Published Science

c-, N-, and L-myc are related nuclear oncoproteins that bind similar DNA sites and cooperate with activated ras oncogenes to transform primary fibroblasts. Although c-myc can also promote apoptosis in some cells after growth factor withdrawal or exposure to cytotoxic agents, roles for N- and L- myc in apoptosis remain undetermined. To address this, c-, N-, or L-myc were stably expressed in the interleukin 3 (IL-3)-dependent 32D hematopoietic cell line. The apoptotic response of each cell line was assessed after IL-3 withdrawal or treatment with four structurally unrelated cytotoxic agents. All three oncoproteins accelerated apoptosis after IL-3 withdrawal. In contrast, whereas c-myc overexpression generally sensitized cells to cytotoxic drugs, N-myc and L-myc overexpression produced resistance. myc expression tended to be associated with a more robust G2-M arrest after drug exposure, but this did not correlate with drug sensitivity or resistance. Bcl-2 and Bcl-X(L) protected control cells against apoptosis after either IL- 3 withdrawal or drug exposure, although in some cases this effect could be overridden by myc oncoproteins, particularly N-myc and L-myc. Our results suggest that the apoptotic pathways activated upon IL-3 withdrawal and cytotoxic drug treatment are distinct and differentially affected by members of the myc and Bcl-2 families.

Mandatory food rationing during World War II significantly challenged the image of the United States as a land of plenty and collapsed the boundaries between women's public and private lives by declaring home production and consumption to be political activities. Examining the food-related propaganda surrounding rationing, Eating For Victory decodes the dual message purveyed by the government and the media: while mandatory rationing was necessary to provide food for U.S. and Allied troops overseas, women on the home front were also "required" to provide their families with nutritious food. Amy Bentley reveals the role of the wartime homemaker as a pivotal component not only of World War II but also of the development of the United States into a superpower.

CONTEXT: Epidemiological studies have established a relationship between cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of ischemic heart disease (IHD), but up to half of patients with IHD may have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to predict the risk of IHD using a cluster of nontraditional metabolic risk factors that includes elevated fasting insulin and apolipoprotein B levels as well as small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and controls were identified from the population-based cohort of the Quebec Cardiovascular Study, a prospective study conducted in men free of IHD in 1985 and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with controls selected from among the sample of men who remained IHD free during follow-up. Matching variables were age, smoking habits, body mass index, and alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level, apolipoprotein B level, and LDL particle diameter to predict IHD events, defined as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary death. RESULTS: The risk of IHD was significantly increased in men who had elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL particles, compared with men who had normal levels for 2 of these 3 risk factors (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) did not attenuate the relationship between the cluster of nontraditional risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of IHD in men having a combination of elevated LDL-C and triglyceride levels and reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after multivariate adjustment for fasting plasma insulin level, apolipoprotein B level, and LDL particle size. CONCLUSION: Results from this prospective study suggest that the measurement of fasting plasma insulin level, apolipoprotein B level, and LDL particle size may provide further information on the risk of IHD compared with the information provided by conventional lipid variables.

Abstract: The fatty acid composition of phosphatidylethanolamine (PE), ethanolamine plasmalogens (EPs), phosphatidylserine (PS), phosphatidylcholine (PC), and sphingomyelin was studied in 22 human forebrains, ranging in age from 26 prenatal weeks to 8 postnatal years. Phospholipids were separated by two-dimensional TLC, and the fatty acid methyl esters studied by capillary column GLC. Docosahexaenoic acid (22:6n-3) increased with age in PE and PC, whereas arachidonic acid (20:4n-6) remained quite constant. In EP, 22:6n-3 increased less markedly than 20:4n-6, adrenic (22:4n-6) and oleic (18:1n-9) acids being the predominant fatty acids during postnatal age. In PS, 18:1n-9 increased dramatically throughout development, and 20:4n-6 and 22:4n-6 increased only until ∼6 months of age. Although 22:6n-3 kept quite constant during development in PS, its percentage decreased due to the accretion of other polyunsaturated fatty acids (PUFAs). As a characteristic myelin lipid, sphingomyelin was mainly constituted by very long chain saturated and monounsaturated fatty acids. Among them, nervonic acid (24:1n-9) was the major very long chain fatty acid in Sp, followed by 24:0, 26:1n-9, and 26:0, and its accretion after birth was dramatic. As myelination advanced, 18:1n-9 increased markedly in all four glycerophospholipids, predominating in EP, PS, and PC. In contrast, 22:6n-3 was the most important PUFA in PE in the mature forebrain.

