top of page
Published Science
Click Search to Filter.
Total Entries: 10690
Title:
Human specific loss of olfactory receptor genes
Authors:
Gilad, Yoav; Man, Orna; Pääbo, Svante; Lancet, Doron
Abstract:
Olfactory receptor (OR) genes constitute the basis for the sense of smell and are encoded by the largest mammalian gene superfamily of >1,000 genes. In humans, >60% of these are pseudogenes. In contrast, the mouse OR repertoire, although of roughly equal size, contains only approximately 20% pseudogenes. We asked whether the high fraction of nonfunctional OR genes is specific to humans or is a common feature of all primates. To this end, we have compared the sequences of 50 human OR coding regions, regardless of their functional annotations, to those of their putative orthologs in chimpanzees, gorillas, orangutans, and rhesus macaques. We found that humans have accumulated mutations that disrupt OR coding regions roughly 4-fold faster than any other species sampled. As a consequence, the fraction of OR pseudogenes in humans is almost twice as high as in the non-human primates, suggesting a human-specific process of OR gene disruption, likely due to a reduced chemosensory dependence relative to apes.
Published:
March 17, 2003
Title:
The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency
Authors:
Knight, Eric L.; Stampfer, Meir J.; Hankinson, Susan E.; Spiegelman, Donna; Curhan, Gary C.
Abstract:
BACKGROUND: In individuals with moderate to severe renal insufficiency, low protein intake may slow renal function decline. However, the long-term impact of protein intake on renal function in persons with normal renal function or mild renal insufficiency is unknown. OBJECTIVE: To determine whether protein intake influences the rate of renal function change in women over an 11-year period. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 1624 women enrolled in the Nurses' Health Study who were 42 to 68 years of age in 1989 and gave blood samples in 1989 and 2000. Ninety-eight percent of women were white, and 1% were African American. MEASUREMENTS: Protein intake was measured in 1990 and 1994 by using a semi-quantitative food-frequency questionnaire. Creatinine concentration was used to estimate glomerular filtration rate (GFR) and creatinine clearance. RESULTS: In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR > or = 80 mL/min per 1.73 m2). Change in estimated GFR in this subgroup over the 11-year period was 0.25 mL/min per 1.73 m2 (95% CI, -0.78 to 1.28 mL/min per 1.73 m2) per 10-g increase in protein intake; the change in estimated GFR was 1.14 mL/min per 1.73 m2 (CI, -3.63 to 5.92 mL/min per 1.73 m2) after measurement-error adjustment for protein intake. In women with mild renal insufficiency (defined as an estimated GFR > 55 mL/min per 1.73 m2 but
Published:
March 17, 2003
Title:
Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury
Authors:
Yonekura, Hideto; Yamamoto, Yasuhiko; Sakurai, Shigeru; Petrova, Ralica G.; Abedin, Md Joynal; Li, Hui; Yasui, Kiyoshi; Takeuchi, Masayoshi; Makita, Zenji; Takasawa, Shin; Okamoto, Hiroshi; Watanabe, Takuo; Yamamoto, Hiroshi
Abstract:
The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. In the present study, we show that the cellular constituents of small vessels, endothelial cells (EC) and pericytes express novel splice variants of RAGE mRNA coding for the isoforms that lack the N-terminal V-type immunoglobulin-like domain (N-truncated) or the C-terminal transmembrane domain (C-truncated), as well as the known full-length mRNA. The ratio of the expression of the three variants was different between EC and pericytes; the content of the C-truncated form was highest in EC, whereas the full-length form was the most abundant in pericytes. Transfection experiments with COS-7 cells demonstrated that those variant mRNAs were translated into proteins as deduced; C-truncated RAGE was efficiently secreted into the culture media, and N-truncated RAGE was located mainly on the plasma membrane. The three isoforms were also detected in primary cultured human EC and pericytes. Further, full-length and C-truncated forms of RAGE bound to an AGE-conjugated column, whereas N-truncated RAGE did not. The AGE induction of extracellular-signal-related kinase phosphorylation and vascular endothelial growth factor in EC and of the growth and cord-like structure formation of EC was abolished completely by C-truncated RAGE, indicating that this endogenous secretory receptor (endogenous secretory RAGE) is cytoprotective against AGE. The results may contribute to our understanding of the molecular basis for the diversity of cellular responses to AGE and for individual variations in the susceptibility to diabetic vascular complications.
