ABSTRACT
Carboxyl ester lipase (bile salt-stimulated lipase) is a pancreatic enzyme capable of hydrolyzing esters of cholesterol and fat-soluble vitamins. It also efficiently digests triglycerides (TG) into free fatty acids and glycerol and is abundant in the milk of humans and several other species. We used the mouse as a model to test the hypothesis that milk-derived carboxyl ester lipase (CEL) digests milk TG and that without its activity milk lipids and their digestion intermediates can disrupt the intestinal epithelium of neonates. CEL protein and enzymatic activity were shown to be abundant in mouse milk. After 24-h administration of the CEL-specific inhibitor, WAY-121,751-5, the small intestines of treated and control neonates were analyzed histologically for signs of fat malabsorption and injury to their villus epithelium. In vehicle-fed controls, TG were digested and absorbed in the duodenum and jejunum, whereas, in inhibitor-fed littermates, large intracellular neutral lipid droplets accumulated in enterocytes of the ileum, resulting in damage to the villus epithelium. Similar results were observed in neonates nursed by CEL knockout females compared with heterozygous controls. The results suggest that lack of CEL activity causes incomplete digestion of milk fat and lipid accumulation by enterocytes in the ileum of neonatal mice.
Subject(s)
Animals, Suckling/physiology , Carboxylic Ester Hydrolases/pharmacology , Dietary Fats , Intestinal Diseases/chemically induced , Intestinal Diseases/prevention & control , Milk/enzymology , Administration, Oral , Animals , Carboxylesterase , Carboxylic Ester Hydrolases/antagonists & inhibitors , Carboxylic Ester Hydrolases/genetics , Carboxylic Ester Hydrolases/metabolism , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Intestinal Diseases/pathology , Intestine, Small/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout/genetics , Milk/chemistryABSTRACT
Because of its multiracial character, Hawaii presents a unique opportunity to carry out demographic investigations of the etiology of certain common cancers. Tumors with substantially different incidence rates among the major ethnic groups in the Islands, or between a given immigrant group and its country of origin, are of particular interest for such studies. Among the cancer sites meeting these criteria, nasopharynx, stomach, prostate, large bowel, liver, female breast, uterine corpus, ovary, bladder, and thyroid are particularly prominent.
Subject(s)
Neoplasms/history , Ethnicity , Female , Hawaii/epidemiology , History, 20th Century , Humans , Incidence , Male , Neoplasms/epidemiology , Neoplasms/mortalityABSTRACT
In view of uncertainty regarding the criteria and significance of gastric dysplasia as a precancerous lesion, members of the Pathology Panel of the International Study Group on Gastric Cancer (ISGGC) reviewed microslides of 93 gastric lesions showing varying degrees of mucosal abnormality, and reached the following consensus: (1) immature and proliferating gastric epithelium can be divided into two categories: hyperplastic and dysplastic; (2) the term dysplasia, especially of high-grade type, should be restricted to precancerous lesions, and hyperplasia is applied to regenerative changes; (3) regenerative hyperplasia may be simple or atypical, but dysplasia includes both moderate and severe abnormalities, since they often coexist and can not be sharply separated; and (4) occasionally the possibility of malignancy can not be excluded in a severely dysplastic epithelium; in such a case rebiopsy and diligent follow-up are necessary to establish the diagnosis. Criteria for diagnosing dysplasia and hyperplasia are presented and discussed. The opinions are offered as guidelines for establishing the diagnosis of gastric dysplasia and for prospective studies.
