Published Science

Author Information Michael P. Richards*†, Paul B. Pettitt*‡, Erik Trinkaus§¶‖, Fred H. Smith**, Maja Paunovi懇, and Ivor Karavani憆*Research Laboratory for Archaeology and the History of Art, University of Oxford, 6 Keble Road, Oxford OX1 3QJ, United Kingdom; †Department of Archaeology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada; ‡Keble College, Oxford OX1 3PG, United Kingdom; §Department of Anthropology, Campus Box 1114, Washington University, St. Louis MO 63130; ¶Unité Mixte de Recherche 5809 du Centre National de la Recherche Scientifique, Laboratoire d'Anthropologie, Université de Bordeaux I, 33405 Talence, France; **Department of Anthropology, Northern Illinois University, DeKalb, IL 60115; ‡‡Zavod za paleontologiju i geologiju kvartara, Hrvatske akademije znanosti i umjetnosti, Ulica A. Kovačića 5/II, HR-10000 Zagreb, Croatia; and ††Arheološki zavod Filozofskog fakulteta Sveučilišta u Zagrebu, I. Lučića 3, HR-10000 Zagreb, Croatia Contributed by Erik Trinkaus Footnotes ↵‖ To whom reprint requests should be addressed. E-mail: trinkaus@artsci.wustl.edu. Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.120178997. Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.120178997

The first reports of the influences of oxidized LDL (oxLDL) on cell function pertained to negative effects on cell growth-growth arrest, injury, and toxicity. Since these studies, it has become apparent that sublethal levels of oxLDL cause some, but not all, cells to proliferate. This review highlights the growth-promoting effects of oxLDL rather than its inhibitory or injurious effects. Smooth muscle cells (SMCs) and monocyte-macrophages proliferate after exposure to oxLDL; endothelial cells do not. Scavenger receptors are involved in the proliferative effects on monocyte-macrophages, whereas the effects of oxLDL on SMCs appear to be receptor independent. Lysophosphatidylcholine (lysoPC), and structurally related lipids are among the growth-promoting constituents of oxLDL. OxLDL exerts at least a part of its effects by inducing expression or causing the release of growth factors. OxLDL (or lysoPC) can cause the release of basic fibroblast growth factor (bFGF) from SMCs; oxLDL (or lysoPC) can induce heparin binding EGF-like growth factor (HB-EGF) synthesis and release from macrophages. An imposing array of changes in cytokine and growth factor expression and/or release can be imposed by oxLDL on a wide variety of cell types. These effects and the studies probing the cell signaling events leading to them are described.

Previously we have shown that deregulated expression of c-myc in M1 myeloid leukemic cells blocked IL-6-induced differentiation and its associated growth arrest; however, the cells proliferated at a significantly reduced rate compared to untreated cells. The basis for the increased doubling time of IL-6-treated M1myc cells was found to be due to the induction of a p53-independent apoptotic pathway. The apoptotic response was not completely penetrant; in the same population of cells both proliferation and apoptosis were continuously ongoing. Down-regulation of Bcl-2 was insufficient to account for the apoptotic response, since deregulated expression of Bcl-2 delayed, but did not block, the onset of apoptosis. Furthermore, our results indicated that the IL-6-induced partial hypophosphorylation of the retinoblastoma gene product (Rb), observed in M1myc cells, was not responsible for the apoptotic response. Finally, the findings in M1 cells were extended to myeloid cells derived from the bone marrow of wild type and p53-deficient mice, where the deregulated expression of c-myc was also shown to block terminal differentiation and induce apoptosis independent of p53. These findings provide new insights into how myc participates in the neoplastic process, and how additional mutations can promote more aggressive tumors. Oncogene (2000) 19, 2967 - 2977