Published:
March 14, 2003
Title:
Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis
Authors:
UK ECT Review Group
Abstract:
BACKGROUND: We aimed to review published work for the efficacy and safety of electroconvulsive therapy (ECT) with simulated ECT, ECT versus pharmacotherapy, and different forms of ECT for patients with depressive illness. METHODS: We designed a systematic overview and meta-analysis of randomised controlled trials and observational studies. We obtained data from the Cochrane Collaboration Depressive Anxiety and Neurosis and Schizophrenia Group Controlled trial registers, Cochrane Controlled Trials register, Biological Abstracts, CINAHL, EMBASE, LILACS, MEDLINE, PsycINFO, and SIGLE, reference lists, and specialist textbooks. Our main outcome measures were depressive symptoms, measures of cognitive function, and mortality. FINDINGS: Meta-analysis of data of short-term efficacy from randomised controlled trials was possible. Real ECT was significantly more effective than simulated ECT (six trials, 256 patients, standardised effect size [SES] -0.91, 95% CI -1.27 to -0.54). Treatment with ECT was significantly more effective than pharmacotherapy (18 trials, 1144 participants, SES -0.80, 95% CI -1.29 to -0.29). Bilateral ECT was more effective than unipolar ECT (22 trials, 1408 participants, SES -0.32, 95% CI -0.46 to -0.19). INTERPRETATION: ECT is an effective short-term treatment for depression, and is probably more effective than drug therapy. Bilateral ECT is moderately more effective than unilateral ECT, and high dose ECT is more effective than low dose.
Published:
March 7, 2003
Title:
Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase
Authors:
Ziouzenkova, O.; Perrey, S.; Asatryan, L.; Hwang, J.; MacNaul, K. L.; Moller, D. E.; Rader, D. J.; Sevanian, A.; Zechner, R.; Hoefler, G.; Plutzky, J.
Abstract:
Published:
March 3, 2003
Title:
Low incidence of cardiovascular disease among the Inuit—what is the evidence?
Authors:
Bjerregaard, Peter; Young, T. Kue; Hegele, Robert A.
Abstract:
Abstract
Background: The notion that the incidence of ischemic heart disease (IHD) is low among the Inuit subsisting on a traditional marine diet has attained axiomatic status. The scientific evidence for this is weak and rests on early clinical evidence and uncertain mortality statistics. Methods: We reviewed the literature and performed new analyses of the mortality statistics from Greenland, Canada, and Alaska. Findings: The evidence for a low mortality from IHD among the Inuit is fragile and rests on unreliable mortality statistics. Mortality from stroke, however, is higher among the Inuit than among other western populations. Based on the examination of 15 candidate gene polymorphisms, the Inuit genetic architecture does not obviously explain putative differences in cardiovascular disease prevalence. Interpretation: The mortality from all cardiovascular diseases combined is not lower among the Inuit than in white comparison populations. If the mortality from IHD is low, it seems not to be associated with a low prevalence of general atherosclerosis. A decreasing trend in mortality from IHD in Inuit populations undergoing rapid westernization supports the need for a critical rethinking of cardiovascular epidemiology among the Inuit and the role of a marine diet in this population.
Published:
January 31, 2003
Title:
Vitamin D: A millenium perspective
Authors:
Holick, Michael F.
Abstract:
Vitamin D is one of the oldest hormones that have been made in the earliest life forms for over 750 million years. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. Vitamin D is metabolized in the liver and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. 1,25(OH)(2)D receptors (VDR) are present not only in the intestine and bone, but in a wide variety of other tissues, including the brain, heart, stomach, pancreas, activated T and B lymphocytes, skin, gonads, etc. 1,25(OH)(2)D is one of the most potent substances to inhibit proliferation of both normal and hyperproliferative cells and induce them to mature. It is also recognized that a wide variety of tissues, including colon, prostate, breast, and skin have the enzymatic machinery to produce 1,25(OH)(2)D. 1,25(OH)(2)D and its analogs have been developed for treating the hyperproliferative disease psoriasis. Vitamin D deficiency is a major unrecognized health problem. Not only does it cause rickets in children, osteomalacia and osteoporosis in adults, but may have long lasting effects. Chronic vitamin D deficiency may have serious adverse consequences, including increased risk of hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes. There needs to be a better appreciation of the importance of vitamin D for overall health and well being.
