Published Science

Civilized nations popularly assume that “primitive” societies are poor, ill, and malnourished and that progress through civilization automatically implies improved health. In this provocative book, Mark Nathan Cohen challenges this belief. Using findings from epidemiology, anthropology, and archaeology, Cohen provides fascinating evidence about the actual effects of civilization on health, suggesting that some aspects of “progress” create as many health problems as they prevent or cure. “[This book] is certain to become a classic—a prominent and respected source on this subject for years into the future…. If you want to read something that will make you think, reflect, and reconsider, Cohen’s Health and the Rise of Civilization is for you.”—S. Boyd Eaton, Los Angeles Times Book Review “A major accomplishment. Cohen is a broad and original thinker who states his views in direct and accessible prose…. This is a book that should be read by everyone interested in disease, civilization, and the human condition.”—David Courtwright, Journal of the History of Medicine “Cohen has done his homework extraordinarily well, and the coverage of the biomedical, nutritional, demographic, and ethnographic literature about foragers and low energy agriculturalists is excellent…. The book deserves a wide readership and a central place in our professional libraries. As a scholarly summary it is without parallel.”—Henry Harpending, American Ethnologist “Deserves to be read by anthropologists concerned with health, medical personnel responsible for communities, and any medical anthropologists…. Indeed, it could provide great profit and entertainment to the general reader.”—George T. Nurse, Current Anthropology

Obentos are boxed lunches Japanese mothers make for their nursery school children. Following Japanese codes for food preparation—multiple courses that are aesthetically arranged—these lunches have a cultural order and meaning. Using the obento as a school ritual and chore—it must be consumed in its entirety in the company of all the children—the nursery school also endows the obento with ideological meanings. The child must eat the obento; the mother must make an obento the child will eat. Both mother and child are being judged; the subjectivities of both are being guided by the nursery school as an institution. It is up to the mother to make the ideological operation entrusted to the obento by the state-linked institution of the nursery school, palatable and pleasant for her child, and appealing and pleasurable for her as a mother.

The dietary intake of population groups may be assessed using food consumption level estimates on a national basis and household food surveys. These may be useful for monitoring secular trends and geographical differences with stable and well-documented populations, but analytical studies of diet and health require data on individuals. Assessment techniques designed to assess the diet of individuals ranging from records with weights of food to questionnaires and biological markers have been critically reviewed in order to assess the accuracy of each. Quantitative estimates of the errors involved will be given. For example, the co-efficients of variation of differences incurred from asking subjects to estimate the weight of food portions, rather than weighing them, may regularly be in the 50% range for foods and 20% for nutrients. A variety of studies suggests that the co-efficients of differences in nutrient intake estimated over 1 day from the 24-hour recall method when compared with observed intakes ranged from 4 to 400%. These errors are believed to be random, and precision can be improved by increasing the numbers of observations on each individual or by increasing the numbers of individuals within each group. However, a substantial loss of power is incurred with errors of this magnitude. A more serious potential source of error is systematic bias due either to differences between different methods of dietary assessment or from deliberate over- or underreporting by the subjects themselves. Studies with the doubly labelled water technique have suggested that substantial underrecording of food intake can occur both in free-living individuals and in athletes. 24-hour urine nitrogen can be used to validate dietary assessments in individuals in nitrogen balance, and on-going studies in Cambridge show that within a group, underreporting occurs in specific individuals rather than in the group as a whole. Independent methods of validating dietary assessments, such as the doubly labelled water technique or the 24-hour urine nitrogen output, must be included in any study of free-living individuals.