We examined in rats the intestinal absorption of nine very different dietary fats (two rapeseed oils, corn, olive, palm and menhaden oil, butter, cocoa butter and lard) to investigate the influence of fatty acid profile and triacylglycerol structure on absorption. Absorption was followed for 24 h after administration of similar amounts of fats, and the accumulated lymphatic transport and amount of triacylglycerols found in lymph in response to the administered fats were calculated, revealing major differences. The transport of olive and low ␣-linolenic rapeseed oil was significantly higher than that of the other fats (P Ͻ 0.05), except corn oil. The lymphatic transport of the other fats followed a slower course, with cocoa butter and menhaden oil having the lowest amounts transported. The amount of triacylglycerols found in lymph in response to the administered fats at 8 h ranged from 27.5% of the administered dose for cocoa butter to 72.1% for olive oil. The value for cocoa butter was significantly lower than that for most other fats. At 24 h, the values ranged from 66.5% for cocoa butter to 121.2% for olive oil. The high value for olive oil suggested transport of endogenous as well as exogenous fatty acids. The low value observed after cocoa butter resulted from decreased lipolysis and possibly also low absorption of triacylglycerols with high levels of long-chain saturated fatty acids in the sn-1/3 position. Furthermore, a low value was observed after menhaden oil administration, suggesting decreased absorption of fats containing (n-3) long-chain polyunsaturated fatty acids. Overall, these results demonstrate the influence of the fatty acid composition and triacylglycerol structure on the lymphatic absorption of dietary fat. J. Nutr. 130: 1619 –1624, 2000.

ABSTRACT. Background: A genetically influenced atherogenic lipoprotein phenotype characterized by a predominance of small, dense LDL particles (subclass patter

Archaeological excavations at the site of Dmanisi in the Republic of Georgia have uncovered two partial early Pleistocene hominid crania. The new fossils consist of a relatively complete cranium and a second relatively complete calvaria from the same site and stratigraphic unit that yielded a hominid mandible in 1991. In contrast with the uncertain taxonomic affinity of the mandible, the new fossils are comparable in size and morphology with Homo ergaster from Koobi Fora, Kenya. Paleontological, archaeological, geochronological, and paleomagnetic data from Dmanisi all indicate an earliest Pleistocene age of about 1.7 million years ago, supporting correlation of the new specimens with the Koobi Fora fossils. The Dmanisi fossils, in contrast with Pleistocene hominids from Western Europe and Eastern Asia, show clear African affinity and may represent the species that first migrated out of Africa.

The heroin analogue 1-methyl-4-phenylpyridinium, MPP+, both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Aβ1–42, is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-β-hydroxybutyrate protected cultured mesencephalic neurons from MPP+ toxicity and hippocampal neurons from Aβ1–42 toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.

ABSTRACT. The assessment of marginal zinc status is problematic. Currently, there is no universally accepted single measure to assess zinc status in humans. Th

Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (≤35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both low density (LDL) and high density lipoproteins (HDL). We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDL-C) levels have different HDL subpopulation profiles. In low HDL-C subjects (≤35 mg/dL), the apoA-I-only subpopulation α1 is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and α1 concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only α1 subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C. —Asztalos, B., M. Lefevre, L. Wong, T. A. Foster, R. Tulley, M. Windhauser, W. Zhang, and P. S. Roheim. Differential response to low-fat diet between low and normal HDL-cholesterol subjects. J. Lipid Res. 2000. 41: 321–328.

Summary Four (Alotau, Mt. Hagen, Goroka, and Rabaul) types of mumu (earth-oven) in Papua New Guinea were evaluated to ascertain their potential to detoxify cassava. The acid hydrolysis method was used for the determination of cyanogens. Each mumu exhibited different detoxification capacity. The loss of cyanogens in the (coconut) creamed cassava dough was lower than in the uncreamed dough. This was more evident when coconut cream–cassava mixture was cooked in boiling water than in a conventional oven set at 180 °C. Certain interactions were suspected to exist between the coconut cream and cyanogens or between the coconut cream and the appropriate enzymes that are responsible for the hydrolysis of the cyanogens. Such interactions resisted the loss of cyanogens and/or their quantification by the analytical method. The results are discussed in the light of nutritional consequences of such interactions, as coconut cream is a popular dietary item in Papua New Guinea (and the South Pacific islands).

