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Title:
Androgen Metabolism and Prostate Cancer: Establishing a Model of Genetic Susceptibility
Authors:
Ross, Ronald K.; Pike, Malcolm C.; Coetzee, Gerhard A.; Reichardt, Juergen K. V.; Yu, Mimi C.; Feigelson, Heather; Stanczyk, Frank Z.; Kolonel, Laurence N.; Henderson, Brian E.
Abstract:
The prostate is an androgen-regulated organ, which has led to long-standing interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones. The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that whereas environmental factors are likely to be important, genetic factors might also play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis focused around a series of genes involved in androgen biosynthesis and androgen activation, transport, and metabolism in the prostate. In this developing model, we have initially targeted four genes based on three main criteria: (a) all encode products that play important roles in inducing androgen stimulation in the prostate; (b) all are polymorphic; and (c) all show substantial allelic variation in the polymorphic marker among the racial-ethnic groups of greatest interest in terms of prostate cancer risk. In addition to studying how the polymorphic markers of interest are related to prostate cancer development within and between racial-ethnic groups, we are concurrently evaluating whether genotypic variations correlate in the anticipated direction with biochemical parameters in vitro and in vivo. We summarize the development of this model and the state of knowledge related to each of the genes comprising the current model. We discuss the extent to which the current model can explain demographic variation in prostate cancer risk as well as the potential for future expansion of the model to incorporate environmental risk factors as well as additional genes. The model, when fully developed, can potentially provide a basis for targeting populations for screening interventions and/or preventive strategies aimed at the multigene products or at the genes themselves.
Published:
October 14, 1998
Title:
The regulation of carbohydrate and fat metabolism during and after exercise
Authors:
Holloszy, J. O.; Kohrt, W. M.; Hansen, P. A.
Abstract:
The rate of carbohydrate utilization during prolonged, strenuous exercise is closely geared to the energy needs of the working muscles. In contrast, fat utilization during exercise is not tightly regulated, as there are no mechanisms for closely matching availability and metabolism of fatty acids to the rate of energy expenditure. As a result, the rate of fat oxidation during exercise is determined by the availability of fatty acids and the rate of carbohydrate utilization. Blood glucose and muscle glycogen are essential for prolonged strenuous exercise, and exhaustion can result either from development of hypoglycemia or depletion of muscle glycogen. Both absolute and relative (i.e. % of maximal O2 uptake) exercise intensities play important roles in the regulation of substrate metabolism. The absolute work rate determines the total quantity of fuel required, while relative exercise intensity plays a major role in determining the proportions of carbohydrate and fat oxidized by the working muscles. As relative exercise intensity is increased, there is a decrease in the proportion of the energy requirement derived from fat oxidation and an increase in that provided by carbohydrate oxidation. During moderately strenuous exercise of an intensity that can be maintained for 90 minutes or longer ( approximately 55-75% of VO2max), there is a progressive decline in the proportion of energy derived from muscle glycogen and a progressive increase in plasma fatty acid oxidation. The adaptations induced by endurance exercise training result in a marked sparing of carbohydrate during exercise, with an increased proportion of the energy being provided by fat oxidation. The mechanisms by which training decreases utilization of blood glucose are not well understood. However, the slower rate of glycogenolysis can be explained on the basis of lower concentrations of inorganic phosphate (Pi) in trained, as compared to untrained, muscles during exercise of the same intensity. The lower Pi level is a consequence of the increase in muscle mitochondria induced by endurance exercise training. A large increase in muscle glycogen concentration, far above the level found in the well-fed sedentary state, occurs in response to carbohydrate feeding following glycogen depleting exercise. It was recently found that this muscle "glycogen supercompensation" is markedly enhanced by endurance exercise training that induces an increase in the GLUT4 isoform of the glucose transporter in skeletal muscle.
Published:
September 14, 1998
Title:
Comparison of Apolipoprotein and Proteoglycan Deposits in Human Coronary Atherosclerotic Plaques: Colocalization of Biglycan With Apolipoproteins
Authors:
O’Brien, Kevin D.; Olin, Katherine L.; Alpers, Charles E.; Chiu, Winnie; Ferguson, Marina; Hudkins, Kelly; Wight, Thomas N.; Chait, Alan
Abstract:
Published:
August 10, 1998
Title:
Essential hypertension is lymphatic: a working hypothesis
Authors:
Mȩkarski, J. E.
Abstract:
Lymphatics, a third component of the circulation, may be deranged by the same factors as veins and arteries. Malfunctioning through overload or dyscrasia, they may foster high blood pressure. It is hypothesized that essential hypertension is caused by lymphatic system aberrations.
Published:
July 31, 1998
Title:
How hardwired is human behavior?
Authors:
Nicholson, Nigel
Abstract:
Time and time again managers have tried to eliminate hierarchies, politics, and interorganizational rivalry--but to no avail. Why? Evolutionary psychologists would say that they are working against nature--emotional and behavioral "hardwiring" that is the legacy of our Stone Age ancestors. In this evolutionary psychology primer for executives, Nigel Nicholson explores many of the Science's central tenets. Of course, evolutionary psychology is still an emerging discipline, and its strong connection with the theory of natural selection has sparked significant controversy. But, as Nicholson suggests, evolutionary psychology is now well established enough that its insights into human instinct will prove illuminating to anyone seeking to understand why people act the way they do in organizational settings. Take gossip. According to evolutionary psychology, our Stone Age ancestors needed this skill to survive the socially unpredictable conditions of the Savannah Plain. Thus, over time, the propensity to gossip became part of our mental programming. Executives trying to eradicate gossip at work might as well try to change their employees' musical tastes. Better to put one's energy into making sure the "rumor mill" avoids dishonesty or unkindness as much as possible. Evolutionary psychology also explores the dynamics of the human group. Clans on the Savannah Plain, for example, appear to have had no more than 150 members. The message for managers? People will likely be most effective in small organizational units. As every executive knows, it pays to be an insightful student of human nature. Evolutionary psychology adds another important chapter to consider.
Published:
June 30, 1998
Title:
Human adaptations to meat eating
Authors:
Henneberg, M.; Sarafis, V.; Mathers, K.