The principles of mitochondrial genetics have evolved over the past 20 years. Careful identification of large pedigrees that were consistent with maternal inheritance has permitted detailed clinical and genetic investigations. Myoclonic epilepsy and ragged-red fiber (MERRF) disease has been a model disease for the application of these principles. MERRF is caused by an A to G mutation of the mitochondrial tRNA(Lys) at position 8344. The mutation is maternally inherited and heteroplasmic. Disease manifestations are dependent on replicative segregation of mutant and wild type mitochondrial DNAs and on the threshold effect. Characterization of the clinical, physiological, biochemical, and genetic manifestations of this disease has provided a better understanding of how to diagnose and manage oxidative phosphorylation diseases which are caused by mutations in the mitochondrial DNA.

The development of hepatocellular, putatively preneoplastic, gamma-glutamyl transpeptidase positive (GGT+) foci and tumors induced by aflatoxin B1 (AFB1) has been shown to be reduced in male F344 rats fed a diet containing 6% protein (as casein). This reduction occurs despite increased energy intake, when compared with animals fed a diet containing 22% protein. Among its many effects, low protein intake is known to increase the proportion of energy intake expended in the form of heat (thermogenesis); thus, this investigation examined the association between the development of GGT+ foci and alterations in indices of thermogenesis induced by feeding varying levels of dietary protein. Five days following the completion of AFB1 dosing, animals were assigned to groups fed 4%, 8%, 12%, 16%, or 22% dietary protein for 6 weeks. Foci development (% liver volume occupied) was markedly reduced in animals fed the low-protein diet (4%, 8%), yet calorie consumption per 100 g body wt was greater. A modest negative linear trend was observed in oxygen consumption with increasing levels of dietary protein intake. Urinary norepinephrine levels were elevated in the groups fed 4% and 8% protein; urinary dopamine and norepinephrine turnover rates in brown adipose tissue were highest in animals fed 4% protein. These results suggest that GGT+ foci development occurs when a "critical level" (approx 12%) of dietary protein intake is reached. Inhibition of foci development at lower levels of protein intake is associated with several indicators of increased thermogenesis.

The late Surgeon Captain T.L. Cleave (1906-1983) completed his life-long RN professional service by promotion to the post of Director of Medical Research to the Royal Navy. His voyaging as a medical officer gave him unique understanding of patterns of disease throughout the world. He concluded that many of the degenerative illnesses which during this century have become so common in advanced countries have a simple basic dietary cause--the consumption of ever increasing quantities of refined carbohydrates; human beings were not, in Cleave's opinion, adapted to the use of these artificially concentrated foods. He suggested the term "Saccharine Disease" to denote many diverse manifestations, including dental decay, obesity, diabetes and coronary thrombosis, of one master disease having one simple cause. The neglect of this concept by most authorities today repeats the attitudes of the 'medical establishment' towards one of Cleave's distinguished eighteenth century naval predecessors, James Lind, whose advocacy of citrus fruit juice for the prevention of scurvy was greeted with derision.

The health and nutritional status (anthropometry, and blood and urine biochemistry) of 44 Dutch apparently healthy vegetarians, aged 65-97 years, refraining from meat, fish, and poultry consumption, was assessed for insight into long-term consequences of ovo-lacto- or lacto-vegetarianism. The results indicate that in comparison to omnivorous elderly the vegetarian elderly (especially men) have aged successfully with respect to cardiovascular risk factors. In contrast, vegetarian elderly are at a higher risk for a marginal iron, zinc, and vitamin B12 status. Although several vegetarian elderly showed low levels of 25-hydroxyvitamin D in plasma and many had low values of 24-hr urine volume (per kg body weight), these values are not likely the result of a vegetarian diet per se. It is concluded that, although some nutrition-related risks are prevalent among vegetarian elderly, these risks can probably be prevented by lifestyle changes.

In a group of 13 strict vegetarian and 6 omnivorous lactating women, relationships were studied among maternal milk and serum vitamin B-12, and milk vitamin B-12 and infant urinary methylmalonic acid (MMA) excretion. Milk vitamin B-12 concentrations were lower in women consuming a strict vegetarian diet compared with an omnivorous diet. Milk vitamin B-12 was inversely related to length of time on a vegetarian diet and positively correlated with maternal serum vitamin B-12 concentrations. Infant urinary MMA excretion was inversely related to milk vitamin B-12 concentrations less than 362 pmol/L. The 1989 recommended dietary allowance for vitamin B-12 of 221 pmol/d for infants is close to the intake below which infant urinary MMA excretion is increased. We conclude that the current RDA for infants provides little margin of safety.