Published:
January 31, 2003
Title:
Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men
Authors:
Mukamal, Kenneth J.; Conigrave, Katherine M.; Mittleman, Murray A.; Camargo, Carlos A.; Stampfer, Meir J.; Willett, Walter C.; Rimm, Eric B.
Abstract:
BACKGROUND: Although moderate drinking confers a decreased risk of myocardial infarction, the roles of the drinking pattern and type of beverage remain unclear. METHODS: We studied the association of alcohol consumption with the risk of myocardial infarction among 38,077 male health professionals who were free of cardiovascular disease and cancer at base line. We assessed the consumption of beer, red wine, white wine, and liquor individually every four years using validated food-frequency questionnaires. We documented cases of nonfatal myocardial infarction and fatal coronary heart disease from 1986 to 1998. RESULTS: During 12 years of follow-up, there were 1418 cases of myocardial infarction. As compared with men who consumed alcohol less than once per week, men who consumed alcohol three to four or five to seven days per week had decreased risks of myocardial infarction (multivariate relative risk, 0.68 [95 percent confidence interval, 0.55 to 0.84] and 0.63 [95 percent confidence interval, 0.54 to 0.74], respectively). The risk was similar among men who consumed less than 10 g of alcohol per drinking day and those who consumed 30 g or more. No single type of beverage conferred additional benefit, nor did consumption with meals. A 12.5-g increase in daily alcohol consumption over a four-year follow-up period was associated with a relative risk of myocardial infarction of 0.78 (95 percent confidence interval, 0.62 to 0.99). CONCLUSIONS: Among men, consumption of alcohol at least three to four days per week was inversely associated with the risk of myocardial infarction. Neither the type of beverage nor the proportion consumed with meals substantially altered this association. Men who increased their alcohol consumption by a moderate amount during follow-up had a decreased risk of myocardial infarction.
Published:
January 8, 2003
Title:
The History of Nutrition: Malnutrition, Infection and Immunity
Authors:
Keusch, Gerald T.
Abstract:
The relationship between nutritional status and the immune system has been a topic of study for much of the 20th century. Dramatic increases in our understanding of the organization of the immune system and the factors that regulate immune function have demonstrated a remarkable and close concordance between host nutritional status and immunity. This report traces the increasing sophistication of our understanding of these relationships and their impact on susceptibility to infection through six stages to the present time. The cyclical relationship between poor nutrition, increased susceptibility to infectious diseases, leading to immunological dysfunction and metabolic responses that further alter nutritional status is described and, wherever possible, related to physiological mechanisms. In addition, the particular role of Nevin Scrimshaw in guiding the progress over the past 50 y is discussed.
Published:
December 31, 2002
Title:
The social determinants of the incidence and management of type 2 diabetes mellitus: are we prepared to rethink our questions and redirect our research activities?
Authors:
Raphael, Dennis; Anstice, Susan; Raine, Kim; McGannon, Kerry R.; Kamil, Rizvi Syed; Yu, Vanessa
Abstract:
This paper discusses the role played by social determinants of health in the incidence and management of type 2 diabetes mellitus (diabetes) among vulnerable populations. This issue is especially important in light of recent data from Statistics Canada indicating that mortality rates from diabetes have been increasing among Canadians since the mid‐1980s, with increases being especially great among those living in low‐income communities. Diabetes therefore appears – like cardiovascular disease – to be an affliction more common among the poor and excluded. It also appears to be especially likely to afflict poor women. Yet we know little about how these social determinants of health influence diabetes incidence and management. What evidence is available is provided and the case is made that the crisis in diabetes requires new ways of thinking about this disease, its causes, and its management.
