David H. Alpers

PSYCHIATRIC ILLNESS AND THE IRRITABLE BOWEL SYNDROME Practical Implications for the Primary Physician

Twenty-nine consecutive outpatients with irritable bowel syndrome were given structured psychiatric interviews, as were 33 consecutive medical controls who did not have irritable bowel syndrome. All were from an internal medicine group practice. Seventy-two percent of irritable bowel syndrome subjects had psychiatric illness, with hysteria and depression the most prevalent syndromes. Only 18% of controls had psychiatric illness. The primary physician made an accurate psychiatric assessment in only 28% of the subjects. An awareness of his patients psychiatric illness is necessary for the physician to provide effective treatment, as for depression, and to spare the patient needless medications, hospitalizations, and surgery, as with hysteria.

The turnover of disaccharidases and brush border proteins in rat intestine

Abstract 1. 1. The incorporation and turnover of amino acids into different protein fractions of the small intestinal mucosa of rats has been measured after the intravenous injection of leucine or mixed amino acids. 2. 2. The incorporation into the brush border fractions was delayed compared with other fractions and was compartible with the time required for the transfer of newly formed proteins from within the epithelial cell to the brush borders. 3. 3. After maximal labeling the half-life of the brush border was shorter (18 h) than the homogenate (31 h) or other subcellular fractions. 4. 4. The separated and purified disaccharides had an even faster turnover rate (11.5 h) than whole brush borders. Since migration per se cannot account for the turnover of disaccaharidases, control of disaccharidase turnover may not depend on cell formation in the intestinal crypts. It is suggested that control may be located at the villus level of the intestinal cells. 5. 5. Although the adult rat is known to have lower lactase activity than the neonatal animal, no differences in turnover between the disaccharidases were found to account for this reduced activity.

Increased lymph alkaline phosphatase after fat feeding: Effects of medium chain triglycerides and inhibition of protein synthesis

Abstract The mechanism involved in the increase of lymph alkaline phosphate after fat feeding has been studied utilizing male rats with mesentric lymph fistulas. There was good correlation between the levels of alkaline phosphatase and triglycerides in mesentric lymph both in the basal state and after administration of micellar solutions of oleic acid. Increased phosphatase activity in lymph occurred within the first hour after fate feeding, and this response was not altered in animals with a bile fistula. After the infusion of micellar solutions of octanoic acid, a medium chain fatty acid absorbed via the portal stream, there was a rise in lymph alkaline phosphatese but without an elevation of triglyceride. The suggests that the stimulus for the elevation of phosphatase in the lymph during lipid absorption involves the uptake or transport of lipid into the cell rather than its exit into the lymph. Acetoxycycloheximide, an inhibitor of protein synthesis, prevented the rise in lymph alkalinee phosphatase after infusion of micellr solutions of both oleic and octanoic acid suggesting that increased synthesisof the enzyme was involved. In acetoxycyoloheximide treated male rats receiving micellar solutions of oleic acid there was still some inrease in lymph triglyceride although there was no elevation of lymph alkaline phosphatase. Therefore alkaline phosphatases is probably not essential for the transport of lipid into lymph.

STIMULATION OF INTESTINAL MUCOSAL PROLIFERATION BY VITAMIN D

Abstract Intestinal mucosal cell turnover was studied in vitamin D-deficient rats in response to vitamin D 3 repletion. Four hours after a single oral dose of 100 U of vitamin D 3 , 3 H-thymidine incorporation into deoxyribonucleic acid was enhanced. Mucosal cell migration rate of the vitamin D-repleted animals was 1.5 times that of the deficient animals. The accelerated mucosal cell turnover was associated with an increase of approximately 20% in villus height. This stimulation of mucosal cell proliferation preceded enhanced calcium transport, and, therefore, may be an important component of action of vitamin D on the intestine.