Height and weight data obtained from a 2-year longitudinal survey were analyzed for 2272 children aged 6 through 18 years who were attending public schools or Seventh-Day Adventist (SDA) schools in southern California. The SDAs do not use alcohol or tobacco, and many adhere to a lacto-ovovegetarian diet. For both sexes, in each school group, the mean height and weight were at or above national reference values. Age-adjusted regression analysis showed that SDA school-boys were 1.6 cm taller than public schoolboys. There were no significant differences in height for girls. After controlling for height, boys and girls in the SDA schools were found to be leaner than their public school peers, ie, 1.27 and 1.16 kg, respectively. These results suggest that a health-oriented life-style in childhood and adolescence, such as the one followed by SDAs, is compatible with adequate growth and associated with a lower weight for height.

The toxicological significance of exposures to synthetic chemicals is examined in the context of exposures to naturally occurring chemicals. We calculate that 99.99% (by weight) of the pesticides in the American diet are chemicals that plants produce to defend themselves. Only 52 natural pesticides have been tested in high-dose animal cancer tests, and about half (27) are rodent carcinogens; these 27 are shown to be present in many common foods. We conclude that natural and synthetic chemicals are equally likely to be positive in animal cancer tests. We also conclude that at the low doses of most human exposures the comparative hazards of synthetic pesticide residues are insignificant.

Two groups of 40 volunteers were given a dietary supplement consisting of 135 g of mackerel or meat (control) paste per day for 6 weeks. Compliance was about 80% in both groups and the daily intake of 20:5(n-3) and 22:6(n-3) from the mackerel supplement was about 1.3 and 2.3 g, respectively. In collagen-activated platelet rich plasma, the potency of blood platelet to produce HHT from arachidonic acid (AA) clearly reduced in the mackerel group, whereas the formation of HHTE from timnodonic acid (TA) increased slightly. Changes in the formation of HHT and HHTE, measured by HPLC, correlated significantly with those of TxB2 and TxB3, respectively, measured by GC/MS. Changes in the formation of the lipoxygenase products HETE (ex AA) and HEPE (ex TA) were qualitatively similar to that seen for the cyclo-oxygenase products, but quantitatively the responses were smaller. Formation of ir TxB2 in clotting blood significantly reduced in the mackerel group. In collagen-activated, citrated whole blood, TxB2 formation tended to be reduced in the mackerel-supplemented volunteers. Mackerel consumption was associated with the formation of considerable amounts of PGI3, as judged from the appearance of 2,3-dinor-delta 17-6-keto-PGF1 alpha in urine. The amount of the major metabolite of PGI2, 2,3-dinor-6-keto-PGF1 alpha was not reduced, or even increased. The daily amount of tetranor prostaglandin metabolites in the urine did not change significantly, which indicates that mackerel supplementation did not alter the formation of prostaglandins E and F.