Published:
December 31, 2002
Title:
New Evidence for the Use of Root Foods in Pre-Agrarian Subsistence recovered from the Late Mesolithic Site at Halsskov, Denmark. Vegetation History and Archaeobotany 11, 23-31.
Authors:
Kubiak-Martens, Lucy
Abstract:
Published:
December 30, 2002
Title:
Dietary fat is not a major determinant of body fat
Authors:
Willett, Walter C.; Leibel, Rudolph L.
Abstract:
The percentage of energy from fat in diets has been thought to be an important determinant of body fat, and several mechanisms have been proposed. Comparisons of diets and the prevalence of obesity between affluent and poor countries have been used to support this relationship, but these contrasts are seriously confounded by differences in physical activity and food availability. Within areas of similar economic development, regional intake of fat and prevalence of obesity have not been positively correlated. Randomized trials are the preferable method to evaluate the effect of dietary fat on adiposity and are feasible because the number of subjects needed is not large. In short-term trials, a modest reduction in body weight is typically seen in individuals randomized to diets with a lower percentage of calories from fat. However, compensatory mechanisms appear to operate, because in randomized trials lasting >or=1 year, fat consumption within the range of 18% to 40% of energy appears to have little if any effect on body fatness. The weighted mean difference was -0.25 kg overall and +1.8 kg (i.e., less weight loss on the low-fat diets) for trials with a control group that received a comparable intensity intervention. Moreover, within the United States, a substantial decline in the percentage of energy from fat during the last 2 decades has corresponded with a massive increase in the prevalence of obesity. Diets high in fat do not appear to be the primary cause of the high prevalence of excess body fat in our society, and reductions in fat will not be a solution.
Published:
December 29, 2002
Title:
Novel markers of susceptibility to carcinogens in diet: associations with colorectal cancer
Authors:
Sweeney, Carol; Coles, Brian F.; Nowell, Susan; Lang, Nicholas P.; Kadlubar, Fred F.
Abstract:
Red meats cooked at high temperatures generate mutagenic heterocyclic amines, which undergo metabolic activation by hepatic cytochrome P450 1A2 and N-acetyltransferase-2. A primary detoxification pathway involves glutathione S-transferase A1 (GSTA1), which catalyzes the reduction of the carcinogenic N-acetoxy derivative back to the parent amine. Recently, we described a polymorphism in the GSTA1 proximal promoter; the variant (GSTA1*B) allele significantly lowers enzyme expression. In a case-control study, GSTA1*B/*B genotype was associated with an increased risk of colorectal cancer, particularly among consumers of well-done meat. Dietary nitrosamines, which are bioactivated by CYP2A6, represent another potential etiologic factor for colorectal cancer. CYP2A6 converts the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7-dimethyluric acid (17U); we investigated CYP2A6 activity using the 17U/17X urinary metabolite ratio from case-control subjects who completed a caffeine phenotype assay. The distribution of CYP2A6 activity was significantly different between CRCa cases and controls, with subjects in the medium and high activity groups having an increased risk (P for trend=0.001). GSTA1 genotype and CYP2A6 phenotype should be evaluated as markers of susceptibility to dietary carcinogens in future studies.
Published:
December 26, 2002
Title:
A trail of research revisted
Authors:
Liener, Irvin E.
Abstract:
The author describes how his interest in the nutritional value of soybeans led to a trail of research that had many ramifications. In an attempt to account for the poor nutritional value of raw soybeans and the beneficial effect of heat treatment, a protein displaying hemagglutinating activity and capable of inhibiting the growth of rats was isolated and characterized. This protein subsequently proved to be an example of a class of proteins that were later referred to as "lectins". Lectins were also isolated from kidney beans and shown to be even more toxic than the soybean lectin. Concurrent studies with the soybean trypsin inhibitors revealed that these proteins inhibited growth by stimulating the secretory activity of the pancreas and could in the long term cause acinar cell adenoma of the pancreas. Acute experiments with human subjects showed that the human pancreas also responded to the stimulatory effects of the so-called Bowman-Birk soybean inhibitor. The studies on soybean trypsin inhibitors were expanded to include a protease inhibitor present in blood, alpha-1-antitrypsin, a deficiency of which leads to emphysema in humans. The mechanism whereby this protein inhibits leucocyte elastase was investigated. On the basis of these results the intratracheal administration of a synthetic peptide inhibitor of elastase attached to albumin microspheres was found to prevent elastase-induced emphysema in hamsters.