Abstract:
It is argued that Homo sapiens is a habitual rather than a facultative meat eater. Quantitative similarity of human gut morphology to guts of carnivorous mammals, preferential absorption of haem rather than iron of plant origin, and the exclusive use of humans as the definitive host by Taenia saginata and the almost complete human specificity of T. solium are used to support the argument.
Published:
June 30, 1998
Title:
Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men
Authors:
Dreon, D. M.; Fernstrom, H. A.; Campos, H.; Blanche, P.; Williams, P. T.; Krauss, R. M.
Abstract:
ABSTRACT. We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were randomly as
Published:
April 30, 1998
Title:
Short-column liquid chromatography with hydride generation atomic fluorescence detection for the speciation of arsenic
Authors:
Le, X. C.; Ma, M.
Abstract:
Increasing concerns over human exposure to arsenic and more stringent environmental regulations require rapid determination of trace levels of individual arsenic species, which presents an analytical challenge. We describe a method that is capable of speciating nanogram-per-milliliter levels of arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) within 3 min. Speciation of two common inorganic species in drinking water, As(III) and As(V), is complete in 1.5 min. The method is based on a combination of fast high-performance liquid chromatography (HPLC) separation of arsenic species on 3-cm HPLC guard columns and the sensitive detection of arsenic hydride by atomic fluorescence spectrometry. Detection limits for the four arsenic species in urine samples are 0.4-0.8 ng/mL. This simple method allows for the direct speciation of arsenic present in natural water samples and in human urine samples from the general population, with no need of any sample pretreatment. Our results from the determination of arsenic species in urine and water standard reference materials are in good agreement with the certified values of total arsenic concentration. The method has been successfully applied to speciation studies of metabolism of arsenosugars following the consumption of arsenosugar-containing mussels by human volunteers. Speciation of arsenic in urine samples collected from four volunteers after the ingestion of musseles reveals significant increases of DMAA concentration, resulting from the metabolism of arsenosugars. These results suggest that the commonly used biomarkers for assessing human exposure to inorganic arsenic, which are based on the determination of urinary arsenite, arsenate, MMAA, and DMAA, are not reliable when arsenosugar-containing seafood is ingested.
Published:
April 30, 1998
Title:
Insulin Enhances Macrophage Scavenger Receptor-mediated Endocytic Uptake of Advanced Glycation End Products
Authors:
Sano, Hiroyuki; Higashi, Takayuki; Matsumoto, Kenshi; Melkko, Jukka; Jinnouchi, Yoshiteru; Ikeda, Kazuyoshi; Ebina, Yousuke; Makino, Hideichi; Smedsrød, Bård; Horiuchi, Seikoh
Abstract:
Published:
April 9, 1998
Title:
The nutritional health of New Zealand vegetarian and non-vegetarian Seventh-day Adventists: selected vitamin, mineral and lipid levels
Authors:
Harman, S. K.; Parnell, W. R.
Abstract:
AIM: To determine whether adult non-vegetarian Seventh-day Adventists differ in selected nutrition related health aspects from adult vegetarian Seventh-day Adventists. METHODS: One hundred and forty-one Seventh-day Adventist church members responded to a general health questionnaire. Forty-seven sex and age matched subjects (23 non-vegetarians and 24 vegetarians) were selected for further investigation. Blood lipids, serum vitamin B12, folate, haemoglobin and ferritin levels were measured along with stature, weight and blood pressure. A quantitative 7-day diet record was also completed. RESULTS: Body mass index was similar between the non-vegetarian and vegetarian groups but diastolic blood pressure was higher for non-vegetarian than vegetarian males. Even though the dietary vitamin B12 intake was significantly lower (p < 0.01) in the vegetarian group both vegetarians and non-vegetarians recorded similar serum vitamin B12 levels. The vegetarian and non-vegetarian groups had similar haemoglobin concentrations. While dietary iron intake was higher in the female vegetarian group, though predominantly in the non-haem form, the difference was not significant. Low serum ferritin levels were found in both female dietary groups even though the vegetarian group had a significantly (p < 0.05) higher vitamin C intake. Blood lipid levels were similar in the two diet groups even though the vegetarian group had a lower percentage energy contribution from total and saturated fat (p
Published:
March 26, 1998
Title:
Effect of low-fat diets on plasma high-density lipoprotein concentrations
Authors:
Katan, M B
Abstract:
Low concentrations of HDLs in plasma are a strong predictor of risk for coronary as well as other cardiovascular diseases. There is increasing evidence that this relation is causal and that interventions that change HDL concentrations also change risk. One such intervention is exchanging fat and carbohydrate. In controlled trials, low-fat, high-carbohydrate diets decrease HDL concentrations. The effect is strongest when carbohydrates replace saturated fatty acids, but is also seen when carbohydrates replace mono- and polyunsaturated fatty acids carbohydrates. The effect is seen in both short- and long-term trials and therefore appears to be permanent. This finding is supported by epidemiologic studies in which populations eating low-fat, high-carbohydrate diets were shown to have low HDL concentrations. Weight losses with consumption of low-fat diets could theoretically counter effects on HDL, but in published trials weight losses have been modest and insufficient to offset the decrease in HDL concentrations induced by carbohydrates. Thus, replacement of saturated fat by carbohydrates adversely affects plasma HDL concentrations; replacement of saturated fat by unsaturated fatty acids deserves consideration as an alternative. Am J Clin Nutr 1998;67(suppl):573S−6S.
Published:
February 28, 1998
Title:
Electrochemical Determination of Ascorbic Acid and Isoascorbic Acid in Ground Meat and in Processed Foods by High Pressure Liquid Chromatography
Authors:
Hidiroglou, Nick; Madere, Rene; Behrens, Willy
Abstract:
Some researchers have reported that ascorbic acid (AA) and/or isoascorbic acid (IAA) was detected in ground meat, prompting our laboratory to undertake a small survey to determine if the addition of AA and IAA to ground meats was common practice. The study was expanded to include dairy products, luncheon meats, meal replacements, diet products, vegetable and fruit drinks, and beverages. Detection of AA, dehydroascorbic acid (DHAA), IAA, and dehydroisoascorbic acid (DHIAA) was done by HPLC with electrochemical detection. Two PLRP-S columns cooled to 5°C were used with a 20 mM sodium phosphate monobasic, monohydrate (NaH2PO4-H2O) and 0.17% (v/v) metaphosphoric acid (HPO3) mobile phase, pH 2.2. The limit of detection was 0.2 mg/100 g sample. Generally, variable amounts of AA and DHAA were detected, although in some foods, traces or no vitamin C was detected while only processed meats and ice tea contained IAA.