ABSTRACT. Background: Very limited data suggest that meat consumption by older people may promote skeletal muscle hypertrophy in response to resistance trainin

This classic book by the `doyen of papyrologists' describes the economy and society of Roman Egypt from the ground level up, using the testimony of papyri. The unique climate of Egypt has preserved tens of thousands of records, covering a period of some 4,000 years from 3000 BC to AD 1000. Focusing on just part of this period (30 BC to AD 285), this book offers the perfect introduction to the possible uses of such material. The author takes a thematic approach, discussing the various areas of daily life into which papyri offer unique insights. From the production of food, to `works and days of Gods and Goblins' and `rendering unto Caesar', Naphtali Lewis uses quotations from the sources combined with an encyclopedic knowledge of the cultural context to bring a seemingly obscure class of evidence to life. "Lewis's writing is masterful in the amount of knowledge displayed and brilliant in the clarity with which complicated subjects are discussed." - Michael Woloch, The American Historical Review.

CONTEXT: Dietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD). OBJECTIVE: To examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components. DESIGN AND SETTING: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. PARTICIPANTS: A total of 2909 healthy black and white adults, 18 to 30 years of age at enrollment. MAIN OUTCOME MEASURES: Body weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values. RESULTS: After adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 microU/mL], P = .007; blacks: 92.4-82.6 pmol/L [13.3-11.9 microU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 microU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 microU/mL], P

The receptor for advanced glycation end products (RAGE) has been proposed as a cell surface receptor that binds amyloid-beta protein (Abeta), thereby triggering its cytotoxic effects [S.D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, T. Slattery, L. Zhao, M. Nagashima, J. Morser, A. Migheli, P. Nawroth, D. Stern, A.M. Schmidt, RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease, Nature 382 (1996) 685-691.]. A cDNA library of human lung was screened for RAGE with an appropriate hybridization probe. In addition to cell surface RAGE, one clone was found which encodes a new version of RAGE, termed hRAGEsec, which lacks the 19 amino acids of the membrane-spanning region and is therefore secreted. Comparison with the genomic sequence revealed that the synthesis of the secreted isoform requires alternative splicing. The deduced protein sequence of the mature hRAGEsec consists of 321 amino acids with a predicted molecular mass of 35.66 kDa. The pattern of expression of hRAGEsec in human brain was analyzed by in situ hybridization histochemistry. The most intense expression of the gene in contrast to cell surface RAGE was detected in hippocampal CA3 pyramidal cells, dentate gyrus granule cells, cortical neurons as well as glial cells in white matter. To investigate the interaction between Abeta and RAGE and another scavenger receptor, SRA, under physiological conditions, they were co-expressed with human betaAPP(695)-SFAD in a human cell and the level of Abeta in the condition medium was assessed by immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) analysis. A nearly 100% reduction of Abeta from the conditioned medium of hRAGE cells and approximately 40% reduction from the SRA-cells implied that hRAGE could be a prominent cell surface receptor interacting with Abeta.

Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol

Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol

High intakes of calcium, potassium, and fluids have been shown to be associated with lowered risk of kidney stones. The authors studied the associations between diet and risk of kidney stones in a cohort of 27,001 Finnish male smokers aged 50-69 years who were initially free of kidney stones. All men participated in the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study and completed a validated dietary questionnaire at baseline. After 5 years of follow-up (1985-1988), 329 men had been diagnosed with kidney stones. After data were controlled for possible confounders, the relative risk of kidney stones for men in the highest quartile of magnesium intake was 0.52 (95% confidence interval (CI) 0.32-0.85) as compared with men in the lowest quartile. Intake of fiber was directly associated with risk (relative risk (RR) = 2.06, 95% CI 1.39-3.03). Calcium intake was not associated with the risk of kidney stones. Beer consumption was inversely associated with risk of kidney stones; each bottle of beer consumed per day was estimated to reduce risk by 40% (RR = 0.60, 95% CI 0.47-0.76). In conclusion, the authors observed that magnesium intake and beer consumption were inversely associated and fiber intake was directly associated with risk of kidney stones.