Published:
October 22, 2002
Title:
Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef
Authors:
Strickland, Paul T.; Qian, Zheng; Friesen, Marlin D.; Rothman, Nathaniel; Sinha, Rashmi
Abstract:
Heterocyclic amines (HAs) are carcinogenic combustion products formed during the cooking of meat at moderate to high temperatures. PhIP is the most common HA formed in fried, grilled or broiled meat, and is a colon, breast, and prostate carcinogen in rodents. The major metabolites of PhIP detected in human urine are N(2)-OH-PhIP-N(2)-glucuronide, PhIP-N(2)-glucuronide, N(2)-OH-PhIP-N(3)-glucuronide, and 4'-PhIP-sulphate. We have measured the time course of PhIP in untreated and acid- or alkali-hydrolyzed urines from 10 healthy non-smoking subjects ingesting identical amounts of char-broiled beef (containing both HAs and PAHs) for 5 days. The morning after the first day of broiled beef consumption (containing 7.7 micro g PhIP), urinary concentration of PhIP increased 14- to 38-fold above mean prefeed concentration. Following cessation of broiled meat consumption, urinary PhIP declined to near prefeed levels within 48-72 h. The ratio of alkali-labile PhIP metabolites to unmetabolized PhIP varied by 2.7-fold among subjects, ranging from 18:1 to 48:1. In a subsequent study we measured PhIP in acid-hydrolyzed urine from 66 subjects ingesting beef pan-fried at high temperature. A significant correlation (r=0.61, P<0.0001) was observed between the amount of fried meat ingested and concentration of PhIP in urines collected between 0 and 12h after feeding. Other investigators have identified 2-OH-PhIP in acid-hydrolyzed urine from these subjects, and also observed a significant correlation (r=0.52, P
Published:
September 29, 2002
Title:
Prevalence of attention deficit/hyperactivity disorder among adults in obesity treatment
Authors:
Altfas, Jules R.
Abstract:
BACKGROUND: Bariatric patients showing poor "focus" during treatment more often failed to lose weight or maintain reduced weight. Evaluation of these patients identified a number having attention deficit/hyperactivity disorder (ADHD), evidently a potent factor limiting successful weight control. After searches found no published reports describing comorbid ADHD and obesity, this report was conceived to begin exploring the prevalence and characteristics of these patients. METHOD: Clinical records of 215 patients receiving obesity treatment during 2000 were reviewed. Data collected and analyzed included age, sex, beginning and ending body mass index (BMI), number of clinic visits, months of treatment, and diagnostic category (ADHD, some ADHD symptoms, non-ADHD). DSM-IV criteria were used, except age of onset was modified to = 40. Mean weight loss among obese patients with ADHD (OB+ADHD) was 2.6 BMI (kg/m2) vs. 4.0 for non-ADHD (NAD) (p = 40, OB+ADHD had BMI loss 2.9 vs. 7.0 (NAD) (p
Published:
September 12, 2002
Title:
Effects of fatty acids on mitochondria: implications for cell death
Authors:
Penzo, Daniele; Tagliapietra, Chiara; Colonna, Raffaele; Petronilli, Valeria; Bernardi, Paolo
Abstract:
Fatty acids have prominent effects on mitochondrial energy coupling through at least three mechanisms: (i) increase of the proton conductance of the inner mitochondrial membrane; (ii) respiratory inhibition; (iii) opening of the permeability transition pore (PTP). Furthermore, fatty acids physically interact with membranes and possess the potential to alter their permeability; and they are also excellent respiratory substrates that feed electrons into the respiratory chain. Due to the complexity of their actions, the effects of fatty acids on mitochondrial function in situ are difficult to predict. We have investigated the mitochondrial and cellular effects of fatty acids of increasing chain length and degree of unsaturation in relation to their potential to affect mitochondrial function in situ and to cause cell death. We show that saturated fatty acids have little effect on the mitochondrial membrane potential in situ, and display negligible short-term cytotoxicity for Morris Hepatoma 1C1 cells. The presence of double bonds increases both the depolarizing effects and the cytotoxicity, but these effects are offset by the hydrocarbon chain length, so that more unsaturations are required to observe an effect as the hydrocarbon chain length is increased. With few exceptions, depolarization and cell death are due to opening of the PTP rather than to the direct effects of fatty acids on energy coupling.