Published:
February 28, 1998
Title:
Alcohol and breast cancer in women: a pooled analysis of cohort studies
Authors:
Smith-Warner, S. A.; Spiegelman, D.; Yaun, S. S.; van den Brandt, P. A.; Folsom, A. R.; Goldbohm, R. A.; Graham, S.; Holmberg, L.; Howe, G. R.; Marshall, J. R.; Miller, A. B.; Potter, J. D.; Speizer, F. E.; Willett, W. C.; Wolk, A.; Hunter, D. J.
Abstract:
OBJECTIVE: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. DATA SOURCES: We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. DATA EXTRACTION: Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. DATA SYNTHESIS: For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. CONCLUSIONS: Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.
Published:
February 17, 1998
Title:
Free fatty acids (FFA), a link between obesity and insulin resistance
Authors:
Boden, G.
Abstract:
Evidence, gained from human studies, is reviewed showing that elevation of plasma FFA levels produce peripheral and probably also hepatic insulin resistance in obese healthy and diabetic subjects. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations of plasma FFA inhibit acutely as well as chronically insulin stimulated glucose uptake in a dose dependent fashion. Responsible for this inhibition is a FFA induced defect in insulin stimulated glucose transport and/or phosphorylation which develops after 3-4 hours of raising plasma FFA and a second defect, consisting of inhibition of glycogen synthase, the rate limiting enzyme of glycogen synthesis, which develops after 4-6 hours. FFA induced inhibition of fatty acid oxidation (Randle effect) does not affect insulin stimulated glucose uptake or glycogen synthesis and thus does not cause insulin resistance. Elevated plasma FFA levels also modestly increase insulin suppressed endogenous glucose production (EGP) although this effect has not been found by all investigators. The reasons why it has been difficult to demonstrate unequivocal effects of FFA on EGP include 1) the fact that FFA promote insulin secretion which counteracts its effect on EGP (FFA increase, while insulin decreases EGP); 2) the recognition that FFA induced increase in gluconeogenesis may be compensated by intrahepatic downregulation of EGP (i.e., by a decrease in glycogenolysis). The FFA induced insulin resistance is physiologically important during starvation by preserving carbohydrate for oxidation in the central nervous system and during pregnancy, where the well recognized accelerated starvation pattern provides carbohydrate for the growing fetus. In obesity, however, there is no need to spare carbohydrate and the FFA induced insulin resistance may result in type 2 diabetes and other cardiovascular risk factors.
Published:
February 14, 1998
Title:
Bringing context back into epidemiology: variables and fallacies in multilevel analysis.
Authors:
Diez-Roux, A V
Abstract:
A large portion of current epidemiologic research is based on methodologic individualism: the notion that the distribution of health and disease in populations can be explained exclusively in terms of the characteristics of individuals. The present paper discusses the need to include group- or macro-level variables in epidemiologic studies, thus incorporating multiple levels of determination in the study of health outcomes. These types of analyses, which have been called contextual or multi-level analyses, challenge epidemiologists to develop theoretical models of disease causation that extend across levels and explain how group-level and individual-level variables interact in shaping health and disease. They also raise a series of methodological issues, including the need to select the appropriate contextual unit and contextual variables, to correctly specify the individual-level model, and, in some cases, to account for residual correlation between individuals within contexts. Despite its complexities, multilevel analysis holds potential for reemphasizing the role of macro-level variables in shaping health and disease in populations.
Published:
January 31, 1998
Title:
Calcium and fructose intake in relation to risk of prostate cancer
Authors:
Giovannucci, E.; Rimm, E. B.; Wolk, A.; Ascherio, A.; Stampfer, M. J.; Colditz, G. A.; Willett, W. C.
Abstract:
Laboratory and clinical data indicate an antitumor effect of 1,25(OH)2 vitamin D (1,25(OH)2D) on prostate cancer. High calcium intake suppresses formation of 1,25(OH)2D from 25(OH)D, thereby decreasing the 1,25(OH)2D level. Ingestion of fructose reduces plasma phosphate transiently, and hypophosphatemia stimulates 1,25(OH)2D production. We thus conducted a prospective study among 47,781 men of the Health Professionals Follow-Up Study free of cancer in 1986 to examine whether calcium and fructose intake influenced risk of prostate cancer. Between 1986 and 1994, 1369 non-stage A1 and 423 advanced (extraprostatic) cases of prostate cancer were diagnosed. Higher consumption of calcium was related to advanced prostate cancer [multivariate relative risk (RR), 2.97; 95% confidence interval (CI), 1.61-5.50 for intakes > or = 2000 mg/day versus < 500 mg/day; P, trend, 0.002] and metastatic prostate cancer (RR, 4.57; CI, 1.88-11.1; P, trend, 70 versus 5 versus
Published:
January 31, 1998
Title:
Primate digestion: Interactions among anatomy, physiology, and feeding ecology
Authors:
Lambert, Joanna
Abstract:
Food is vital for life. It provides nutrients for growth, maintenance, and reproduction, and is the source of energy that drives the chemical reactions occurring in every cell.1,2 However, most food, as it is initially procured, is not in a form suitable for use; it must first be broken down so that it can be transported through cell membranes.1 The breaking down of food molecules via a system of both mechanical and chemical processes so that they are of use to the body is called digestion.2,3 © 1998 Wiley-Liss, Inc.
Published:
December 31, 1997
Title:
[Risks and advantages of the vegetarian diet]
Authors:
Krajcovicová-Kudlácková, M.; Simoncic, R.; Béderová, A.
Abstract:
The authors summarize the health risks and advantages of alternative nutrition-lactovegetarian, lactoovovegetarian and vegan. These dietary patterns involve risk in particular during pregnancy, lactation and for the growing organism. Veganism excluding all foods of animal origin involves the greatest risk. General nutritional principles for the prevention of cardiovascular diseases, oncological diseases and diabetes are fully met by the vegetarian diet. Vegetarians and vegans have low risk factors of atherosclerosis and conversely higher levels of antisclerotic substances. Overthreshold values of essential antioxidants in vegetarians imply a protective action against reactive metabolic oxygen products and toxic products of lipid peroxidation and may reduce the incidence of free radical diseases. The authors also draw attention to some still open problems of vegetarianism (higher n-3 fatty acids, taurine, carnitine). In the conclusion semivegetarianism is evaluated.