ABSTRACT. Background: Although several studies have investigated the relation between fish consumption and the risk of cardiovascular diseases, less attention

Dietary habits have been implicated in the occurrence of cardiovascular diseases. Elevated plasma fibrinogen levels and decreased fibrinolytic activity have been identified as major independent cardiovascular risk factors. In this study, we compared the blood pressure, plasma fibrinogen concentration, and fibrinolytic activity of 40 nonvegetarians (NON-VEGs) with 36 vegetarians (8 VEGs and 28 SEMI-VEGs). The latter group consisted of students and lecturers of the Adventist Seminary Institute of West Africa, Ilishan Remo. All subjects had blood pressures below 140/90 mmHg, no underlying haemostatic disorders and were not on any medical treatment. The NON-VEGs had significantly decreased fibrinolytic activity (p<0.001) and increased plasma fibrinogen levels (p

Tybrind Vig is a late Mesolithic (Erteblle) coastal settlement, dated to the period 5600–4000 BC. The site has yielded some very important finds associated with fishing activity, probably the best preserved example from the Mesolithic in Europe. Recently analysed botanical samples from submerged cultural deposits have provided evidence for the contribution of plants to the subsistence diet of the inhabitants of Tybrind Vig. The food plant remains are represented by the charred fragments of parenchymatous tissue from roots ofBeta vulgaris ssp.maritima (sea beet), fragments ofQuercus sp. parenchyma (acorn), and shell fragments ofCorylus avellana (hazelnut). The possibility that the grains ofGlyceria fluitans (floating sweet grass) and stems ofPhragmites australis (reed) were collected for food should not be excluded. In addition to the species identified in the charred remains, an abundance of edible plant seeds and fruits were represented in the waterlogged remains, suggesting that a much broader range of food plants was available in the area. These additional foods could have included a large variety of wild berries and other fruits, such asRubus idaeus, R. caesius, Fragaria vesca, Malus sylvestris, Cornus sanguinea, Crataegus monogyna/laevigata, Sorbus aucuparia, Viburnum opulus andRosa spp. Several other plants could have been gathered as green vegetables (Rumex crispus, Urtica dioica andCakile maritima), or could have been utilized for both their greens and seeds (Chenopodium album, Atriplex andScirpus maritimus).

Tissue-specific activation and inactivation of ligands of nuclear receptors which belong to the steroid retinoid-thyroid hormone superfamily of transcription factors represents an important principle of development- and tissue-specific local modulation of hormone action. Recently, several enzyme families have been identified which act as 'guardians of the gate' of ligand-activated transcription modulation. Three monodeiodinase isoenzymes which are involved in activation the 'prohormone' L-thyroxine (T4), the main secretory product of the thyroid gland, have been identified, characterized, and cloned. Both, type I and type II 5'-deiodinase generate the thyromimetically active hormone 3,3',5-triiodothyronine (T3) by reductive deiodination of the phenolic ring of T4. Inactivation of T4 and its product T3 occurs by deiodination of iodothyronines at the tyrosyl ring. This reaction is catalyzed both the type III 5-deiodinase and also by the type I enzyme, which has a broader substrate specificity. The three deiodinases appear to constitute a newly discovered family of selenocysteine-containing proteins and the presence of selenocysteine in the protein is critical for enzyme activity. Whereas the selenoenzyme characteristics of the type I and type III deiodinases are definitively established some controversy still exists for the type II 5'-deiodinase in mammals. The mRNA probably encoding the type II 5'-deiodinase subunit is markedly longer than those of the two other deiodinases and its selenocysteine-insertion element is located more than 5 kB downstream of the UGA-codon in the 3'-untranslated region. The three deiodinase isoenzymes show a distinct development- and tissue-specific pattern of expression, operate at individual optimal substrate levels, are differently regulated and modulated by hormones, cytokines, signaling pathways, natural factors, and pharmaceuticals. Whereas circulating T3 mainly originates from hepatic production via the type I 5'-deiodinase, the local cellular thyroid hormone concentration in various tissues including the central nervous system is controlled by complex para-, auto-, and intracrine interactions of all three deiodinases. Local thyroid hormone availability is further modulated by conjugation reactions of the phenolic 4'-OH-group of iodothyronines, which also inactivate the thyroid hormones.