Recommendations to Americans concerning dietary fat and heart disease began to appear in the late 1950s. This followed the publications of Gofman et al. (1950) and Keys (1953) relating to techniques for separating plasma lipoprotein fractions and the epidemiologic correlations between dietary fat, serum cholesterol and heart disease, respectively. Advice to the public after 40 years is similar to that given originally, namely, to reduce total fat, saturated fat and cholesterol intake, although cholesterol intake per se is not correlated strongly with cholesterolemia. Newer players on the heart disease stage are homocysteinemia, chlamydia infection and cytomegalovirus. These findings, when amplified, may alter the thrust of medical and dietary advice. In the meantime, since 1950, deaths from all causes in the U.S. (per 100,000, age-adjusted) have fallen by 40% and deaths from heart disease and stroke have fallen by 53 and 70%, respectively.

The number of people who avoid eating meat is growing, especially among young people. Benefits to health from a vegetarian diet have been reported in adults but it is not clear to what extent these benefits are due to diet or to other aspects of lifestyles. In children concern has been expressed concerning the adequacy of vegetarian diets especially with regard to growth. The risks/benefits seem to be related to the degree of restriction of he diet; anaemia is probably both the main and the most serious risk but this also applies to omnivores. Vegan diets are more likely to be associated with malnutrition, especially if the diets are the result of authoritarian dogma. Overall, lacto-ovo-vegetarian children consume diets closer to recommendations than omnivores and their pre-pubertal growth is at least as good. The simplest strategy when becoming vegetarian may involve reliance on vegetarian convenience foods which are not necessarily superior in nutritional composition. The vegetarian sector of the food industry could do more to produce foods closer to recommendations. Vegetarian diets can be, but are not necessarily, adequate for children, providing vigilance is maintained, particularly to ensure variety. Identical comments apply to omnivorous diets. Three threats to the diet of children are too much reliance on convenience foods, lack of variety and lack of exercise.

This study was designed to investigate factors influencing the maintenance of a vegetarian diet. An interpretivist approach and qualitative research methods were used in the study design. Nineteen vegetarians from a metropolitan area in Western New York State were purposefully recruited using snowball sampling to participate in in-depth interviews. Respondents varied in age, gender and type and duration of vegetarian diet, although the sample was predominantly middle-aged, middle-class and female and had ties to community groups. Interview transcripts were analyzed using the constant comparative method of qualitative data analysis. The maintenance of vegetarian diets was supported by personal factors, social networks and environmental resources. Personal factors included: internal beliefs, skills and habits and physical feedback. Social networks included: organized vegetarian groups as well as animal rights, environmental, or health groups supporting vegetarianism and vegetarian friends. Environmental resources, such as the availability of new vegetarian foods in supermarkets and restaurants, facilitated maintenance of vegetarian diets. Respondents perceived that society viewed vegetarianism as increasingly "mainstream," although diet-centred family conflicts were still common. These findings can assist dietitians in developing strategies for working with vegetarian clients by providing better understanding of personal, social and environmental supports for vegetarians' dietary behaviours.

"Explores the evolution and transformation of the American diet from colonial times to the present." Includes the introduction of exotic foods into an originally bland diet, the disappearance of early staples from the average modern diet, the influence of grocery stores and restaurants on modern diet, and more.

The prostate gland of humans and many other animals has the major function of accumulating and secreting extraordinarily high levels of citrate. This specialized metabolic process of “net citrate production” is the result of unique metabolic capabilities of the secretory epithelial cells. Most importantly, in prostate cancer (Pca) the capability for net citrate production is lost. In addition to citrate, the normal and BPH (benign prostatic hyperplasia) prostate also accumulates the highest levels of zinc in the body. As with citrate, in Pca the ability for high zinc accumulation is diminished. These and other correlations between zinc and citrate in the prostate have been indicative of an important role of zinc in the regulation of citrate metabolism in normal and malignant prostate epithelial cells. The link between zinc and citrate metabolism has now been established. The intramitochondrial accumulation of high zinc levels inhibits mitochondrial (m-) aconitase activity, which inhibits citrate oxidation. This essentially truncates the Krebs cycle and markedly decreases the cellular energy (ATP) production normally coupled to citrate oxidation. It is also clear that zinc accumulation in citrate-producing prostate epithelial cells is regulated by testosterone and by prolactin. These relationships form the basis for a new concept of the role of zinc and citrate-related energy metabolism in prostate malignancy. The inability of malignant prostate cells to accumulate high zinc levels results in increased citrate oxidation and the coupled ATP production essential for the progression of malignancy. The concept offers new approaches to the treatment of Pca. Prostate 35:285–296, 1998. © 1998 Wiley-Liss, Inc.

BACKGROUND Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure. METHODS AND RESULTS This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction \textless 45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group 1. Forty percent of all patients had central sleep apnea, and 11% had obstructive sleep apnea. The latter patients had significantly greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus 23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%) were similar in patients with these different types of apnea. CONCLUSIONS Fifty-one percent of male patients with stable heart failure suffer from sleep-related breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both obstructive and central types of sleep apnea result in sleep disruption and arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high prevalence of atrial fibrillation and ventricular arrhythmias.