Published:
December 2, 1997
Title:
Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2
Authors:
DeMarini, D. M.; Hastings, S. B.; Brooks, L. R.; Eischen, B. T.; Bell, D. A.; Watson, M. A.; Felton, J. S.; Sandler, R.; Kohlmeier, L.
Abstract:
Epidemiological and experimental evidence indicates that consumption of fried meats in conjunction with certain genotypes of phase I and II metabolism genes poses an elevated risk for colorectal cancer. Parallel to this, the consumption of cruciferous vegetables is associated with a reduced risk of colon cancer. Therefore, we designed a 6-week pilot feeding study to evaluate the effect of these variables on urinary mutagenicity, which is a biomarker associated with fried-meat consumption. Eight subjects were fed fried meats daily for six weeks; four ate cruciferous vegetables, and four ate non-cruciferous vegetables. Urinary mutagenicity was evaluated in the presence of S9 in strain YG1024 of Salmonella, which is a frameshift strain that overproduces acetyltransferase. C18/methanol extracts of 24-h urines collected once each week were tested unhydrolyzed (free mutagenicity) and hydrolyzed (total mutagenicity); the difference between the two was the conjugated mutagenicity. Although not significant, the levels of conjugated urinary mutagenicity doubled among crucifera consumers and decreased to 30% of the initial levels among non-crucifera consumers, suggesting the possibility that crucifera may enhance the level of conjugated urinary mutagenicity resulting from consumption of fried meats. Such an effect would be consistent with the documented ability of cruciferous vegetables to induce phase II enzymes. The NAT2 rapid phenotype was significantly associated with approximately 2-fold increases in conjugated (p = 0.05) and total (p = 0.004) urinary mutagenicity relative to NAT2 slow subjects, consistent with the elevated risk confirmed by the NAT2 rapid phenotype for colorectal cancer among meat consumers. An approximately 2-fold increase in urinary mutagenicity among the GSTM1- subjects relative to the GSTM1+ subjects approached significance for free (p = 0.18) and total (p = 0.13) urinary mutagenicity. This is the first report on (a) the mutagenicity of hydrolyzed urine, which was consistently more mutagenic than unhydrolyzed urine; (b) the potential enhancement of conjugated urinary mutagenicity by crucifera; and (c) the association of the rapid NAT2 and possibly the GSTM1- phenotype with elevated levels of fried meat-associated urinary mutagenicity.
Published:
November 18, 1997
Title:
The Western Lowland Gorilla Diet Has Implications for the Health of Humans and Other Hominoids
Authors:
Popovich, David G.; Jenkins, David J. A.; Kendall, Cyril W. C.; Dierenfeld, Ellen S.; Carroll, Richard W.; Tariq, Nauman; Vidgen, Edward
Abstract:
Abstract. We studied the western lowland gorilla diet as a possible model for human nutrient requirements with implications for colonic function. Gorillas in t
Published:
September 30, 1997
Title:
Early Research into the Vitamins: The Work of Wilhelm Stepp
Authors:
Wolf, George; Carpenter, Kenneth J.
Abstract:
Wilhelm Stepp has been described in Germany as the “founder of the science of vitamins” (Schröder 1964). The purpose of this article is to reexamine his work first in the context of the knowledge and beliefs in 1907, the time at which he began his experiments, and then in the light of present-day knowledge. For the 50 years previous to 1907, German scientists had been recognized as the leaders in the field of nutrition, and their laboratories were the places to which many Americans and other Europeans would go for postgraduate training.
Published:
June 30, 1997
Title:
Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation
Authors:
Rozen, F.; Yang, X. F.; Huynh, H.; Pollak, M.
Abstract:
BACKGROUND AND PURPOSE: Vitamin D-related compounds can inhibit cancer cell growth, but the biologic mechanism of this inhibition remains to be determined. We investigated the possibility that these compounds interfere with the activity of insulin-like growth factors. Such activity can be suppressed or otherwise modulated by specific insulin-like growth factor-binding proteins. METHODS: The human breast cancer cell line MCF-7 was used in this study. The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and two related compounds, EB1089 and KH1060, on cell proliferation were assessed by monitoring cell numbers and by measuring cellular incorporation of [3H]thymidine. Changes in the accumulation of insulin-like growth factor-binding proteins in cell-conditioned media (i.e., culture fluids) were assessed by means of standard protein blotting techniques; ligand blots were probed with [125I]insulin-like growth factor I, and immunoblots were probed with antibodies raised against specific binding proteins. Binding protein messenger RNA levels were determined by use of RNA blotting methods and complementary DNA probes. RESULTS: At concentrations of 10(-8) M and 10(-9) M, EB1089 and KH1060 exhibited stronger antiproliferative activity than 1,25(OH)2D3. When each of the vitamin D-related compounds was used separately at a concentration of 10(-9) M, a 20- to 25-fold increase in the concentration of insulin-like growth factor-binding proteins in MCF-7 cell-conditioned media was observed; this binding capacity was increased nine-fold, ninefold, and threefold, respectively, in the presence of 10(-10) M EB1089, KH1060, and 1,25(OH)2D3. Immunoblotting experiments demonstrated that all three vitamin D-related compounds induced the accumulation of insulin-like growth factor-binding protein 5 in cell-conditioned media. The accumulation of this binding protein was associated with an increase in cellular expression of its messenger RNA. EB1089 and 1,25(OH)2D3 attenuated the growth-promoting activity of insulin-like growth factor I on MCF-7 cells; however, these compounds did not inhibit the growth-promoting activity of long R3 IGF-I, an insulin-like growth factor I analogue with greatly reduced affinity for insulin-like growth factor-binding proteins. CONCLUSIONS AND IMPLICATIONS: Our results indicate that vitamin D-related compounds stimulate production of insulin-like growth factor-binding protein 5, thereby indirectly suppressing cell proliferation.
Published:
May 6, 1997
Title:
[Natural toxic substances in food]
Authors:
Pokorný, J.
