Nutrient absorption.

Some key advances occurred last year in understanding mechanisms involved in nutrient absorption. A novel "prechylomicron transport vesicle" was identified; its movement to the Golgi is the rate-limiting step for triacylglycerol absorption. A scavenger receptor (type BI) in the brush border membrane appears to facilitate cholesterol uptake. Several studies define mechanisms for gastrointestinal peptide hormone stimulation of glucose uptake. An oligopeptide transporter, PepT1, is transcriptionally upregulated by certain dietary amino acids and dipeptides. Surprisingly, both insulin and fasting double the maximum velocity for dipeptide uptake (via PepT1), but they act by different mechanisms. Three transporters, SMVT (sodium-dependent multivitamin transporter for biotin and pantothenate), SVCT (for vitamin C), and CaT1 (for Ca uptake from the lumen) have been cloned and are active when expressed in various cells. Additional studies provide insights on Ca absorption and vitamin D action in aging, estrogen deficiency, and adaptation to a low Ca diet. Nramp2, also called DMT1 (divalent metal ion transporter), seems to be a major regulator of transferrin-independent, nonheme iron uptake. Finally, the protein HFE associates with the transferrin receptor and is part of an iron-sensing mechanism that regulates iron absorption. It is defective in hereditary hemochromatosis. HFE and Nramp2 (DMT1) genes are reciprocally regulated.

Nutrient absorption.

Interesting advances occurred recently in nutrient absorption. Kinetics of triacylglycerol appearance in endoplasmic reticulum, Golgi apparatus, and lymph support the hypothesis that endoplasmic reticulum-to-Golgi transport is rate-limiting for lipid absorption. Apolipoprotein B does not appear necessary for initial formation of chylomicron-sized lipid particles in the endoplasmic reticulum, but rather for their movement out of the endoplasmic reticulum and to the Golgi. If peptides are protected from luminal proteolysis by fatty acylation, or if a nonpeptide drug, acyclovir, is esterified with valine to enhance bioavailability, the peptides nevertheless are absorbed by peptide transporters. Experimental conditions needed to use human ileal mucosa for in vitro absorption studies are described. Intestinal mucosa contains leptin receptors, and leptin inhibits galactose absorption, suggesting a new site for leptin's modulation of body mass. The enhancer element for the apoB gene is located much farther from its structural gene in the intestine than in the liver.

Nutrient absorption.

Interesting advances occurred recently in nutrient absorption. Kinetics of triacylglycerol appearance in endoplasmic reticulum, Golgi apparatus, and lymph support the hypothesis that endoplasmic reticulum-to-Golgi transport is rate-limiting for lipid absorption. Apolipoprotein B does not appear necessary for initial formation of chylomicron-sized lipid particles in the endoplasmic reticulum, but rather for their movement out of the endoplasmic reticulum and to the Golgi. If peptides are protected from luminal proteolysis by fatty acylation, or if a nonpeptide drug, acyclovir, is esterified with valine to enhance bioavailability, the peptides nevertheless are absorbed by peptide transporters. Experimental conditions needed to use human ileal mucosa for in vitro absorption studies are described. Intestinal mucosa contains leptin receptors, and leptin inhibits galactose absorption, suggesting a new site for leptin's modulation of body mass. The enhancer element for the apoB gene is located much farther from its structural gene in the intestine than in the liver.

Hepatic sequestration and biliary secretion of epidermal growth factor: evidence for a high-capacity uptake system.

Epidermal growth factor (EGF) promotes hepatocyte growth and is bound in the liver by specific receptors. We have determined hepatic uptake of EGF in intact rats after an intravenous or intraportal injection of a bolus of 125I-labeled EGF. Ninety-nine percent of the intraportal dose was taken up by the liver in 3 min, whereas only 58% of the intravenous dose appeared in the liver in 10 min. Uptake was inhibited by simultaneous treatment with an excess of unlabeled EGF. At time zero, uptake appeared to be complete. Disappearance from the liver followed first-order kinetics. Within 90 min of an intraportal injection, an average of 19% of the injected radioisotope appeared in bile, of which approximately one-fifth was shown to be immunoprecipitable with a specific anti-EGF antiserum. Light microscopic autoradiography demonstrated a very steep portal-to-central lobular concentration gradient consistent with a high-capacity uptake system. After intraportal injection or after incubation with cultured hepatocytes, labeled EGF was shown to be bound to its hepatic receptors. The main receptor-ligand complex had a Mr of approximately equal to 160,000-170,000, determined by NaDodSO4/polyacrylamide gel electrophoresis.

Familial chylomicronemia due to a circulating inhibitor of lipoprotein lipase activity.

A mother and her son who have lipoprotein phenotype I are described. They differed from subjects with lipoprotein lipase deficiency in that lipoprotein lipase was present in adipose tissue respectively at 30- and 2-fold the levels seen in normal subjects, and from subjects with apoprotein C-II deficiency in that apoprotein C-II was present in their plasma. They appeared to have an inhibitor to lipoprotein lipase activity in their whole plasma that inhibited that activity eluted from adipose tissue with heparin and that activity present in postheparin plasma of normals. The inhibitor was non-dialyzable, heat-stable, sensitive to repeated freezing and thawing, and appeared to be present in the non-lipoprotein fraction of plasma. The presence of chylomicronemia and the plasma inhibitor in the mother and her son, and possibly in her father and grandson, argues against this being inherited as an autosomal recessive abnormality, as are lipoprotein lipase deficiency and apoprotein C-II deficiency.

Salmonella meningitis. Occurrence in an adult.

Salmonella meningitis is predominantly a disease of infants. An adult patient is described who had meningitis due to S typhimurium following a traumatic fracture of the first lumbar vertebra. A review of previous cases of Salmonella meningitis in adults revealed a predominance of infection due to S typhi prior to 1940 with a variety of other serotypes isolated since then. Only one of nine patients survived prior to the antibiotic era, but three of five patients with Salmonella meningitis since 1940 have survived.