Sweet potato has been selected as one of the crops for NASA's Advanced Life Support Program. Sweet potato primarily provides carbohydrate--an important energy source, beta-carotene, and ascorbic acid to a space diet. This study focuses on menus incorporating two sets of sweet potato recipes developed at Tuskegee University. One set includes recipes for 10 vegetarian products containing fom 6% to 20% sweet potato on a dry weight basis (pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels) that have been formulated, subjected to sensory evaluation, and determined to be acceptable. These recipes and the other set of recipes, not tested organoleptically, were substituted in a 10-day vegetarian menu plan developed by the American Institute of Biological Sciences (AIBS) Kennedy Space Center Biomass Processing Technical Panel. At least one recipe containing sweet potato was included in each meal. An analysis of the nutritional quality of this menu compared to the original AIBS menu found improved beta-carotene content (p

The Magic Harvest offers a wide-ranging account of the history of popular beliefs about food in Europe. Focusing on Italy, the text examines the social symbolism of food, and its associated rituals.

We provide a comprehensive review of the neurobiological basis of attention-deficit/hyperactivity disorder. This summary was accomplished by a review of research in three areas: neuroimaging, genetics, and neurochemistry. Additionally, we also discuss a newer conceptualization of the disorder. Although none of the current findings present a unified picture of the pathophysiology of the disorder, the vast array of studies reviewed do highlight CNS abnormalities that, when taken together, present a convincing argument that the cause clearly resides within the realm of developing brain.

This article reviews the history of the US Department of Agriculture School Breakfast Program (SBP) and provides a synthesis of factors influencing participation rates. Certain children are more likely to participate than others, such as those in lower grades and those from low-income households, and African American, Hispanic, and male students. A few studies in the past 25 y have examined the effectiveness of the SBP in improving the diets and nutritional status of children. The overall pattern that emerges from these studies is that the SBP contributes to improved nutrient intake in program participants. Less attention has been devoted to assessing the effects of SBP on cognitive development. Some of the evidence reviewed here suggests that the SBP significantly improves school performance and reduces absenteeism and tardiness. Future directions for research and operation of the SBP are discussed in light of the changing dietary profile of American children.

We determined the quantitative relationships between graded oral dosing with vitamin D3, 25(OH)D3, and 1,25(OH)2D3 for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 +/- 4 years, with usual milk consumption of

In recent decades, prostate cancer has emerged as one of the most common diseases among older men, particularly in Western society. Several years ago, only one age, race, and family history were known risk factors of this disease. However, today, much progress has been made towards discovering nutritional and hormonal risk factors for prostate cancer. Biomarkers, including testosterone and insulin-like growth factor, and nutritional factors, especially meat, fat, and dairy intake, have been linked to greater risk of disease. Higher consumption of selenium and vitamin E, fructose/fruits, and tomatoes all have been associated with reduced occurrence of prostate cancer, but as yet their efficacy for prevention remains unproven. The challenge of understanding the enigmas of this disease will continue into future decades, as we convert current knowledge into preventive and therapeutic recommendations.

Health status, the way of life and nourishment of 84 vegans in Siberian village (Krasnoyarsk region) were studied and compared with those of 26 meat-eaters. The investigation included work with a questionnaire, clinico-diagnostic and laboratory research. It was shown that a vegetarian diet improves the serum lipid spectrum (cholesterol, LPLD, cholesterol of LPNP, atherogenic coefficient), normalizes weight and cardiovascular system. The vegans had normal levels of vitamin B12 and serum Fe but the calcium level in this group was lowered as compared with the control group. The pathology of internals (nephroptosis, lithic diathesis, tendency to lithogenesis) was observed. Apparently, the high serum Zn levels found in both groups aren't directly caused by the diet but by climate and geographic factors.

The aim of my work was the answer to the following questions: how often does the deficiency of magnesium, copper, zinc, calcium, iron occur among hyperactive children in comparison with healthy children, deficiency of which of the considered bioelements is the most frequent, what is the effect of supplementation of deficit element on hyperactivity and does it depend on other certain disorders that coexist with hyperactivity? In a process of establishing the subject diagnosis I have followed the DSM IV criteria recognizing ADHD among examined ones. I have determined the deficiency of magnesium, copper, zinc, calcium, iron in the group of 116 children with diagnosed ADHD. Consequently, as a result, I have found out that shortage of above-mentioned bioelements occurs more often among hyperactive children than among those being healthy, and deficiency of magnesium is the most frequent in this respect. Further, I have divided the group of 110 children with magnesium deficiency into two groups according to the other mental disorders that coexist with ADHD: 1) the group where hyperactivity coexists with disorders typical for developmental age such as enuresis, tics, separation anxiety, stuttering, selective mutism (63 children); 2) the group where hyperactivity coexists with disruptive behaviour disorders: conduct disorder and oppositional defiant disorder (47 children). The content of magnesium, copper, zinc, calcium, iron has been determined respectively in blood (serum and red cells) and in hair by atomic absorption spectroscopy method in both groups accordingly. At the same time, the hyperactivity tests were carried out using Conner's Rating Scales for Parents and Teachers, Wender's Scale as well as Quotient of Development to Freedom from Distractibility. During the statistical analysis the inparametric tests have been used taking as a significance level p