Abstract:
Foods, mainly those of plant origin and mushrooms, contain natural toxic substances. Their acute toxicity is as a rule mild, but carcinogenic and teratogenic effects cannot be ruled out. They include e.g. cyanogens, lathyrogens, hydrazines, glucosinolates and related goitrogens, cumarins, saponins, alkaloids and glycoalkaloids, biogenic amines, enzyme inhibitors, such as lectins (haemagglutinins) and trypsin inhibitors and chelating substance e.g. phytates and oxalates. These toxic substances are partly removed by technological processes. When principles of a varied diet are respected, the health risk is reduced to a minimum.
Published:
May 6, 1997
Title:
Search for the Competitive Edge: A History of Dietary Fads and Supplements
Authors:
Applegate, Elizabeth A.; Grivetti, Louis E.
Abstract:
The premise and promise of ergogenic aid use is rooted in antiquity and is based upon superstition and ritualistic behavior of athletes who perceive that past performances were predicated upon unique dietary constituents or dietary manipulation. Accounts from ancient times recommended that athletes and soldiers preparing for battle consume specific animal parts to confer agility, speed or strength associated with that animal. Scientific understanding of the chemical and physiological nature of muscular work in the early 20th century was followed by ergogenic aid use by athletes and rationalized as “scientific” justification. Ergogenic aids such as alkaline salts, caffeine, carbohydrate and protein have been used by athletes with variable success. As nutritionists and exercise physiologists discovered and perfected the scientific understanding of metabolic reactions, athletes in turn experimented with the amount, form and timing of administration in the search for optimal performance. Anabolic steroids and blood doping enhance athletic performance, but health risks, ethics and sportsmanship contravene their use. Popularity and use of ergogenic aids often have preceded scientific substantiation of claims. Current products such as protein isolates and antioxidant nutrients commonly are used by athletes, and many ergogenic aids available today differ little from those used long ago.
Published:
April 30, 1997
Title:
The acid lipase gene family: three enzymes, one highly conserved gene structure.
Authors:
Lohse, P.; Lohse, P.; Chahrokh-Zadeh, S.; Seidel, D.
Abstract:
Human gastric lipase (HGL; triacylglycerol lipase; EC 3.1.1.3) plays an important role in the digestion of dietary triglycerides in the gastrointestinal tract, especially in patients suffering from pancreatic lipase deficiencies. The enzyme is secreted by the fundic mucosa of the stomach and hydrolyzes the ester bonds of triglycerides under acidic pH conditions, while cholesteryl esters are not attacked. The 379-amino acid protein is highly homologous to two other acidic lipases, rat lingual lipase (RLL; triacylglycerol lipase; EC 3.1.1.3) and human lysosomal acid lipase (HLAL; cholesteryl esterase; EC 3.1.1.13). To determine whether this remarkable similarity is also present at the genomic level, we have elucidated the respective gene structures by screening three bacteriophage lambda libraries and by polymerase chain reaction-based intron amplification. The genes encoding HGL, RLL, and HLAL are composed of 10 exons interrupted by nine introns and span about 14 kb, 18.7 kb, and 38.8 kb of genomic DNA, respectively. The HGL and RLL gene organizations are identical, suggesting that RLL is the rat gastric lipase expressed in the serous von Ebner glands of the tongue. The positions of the HLAL intervening sequences are also absolutely conserved, except for the location of intron 1. Our results support the concept that HLAL and HGL/RLL are members of a gene family of lipases that most likely have evolved by duplication of an ancestral gene and subsequently assumed distinct roles in neutral lipid metabolism due to sequence divergence and different expression patterns.
Published:
April 30, 1997
Title:
Effect of a single high-fat meal on endothelial function in healthy subjects
Authors:
Vogel, R. A.; Corretti, M. C.; Plotnick, G. D.
Abstract:
Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p
Published:
January 31, 1997
Title:
Testosterone and cortisol in relationship to dietary nutrients and resistance exercise
Authors:
Volek, Jeff S.; Kraemer, William J.; Bush, Jill A.; Incledon, Thomas; Boetes, Mark
Abstract:
Volek, Jeff S., William J. Kraemer, Jill A. Bush, Thomas Incledon, and Mark Boetes. Testosterone and cortisol in relationship to dietary nutrients and resistance exercise.J. Appl. Physiol. 82(1): 49–54, 1997.—Manipulation of resistance exercise variables (i.e., intensity, volume, and rest periods) affects the endocrine response to exercise; however, the influence of dietary nutrients on basal and exercise-induced concentrations of hormones is less understood. The present study examined the relationship between dietary nutrients and resting and exercise-induced blood concentrations of testosterone (T) and cortisol (C). Twelve men performed a bench press exercise protocol (5 sets to failure using a 10-repetitions maximum load) and a jump squat protocol (5 sets of 10 repetitions using 30% of each subject’s 1-repetition maximum squat) with 2 min of rest between all sets. A blood sample was obtained at preexercise and 5 min postexercise for determination of serum T and C. Subjects also completed detailed dietary food records for a total of 17 days. There was a significant (P ≤ 0.05) increase in postexercise T compared with preexercise values for both the bench press (7.4%) and jump squat (15.1%) protocols; however, C was not significantly different from preexercise concentrations. Significant correlations were observed between preexercise T and percent energy protein (r = −0.71), percent energy fat (r = 0.72), saturated fatty acids (g ⋅ 1,000 kcal−1 ⋅ day−1;r = 0.77), monounsaturated fatty acids (g ⋅ 1,000 kcal−1 ⋅ day−1;r = 0.79), the polyunsaturated fat-to-saturated fat ratio (r = −0.63), and the protein-to-carbohydrate ratio (r = −0.59). There were no significant correlations observed between any nutritional variables and preexercise C or the absolute increase in T and C after exercise. These data confirm that high-intensity resistance exercise results in elevated postexercise T concentrations. A more impressive finding was that dietary nutrients may be capable of modulating resting concentrations of T.
Published:
December 31, 1996
Title:
Health care in North must acknowledge Inuit values, traditional medicine
Authors:
Gray, G.
Abstract:
Dr. Gail Gray spent a week on Baffin Island in a retreat devoted to discussions about health care delivery in the North. She says it is obvious that traditional medical practices and Inuit cultural values must be part of any new health care initiatives if the initiatives are to be successful.
