorphisms on adipose tissue metabolism and cardiovascular risk factors, we set out to establish a biobank with the unique feature of allowing a prospective recruit-by-genotype approach. The first use of this biobank investigates the effects of the peroxisome proliferator-activated receptor (PPAR) Pro12Ala polymorphism on integrative tissue-specific physiology. We hypothesised that Ala12 allele carriers demonstrate greater adipose tissue metabolic flexibility and insulin sensitivity.

CARD15 polymorphisms in Behçet's disease.

Background: Behçet's disease (BD) is a chronic multi-system inflammatory disorder of unknown aetiology, which shares many features of the inflammatory bowel diseases (IBDs). CARD15 has recently been identified as the first susceptibility gene in Crohn's disease (CD).

Objective: Given certain clinical and pathological similarities between CD and BD, and recent evidence of linkage of BD to the CARD15 genomic region, the aim of this study was to investigate the role of CARD15 variants in determining susceptibility to BD.

Calcium secretion into milk.

Ionized calcium ([Ca(2+)]) is present in milk at concentrations around 3 mM, a concentration that drives the formation of complexes with citrate, phosphate, and casein, thereby generating compounds that carry the major portion of calcium in milk. In humans and cows, where it has been studied, changes in milk calcium appear to be regulated by the amount of citrate and casein in milk rather than changes in [Ca(2+)]. Most or all of the calcium in milk is likely derived through exocytosis of secretory vesicles derived from the Golgi compartment where a calcium ATPase mediates transport from the cytoplasm.

Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma.

Fatty acid desaturases such as steaoryl-CoA desaturase (SCD) convert saturated to unsaturated fatty acids and are involved in lipogenesis. Observational and animal data suggest that SCD-1 activity is related to insulin sensitivity. However, the effects of insulin-sensitizing drugs on SCD gene expression and desaturase activities are unknown in humans.

Epidemiology and microbiology of subclinical mastitis among HIV-infected women in Malawi.

The epidemiology and microbiology of subclinical mastitis, a risk factor for perinatal HIV transmission, have not been well characterized. In all, 250 HIV-infected women were followed from two weeks to 12 months postpartum in Blantyre, Malawi, and subclinical mastitis was assessed by breast milk leukocyte counts. The point prevalence of subclinical mastitis at 2, 4, 6, 10, and 14 weeks, and 6, 9, and 12 months was 12.

Claudin 7 expression and localization in the normal murine mammary gland and murine mammary tumors.

Introduction: Claudins, membrane-associated tetraspanin proteins, are normally associated with the tight junctions of epithelial cells where they confer a variety of permeability properties to the transepithelial barrier. One member of this family, claudin 7, has been shown to be expressed in the human mammary epithelium and some breast tumors. To set the stage for functional experiments on this molecule, we examined the developmental expression and localization of claudin 7 in the murine mammary epithelium and in a selection of murine mammary tumors.

Breast milk retinol concentrations are not associated with systemic inflammation among breast-feeding women in Malawi.

The acute phase response and inflammation are associated with lower plasma retinol concentrations, but their effect on breast milk retinol concentrations is unclear. We measured plasma retinol concentrations, acute phase proteins, and breast milk retinol concentrations in 237 breast-feeding women at 2 wk postpartum in Blantyre, Malawi; 16.5% of the women had plasma retinol < 0.

Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release.

Clearance of apoptotic cells is critical to tissue homeostasis and resolution of inflammatory lesions. Macrophages are known to remove dying cells and release anti-inflammatory mediators in response; however, many cells traditionally thought of as poor phagocytes can mediate this function as well. In the lactating mammary gland following weaning, alveolar epithelial cell death is massive, yet the gland involutes rapidly, attaining its prepregnancy state in a matter of days.

Bovine glucose transporter GLUT8: cloning, expression, and developmental regulation in mammary gland.

GLUT8 is a newly identified member of the facilitative glucose transporter family, which characteristically exhibits high-affinity glucose transport activity. The expression of GLUT8 has been shown to depend on gonadotropin secretion in human testes and to be regulated by insulin in the blastocyst. To characterize GLUT8 and investigate its role in normal mammary gland function, we cloned and sequenced the full-length cDNA of bovine GLUT8.