The high fat, low carbohydrate, low protein ketogenic diet (KD) has been used to control refractory epilepsy in children since 1920, although its mechanism of action is unknown. Previous animal studies have shown that the KD can increase acute seizure threshold, but the effect of the KD on the process of epileptogenesis has not been studied. We tested the effect of an experimental KD on epileptogenesis in adult rats using the kainic acid (KA) model. P54 rats underwent KA-induced status epilepticus, followed by assignment to a control diet or a KD consisting of (by weight), 14% protein, 70% fat and no carbohydrate. KD-fed animals tolerated the diet and maintained ketosis. KD-fed rats had significantly fewer and briefer spontaneous recurrent seizures and less supragranular mossy fiber sprouting, although the degree of hippocampal pyramidal cell damage was similar in both groups. These results provide the first evidence that the KD retards epileptogenesis in an experimental model.

In the early 1920s, workers in both England and the US had discovered that rats on a rachitic diet would remain healthy if irradiated with ultraviolet light. However, they also found, to their surprise, that “control” rats too would recover if either their jar was irradiated without the rat in it or if a cage-mate was removed for irradiation and then returned. The ideas that either air or material objects that had been irradiated continued themselves to convey healthful secondary radiations were investigated but not confirmed. There was then the commercially important finding that with irradiation, some rachitic diets would become anti-rachitic. However, this effect did not explain all the previous findings. Consumption of either small irradiated fecal particles or of feces from irradiated rats was the likely explanation for the recovery of nonirradiated rats, but this was not tested by direct experiment, and it now appears unlikely that feces from irradiated rats would show significant antirachitic activity. It is suggested that an alternative possibility—activity of grease from irradiated fur—deserves investigation.

The present review focuses on the background and progress that led to discovery of specific inhibition of post-Amadori formation of advanced glycation end products, or AGEs. The “classic” or Hodge pathway begins with glucose condensation with amino groups to form a Schiff base aldimine adduct that undergoes rearrangement to a ketoamine Amadori product. This pathway is considered an important route to AGE formation that has been implicated in glucose-mediated damagein vivo(3–5). We recently described a facile procedure for isolation of proteins rich in Amadori adducts but free of AGEs, thus permitting study of pathways of conversion of Amadori compounds to AGEs. This in turn led to a unique and rapid post-Amadori screening assay for putative “Amadorins,” which we define here as inhibitors of the conversion of Amadori intermediates to AGEs in the absence of excess free or reversibly bound (Schiff base) sugar. Our screening assay then led to the identification of pyridoxamine (Pyridorin) as the first member of this class of Amadorin compounds. Rather unexpectedly, the assay also led to the clear demonstration that the well-known AGE inhibitor aminoguanidine, currently in Phase 3 clinical trials for treatment of diabetic nephropathy, has negligible Amadorin activity. In view of the importance of Amadori compounds as intermediates in AGE formationin vivo,the therapeutic potential of Pyridorin is currently being investigated and is now showing highly promising results in different animal models.

Debates about the development of the science of nutrition have been limited to either ascetic views of the body in eighteenth-century Europe or to scientific ideas about physiological economy of food. These debates do not allow a full appreciation of the heritage of the ideas that are part of nutrition discourse. Using Foucault's work on governmentality it is shown here that ideas embedded in nutrition emerged from both scientific knowledges which sought to understand and manage the eating habits of populations, and from moral issues which problematize individual food choices. The result is a knowledge of food that can be understood as a ‘discipline' in two senses: first as field of scientific endeavour and second as a form of moral correction.

Current consensus holds that the 3-million-year-old hominidAustralopithecus africanus subsisted on fruits and leaves, much as the modern chimpanzee does. Stable carbon isotope analysis ofA. africanus from Makapansgat Limeworks, South Africa, demonstrates that this early hominid ate not only fruits and leaves but also large quantities of carbon-13–enriched foods such as grasses and sedges or animals that ate these plants, or both. The results suggest that early hominids regularly exploited relatively open environments such as woodlands or grasslands for food. They may also suggest that hominids consumed high-quality animal foods before the development of stone tools and the origin of the genus Homo.