To assess the adequacy of a vegetarian diet at old age, the dietary intake (assessed through dietary history with cross-check) of 44 apparently healthy lacto-(ovo-)vegetarians, aged 65-97 years, was evaluated. Adequacy was assessed by a comparison of nutrient intake with (Dutch) recommendations and by evaluating data on nutritional status. The results were also compared with data of elderly omnivores. In contrast to elderly omnivores, percentages of energy from protein (13%), fat (37%), and carbohydrates (50%) as well as P/S ratio (0.63) were close to or within the range of Dutch guidelines regarding a healthy diet (percentages of energy from protein, fat, and carbohydrates 10-15, 30-35, and 55%, respectively: P/S ratio 0.5-1.0). For most of the micronutrients studied intake was adequate, and nutrient density of the vegetarian diet was higher than of the omnivorous diet. However, the supply of zinc (average daily intake 8.5 and 7.6 mg for men and women, respectively), iron (because of lower bioavailability of nonheme iron), vitamin B12 (women only: intake 2.3 micrograms/day), and water (daily intake less than 1600 ml for 30% of the vegetarians) need special attention, considering the relatively high prevalence of a marginal status of these nutrients. In conclusion, a lacto-(ovo-)vegetarian diet can be adequate at old age, provided that it is carefully planned, especially with respect to the supply of iron, zinc, and vitamin B12.

The stool-bulking effect of dietary fibre (DF) is well-documented and believed to be important in the postulated beneficial effect of DF on human health. The aim of the present study was to investigate the digestibility of DF in relation to its stool-bulking properties and to study possible mechanisms for this effect. Four diets, based on conventional foods only, were studied in balance experiments on human subjects. Diet A contained DF mainly from whole-grain cereals while diets B1 and B2 contained DF mainly from pulses, vegetables and fruit. Diet C was a low-fibre diet. Faeces was fractionated into four fractions, each enriched in one of the following three components: undigested DF (fractions 1 + 2), faecal bacteria (fraction 3) and soluble components (fraction 4). The digestibility of DF in diets A, B1 and B2 was 0.62, 0.88 and 0.90 respectively. Subjects consuming diet A excreted slightly more fraction 3 than subjects consuming the other diets. Thus, the statement that DF of high digestibility stimulates microbial growth in the gut was not supported. The water-holding capacity of fraction 1 was studied in vitro and was found to be low. It is suggested that undigested soluble DF is important in the stool-bulking properties of DF.

Recent evidence suggests that bacterial lipopolysaccharide binds to serum lipoproteins in vitro and in vivo and that lipopolysaccharide in the form that is bound to lipoprotein is less biologically active in several experimental models. In order to study the mechanism of this apparent detoxification, we compared the ability of free and lipoprotein-bound lipopolysaccharide from Escherichia coli O18 to stimulate interleukin-1, interleukin-6, and tumor necrosis factor from elicited murine peritoneal macrophages and circulating human monocytes. Lipopolysaccharide bound to lipoprotein was 20- to 1,000-fold less active than the unbound form in inducing the release of each cytokine. We also studied the binding of each form of lipopolysaccharide to the macrophage surface. Lipopolysaccharide complexed to lipoprotein was unable to compete for the binding of radiolabeled heterologous lipopolysaccharide to murine macrophages, and radiolabeled lipopolysaccharide-lipoprotein complexes bound poorly compared with molar equivalents of free lipopolysaccharide. Our experiments suggest that in the process of binding to lipoproteins, lipopolysaccharide may be rendered less toxic through a mechanism of decreased ability to induce monocytes and macrophages to release cytokines, perhaps because of an altered interaction at the cell surface.

The satiating effect of duodenally administered fats was investigated with intraduodenal infusions of Intralipid in sham-feeding rats. Intralipid rapidly inhibited sham feeding and elicited the behavioral sequence of satiety. The satiating potency of Intralipid infusions in concentrations of 0.125-1 kcal/ml was a function of the concentration infused. The time course for Intralipid-induced satiety showed that fats inhibited feeding and led to the behavioral sequence of satiety within 15 min after the infusions began. This time course is evidence for a preabsorptive site of action to the small intestine. To test this hypothesis we added the local anesthetic tetracaine to Intralipid infusions. Tetracaine significantly reduced the satiating potency of Intralipid infusion. This result supports the hypothesis of a preabsorptive site of action. We also tested the specificity of intraduodenal Intralipid for feeding by administering Intralipid to rats that were sham drinking. The effect of Intralipid was relatively specific because the threshold concentration of Intralipid necessary to inhibit sham drinking was higher than the threshold for sham feeding. In addition, at superthreshold concentrations, Intralipid inhibited sham drinking less than sham feeding and elicited different behaviors than were observed during sham feeding.