Published:
September 9, 2002
Title:
Effects of fatty acids on mitochondria: implications for cell death
Authors:
Penzo, Daniele; Tagliapietra, Chiara; Colonna, Raffaele; Petronilli, Valeria; Bernardi, Paolo
Abstract:
Fatty acids have prominent effects on mitochondrial energy coupling through at least three mechanisms: (i) increase of the proton conductance of the inner mitochondrial membrane; (ii) respiratory inhibition; (iii) opening of the permeability transition pore (PTP). Furthermore, fatty acids physically interact with membranes and possess the potential to alter their permeability; and they are also excellent respiratory substrates that feed electrons into the respiratory chain. Due to the complexity of their actions, the effects of fatty acids on mitochondrial function in situ are difficult to predict. We have investigated the mitochondrial and cellular effects of fatty acids of increasing chain length and degree of unsaturation in relation to their potential to affect mitochondrial function in situ and to cause cell death. We show that saturated fatty acids have little effect on the mitochondrial membrane potential in situ, and display negligible short-term cytotoxicity for Morris Hepatoma 1C1 cells. The presence of double bonds increases both the depolarizing effects and the cytotoxicity, but these effects are offset by the hydrocarbon chain length, so that more unsaturations are required to observe an effect as the hydrocarbon chain length is increased. With few exceptions, depolarization and cell death are due to opening of the PTP rather than to the direct effects of fatty acids on energy coupling.
Published:
September 9, 2002
Title:
Role of the phosphatidylinositol 3'-kinase/PTEN/Akt kinase pathway in tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in non-small cell lung cancer cells
Authors:
Kandasamy, Karthikeyan; Srivastava, Rakesh K.
Abstract:
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/APO-2L is a member of the TNF superfamily and has been shown to have selective antitumor activity. We here show that TRAIL does not induce apoptosis in some non-small cell lung cancer (NSCLC) cells. These cells are resistant to TRAIL because of the phosphatidylinositol 3'-kinase (PI3-K)-dependent activation of Akt/protein kinase B. The expression of phospho-Akt varies at the functional level but not at the mRNA level in NSCLC cells. Akt induces cell survival in NSCLC cells by blocking the Bid cleavage, upstream of cytochrome c release in the mitochondrial-dependent apoptotic pathway. The use of PI3-K inhibitors, Wortmannin or LY-294002, down-regulates the active Akt and reverses cellular resistance to TRAIL. In addition, genetically altering Akt expression by transfecting dominant negative Akt, sensitizes NSCLC cells to TRAIL. Conversely, transfection of constitutively active Akt into cells that express low, constitutively active Akt, increases TRAIL resistance. Alternate to this approach, transfection with PTEN, a lipid phosphatase, promotes sensitivity to TRAIL, whereas a PTEN mutant (PTEN-G129E) at the catalytic site is inactive in dephosphorylating active Akt. Furthermore, the loss of PTEN activity or overexpression of PI3-K-dependent Akt/protein kinase B activity promotes the survival of NSCLC cells. Modulation of Akt activity by combining pharmacological drugs or genetic alterations of the Akt expression induces cellular responsiveness to TRAIL. Thus, TRAIL can be used to treat NSCLC-resistant cells when combined with agents that down-regulate Akt activity.