Published:
November 30, 1996
Title:
An isotopic palaeoenvironmental study of human skeletal remains from the Nile Valley
Authors:
Iacumin, P.; Bocherens, H.; Mariotti, A.; Longinelli, A.
Abstract:
Stable isotope measurements were carried out on human skeletal remains from the Nile Valley, ranging in age from about 7000 to 1750 yr B.P. and on a set of other samples among which are archaeological food remains. Bone samples were analyzed for δ18O(PO3−4), δ18O(CO2−3) and δ13C(CO−3) of carbonate hydroxylapatite and δ13C and δ15N of collagen. Food remains and tissue samples were analyzed for their δ13C and δ15N values. The isotopic composition of bone collagen, apatite and food remains (partially representative of the diet in ancient Egypt) suggest a mixed diet including C3 plant food and, probably, animal resources (both fresh-water fish and C3 animals). A rather surprising observation is the lack of differences between isotopic composition of remains of different social classes spanning from the very poor village of Gebelein to the middle class of the rich town of Asyut to the distinguished people who underwent mummification processes after their death. From the palaeoclimatological point of view, the δ18O(PO3−4) values, ranging from 20.6 to 24.5‰, seem to reflect the isotopic composition of Nile river water (also related to relative humidity) rather than real climatic (temperature) variations through time. The oxygen isotope compositions of carbonate and phosphate of the same samples (from 30.2 to 32.5 and from 20.6 to 22.2, respectively) suggest isotopic equilibrium conditions, thus confirming the possibility of also using the carbonate measurements for palaeoclimatological studies, at least in the case of recent and well preserved samples.
Published:
October 31, 1996
Title:
An isotopic palaeoenvironmental study of human skeletal remains from the Nile Valley
Authors:
Iacumin, P.; Bocherens, H.; Mariotti, A.; Longinelli, A.
Abstract:
Stable isotope measurements were carried out on human skeletal remains from the Nile Valley, ranging in age from about 7000 to 1750 yr B.P. and on a set of other samples among which are archaeological food remains. Bone samples were analyzed for δ18O(PO3−4), δ18O(CO2−3) and δ13C(CO−3) of carbonate hydroxylapatite and δ13C and δ15N of collagen. Food remains and tissue samples were analyzed for their δ13C and δ15N values. The isotopic composition of bone collagen, apatite and food remains (partially representative of the diet in ancient Egypt) suggest a mixed diet including C3 plant food and, probably, animal resources (both fresh-water fish and C3 animals). A rather surprising observation is the lack of differences between isotopic composition of remains of different social classes spanning from the very poor village of Gebelein to the middle class of the rich town of Asyut to the distinguished people who underwent mummification processes after their death. From the palaeoclimatological point of view, the δ18O(PO3−4) values, ranging from 20.6 to 24.5‰, seem to reflect the isotopic composition of Nile river water (also related to relative humidity) rather than real climatic (temperature) variations through time. The oxygen isotope compositions of carbonate and phosphate of the same samples (from 30.2 to 32.5 and from 20.6 to 22.2, respectively) suggest isotopic equilibrium conditions, thus confirming the possibility of also using the carbonate measurements for palaeoclimatological studies, at least in the case of recent and well preserved samples.
Published:
October 31, 1996
Title:
Progression of Prostatic Intraepithelial Neoplasia to Invasive Carcinoma in C3(1)/SV40 Large T Antigen Transgenic Mice: Histopathological and Molecular Biological Alterations
Authors:
Shibata, Masa-Aki; Ward, Jerrold M.; Devor, Deborah E.; Liu, Min-Ling; Green, Jeffrey E.
Abstract:
The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)/TAG transgenic mouse model and appears very similar to the process proposed to occur in humans. PIN lesions in these transgenic mice histologically resemble those found in human PIN. Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age. A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, were found by 7 months of age in the ventral lobe and 11 months of age in the dorsolateral lobe. Expression of TAG mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein. Apoptosis levels were quite low in normal epithelial cells, moderate in low-grade PIN, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, therefore, be an early event in a significant portion of PIN lesions. Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans.
Published:
October 31, 1996
Title:
Dietary habits and mortality in 11,000 vegetarians and health conscious people: results of a 17 year follow up
Authors:
Key, T. J.; Thorogood, M.; Appleby, P. N.; Burr, M. L.
Abstract:
OBJECTIVE: To investigate the association of dietary habits with mortality in a cohort of vegetarians and other health conscious people. DESIGN: Observational study. SETTING: United Kingdom. SUBJECTS: 4336 men and 6435 women recruited through health food shops, vegetarian societies, and magazines. MAIN OUTCOME MEASURES: Mortality ratios for vegetarianism and for daily versus less than daily consumption of wholemeal bread, bran cereals, nuts or dried fruit, fresh fruit, and raw salad in relation to all cause mortality and mortality from ischaemic heart disease, cerebrovascular disease, all malignant neoplasms, lung cancer, colorectal cancer, and breast cancer. RESULTS: 2064 (19%) subjects smoked, 4627 (43%) were vegetarian, 6699 (62%) ate wholemeal bread daily, 2948 (27%) ate bran cereals daily, 4091 (38%) ate nuts or dried fruit daily, 8304 (77%) ate fresh fruit daily, and 4105 (38%) ate raw salad daily. After a mean of 16.8 years follow up there were 1343 deaths before age 80. Overall the cohort had a mortality about half that of the general population. Within the cohort, daily consumption of fresh fruit was associated with significantly reduced mortality from ischaemic heart disease (rate ratio adjusted for smoking 0.76 (95% confidence interval 0.60 to 0.97)), cerebrovascular disease (0.68 (0.47 to 0.98)), and for all causes combined (0.79 (0.70 to 0.90)). CONCLUSIONS: In this cohort of health conscious individuals, daily consumption of fresh fruit is associated with a reduced mortality from ischaemic heart disease, cerebrovascular disease, and all causes combined.
Published:
September 27, 1996
Title:
Genotoxic effects of crude juices from Brassica vegetables and juices and extracts from phytopharmaceutical preparations and spices of cruciferous plants origin in bacterial and mammalian cells
Authors:
Kassie, F.; Parzefall, W.; Musk, S.; Johnson, I.; Lamprecht, G.; Sontag, G.; Knasmüller, S.