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

To obtain more insight into the effect of dietary fiber on vitamin B6 status among elderly people, we studied dietary interrelationships as well as associations between dietary intake and plasma pyridoxal-5'-phosphate (PLP) and cofactor stimulation of aspartate aminotransferase in erythrocytes (EAST-AC) among 441 nonvegetarian (aged 65-79) and 32 vegetarian elderly (aged 65-94). EAST-AC was found to be inversely related with intake of vitamin B6 and dietary fiber in bivariate regression analyses. After adjustment for age, intake of energy, protein, and fiber, the intake of vitamin B6 was still inversely related with EAST-AC. The association between EAST-AC and dietary fiber disappeared in the multivariate analysis, whereas total protein intake proved to be positively related with EAST-AC in the multivariate analysis only. The differences between bi- and multivariate analyses are most likely due to the observed interrelationships between intake of vitamin B6, fiber, and protein. It is concluded that dietary fiber does not have a significant impact on the vitamin B6 status among Dutch elderly people, since only protein (positively) and vitamin B6 (inversely) intake appeared to be related with EAST-AC in the multivariate analysis.

An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the TψC loop of the tRNALys gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.

OBJECTIVE: To determine the nature, frequency and effects of internal medicine housestaff and faculty contacts with pharmaceutical representatives (PRs). DESIGN AND SETTING: The authors surveyed internal medicine faculty at seven midwest teaching hospitals and housestaff from two of the teaching programs. The survey asked about type and frequency of contacts with PRs and behavior that might be related to these contacts. T-tests and logistic regression were used to estimate the relationship between reported physician contacts and behavioral changes. PARTICIPANTS: Two hundred forty faculty (78%) and 131 house officers (75%) responded to the survey. RESULTS: Faculty and housestaff averaged 1.5 brief contacts per month with PRs. Housestaff averaged more than one meal/month at pharmaceutical company expense. Twenty-five percent of faculty and 32% of residents reported changing their practices at least once based on PR contact. Independent predictors of faculty change in practice were brief or extended conversations and free meals. Predictors of faculty requests for formulary addition were brief conversations and receipt of honoraria or research support. Only brief conversations independently predicted housestaff changes in practice. CONCLUSION: Academic housestaff and faculty have frequent PR contact; such contact is related to changes in behavior. The potential for influence of PRs in academic medical centers should be recognized, and their activities should be evaluated accordingly.

The effect of 48-hour starvation on glucose metabolism was studied in six non-diabetic, normal weight men using a hyperinsulinemic (100 mU/min/m2) glucose clamp (3.5 mmol/L). The rate of glucose oxidation was calculated from measurements of respiratory gas exchange, after allowing for the oxidation of ketones and of protein. During the glucose clamp, the whole body glucose disposal rate decreased from 39.8 (SEM 4.6) mumol/kg/min in the fed state to 24.1 (2.1) mumol/kg/min in the starved state (P less than .01), consistent with insulin "resistance." The glucose oxidation rate decreased from 21.8 (1.3) to 3.9 (1.4) mumol/kg/min with starvation (P less than .001), but the nonoxidative glucose disposal rate was unchanged (18.0 [3.9] mumol/kg/min normally fed, and 20.2 [1.2] mumol/kg/min starved). With starvation, the rate of glucose uptake in the forearm during the glucose clamp was reduced from 59.4 to 15.4 mumol/min/L forearm (SE 5.6, P less than .01, ANOVA). There was a significant net increase in thermogenesis during the glucose clamp in the normally fed state (0.27 [0.08] kJ/min, P less than .01, ANOVA), but not following starvation (0.11 [0.09] kJ/min, NS, ANOVA). Therefore, starvation caused decreases in oxidative glucose disposal and in forearm glucose uptake; despite the whole body nonoxidative disposal rate of glucose being unchanged, the associated net thermogenic response was diminished.