Published:
August 31, 2002
Title:
Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer
Authors:
Chan, June M.; Stampfer, Meir J.; Ma, Jing; Gann, Peter; Gaziano, J. Michael; Pollak, Michael; Giovannucci, Edward
Abstract:
BACKGROUND: Plasma levels of insulin-like growth factor-I (IGF-I) have been associated with the risk of prostate cancer. However, the association of IGF-I with specific tumor stage and grade at diagnosis, which correlate with risk of recurrence and mortality, has not been studied rigorously. To determine whether plasma levels of IGF-I and its main circulating binding protein, IGF binding protein-3 (IGFBP-3), predict more aggressive forms of prostate cancer, we investigated the association between plasma levels of each and specific stages and grades of prostate cancer. METHODS: We examined 530 case patients and 534 control subjects in a nested case-control study in the prospective Physicians' Health Study. Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status. IGF-I and IGFBP-3 were measured in prospectively collected plasma samples. Conditional logistic regression models were used to estimate the relative risks (RRs) for prostate cancer associated with IGF-I and IGFBP-3, stratified on grade (Gleason score > or = 7 versus
Published:
July 16, 2002
Title:
A guidebook for the cell culture facility: Basic Cell Culture, 2nd edn
Authors:
Sköld, Helén Nilsson
Abstract:
edited by J. M. Davis Oxford University Press (2002) 381 pages. ISBN 0-19-963853-5 £30 ![Figure][1] If you are planning to set up any functional cell culture facility, small- or large-scale, Basic Cell Culture could be very useful. The book has high practical and scientific value
Published:
July 14, 2002
Title:
Urinary arsenic speciation in subjects with or without restriction from seafood dietary intake
Authors:
Hsueh, Yu Mei; Hsu, Miao Kan; Chiou, Hung Yi; Yang, Mo Hsiung; Huang, Chuan Chieh; Chen, Chien Jen
Abstract:
In order to understand whether ingestion of seafood affects the urinary arsenic metabolites. About 42 women and 36 men were recruited from the students, parents and teachers in Taipei Medical University and National Taiwan University. The study subjects were interviewed about dietary habits, cigarette smoking habits, drug and vitamin intake, and consumption of seafood. Urine samples were collected from study subjects before and after refraining from eating seafood for 3 days, respectively. The urine samples were frozen at -20 degrees C separated by high-performance liquid chromatography (HPLC), and on line linked to hydride generator atomic absorption spectrometry (HGAAS) to quantify the levels of various species of inorganic arsenic and its metabolites. The levels of arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), total inorganic arsenic metabolites, inorganic arsenic percent, MMA percent and DMA percent were similar before and after refraining from eating seafood for 3 days. The frequencies of fish, shellfish and seaweed dietary intake were not significantly correlated with urinary arsenic species.
Published:
July 6, 2002
Title:
What if It's All Been a Big Fat Lie?
Authors:
Taubes, Gary
Abstract:
If the members of the American medical establishment were to have a collective find-yourself-standing-naked-in-Times-Square-type nightmare, this might be it. They spend 30 years ridiculing Robert Atkins, author of the phenomenally-best-selling ''Dr. Atkins' Diet Revolution'' and ''Dr. Atkins' New Diet Revolution,'' accusing the Manhattan doctor of quackery and fraud, only to discover that the unrepentant Atkins was right all along. Or maybe it's this: they find that their very own dietary recommendations -- eat less fat and more carbohydrates -- are the cause of the rampaging epidemic of obesity in America. Or, just possibly this: they find out both of the above are true. When Atkins first published his ''Diet Revolution'' in 1972, Americans were just coming to terms with the proposition that fat -- particularly the saturated fat of meat and dairy products -- was the primary nutritional evil in the American diet. Atkins managed to sell millions of copies of a book promising that we would lose weight eating steak, eggs and butter to our heart's desire, because it was the carbohydrates, the pasta, rice, bagels and sugar, that caused obesity and even heart disease. Fat, he said, was harmless.
Published:
July 6, 2002
Title:
A Ketogenic Diet Favorably Affects Serum Biomarkers for Cardiovascular Disease in Normal-Weight Men
Authors:
Sharman, Matthew J.; Kraemer, William J.; Love, Dawn M.; Avery, Neva G.; Gómez, Ana L.; Scheett, Timothy P.; Volek, Jeff S.