Abstract:
Crude juices of eight Brassica vegetables as well as juices and extracts of spices and phytopharmaceutical preparations from cruciferous vegetables were tested for induction of point mutations in Salmonella TA98 and TA100, repairable DNA damage in E.coli K-12 cells and clastogenic effects in mammalian cells. In bacterial assays, all juices caused genotoxic effects in the absence of metabolic activation, the ranking order being: Brussels sprouts > white cabbage > cauliflower > green cabbage > kohlrabi > broccoli > turnip > black radish. In experiments with mammalian cells, six juices induced structural chromosome aberrations. Brussels sprouts, white and green cabbage caused the strongest effects (800 microliters of juice induced a 5-fold increase over the background). In sister chromatid exchange assays, positive results were measured as well, but the effects were less pronounced. With all juices the genotoxic effects seen in mammalian cells were paralleled by a pronounced decrease in cell viability. Column fractionation experiments showed that 70-80% of the total genotoxic activity of the juices is found in the fraction which contains isothiocyanates and other breakdown products of glucosinolates, whereas phenolics and flavonoids contributed to a lesser extent to the overall effects. On the basis of these findings, and considering the negative results obtained with non-cruciferous vegetables (tomato, carrot and green pepper), it seems likely that the genotoxic effects of the juices are due to specific constituents of cruciferous plants such as glucosinolates and/or their breakdown products, in particular, isothiocyanates, which we found previously to be potent genotoxins in bacterial and mammalian cells. Finally, spices (mustards and horse radish paste) and phytopharmaceutical preparations were tested in bacterial assays. Mustards and horse radish caused very weak effects while most of the pharmaceutical preparations gave negative results, except cabbage tablets, which caused a strong and dose dependent induction of his revertants in Salmonella TA100. The present findings clearly indicate that cruciferous vegetables contain DNA damaging constituents. These observations are in contrast to earlier findings, which emphasized the antimutagenic effects of vegetable juices and also raise the question whether greatly increased consumption of Brassica vegetables or their concentrated constituents as a means for cancer prevention is indeed recommendable.
Published:
September 26, 1996
Title:
Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study
Authors:
Pauletto, P.; Puato, M.; Caroli, M. G.; Casiglia, E.; Munhambo, A. E.; Cazzolato, G.; Bittolo Bon, G.; Angeli, M. T.; Galli, C.; Pessina, A. C.
Abstract:
BACKGROUND: There is evidence that populations with a high intake of fish, and specifically fish oils, are at reduced risk of cardiovascular disease. To explore the effect of fish intake, we compared two groups of Bantu villagers in Tanzania; one group live on the shores of Lake Nyasa and their diet includes large amounts of freshwater fish; the other group live in the nearby hills and have a vegetarian diet. METHODS: We carried out a cross-sectional study of 622 fish-consuming villagers and 686 vegetarian villagers. 618 (99.4%) and 645 (94.0%), respectively, agreed to take part. Anthropometric and self-reported medical history data were collected by one local physician and a medical assistant, who also measured blood pressure and took blood samples for measurement of plasma lipids. A dietary questionnaire was administered to 25 families (about 15% of the study population) in each village. FINDINGS: After adjustment for age, sex, and alcohol intake the fish-consuming group had lower mean blood pressure than the vegetarian group (123/72 vs 133/76 mm Hg, p < 0.001). The frequencies of definite and borderline hypertension (by WHO criteria) were lower in the fish-consuming than in the vegetarian group (2.8 vs 16.4%; 9.7 vs 22.3%, respectively). Plasma concentrations of total cholesterol (mean 3.53 [SD 1.04] vs 4.10 [1.04] mmol/L), triglycerides (0.92 [0.64] vs 1.31 [0.64] mmol/L), and lipoprotein(a) (201 [213] vs 321 [212] mg/L), were all lower (p < 0.0001) in the fish-consuming group than in the vegetarian group. The proportions of n-3 polyunsaturated fatty acids in plasma lipids were higher (p
Published:
September 20, 1996
Title:
Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes
Authors:
Sinnis, P.; Willnow, T. E.; Briones, M. R.; Herz, J.; Nussenzweig, V.
Abstract:
Remnants of lipoproteins, intestinal chylomicrons, and very low density lipoprotein (VLDL), are rapidly cleared from plasma and enter hepatocytes. It has been suggested that remnant lipoproteins are initially captured in the space of Disse by heparan sulfate proteoglycans (HSPGs), and that their subsequent internalization into hepatocytes is mediated by members of the LDL-receptor gene family. Similarly to lipoprotein remnants, malaria sporozoites are removed from the blood circulation by the liver within minutes after injection by Anopheles mosquitoes. The sporozoite's surface is covered by the circumsporozoite protein (CS), and its region II-plus has been implicated in the binding of the parasites to glycosaminoglycan chains of hepatocyte HSPGs. Lactoferrin, a protein with antibacterial properties found in breast milk and neutrophil granules, is also rapidly cleared from the circulation by hepatocytes, and can inhibit the hepatic uptake of lipoprotein remnants. Here we provide evidence that sporozoites, lactoferrin, and remnant lipoproteins are cleared from the blood by similar mechanisms. CS, lactoferrin, and remnant lipoproteins compete in vitro and in vivo for binding sites on liver cells. The relevance of this binding event for sporozoite infectivity is highlighted by our demonstration that apoliprotein E-enriched beta-VLDI and lactoferrin inhibit sporozoite invasion of HepG2 cells. In addition, malaria sporozoites are less infective in LDL-receptor knockout (LDLR -/-) mice maintained on a high fat diet, as compared with littermates maintained on a normal diet. We conclude that the clearance of lipoprotein remnants and sporozoites from the blood is mediated by the same set of highly sulfated HSPGs on the hepatocyte plasma membrane.
Published:
August 31, 1996
Title:
The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis.