ABSTRACT. Background: Ingestion of soy products may cause excessive intestinal gas. This gas results from colonic bacterial fermentation of the indigestible ol

Deregulated expression of c-Myc not only promotes proliferation, but also can either induce or sensitize cells to apoptosis. Inappropriate expression of c-Myc under conditions which inhibit growth and down-regulate endogenous c-Myc expression, including serum deprivation and exposure to cytotoxic agents including the anticancer agents vinblastine, etoposide, Ara-C, and nocodazole, usually results in programmed cell death in many different cell types. Also, inappropriate Myc expression is associated with an apoptotic response elicited by induction of differentiation. The proapoptotic property of c-Myc requires an intact N-terminal transactivation domain and bHLHZip domain, as well as interaction with Max, thereby implicating c-Myc target genes in this apoptotic process. Although some target genes, namely cdc25A and ODC, have been shown to participate in Myc-mediated apoptosis, no target gene has yet been identified which is essential for this apoptotic response. It is possible that the response of cells inappropriately expressing c-Myc is due not only to the growth arrest signals per se, but also to signals elicited by specific growth inhibitors in the context of a particular biological setting. Also regulating the response of the cells is expression of other oncogenes and tumor suppressor genes, as well as paracrine and autocrine survival factors. Apoptosis associated with inappropriate Myc expression limits the tumorigenic effect of the c-myc proto-oncogene. Mechanisms which inhibit apoptosis should enhance or promote tumorigenesis.

CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

A study was carried out to determine whether hands-on classroom experience with low-fat foods would increase children's acceptance of those foods in the school's lunch program. The 9-month project took place at an elementary school in upstate New York. Half of the classrooms served as the intervention group and received classroom experience with new foods; the other half served as the control group and received no classroom experience. Consumption measurements of 16 new foods, introduced at approximately 2-week intervals, were taken for all students who ate school lunches. Compared with children in the control group, those in the intervention group ate significantly more of the new foods when they were offered in the lunch program. The study demonstrated that experiential learning about food in the classroom is an effective way to gain acceptance of diverse, low-fat foods in the school lunch program.

Our understanding of coronary artery disease risk and the atherosclerotic process has changed greatly in recent years. For example, it is now known that angiographically apparent coronary artery plaque is not the major cause of myocardial infarction (MI). Rather, it is unstable, soft plaque that can …

OBJECTIVE: The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder (ADHD). The statement provides state-of-the-art information regarding effective treatments for ADHD and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas of study that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience of clinicians for this statement includes, but is not limited to, psychiatrists, family practitioners, pediatricians, internists, neurologists psychologists, and behavioral medicine specialists. PARTICIPANTS: Participants were a non-Federal, nonadvocate, 13-member panel representing the fields of psychology, psychiatry, neurology, pediatrics, epidemiology, biostatistics, education and the public. In addition, 31 experts from these same fields presented data to the panel and a conference audience of 1215. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: Attention deficit hyperactivity disorder or ADHD is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem. Children with ADHD have pronounced impairments and can experience long-term adverse effects on academic performance, vocational success, and social-emotional development which have a profound impact on individuals, families, schools, and society. Despite progress in the assessment, diagnosis, and treatment of ADHD, this disorder and its treatment have remained controversial, especially the use of psychostimulants for both short and long-term treatment. Although an independent diagnostic test for ADHD does not exist, there is evidence supporting the validity of the disorder. Further research is needed on the dimensional aspects of ADHD, as well as the comorbid (coexisting) conditions present in both childhood and adult forms. Studies, (primarily short term, approximately three months) including randomized clinical trials, have established the efficacy of stimulants and psychosocial treatments for alleviating the symptoms of ADHD and associated aggressiveness and have indicated that stimulants are more effective than psychosocial therapies in treating these symptoms. Because of the lack of consistent improvement beyond the core symptoms and the paucity of long-term studies (beyond 14 months), there is a need for longer term studies with drugs and behavioral modalities and their combination. Although trials are underway, conclusive recommendations concerning treatment for the long term cannot be made presently. There are wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus regarding which ADHD patients should be treated with psychostimulants. (ABSTRACT