THE CHARACTERIZATION OF RAT INTESTINAL AMYLASE

An intestinal amylase has been separated and identified in the rat. Intestinal amylase is located on the brush border and is identical with one or both of the heat-stable maltases. Intestinal amylase is particularly active against oligosaccharides, slightly active against soluble starch, inactive against oligosaccharides, slightly active against soluble starch, and inactive against insoluble starch. This amylase may be important in the digestion of small oligosaccharides derived from starch. Pancreatic contamination of intestinal mucosa was extremely difficult to eliminate. Biliary or pancreatic diversion removed most of the contamination; washing procedures alone were not adequate. Pancreatic amylase was adherent to intestinal mucosa in vitro. Thus, when studying intestinal enzymes, pancreatic contamination must be carefully excluded as a source of enzymatic activity.

Regulation of Small Intestinal Protein Metabolism

The gastrointestinal tract plays a signifxad icant role in protein metabolism of the whole body. 1 Endogenous proteins are dixad gested within the intestinal tract and largely reabsorbed. Of the 70 g estimated to be secreted daily into the gut lumen, less than 12 g of protein are excreted daily. Ingested protein also forms a large reserxad voir of amino acids within the lumen of the intestine. The amino acids from endogexad nous and exogenous sources are then transxad ported across the intestine for use in the body. These processes of protein digesxad tion and absorption have been extensively studied. 1 4 Less attention, however, has been paid to the metabolism of protein within the small intestinal epithelial cells themselves. The mucosa is one organ in which cell division and differentiation ocxad curs continuously throughout life. This process is subject to regulation by various stimuli, and it would necessitate the conxad trolled production of various specific proxad teins.

Serum Amylase Determinations and Amylase to Creatinine Clearance Ratios in Patients With Chronic Renal Insufficiency

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.

Identification of two Calcium-Binding Proteins in Human Small Intestine: A preliminary report

At least two separate proteins with calcium-binding activity have been detected in the human duodenum. One of these proteins migrates rapidly during electrophoresis, has a molecular weight of about 20,000 (similar to the vitamin D-sensitive protein in the chick or monkey), and contains no detectable carbohydrate or phosphate. Whether it is vitamin D-dependent is as yet uncertain. The activity of the calcium-binding protein has been found to vary linearly as a function of the background binding activity of the resin used in the assay. Accurate determinations of calcium-binding activity depend, therefore, upon correction of all values to correspond to a standard background binding activity.

The effect of carbon tetrachloride on rat-liver lysosomes.

Abstract 1. 1.The effects of CCl 4 on isolated lysosomes and rat-liver slices have been examined. The addition of CCl 4 to rat-liver lysosomes caused the release of β-glucuronidase, acid phosphatase, and acid ribonuclease activity. The release occurred without a lag period and was linear. In addition, the rate of release was found to be dependent on the CCl 4 concentration. 2. 2.CCl 4 added to liver slices caused a redistribution of the lysosomal enzyme activity such that a greater percentage was found in the supernatant versus the particulate fraction. Under these conditions [ 14 C]leucine incorporation into protein was inhibited. The effects on lysosomal enzymes and on leucine incorporation were roughly comparable for a given concentration of CCl 4 . Studies of the kinetics of these changes revealed both to be linear and to occur without any detectable lag period. 3. 3.Lysosomes were isolated by two different methods, such that lipid peroxidation occurred to a much greater extent in one preparation compared with the other. Despite this difference CCl 4 produced comparable release of lysosomal enzyme activity in both preparations. Furthermore, in neither lysosomal fraction was CCl 4 found to augment lipid peroxidation at a time when its effect on enzyme activity was maximal.

Method for determination of specific activity of proteins in polyacrylamide gels

Abstract A method is described for estimating protein content and radioactivity from the same solution of dissolved acrylamide gel. The gels are made utilizing ethylene diacrylate as a cross-linking agent, which permits the gel to be dissolved in 1 N NaOH. Protein is then determined by standard methods and NCS is used as a solubilizer for liquid scintilation.