Dietary consumption of meat, fat, animal products and advanced glycation end-products and the risk of Barrett's oesophagus.

BACKGROUND: Advanced glycation end-products (AGEs) are found in high quantity in high-fat foods and meat cooked at high temperature. AGEs have been shown to contribute to chronic inflammation and oxidative stress in humans. AIM: To investigate the associations between consumption of meat, fat and AGEs, and the risk of Barrett's oesophagus (BO). METHODS: We conducted a case-control study using data from the patients who were scheduled for elective esophagogastroduodenoscopy (EGD) and from a random sample of patients who were identified at primary care clinics. Daily consumption of meat, fat and Nε-(carboxymethyl) lysine (CML), a major type of AGEs, was derived from the food frequency questionnaire (FFQ). Multivariate logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) for BO. RESULTS: A total of 151 cases with BO and 777 controls without BO completed the FFQ. The multivariate OR (95% CI) for BO was 1.91 (1.07-3.38) for total meat, 1.80 (1.02-3.16) for saturated fat and 1.63 (0.96-2.76) for CML-AGE, when the highest tertile of intake was compared with the lowest. The association for total meat was attenuated to 1.61 (0.82-3.16), and that for saturated fat to 1.54 (0.81-2.94) after adjusting for CML-AGE. CONCLUSIONS: Higher consumption of total meat, saturated fat or possibly CML-AGE was associated with an increased risk of Barrett's oesophagus. CML-AGE may partly explain the association between total meat and saturated fat consumption and the risk of Barrett's oesophagus.

The prevalence of oesophageal eosinophilia and eosinophilic oesophagitis: a prospective study in unselected patients presenting to endoscopy.

BACKGROUND: Oesophageal eosinophilia (EE) is encountered in clinical practice as oesophageal biopsies are being obtained in patients with GI symptoms other than classical symptoms of eosinophilic oesophagitis (EoE). The prevalence, determinants and clinical relevance of EE identified irrespective of symptoms are unclear. AIM: To determine the prevalence and risk factors of EE with or without EoE in a nonselected group of patients undergoing endoscopy and in primary care patients. METHODS: A cross-sectional study in a single VA centre in which we obtained at least one oesophageal biopsy from patients presenting to elective endoscopy, as well as a sample of patients eligible for screening colonoscopy recruited from primary care clinics. EE was defined by >15 eosinophils in a single HPF; and EoE was defined as definite, probable or none depending on the presence of EE, acid-suppressive therapy and oesophageal symptoms. RESULTS: EE was identified in 33 of 1357 patients (2.4%, 95% CI: 1.7-3.4); of whom 9 had definite EoE (0.66%, 95% CI: 0.23-1.10), 17 had probable EoE (1.25%), and the only 7 patients had EE without EoE. The prevalence of EE was 2.3% among patients undergoing elective endoscopy and 0.1% among patients eligible for screening colonoscopy. Seasonal allergies (adjusted OR: 2.78; 95% CI: 1.26-6.11) and oesophageal strictures (4.50; 0.90-22.40) were associated with EE. CONCLUSIONS: The prevalence of EE was 2.3% among unselected patients presenting to endoscopy most of whom have EoE. EE was present in 0.1% in primary care patients none of whom had EoE.

Alterations in the expression and localization of protein kinase C isoforms during mammary gland differentiation.