The relationships among anthropometric variables, dietary nutrients, and plasma steroid, polypeptide, and binding-protein hormone concentrations were investigated in 24 Seventh-day Adventist postmenopausal women, 12 vegetarian (SV) and 12 nonvegetarian (SNV). Fasting blood and 7-d dietary intake information were collected. SVs consumed significantly more crude and dietary fiber and fewer saturated fatty acids than did SNVs. The thigh and sum of three skinfold-thickness measurements were significantly greater for SNVs than for SVs. Plasma concentrations of estradiol-17 beta were significantly lower in SVs than in SNVs. Significant relationships were observed for the combined groups (SV and SNV) between estradiol-17 beta and triceps and suprailiac skinfold thickness and body fat. Plasma concentrations of estradiol-17 beta of the combined groups revealed a significant negative relationship between their crude and dietary fiber intakes. Further study delineating the effects of adiposity and dietary nutrients on basal concentrations of sex hormones is warranted.

The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.

It is well accepted that exercise endurance is directly related to the amount of carbohydrate stored in muscle and that a low carbohydrate diet reduces glycogen storage and exercise performance. However, more recent evidence has shown that when the organism adapts to a high fat diet endurance is not hindered. The present study was designed to test that claim and to further determine if animals adapted to a high fat diet could recover from exhausting exercise and exercise again in spite of carbohydrate deprivation. Fat-adapted (3 to 4 weeks, 78% fat, 1% carbohydrates) rats (FAT) ran (28 m/min, 10% grade) as long as carbohydrate-fed (69% carbohydrates) animals (CHO) (115 v 109 minutes, respectively) in spite of lower pre-exercise glycogen levels in red vastus muscle (36 v 54 mumols/g) and liver (164 v 313 mumols/g) in the FAT group. Following 72 hours of recovery on the FAT diet, glycogen in muscle had replenished to 42 mumols/g (v 52 for CHO) and liver glycogen to 238 mumols/g (v 335 for CHO). The animals were run to exhaustion a second time and run times were again similar (122 v 132 minutes FAT v CHO). When diets were switched after run 1, FAT-adapted animals, which received carbohydrates for 72 hours, restored muscle and liver glycogen (48 and 343 mumols/g, respectively) and then ran longer (144 minutes) than CHO-adapted animals (104 minutes) that ate fat for 72 hours and that had reduced glycogen repletion. We conclude that, in contrast to the classic CHO loading studies in humans that involved acute (72 hours) fat feedings and subsequently reduced endurance, rats adapted to a high fat diet do not have a decrease in endurance capacity even after recovery from previous exhausting work bouts. Part of this adaptation may involve the increased storage and utilization of intramuscular triglycerides (TG) as observed in the present experiment.

Lipid fractions such as phospholipids (PLs), cholesteryl esters (CEs), and free fatty acids (FFAs) represent source pools for eicosanoid synthesis. To determine whether dietary habits affect the enrichment of 20:4n-6 in these precursor pools, we studied humans with partial or complete arachidonate restriction resulting from chronic avoidance of animal fat and tissue. Fasting serum was obtained from omnivorous control subjects (Omni, n = 100), semivegetarians (Semiveg, n = 16), and vegetarians (Veg, n = 25). PLs, CEs, FFAs, and triglyceride (TG) fatty acids were quantitated by thin-layer and gas chromatography. Serum 20:4n-6 was lower in the PL fraction in both Veg (p less than 0.01) and Semiveg groups (p less than 0.05) than in the Omni group and lower in the CE fraction in the Veg group (p less than 0.05). Serum 18:2n-6 did not differ between groups for any serum lipid fraction. 18:3n-3 was elevated in PLs and CEs of both Veg (p less than 0.05 and 0.01) and Semiveg groups (p less than 0.05 and 0.01) compared with the Omni group but did not result in differences in 20:5n-3 in PLs or CEs between diet groups. The lower concentration of 20:4n-6 in serum PLs and CEs of the Veg group indicates that dietary arachidonic acid enriches its circulating pool in humans; however, 20:5n-3 is not similarly responsive to dietary restriction.