In a search for suitable biomarkers for human dietary exposure to heterocyclic aromatic amines (HAAs), we have investigated the concentrations of three common fried food mutagens in food and urine after consumption of a fried meat meal. In this connection we developed a method for the determination of HAAs and have investigated the common fried red meat HAAs 2-amino-1-methyl-6-phenylimidazo[4,5-beta]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). Eight volunteers participated in the study, each consuming a meal of fried minced beef patties (295 g), boiled potatoes, and a green salad. Urine was collected for two 12-hr periods prior to and following the meal. HAAs were determined in cooked meat and in untreated and acid hydrolysed urine by a series of liquid/liquid extractions, followed by Blue cotton adsorption and finally by a novel derivatized technique for gas chromatography-mass spectrometry (GC-MS). The primary amino groups were derivatized by acylation with heptafluorobutyric acid anhydride, and the resulting amide methylated using diazomethane. Phenolic hydroxyl groups were also methylated by this procedure, making it possible to detect hydroxylated HAAs, possible metabolites or constituents of the fried meat. 4'-Hydroxy-PhIP ¿2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-beta]pyridine¿ (4'-OH-PhIP) was indeed found in meat as well as in urine. The contents of PhIP, MeIQx and DiMeIQx in meat were 4.0 +/- 2.6, 3.5 +/- 0.9 and 0.3 +/- 0.1 ng g-1 (mean +/- SD, n = 4), from which the mean amounts ingested were calculated to be 1180, 1030 and 90 ng, respectively. Total amounts of HAAs in the 0-24-hr post-meal untreated urine (and percent of ingested dose) were 6-23 ng PhIP (0.5-2%) and 10-63 ng MeIQx (1-6%). In hydrolysed urine, the levels of HAAs were higher, totalling 24-100 ng PhIP (2-8.5%) and 133-329 ng of MeIQx (13-32%). DiMeIQx was below detection limit in all urine samples. Judged from our study, there were rather large inter-individual variations in the amounts of excreted HAAs, possibly caused by variations in the activities of enzymes taking part in HAA metabolism.

In a national survey, 199 male and 152 female vegetarian runners and 7054 male and 1837 female omnivorous runners provided data on weekly intakes of alcohol, red meat, fish, and fruit, and weekly distance run. This information was compared with physician-supplied medical data to test whether 1) running benefits vegetarians, 2) alcohol and running distance contribute independently to concentrations of high-density-lipoprotein (HDL) cholesterol, and 3) running mitigates the hypertensive effects of alcohol. Greater reported weekly distance run by vegetarians was associated with greater HDL-cholesterol concentrations [slopes +/- SEs for men and women, respectively: 0.003 +/- 0.001 and 0.005 +/- 0.002 (mmol/L)/km] and lower waist (-0.06 +/- 0.02 and-0.08 +/- 0.02 cm/km), hip (-0.05 +/- 0.03 and -0.07 +/- 0.02 cm/km), and chest (-0.05 +/- 0.02 cm/km for both) circumferences. In men and women, alcohol and running distance contributed independently to higher HDL-cholesterol concentrations. Men who ran > 72 km and drank > 177 mL (6 oz) alcohol/wk were five times more likely to have clinically defined high HDL cholesterol (> or = 1.55 mmol/L, or > or = 60 mg/dL) than were nondrinkers running

This article discusses the potential health benefits of a vegetarian diet, while highlighting some potential problems that may occur if such a dietary regimen is adopted, particularly in certain groups. It emphasises the importance of health professionals contributing to people's knowledge of nutrition in order to allow them to choose a healthy diet, whether they are vegetarian or meat eaters.

OBJECTIVE: Low cerebral metabolic rates for glucose (CMRglc) have been reported in a small sample of girls with attention-deficit/hyperactivity disorder (ADHD). This study was an effort to replicate this finding in a larger independent sample. METHOD: Using positron emission tomography and [18F]fluorodeoxyglucose, CMRglc were compared between 10 girls with ADHD (14.10 +/- 1.91 years) and 11 normal girls (14.3 +/- 1.70 years). RESULTS: Global CMRglc was similar between ADHD and control girls. Lateralization of normalized CMRglc differed significantly between ADHD and control girls in parietal and subcortical regions, with rCMRglc lower on the left than on the right side in girls with ADHD, and conversely in control girls. The sylvian area of the parietal region and the anterior putamen of the subcortical region were the main contributors to this effect. Normalized rCMRglc of the hippocampus was higher in ADHD than in control girls. Sexual maturation was the only clinical characteristic that differed between present and previous samples, and it correlated with global CMRglc. CONCLUSIONS: Although failing to confirm abnormally low CMRglc in girls with ADHD, this study suggested that (1) functional interactions between sex and brain development may contribute to ADHD pathophysiology, and (2) sexual maturation should be controlled in future CMRglc studies of adolescent girls.