Authors:
Miyata, T; Hori, O; Zhang, J; Yan, S D; Ferran, L; Iida, Y; Schmidt, A M
Abstract:
An important component of amyloid fibrils in dialysis-related amyloidosis is a form of beta2microglobulin modified with advanced glycation end products (AGEs) of the Maillard reaction, known as AGE-beta2M. We demonstrate here that the interaction of AGE-beta2M with mononuclear phagocytes (MPs), cells important in the pathogenesis of the inflammatory arthropathy of dialysis-related amyloidosis, is mediated by the receptor for AGEs, or RAGE. 125I-AGE-beta2M bound to immobilized RAGE or to MPs in a specific, dose-dependent manner (Kd approximately 53.5 and approximately 81.6 nM, respectively), a process inhibited in the presence of RAGE blockade. AGE-beta2M-mediated monocyte chemotaxis was prevented by excess sRAGE or anti-RAGE IgG. Induction of tumor necrosis factor-alpha (TNF) expression by MPs exposed to AGE-beta2M resulted from engagement of RAGE, as appearances of TNF transcripts and TNF antigen release into culture supernatants were prevented by addition of sRAGE, a process mediated, at least in part, by oxidant stress. AGE-beta2M reduced cytochrome c and the elaboration of TNF by MPs was inhibited by N-acetylcysteine. Consistent with these data, immunohistochemical studies of AGE-laden amyloid deposits of a long-term hemodialysis patient revealed positive staining for RAGE in the MPs infiltrating these lesions. These data indicate that RAGE is a central binding site for AGEs formed in vivo and suggest that AGE-beta2M-MP-RAGE interaction likely contributes to the initiation of an inflammatory response in amyloid deposits of long-term hemodialysis patients, a process which may ultimately lead to bone and joint destruction.
Published:
August 31, 1996
Title:
1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis
Authors:
Cantorna, M. T.; Hayes, C. E.; DeLuca, H. F.
Abstract:
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease believed to be a model for the human disease multiple sclerosis (MS). Induced by immunizing B10.PL mice with myelin basic protein (MBP), EAE was completely prevented by the administration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. 1,25-(OH)2D3 could also prevent the progression of EAE when administered at the appearance of the first disability symptoms. Withdrawal of 1,25-(OH)2D3 resulted in a resumption of the progression of EAE. Thus, the block by 1,25-(OH)2D3 is reversible. A deficiency of vitamin D resulted in an increased susceptibility to EAE. Thus, 1,25-(OH)2D3 or its analogs are potentially important for treatment of MS.
Published:
July 22, 1996
Title:
Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones
Authors:
Hiatt, R. A.; Ettinger, B.; Caan, B.; Quesenberry, C. P.; Duncan, D.; Citron, J. T.
Abstract:
Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis, who account for > 80% of new diagnoses of kidney stones. This dietary advice is supported by metabolic studies and epidemiologic observational studies but has not been evaluated in a controlled trial. Using 1983-1985 data from three Northern California Kaiser Permanente Medical Centers, the authors randomly assigned 99 persons who had calcium oxalate stones for the first time to a low animal protein, high fiber diet that contained approximately 56-64 g daily of protein, 75 mg daily of purine (primarily from animal protein and legumes), one-fourth cup of wheat bran supplement, and fruits and vegetables. Intervention subjects were also instructed to drink six to eight glasses of liquid daily and to maintain adequate calcium intake from dairy products or calcium supplements. Control subjects were instructed only on fluid intake and adequate calcium intake. Both groups were followed regularly for up to 4.5 years with food frequency questionnaires, serum and urine chemistry analysis, and abdominal radiography; and they were urged to comply with dietary instructions. In the intervention group of 50 subjects, stones recurred in 12 (7.1 per 100 person-years) compared with two (1.2 per 100 person-years) in the control group; both groups received a mean of 3.4 person-years of follow-up (p = 0.006). After adjustment for possible confounding effects of age, sex, education, and baseline protein and fluid intake, the relative risk of a recurrent stone in the intervention group was 5.6 (95% confidence interval 1.2-26.1) compared with the control group. The authors conclude that advice to follow a low animal protein, high fiber, high fluid diet has no advantage over advice to increase fluid intake alone.
Published:
June 30, 1996
Title:
N (epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction
Authors:
Ikeda, K.; Higashi, T.; Sano, H.; Jinnouchi, Y.; Yoshida, M.; Araki, T.; Ueda, S.; Horiuchi, S.
Abstract:
Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE-proteins indicated that N(epsilon)-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML-protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to approximately 8 mol/mol of protein. Further experiments with CML analogs revealed that the epitope of 6D12 is a CML-protein adduct with an important carbonyl group. In contrast to 6D12, our polyclonal anti-AGE antibody showed a significant but much weaker immunoreactivity to CML-BSA, suggesting that the polyclonal antibody contains two populations, one reactive to CML (CML-PA) and the other unreactive to CML (Non-CML-PA). Non-CML-PA separated from CML-PA by CML-BSA affinity chromatography did not react with all CML-modified preparations, but retained its property to react commonly with AGE preparations obtained from proteins, lysine derivatives, and monoaminocarboxylic acids. Therefore, it is clear that a CML-protein adduct is a major immunological epitope in AGE structures, but there still exist other major epitope(s) expressed commonly in AGE-proteins.
Published:
June 17, 1996
Title:
Evidence for possible use of plant foods in Palaeolithic and Mesolithic diet from the site of Całowanie in the central part of the Polish Plain
Authors:
Kubiak-Martens, Lucy
Abstract:
Całowanie site, which supported hunter-gatherer populations from ca. 11 380±95 until 8270±100 B.P., is the major terminal Palaeolithic and early Mesolithic occupation complex of the North European Plain. The archaeological layers are intercalated with biogenic sediments. The remains of plants that probably served as food were recovered from terminal Palaeolithic and early Mesolithic layers. Most of the charred plant remains, apart from wood charcoal, derives from vegetative parenchyma which forms a major part of organs such as root and tuber. Two taxa have been identified on the basis of the anatomy of parenchymatous tissue, namely Sagittaria cf. sagittifolia and Polygonum sp. In addition, several charred seeds and fruits were recovered. This is the first evidence for the probable use of plant foods, other than hazel nuts or water-chestnuts, in the diet of hunter-gatherers in the North European Plain during the Palaeolithic and Mesolithic.
Published:
May 31, 1996
Title:
Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
Authors:
Omenn, G. S.; Goodman, G. E.; Thornquist, M. D.; Balmes, J.; Cullen, M. R.; Glass, A.; Keogh, J. P.; Meyskens, F. L.; Valanis, B.; Williams, J. H.; Barnhart, S.; Hammar, S.
Abstract:
BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
Published:
May 1, 1996
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