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Several letters to the editor are presented in response to articles in previous issues including an article on U.S. Secretary John Foster Dulles' moral order in politics in the September 28, 1953 issue, "Bombs for Everybody," and a report on the decision of John L. Lewis to stop buying coal in the September 28, 1953 issue.

The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol Delta(7)-reductase. This enzyme converts 7-dehydrocholesterol (7-DHC) to cholesterol in the last step in cholesterol biosynthesis. The pathology of this condition may result from two different factors: the deficiency of cholesterol itself and/or the accumulation of precursor sterols such as 7-DHC. Although cholesterol synthesis is defective in cultured SLOS cells, to date there has been no evidence of decreased whole body cholesterol synthesis in SLOS and only incomplete information on the synthesis of 7-DHC and bile acids. In this first report of the sterol balance in SLOS, we measured the synthesis of cholesterol, other sterols, and bile acids in eight SLOS subjects and six normal children. The diets were very low in cholesterol content and precisely controlled. Cholesterol synthesis in SLOS subjects was significantly reduced when compared with control subjects (8.6 vs. 19.6 mg/kg per day, respectively, P < 0.002). Cholesterol precursors 7-DHC, 8-DHC, and 19-nor-cholestatrienol were synthesized in SLOS subjects (7-DHC synthesis was 1.66 +/- 1.15 mg/kg per day), but not in control subjects. Total sterol synthesis was also reduced in SLOS subjects (12 vs. 20 mg/kg per day, P < 0.022). Bile acid synthesis in SLOS subjects (3.5 mg/kg per day) did not differ significantly from control subjects (4.6 mg/kg per day) and was within the range reported previously in normals. Normal primary and secondary bile acids were identified.This study provides direct evidence that whole body cholesterol synthesis is reduced in patients with SLOS and that the synthesis of 7-DHC and other cholesterol precursors is profoundly increased. It is also the first reported measure of daily bile acid synthesis in SLOS and provides evidence that bile acid supplementation is not likely to be necessary for treatment. These sterol balance studies provide basic information about the biochemical defect in SLOS and strengthen the rationale for the use of dietary cholesterol in its treatment.

In order to study the biosynthesis, composition, and origin of sterols in the Florida land crabs, Cardisoma guanhumi (Latreille), we fed 17 male crabs either a cholesterol-free or a high cholesterol diet for 2 to 7 weeks. The origin of sterols in these crabs, whether from biosynthesis or from the diet, was determined by tahree procedures: the incorporation of isotopic mevalonate into the cholesterol when the diet was cholesterol-free; the absorption of isotopic cholesterol and sitosterol from the diet; the cholesterol and plant sterol concentrations of hepatopancreas, plasma, and muscle under conditions of cholesterol-free and high cholesterol diets. In addition, the interconversion of cholesterol and sitosterol was investigated. Dietary sterols of plant and animal sources were readily absorbed and provided the major source of sterols for this species of crab. The biosynthesis of cholesterol from mevalonate in this crab was minimal. However, cholesterol was synthesized from dietary sitosterol by dealkylation. Cholesterol and the three plant sterols (24 epsilon-methyl cholesterol, stigmasterol, and sitosterol) were found in the hepatopancreas, plasma, and muscle of the crab. Plant sterols contributed from 9 to 37% of the total sterols in the hepatopancreas, plasma, and muscle of the crabs fed a cholesterol-free diet.

Docosahexaenoic acid [22:6 omega 3; 22:6-(4,7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other omega 3 fatty acids, chiefly alpha-linolenic acid (18:3 omega 3). We tested the effect of dietary omega 3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurified diets very low in 18:3 omega 3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3 omega 3. In near-term fetuses and newborn infants of the deficient group, the 22:6 omega 3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6 omega 3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6 omega 3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain omega 6 fatty acids, particularly 22:5 omega 6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary omega 3 fatty acids are retina and brain.

