Per Helgerud

Esterification of cholesterol in human small intestine: the importance of acyl-CoA:cholesterol acyltransferase.

Abstract. Human intestinal mucosa contains acyl‐CoA: cholesterol acyltransferase activity. The enzyme has been studied by using oleylcarnitine, CoA and carnitine palmitoyltransferase as an oleyl‐CoA regenerating system. The enzyme was found in the particulate fraction of the cells, it had a pH optimum between 7.2 and 8.2, and was inhibited by taurocholate. The specific enzymic activity in biopsies from intestinal mucosa of normal men was found to be 3.6 ± 1.37 nmol cholesteryl ester formed mg protein‐1 h‐1, an activity which can account for all cholesteryl esters in intestinal lymph. Low enzymic activity was found in biopsies from patients with small intestinal disorders. Two pancreatectomized patients had values within the normal range.

Lymphatic absorption and transport of retinol and vitamin D-3 from rat intestine Evidence for different pathways

The lymphatic absorption and transport of retinol and vitamin D-3 from rat intestine has been studied. When rats were cannulated in the intestinal lymph duct and given an intraduodenal bolus of [3H]retinol and 14C-labelled vitamin D-3, 14C-labeled vitamin D-3 appeared later in the intestinal lymph than [3H]retinol and the rate of absorption of vitamin D-3 was still maximal at a time when that of retinol had declined. Both vitamins were absorbed via the lymphatic route in association with chylomicrons. Almost all the retinol was esterified, while vitamin D-3 appeared in the chylomicrons as free vitamin D-3. In vitro incubations and in vivo studies using hepatectomized and normal rats showed that the retinyl ester was a relatively nonexchangeable component of the chylomicrons and their remnants. Hence, all the vitamin A followed the remnants in their clearance from plasma. In contrast, significant amounts of vitamin D-3 were transferred from the chylomicrons to other plasma fractions. Therefore, only a fraction of this vitamin may be removed in association with the chylomicron remnants.

Influence of diets on acyl-CoA:cholesterol acyltransferase and on acyl-CoA:retinol acyltransferase in villous and crypt cells from rat small intestinal mucosa and in the liver

Cholesterol and retinol are both esterified with long-chain fatty acid within the mucosal cells of the small intestine. The reactions are catalyzed by microsomal acyl-CoA:cholesterol and acyl-CoA:retinol acyltransferases (EC 2.3.1.26, and EC 2.3.1.-, respectively). To gain more insight into the physiological importance of these acyltransferases, they were studied in villous and crypt cells from rats either fasting or on diets which varied in fat and cholesterol content. Both enzymes had a higher activity in villous than in crypt cells. The activities in villous cells varied with feeding and fasting and the composition of diet when the animals were killed postprandially. Acyl-CoA:cholesterol acyltransferase activity went up upon cholesterol feeding whereas retinol acyltransferase in the mucosa was reduced by high-fat diets. The liver cholesterol acyltransferase activity varied with diet, it increased with both cholesterol and fat feeding, whereas retinol acyltransferase activity remained relatively constant. The results obtained suggest that different diets are of importance for cholesterol and retinol acyltransferase activities both in the intestinal mucosa and in the liver. The variation in activities of the two acyltransferases suggests that they may be different enzymes.

Prospective findings in breast cancer kindreds: annual incidence rates according to age, stage at diagnosis, mean sojourn time, and incidence rates for contralateral cancer

Abstract 2102 women over 55 years of age from breast cancer kindreds as clinically defined were examined with annual clinical examination and mammography every second year. Initially, all family histories were obtained and all women were invited for genetic counselling. During screening, 37 infiltrating cancers (CA) and 9 carcinomas in situ (CIS) were found. Annual incidence rates for CA or CIS were calculated to be 0.82% for those aged 30 years or more. Annual incidence rate for contralateral cancer among those who had contracted one cancer was 6%. In the first round, 17 of 23 cancers (74%) were without spread, and this increased to 20 of 23 (87%) during follow-up. Two of 23 cancers (18%) were CIS at the first round, increasing to 7 of 23 (30%) at follow-up visits. CIS was diagnosed at a younger age than CA. Employing figures for mean sojourn time from sporadic cancer to calculate the annual incidence rate underlying the observation in the first round gave the same incidence as observed during actual follow-up. This indicates that inherited breast cancer progression is comparable with that of sporadic cancer.

Inherited Breast Carcinoma: Prospective findings in 1 194 women at risk

According to preset criteria, 1,194 women at risk for inherited breast carcinoma were selected and subjected to examination. Six hundred and three women were examined once, 591 were followed for a mean of 1.8 years. Twenty infiltrating cancers (median age 49 years) and 16 precancers (median age 44 years) were found, demonstrating that breast carcinoma continued to occur in the selected families as expected under the hypothesis of dominant inheritance. At first round, 14 (1.2%) infiltrating carcinomas and a total of 22 (1.8%) cancers or precancers were found. Incidence rates of 0.58% pr. year for infiltrating cancers, and 1.04% pr. year for cancer or precancer were calculated. This confirms the tentative conclusions that were drawn in our previous report. These are the first prospective reports documenting how to delineate a high risk group for premenopausal breast cancer, and how to diagnose cancer at an early stage. All but two affected women had cancer without lymph node metastasis. Although a longer observation time is needed, we cautiously conclude that the results are in keeping with our aim of providing safety for those at risk. Clinical use of predictive genetic testing may be implemented within these families.

Horseshoe Kidney and Ruptured Abdominal Aortic Aneurysm

Ruptured aortic abdominal aneurysm associated with horseshoe kidney is seldom encountered. The surgical procedure is complicated by the overlying kidney and the frequent occurrence of multiple aberrant renal arteries, which may arise from the aneurysmic part or from adjacent arteries. One case successfully treated surgically is reported. Renal function declined during the early postoperative period, but returned to preoperative values within three weeks, and remained at pre-rupture levels for the next three months.