We describe the distribution in human tissues of three enzymes of ketone body utilization: succinyl-CoA:3-ketoacid CoA transferase (SCOT), mitochondrial acetoacetyl-CoA thiolase (T2), and cytosolic acetoacetyl-CoA thiolase (CT). Hereditary deficiency of each of these enzymes has been associated with ketoacidosis. Physiologically the two mitochondrial enzymes have different roles: SCOT mediates energy production from ketone bodies (ketolysis), whereas T2 functions both in ketogenesis and ketolysis. In contrast, CT is implicated in cytosolic cholesterol synthesis. We investigated the tissue distribution of these enzymes in humans by quantitative immunoblots and by Northern blots. In most tissues, polypeptide and mRNA levels were proportional. CT and T2 proteins were detected in all tissues examined. CT levels were highest in liver, were 4-fold lower in adrenal glands, kidney, brain, and lung, and were lowest in skeletal and heart muscles. T2 was most abundant in liver but substantial amounts were present in kidney, heart, adrenal glands, and skeletal muscle. SCOT was detected in all tissues except liver: myocardium > brain, kidney and adrenal glands. The relative amounts of T2 and SCOT were similar in all tissues except for liver (T2 > > SCOT) and brain (SCOT > T2). The observed distribution of SCOT, T2, and CT is consistent with current views of their physiologic roles.

To evaluate the health and nutritional status of children with two different nutritional habits, the authors examined 26 vegetarians (lacto- and lacto-ovo; an average period of vegetarianism 2.8 years) and 32 individuals on mixed diet (omnivores) in the age range 11-14 years. Vegetarian children had significantly lower erythrocyte number as well as reduced levels of haemoglobin and iron compared to omnivores. The average level of iron did not reach the lower limit of the physiological range and hyposiderinemia was found in 58% of vegetarians vs 9% of omnivores. Reduced iron levels were observed in spite of increased intake of vegetable iron sources and vitamin C (which facilitates the conversion to ferro-form). This reduction can be attributed to the absence of animal iron sources with high utilizability and to lower iron utilization in the presence of phytic acid (higher intake of grains compared to omnivores). The incidence of hypoalbuminemia and hypoproteinemia in vegetarian children was 38 and 12%, respectively, compared to 0% in omnivores. The protein mixture from milk, eggs and vegetable sources is complete, but vegetarian children had significantly reduced intake of milk and dairy products. Favourable lipid and antioxidant parameters in vegetarian children reflect the optimal nutrition composition with respect to the prevention of free radical diseases. Such a nutrition results in significantly lower levels of cholesterol and LDL-cholesterol compared to omnivores and significantly higher and over threshold values of essential antioxidants--vitamin C, vitamin E/cholesterol (more effective protection against LDL oxidation), beta-carotene, vitamin A.

This study investigated whether lipoprotein(a) [Lp(a)] is an acute-phase reactant that can cause important bias in risk factor analysis for coronary heart disease among patients with an acute-phase response (APR patients). To determine whether serum Lp(a) concentrations increase among APR patients, we compared the Lp(a) concentrations and apolipoprotein(a) [apo(a)] phenotypes of 100 controls with those of a random sampling of 100 APR patients. Serum Lp(a) concentration was measured by ELISA; Lp(a) phenotyping was performed by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel. Lp(a) was significantly (P

It is proposed that obsessions are caused by catastrophic misinterpretations of the significance of one's thoughts (images, impulses). The obsessions persist as long as these misinterpretations continue and diminish when the misinterpretations are weakened. Evidence and arguments in support of the theory are presented, and the questions of vulnerability and the origins of the thoughts are addressed. A firmly focused treatment strategy is deduced from the theory.