Previously we demonstrated high concentrations of desmosterol and docosahexaenoic acid (DHA, 22:6 n-3) in monkey testes and sperm. Desmosterol, a cholesterol precursor, is not present elsewhere in the body. High concentrations of DHA are found elsewhere only in the retina and brain. To examine the distribution of these compounds in the heads and tails of sperm, we separated them and determined their sterol, fatty acid, and phospholipid molecular species composition. Desmosterol predominated in tails (134.4 vs. 1.7 microg/10(9) cells in heads). The cholesterol content was also greater in the tails (66.2 vs. 30.3 microg/10(9) cells in heads). Sperm tails had more polyunsaturated fatty acids than the heads (34.1 vs. 12.1% of total fatty acids) which resulted mainly from the higher contents of DHA (19.6 vs. 1.1%) and arachidonic acid (20:4 n-6) (6.4 vs. 1.6%) in the tails. These differences in fatty acid composition occurred mainly in phospholipids: phosphatidyl choline and phosphatidyl ethanolamine for n-3 fatty acids and phosphatidyl serine and cardiolipin for n-6 fatty acids. Fifteen phospholipid molecular species were identified. Sperm tails had more molecular species containing unsaturated fatty acids than the heads. Our results reveal the large differences in membrane lipid composition between the heads and tails of sperm. Most (99%) of the desmosterol and DHA in sperm is located in the tail. These differences may be responsible for the different functions of these two components of sperm. The large number of double bonds in DHA, six, and in desmosterol, two, may contribute to the membrane fluidity necessary for the motility of the sperm tails.

To explore the mechanisms of the profound plasma cholesterol elevations in familial homozygous hypercholesterolemia (type IIa), cholesterol turnover, sterol balance, cholesterol absorption, and low density lipoprotein studies were carried out under controlled dietary conditions in two sisters (aged 13 and 16). Cholesterol turnover was prolonged. The half-life of the first exponential of the plasma cholesterol specific activity decay curve was double that of normal adults. The rate constants for the removal of cholesterol from pool A (KAA = 0.0652) and for the excretion of cholesterol from the system (Kaa = 0.0197) were less than half of normal. The production rates of cholesterol were low, only 6.30 and 6.86 mg/kg per day as measured by cholesterol turnover and sterol balance techniques, respectively. Fecal neutral steroid and bile acid excretion were 5.22 and 1.64 mg/kg per day, which is remarkably low in comparison to those of normal and heterozygous children. Cholesterol absorption was within the upper limit of the values reported for normal adults. THE HDL cholesterol values were extremely low (27 mg/dl) in contrast to profoundly elevated LDL levels. The fractional catabolic rate of LDL (0.127 per day) and the rate of synthesis and catabolism of apo-LDL (15 mg/kg per day) were low in comparison to previously reported values in homozygotes. These composite data indicated that the definable metabolic defects of these two sisters with homozygous familial hypercholesterolemia were the sluggish clearance of cholesterol from the body coupled with low total body synthesis of cholesterol.

Rhesus monkeys were fed high cholesterol and cholesterol-free diets for 21-24 months. The animals were then given isotopic cholesterol intravenously and autopsied from 1 to 51 weeks later. The plasma and aortic cholesterol contents were 633 +/- 130 mg/dl and 35.6 +/- 11.4 mg/g dried tissue (45.5% in ester form) for atherosclerotic monkeys and 135 +/- 25 mg/dl and 9.9 +/- 3.6 mg/g (15.0% in ester form) for control monkeys, respectively. The minimal influx rate of cholesterol from plasma into the aorta was much greater for atherosclerotic animals, 0.470 +/- 0.20 mg/g per day versus 0.088 +/- 0.031 for control monkeys. There was a rapid turnover of both free and esterified cholesterol in the atherosclerotic aortas, greater than for normal aortas. These studies of cholesteryl ester metabolism indicated a likely origin of aortic cholesteryl ester from the plasma cholesteryl esters. Our data indicated a dynamic cholesterol metabolism and turnover in the aorta during atherogenesis.

Six samples of human coprolites, some more than 2,000 years old, were analyzed for fecal steroid composition. Despite this very lengthy period of storage, the fecal steroids of coprolites were remarkably similar to those of stool samples collected today. The sterol nucleus was clearly rather stable under the dry environmental conditions of the Nevada Caves. The steroid content (µg/g dried weight) of coprolite was low in comparison to that of modern man. The bile acid/cholesterol and plant sterol/cholesterol ratios of the coprolite, however, were similar to these ratios of the stools of modern man. In the six coprolites, an average 73% of the neutral steroids was digitonin-precipitable. This precipitate was composed of cholesterol and three plant sterols (campesterol, stigmasterol, and β-sitosterol) and their bacteria-modified products. A portion of the neutral steroids had been converted to products tentatively identified as epimers of these steroids. Individual bile acids were identified in the coprolite. The bile acid composition of the coprolite was similar to that of the stool of modern man.