Three family members are reported with functional symptoms considered to be caused by intracellular deficiency of thiamin. Persistence of desaturation of erythrocyte transketolase in the face of megadose thiamin hydrochloride (THCl), accompanied by a balanced multivitamin and mineral formula, suggested a familial thiamin dependency state. Each of three individuals responded clinically to the administration of thiamin tetrahydrofurfuryl disulfide (TTFD), and erythrocyte transketolase (TKA) became fully saturated with thiamin pyrophosphate (TPP). Dysautonomic symptoms observed are compared with those seen in classical beriberi, the nutritional prototype for dysautonomia, and changes in blood pressure are described which support this premise. Although there is no proof from the laboratory, it is hypothesized that the biochemical lesion might be due either to malabsorption of thiamin or its inadequate phosphorylation.

Diets that reduce atherosclerosis risk lower levels of HDL cholesterol (HDL-C), but the significance of this is unclear. To better understand the mechanism of this phenomenon we studied the turnover of HDL apolipoproteins A-I and A-II in 13 subjects on two contrasting metabolic diets. Upon changing from high to low intake of saturated fat and cholesterol the mean HDL-C decreased 29% from 56 +/- 13 (SD) to 40 +/- 10 mg/dl, while apo A-I levels fell 23% from 139 +/- 22 to 107 +/- 22 mg/dl (both P less than 0.001). Mean apo A-II levels did not change. The fractional catabolic rate (FCR) of apo A-I increased 11% from 0.228 +/- 0.048 to 0.254 +/- 0.063 pools/d, while its absolute transport rate (TR) decreased 14% from 12.0 +/- 2.7 to 10.3 +/- 3.4 mg/kg per d (both P = 0.005). The decrease in HDL-C and apo A-I levels correlated with the decrease in apo A-I TR (r = 0.79 and 0.83, respectively; P less than 0.001), but not with the increase in apo A-I FCR (r = -0.04 and -0.02, respectively). In contrast, within each diet the HDL-C and apo A-I levels were inversely correlated with apo A-I FCR both on the high-fat (r = -0.85 and -0.77, P less than 0.001 and = 0.002, respectively) and low-fat diets (r = -0.67 and -0.48, P = 0.012 and 0.098, respectively) but not with apo A-I TR. In summary, diet-induced changes in HDL-C levels correlate with and may result from changes in apo A-I TR. In contrast, differences in HDL-C levels between people on a given diet correlate with and may result from differences in apo A-I FCR. Therefore, the mechanism of dietary effects on HDL levels differs substantially from the mechanism explaining the differences in levels between individuals on a fixed diet. In assessing coronary heart disease risk, it may be inappropriate to conclude that diet-induced decreases in HDL are equivalent to low HDL within a given diet.