Vitamin D plays a major role in bone mineral homeostasis by promoting the transport of calcium and phosphate to ensure that the blood levels of these ions are sufficient for the normal mineralization of type I collagen matrix in the skeleton. In contrast to classic vitamin D-deficiency rickets, a number of vitamin D-resistant rachitic syndromes are caused by acquired and hereditary defects in the metabolic activation of the vitamin to its hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or in the subsequent functions of the hormone in target cells. The actions of 1,25(OH)2D3 are mediated by the nuclear vitamin D receptor (VDR), a phosphoprotein which binds the hormone with-high affinity and regulates the expression of genes via zinc finger-mediated DNA binding and protein-protein interactions. In hereditary hypocalcemic vitamin D-resistant rickets (HVDRR), natural mutations in human VDR that confer patients with tissue insensitivity to 1,25(OH)2D3 are particularly instructive in revealing VDR structure function relationships. These mutations fall into three categories: (i) DNA binding/nuclear localization, (ii) hormone binding and (iii) heterodimerization with retinoid X receptors (RXRs). That all three classes of VDR mutations generate the HVDRR phenotype is consistent with a basic model of the active receptor as a DNA-bound, 1,25(OH)2D3-liganded heterodimer of VDR and RXR. Vitamin D responsive elements (VDREs) consisting of direct hexanucleotide repeats with a spacer of three nucleotides have been identified in the promoter regions of positively controlled genes expressed in bone, such as osteocalcin, osteopontin, beta 3-integrin and vitamin D 24-OHase. The 1,25(OH)2D3 ligand promotes VDR-RXR heterodimerization and specific, high affinity VDRE binding, whereas the ligand for RXR, 9-cis retinoic acid (9-cis RA), is capable of suppressing 1,25(OH)2D3-stimulated transcription by diverting RXR to form homodimers. However, initial 1,25(OH)2D3 liganding of a VDR monomer renders it competent not only to recruit RXR into a heterodimer but also to conformationally silence the ability of its RXR partner to bind 9-cis RA and dissociate the heterodimer. Additional probing of protein-protein interactions has revealed that VDR also binds to basal transcription factor IIB (TFIIB) and, in the presence of 1,25(OH)2D3, an RXR-VDR-TFIIB ternary complex can be created in solution. Moreover, for transcriptional activation by 1,25(OH)2D3, both VDR and RXR require an intact short amphipathic alpha-helix, known as AF-2, positioned at their extreme C-termini. Because the AF-2 domains participate neither in VDR-RXR heterodimerization nor in TFIIB association, it is hypothesized that they contact, in a ligand-dependent fashion, transcriptional coactivators such as those of the steroid receptor coactivator family, constituting yet a third protein-protein interaction for VDR. Therefore, in VDR-mediated transcriptional activation, 1,25(OH)2D3 binding to VDR alters the conformation of the ligand binding domain such that it: (i) engages in strong heterodimerization with RXR to facilitate VDRE binding, (ii) influences the RXR ligand binding domain such that it is resistant to the binding of 9-cis RA but active in recruiting coactivator to its AF-2 and (iii) presents the AF-2 region in VDR for coactivator association. The above events, including bridging by coactivators to the TATA binding protein and associated factors, may position VDR such that it is able to attract TFIIB and the balance of the RNA polymerase II transcription machinery, culminating in repeated transcriptional initiation of VDRE-containing, vitamin D target genes. Such a model would explain the action of 1,25(OH)2D3 to elicit bone remodeling by stimulating osteoblast and osteoclast precursor gene expression, while concomitantly triggering the termination of its hormonal signal by inducing the 24-OHase catabolizing enzyme.

OBJECTIVE: To quantitatively review and critically evaluate literature examining gender differences in attention-deficit hyperactivity disorder (ADHD). METHOD: A meta-analysis of relevant research based on 18 studies meeting inclusion criteria was performed. Domains evaluated included primary symptomatology, intellectual and academic functioning, comorbid behavior problems, social behavior, and family variables. RESULTS: Gender differences were not found in impulsivity, academic performance, social functioning fine motor skills, parental education, or parental depression. However, compared with ADHD boys, ADHD girls displayed greater intellectual impairment, lower levels of hyperactivity, and lower rates of other externalizing behaviors; it was not possible to evaluate the extent to which referral bias affected these findings. Some gender differences were clearly mediated by the effects of referral source; among children with ADHD identified from nonreferred populations, girls with ADHD displayed lower levels of inattention, internalizing behavior, and peer aggression than boys with ADHD, while girls and boys with ADHD identified from clinic-referred samples displayed similar levels of impairment on these variables. CONCLUSIONS: The need for future research examining gender differences in ADHD is strongly indicated, with attention to methodological limitations of the current literature, including the potential confounding effects of referral bias, comorbidity, developmental patterns, diagnostic procedures, and rater source.

A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother's vegan diet. Clinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy …

The association between dietary fat consumption and risk of cancer, especially colon, breast, prostate, and ovary cancer, has been debated for many years. Ecologic studies over the past 30 years have demonstrated the correlation of greater dietary fat intake with higher mortality due to various cancers. Migrant studies also have shown that increased fat consumption may be associated with increased risk of cancer. Specific saturated fatty acids raise blood cholesterol levels and, thereby, increase the risk of atherosclerosis. Greater fat, intake is a major cause of obesity and hypertension, diabetes, and gallbladder disease. Higher fat intake may heighten the risk of breast cancer directly through increased blood estrogen levels and/or secondarily through increased obesity. The critical experimental studies to determine the effects of a low-fat diet on disease risk have not been completed, but reducing fat in the US diet has the potential to decrease morbidity and mortality substantially.