Protein kinase C (PKC) is involved in signaling that modulates the proliferation and differentiation of many cell types, including mammary epithelial cells. In addition, changes in PKC expression or activity have been observed during mammary carcinogenesis. In order to examine the involvement of specific PKC isoforms during normal mammary gland development, the expression and localization of PKCs alpha, delta, epsilon and zeta were examined during puberty, pregnancy, lactation, and involution. By immunoblot analysis, expression of PKC alpha, delta, epsilon and zeta proteins was increased in mammary epithelial organoids during the transition from puberty to pregnancy. In mammary gland frozen sections, PKCs alpha, delta, epsilon and zeta were stained in the luminal epithelium and myoepithelium, in varying isoform-and developmental stage-specific locations. PKC alpha was found in a punctate apical localization in the luminal epithelium during pregnancy. During lactation, PKC epsilon was present in the nucleus, and PKC zeta was concentrated in the subapical region of the luminal epithelium. Additionally, marked staining for PKCs alpha, delta, epsilon, and zeta was observed in the myoepithelial cells at the base of ducts and alveoli. This basal ductal and alveolar staining differed in intensity in a developmentally-specific fashion. During most time points (virgin, pregnant, lactating, and early involution), myoepithelial cells of the duct were more intensely stained than those lining the alveoli for PKCs alpha, delta, epsilon and zeta. During late involution (days 9-12), the preferential staining of ducts was lost or reversed, and the myoepithelial cells lining the regressing alveolar structures stained equally (PKCs epsilon and zeta) or more intensely (PKCs alpha and delta), coincident with the thickening of the myoepithelial cells surrounding the regressing alveoli. The increased PKC isoform staining at the base of alveoli during involution suggests that alveolar regression may be influenced by alterations in signaling in the alveolar myoepithelium.

Protein kinase C eta upregulation and secretion during postnatal rat mammary gland differentiation.

The mammary gland has the ability to undergo repeated cycles of tightly regulated postnatal proliferation, differentiation, and apoptosis-mediated regression, providing a model to investigate potential regulators of mammary epithelial growth and differentiation. Protein kinase C eta is a candidate regulator of mammary epithelial differentiation, as increased expression of PKC eta is often observed during the terminal differentiation of many epithelial tissues. In this study, PKC eta expression and localization were characterized during puberty, pregnancy, lactation and involution in isolated rat mammary epithelial cells (MEC), as well as in paraffin-embedded and frozen rat mammary gland sections. By Western blot analysis of whole cell lysates from purified MEC, PKC eta protein expression increased during the shift from resting to a pregnant state. This increased PKC eta protein expression during pregnancy was associated with alveolar rather than ductal development, as immunohistochemical staining for PKC eta was increased in differentiating secretory alveoli, but not ducts. By immunofluorescent staining, PKC eta was stained intensely in an intracellular reticular meshwork throughout the cytosol of alveolar epithelial cells from pregnant mammary gland. During lactation, PKC eta was abundant in apocrine bodies budding from the alveolar epithelium, in the lumen of alveoli, and was present in milk, in association with casein, while being decreased in the cytoplasm of the luminal alveolar epithelium. Staining intensity of alveoli for PKC eta decreased further during involution. Western blotting of subcellular fractions from isolated mammary epithelial cells demonstrated that PKC eta remained associated with the membrane and particulate fractions throughout development. The upregulation of PKC eta in alveolar but not ductal epithelium during pregnancy suggests an association with functional secretory differentiation.

Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes.

BACKGROUND & AIMS: Colon cancer cells express reduced levels of protein kinase C (PKC). This study examines the regulation of PKC isozymes in normal colonic epithelium, as a basis for understanding the significance of alterations in this enzyme system in colon carcinogenesis. METHODS: The expression and localization of PKC isozymes in mouse and rat colonocytes at different developmental stages were determined using a combined morphological and biochemical approach. PKC alpha expression was compared in colonic adenocarcinomas and adjacent normal mucosa by immunoblot analysis. RESULTS: Mouse and rat colonocytes express PKC alpha, beta II, delta, epsilon, and zeta. Relatively low levels of these isozymes were detected in proliferating cells of the crypt base, predominantly in the cytosolic compartment. Coincident with colonocyte growth arrest/differentiation, PKC isozyme expression markedly increased in both the cytosolic and, more significantly, in the membrane/cytoskeletal fraction. Colonic tumors express reduced levels of PKC alpha, an isozyme that has been implicated in negative control of intestinal cell growth. CONCLUSIONS: These findings are supportive of a role for certain PKC isozyme(s) in signaling pathways mediating postmitotic events in colonocytes in situ, and suggest that diminished activity of these pathway(s) may contribute to the alterations in growth control/differentiation associated with colonic neoplasia.