Regulation of milk lipid formation and secretion in the mouse mammary gland.

Cytosolic lipid droplets (CLDs), the immediate precursors of milk lipids in lactating animals, undergo cell-specific changes in their formation and intracellular distribution during mammary gland differentiation. Cell biological studies indicate that CLD formation in mammary epithelial cells is regulated in part by AKT-dependent increases in glucose uptake. Proteomic studies show that CLDs from lactating mammary epithelial cells possess a distinct protein composition enriched in molecules involved in their secretion and intracellular transport.

Albumin transcytosis across the epithelium of the lactating mouse mammary gland.

Murine milk contains 18 mg ml(-1) serum albumin, a concentration equal to that in the serum of the lactating mouse. We examined cellular transport using in vivo methods in the mouse. At steady state the specific activity of (125)I-albumin injected into the blood stream was equal in plasma and whey, confirming that milk albumin is extra-mammary in origin.

Inflammatory bowel disease is linked to 19p13 and associated with ICAM-1.

Genome-wide scans have implicated several susceptibility loci, but linkage of 19p13 (IBD6) to Crohn's disease (CD) has not been fully replicated. We report a replication study of IBD6 in a UK Caucasian population. Two hundred eighty-four affected sibling pairs from 234 families were used for the linkage study.

Identification of CYP2B6 sequence variants by use of multiplex PCR with allele-specific genotyping.

Background: Cytochrome P450 2B6 (CYP2B6) has a role in the metabolism of many clinically important substances, but the variation within the CYP2B6 gene has not been fully characterized. The aim of the present study was to develop a reliable and robust assay for determining genotypic variants.

Methods: We used a two-stage procedure.

Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1.

The dopamine D2 receptor has been extensively studied in relation to alcoholism, substance abuse, and nicotine dependence. The most frequently examined polymorphism linked to this gene is the Taq1A restriction fragment length polymorphism (RFLP) (dbSNP rs1800497; g.32806C>T in GenBank AF050737.

The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease.

Background: The microsomal triglyceride transfer protein (MTP) transfers lipids into apolipoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. The T-variant of a functional polymorphism in the MTP promoter, MTP-493G/T, has been associated with reduced low-density lipoprotein cholesterol concentrations. We hypothesize that this polymorphism impacts on coronary heart disease (CHD) risk.

Functional development of the mammary gland: use of expression profiling and trajectory clustering to reveal changes in gene expression during pregnancy, lactation, and involution.

To characterize the molecular mechanisms by which progesterone withdrawal initiates milk secretion, we examined global gene expression during pregnancy and lactation in mice, focusing on the period around parturition. Trajectory clustering was used to profile the expression of 1358 genes that changed significantly between pregnancy day 12 and lactation day 9. Predominantly downward trajectories included stromal and proteasomal genes and genes for the enzymes of fatty acid degradation.

The calcium-sensing receptor regulates mammary gland parathyroid hormone-related protein production and calcium transport.

The transfer of calcium from mother to milk during lactation is poorly understood. In this report, we demonstrate that parathyroid hormone-related protein (PTHrP) production and calcium transport in mammary epithelial cells are regulated by extracellular calcium acting through the calcium-sensing receptor (CaR). The CaR becomes expressed on mammary epithelial cells at the transition from pregnancy to lactation.

The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis.

Linkage and association studies implicate the human leucocyte antigen (HLA) region in genetic susceptibility to ulcerative colitis (UC). However, associations with specific variants have been inconsistent, even within defined ethnic groups. A genetic basis for the disease heterogeneity of UC may account for these discrepant findings from studies in unselected populations.

Complex haplotypic structure of the central MHC region flanking TNF in a West African population.

TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing TNF and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample.

Blackboard allows students to take quizzes on the go.

New Web-based technologies offer innovative opportunities in nursing courses. Blackboard is one such program that allows faculty to interact with students in new ways. Experimentally, this software's online quizzes were substituted for traditional in-class quizzes in a master's level advanced pharmacology course.