Barrows were restrictively fed starting at 20 kg BW to determine the effects of endotoxin on growth performance of control and somatotropin-treated pigs. The following treatments were used: 1) daily i.m. vehicle injection until 55 kg BW; 2) daily i.m. injections of 100 micrograms of recombinant porcine somatotropin (pST)/kg BW, until 55 kg; 3) i.v. saline injections for 7 d consecutively starting at 60 kg BW; 4) i.v. injections of 1 microgram of bacterial lipopolysaccharide (LPS)/kg BW for 7 d starting at 60 kg BW; and 5) the combined LPS+pST treatment, with pST injections from 20 kg through the 7 d of LPS treatment. Pigs evaluated for LPS effects were fed to 60 kg anticipating a weight loss. Pigs were bled at 0800 and 1100 at 55 kg and on d 7 of LPS treatment. Rectal temperatures were taken on d 7. Treatment with pST increased ADG by 13 to 20% and improved feed:gain by 17 to 23% before LPS treatment. During the 7 d of LPS injections, ADG and feed:gain did not differ, although feed efficiency was impaired and variable. Rectal temperatures at 1100 were progressively increased: control < LPS < LPS-pST (P < .01). Protein accretion was improved 27% by pST treatment, and lipid accretion was decreased 45% before LPS. Lipid stores decreased (P < .01) after LPS treatment in the pST-treated pigs. Lipopolysaccharide treatment and(or) decreased feed intake reduced the hyperinsulinemia and hyperglycemia (P

PURPOSE: Despite use of the ketogenic diet (KD) for >75 years its effectiveness or mechanism of action has been examined in few animal studies. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in adult rats. METHODS: Rats fully kindled from the amygdala were divided into KD-fed or standard rat diet-fed groups; diet treatment continued for 5 weeks. The KD approximated at 4:1 ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was contributed by fat and 8% was contributed by protein. Afterdischarge threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST, SD) were assessed weekly for 5 weeks. During week 3, learning and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test. RESULTS: Rats receiving the KD became ketonemic and had weight gains similar to those of control rats. As compared with rats receiving a standard diet, those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard to ADD or SD at any time during the study, and both groups performed similarly in the water maze and open field test. CONCLUSIONS: In the kindling model, the KD afforded transient protection against the focal generation of kindled seizures but not seizure spread. Rats that received the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promising model for study of the anticonvulsant mechanisms of ketosis.

Evidence that the thyroid may play a role in the pathogenesis of attention deficit hyperactivity disorder (ADHD) comes from observations that 48% to 73% of children with the syndrome of resistance to thyroid hormone (RTH) have ADHD. Casual observations in subjects with RTH have suggested that treatment with thyroid hormone may improve the symptoms of ADHD. The aim of this study was to determine whether thyroid hormone has a beneficial effect on the behavior of children with RTH. A prospective, randomized, double-blinded, placebo-controlled, cross-over study was conducted to evaluate the effect of the rapid acting thyroid hormone, liothyronine (L-T3), on the behavior of 8 children with ADHD + RTH, and 9 children with ADHD and normal thyroid function (ADHD Only). Parent and teacher ratings of hyperactivity (Conners scale) and a computerized continuous performance test (CPT) were used as objective measures of hyperactivity, attention and impulsivity. L-T3 had no effect on Conners Hyperactivity Index in 7 of 9 children with ADHD Only; it caused improvement and deterioration in 1 subject each. In contrast, the rating in 5 of 8 subjects with ADHD + RTH showed improvement, whereas 3 of 8 subjects remained unchanged. L-T3 was associated with increased commission errors in 5 of 8 children with ADHD Only and decreased commission errors in 4 of 7 with ADHD + RTH. In children with RTH and ADHD, particularly those that exhibit hyperactivity, L-T3 in supraphysiological doses may be beneficial in reducing hyperactivity and impulsivity. In the majority of children with ADHD who do not have RTH, L-T3 treatment has no effect or may be detrimental.

Calcium bioavailability of vegetarian diets containing various proportions of candidate crops for a controlled ecological life-support system (CELSS) was determined by femur 45Ca uptake. Three vegetarian diets and a control diet were labeled extrinsically with 45Ca and fed to 5-wk old male rats. A fifth group of rats fed an unlabeled control diet received an intraperitoneal (IP) injection of 45Ca. There was no significant difference in mean calcium absorption of vegetarian diets (90.80 +/- 5.23%) and control diet (87.85 +/- 5.25%) when calculated as the percent of an IP dose. The amounts of phytate, oxalate, and dietary fiber in the diets did not affect calcium absorption.