Prior to the 17th century, there was considerable confusion regarding the process of digestion. Although some physicians were certain that it was initiated by acid in the stomach, both the source and the nature of the acid were unclear. In the early 19th century, Prout confirmed the active secretion of hydrochloric acid by the stomach and related it to the symptoms of dyspepsia. Jacob Helm and, subsequently, Beaumont studied digestion in humans with gastric fistulas and each commented extensively on the physiologic manifestation of digestion. The role of the vagus nerves in the control of gastric acid secretion was identified in the early and mid-19th century by Brodie, and subsequently elaborated upon by Pavlov. By the early 20th century, Latarjet and Jaboulay in France, performing operations for abdominal pain and tabes, reported the effects of vagotomy on acid secretion and gastric motility. In 1943, Dragstedt, in the United States, reported the cure of duodenal peptic ulcer disease by supradiaphragmatic vagotomy. He later observed the substantial delays in emptying of the stomach, which necessitated the introduction of concomitant gastric drainage procedures, such as gastrojejunostomy and pyloroplasty. In 1902, Bayliss and Starling had described the existence of a chemical regulator of function--secretin--which they termed a hormone. Shortly thereafter, Edkins reported results of studies that supported the presence of an acid regulatory hormone, gastrin, in the antrum of the stomach. Unfortunately, controversy marred this observation, and the action of gastrin was for more than 30 years ascribed to histamine. Komarov, in 1938, confirmed the existence of gastrin and its stimulatory effects on acid secretion. Physiologic recognition of the roles of vagal stimulation and antral gastrin in the secretion of acid from the stomach resulted in the development of the operation of vagotomy and antrectomy for peptic ulcer disease. Studies of the pylorus and the motility of the stomach resulted in an appreciation of the genesis of the postgastrectomy syndromes. By the middle of the 20th century, a clear appreciation of the morphologic characteristics of the parietal cell and its ability to secrete hydrochloric acid was under way. The complex metabolic process of the cell was correlated with the major morphologic transformation necessary to generate secretion of hydrochloric acid. The development of sophisticated research technology allowed the appreciation of the complex intracellular processes necessary to allow the generation of a 2.5 million-fold gradient of hydrogen ion secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Several studies suggest that behavioral techniques such as meditation and relaxation may be associated with reduced end organ adrenergic receptor sensitivity. Thus far the evidence supporting this hypothesis has been indirect. We present preliminary findings showing reduced beta-adrenergic receptor sensitivity in a group of subjects practicing Transcendental Meditation. The meditation group (N = 10), compared to controls (N = 10), had a lower percentage of functional lymphocyte beta-adrenergic receptors (p=0.009), but showed no difference in total receptor number or plasma catecholamines. There were no differences between the groups in Type A behavior, the Type A components, exercise, or family history of hypertension. The results provide some support for studies postulating that meditation is associated with reduced sympathetic adrenergic receptor sensitivity, and provide encouragement for the efficacy of receptor measurement in psychophysiology research. © 1990.

The N-myc gene is expressed specifically in the early developmental stages of numerous cell lineages. To assay for sequences that could potentially regulate N-myc expression, we transfected constructs that contained murine N-myc genomic sequences linked to a reporter gene and genomic clones that contained the comlete human or murine N-myc genes into cell lines that either express or do not express the endogenous N-myc gene. Following either transient or stable transfection, the introduced N-myc sequences were expressed regardless of the expression status of the endogenous gene. In contrast, when the clones containing the complete human N-myc gene were introduced into the germline of transgenic mice, expression in some transgenic lines paralleled the tissue- and stage-specific expression of the endogenous murine gene. These findings demonstrate differences in the regulation of N-myc genes in recipient cells following in vitro versus in vivo introduction, suggesting that early developmental events may play a role in the regulation of N-myc expression.

The effects of beta-carotene, canthaxanthin, and extracts of tomato paste (containing lycopene) and orange juice (containing cryptoxanthin) on aflatoxin B1 (AFB1)-induced mutagenesis in S. typhimurium TA 100 and TA 98 were investigated. Inhibition of mutagenesis was studied during and following completion of AFB1 metabolism (i.e., after the addition of menadione), thereby permitting separate examination of the metabolic activation and phenotypic expression phases. Each experimental carotenoid, except lycopene, inhibited AFB1-induced mutagenesis in both tester strains. Cryptoxanthin was the most potent inhibitor, being at least an order of magnitude more potent than the other carotenoids. Inhibition by beta-carotene and canthaxanthin was more prominent during the activation phase, whereas cryptoxanthin was more effective during the subsequent phenotypic expression phase. These inhibitory effects were not dependent on conversion to retinol.