Carbohydrate ingestion before and during endurance exercise delays the onset of fatigue (reduced power output). Therefore, endurance athletes are recommended to ingest diets high in carbohydrate (70% of total energy) during competition and training. However, increasing the availability of plasma free fatty acids has been shown to slow the rate of muscle and liver glycogen depletion by promoting the utilization of fat. Ingested fat, in the form of long-chain (C16-22) triacylglycerols, is largely unavailable during acute exercise, but medium-chain (C8-10) triacylglycerols are rapidly absorbed and oxidized. We have shown that the ingestion of medium-chain triacylglycerols in combination with carbohydrate spares muscle carbohydrate stores during 2 h of submaximal ( 70% by energy). Dietary fat adaptation for a period of at least 2-4 weeks has resulted in a nearly two-fold increase in resistance to fatigue during prolonged, low- to moderate-intensity cycling (

Foods which increase tissue arachidonic acid levels have been proposed to increase thrombosis tendency, presumably through increased platelet aggregation. This study examined the effect of doubling the dietary arachidonic acid (20:4n-6) using meat- or fish-based diets on the systemic production of prostacyclin (PGI2) and thromboxane (TXA2) in 29 healthy, nonsmoking adults. There were three, 3-wk low-fat dietary periods (< 15% energy as fat) in which subjects consumed a vegetarian diet for 1 wk followed by 2 wk on diets containing meat or fish as sources of 20:4n-6. Between each diet period, there was a 3-wk washout period, during which subjects returned to their normal diets. The level of 20:4n-6 consumed during the last 2 wk of each study was approximately double the usual intake (mean 140 mg/d), while the mean eicosapentaenoic acid (20:5n-3) content of the diets varied from 1 mg/d on the white meat diet to 70 mg/d on the red meat diet and to 847 mg/d on the fish diet. The serum phospholipid (PL) 20:4n-6/20:5n-3 ratios were 11:1 on the vegetarian diet, 15:1 on the white meat diet, 8:1 on the red meat diet, and 2:1 on the fish diet (P < 0.001). Neither white nor red meat diets affected platelet 20:4n-6 levels, platelet aggregation, ex vivo platelet TXB2 production, or the systemic PGI2 or TXA2 production as measured by gas chromatography-mass spectrometry analysis of the excretion levels of the principal urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and 11-dehydro-TXB2 (TXA2-M), respectively. The fish diet decreased the 20:4n-6/20:5n-3 ratio in platelet PL from the baseline level of 45:1 to 13:1 (P

CLINICAL RELEVANCE: In contrast to observations in human beings, allopurinol metabolism is not influenced by diet. Therefore, formation of xanthine-containing calculi in dogs consuming a high-protein diet and receiving allopurinol is probably not attributable to alteration of allopurinol metabolism.

To better understand the physiology of colonic gas production, each flatus passage of 16 subjects over a 4-h period was analyzed by gas chromatography for N2, O2, H2, CO2, CH4, and for odoriferous sulfur-containing gases. Appreciable intraindividual and enormous interindividual variability was observed, indicating that each gas passage reflected the interaction of highly variable liberation and/or removal mechanisms. The predominant flatus gas was CO2, H2, and N2 in seven, six, and three subjects, respectively. Gases produced intraluminally (H2, CO2, and CH4) comprised approximately 74% of flatus, and rapid CO2 and H2 productions were responsible for high passage rates. A positive correlation between flatus H2 and CO2 suggested that CO2, like H2, mainly was a bacterial product. Whereas methanogens and H2S-producing bacteria usually are mutually exclusive in feces, CH4 and H2S did not negatively correlate, indicating coexistence of both organisms in the colon. We conclude that analysis of flatus composition provides a novel means of assessing colonic physiology, particularly ongoing bacterial metabolism throughout the unperturbed colon.

The toxicological consequences of exposure to mercury (Hg) from dental amalgam fillings is a matter of debate in several countries. The purpose of this study was to obtain data on Hg concentrations in saliva and feces before and after removal of dental amalgam fillings. In addition Hg concentrations in urine, blood, and plasma were determined. Ten subjects had all amalgam fillings removed at one dental session. Before removal, the median Hg concentration in feces was more than 10 times higher than in samples from an amalgam free reference group consisting of 10 individuals (2.7 vs 0.23 mumol Hg/kg dry weight, p

OBJECTIVE: To assess the information pharmaceutical sales representatives provide to physicians. DATA SOURCES: A MEDLINE search from January 1966 to May 1996 was done using combinations of the terms pharmaceutical industry, drug information services, drug utilization, physician's practice patterns and prescriptions, and drugs. Studies identified from this search were supplemented by material from my personal library. STUDY SELECTION: Studies had to be conducted in industrialized countries, based on direct observations of actual physician and sales representative contacts, and reporting quantitative results on the quality of information transmitted. SYNTHESIS: Four studies were included. Representatives usually mentioned the indications for their drugs, but omitted safety information. Representatives' information frequently contained inaccuracies. CONCLUSION: Sales representatives present only selected, usually positive, information about their products. Canadian doctors should not be passive recipients of information provided by sales representatives. Physicians who choose to continue to see representatives must critically compare the information they get from them with that contained in scientific publications.