Abstract:
ABSTRACT. Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). T
Published:
June 30, 2002
Title:
Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals
Authors:
Musa-Veloso, Kathy; Likhodii, Sergei S.; Cunnane, Stephen C.
Abstract:
ABSTRACT. Background: Ketogenic diets are used therapeutically to treat intractable seizures. Clinically, it appears that the maintenance of ketosis is crucial
Published:
June 30, 2002
Title:
Justus Von Liebig: The Chemical Gatekeeper
Authors:
Brock, William H.
Abstract:
One of the founding fathers of organic chemistry and also a great teacher, Liebig (1803-73) enjoyed a close relationship with Britain, whose scientific education, medical practice and agriculture he transformed. Brock's fresh interpretation of Liebig's stormy career shows how he moved chemistry into the socio-political marketplace, demonstrating chemistry's significance for society in food production, nutrition and public health. Through popular lectures and his readable Chemical Letters, Liebig also commented on issues such as scientific methodology and materialism. This is the first English-language biography of Liebig since 1901.
Published:
June 19, 2002
Title:
[The debate in Science: dietary guidelines against myocardial infarction are defended by wrong citations]
Authors:
Ravnskov, Uffe
Abstract:
Published:
June 5, 2002
Title:
Charred plant remains from a 10th millennium B.P. kitchen at Jerf el Ahmar (Syria)
Authors:
Willcox, George
Abstract:
The Pre-potteryNeolithic A (PPNA) site of Jerf el Ahmar, Syria, dated to the 10th millennium uncal B.P., has produced over 657 flotation samples which are now under study. The results described in this article were obtained from the analysis of 32 samples of charred plant remains taken from a room of 2.5 × 3 m, which had been destroyed by fire. The room contained three saddle querns, two flat polished stone plates (each of 60 cm in diameter), one hearth, and three limestone "basins". These objects were in situ and the room appeared to represent a food preparation area (kitchen). On one of the querns two charred seed cakes were found. The finely ground seeds have been identified as Brassica/Sinapis, a rare taxon for this period. The major taxa, which are morphologically wild, have distinct spatial distributions, which provide evidence for plant processing activities. Hordeum spontaneum and Triticum/Secale were processed separately. The association of H. spontaneum with stone basins suggests soaking of this grain.
Published:
May 31, 2002
Title:
Vitamin C in Inuit Traditional Food and Women's Diets
Authors:
Fediuk, Karen; Hidiroglou, Nick; Madère, René; Kuhnlein, Harriet V.
Abstract:
Vitamin C values for 37 traditional foods (TFs) of the Inuit of the Canadian Arctic and women's intakes from TF and market food (MF) are reported. This is the first report on vitamin C values in several traditional food samples. There are a variety of rich sources of vitamin C from animal and plant food with the most notable among items with multiple samples being raw fish (Coregonus spp.) eggs (49.6±12.3 mg/100 g, mean± S.D.), raw whale (Delphinapterus leucas and Monodon monoceros) skin, locally termed “mattak”, (36.0±8.7 and 31.5±7.0 mg/10 g), caribou liver (Rangifer tarandus) (23.8±4.9 mg/100 g), ringed seal liver (Phoca hispida) (23.8±3.8 mg/100 g), and blueberries (Vaccinium uliginosum) (26.2±4.9 mg/100 g). Dietary analysis of 20–40-year-old women's 24-h recalls for vitamin C as TF and MF revealed total mean intake of 60±8 mg/day (mean± S.E.). TF contributed only 20% of total intake, although there was significant seasonal variation (P
Published:
May 31, 2002
Title:
Environmental factors in the etiology of type 1 diabetes
Authors:
Akerblom, Hans K.; Vaarala, Outi; Hyöty, Heikki; Ilonen, Jorma; Knip, Mikael
Abstract:
Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial. Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes.
Published:
May 29, 2002
Title:
Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery
Authors:
Cummings, David E.; Weigle, David S.; Frayo, R. Scott; Breen, Patricia A.; Ma, Marina K.; Dellinger, E. Patchen; Purnell, Jonathan Q.
Abstract:
BACKGROUND: Weight loss causes changes in appetite and energy expenditure that promote weight regain. Ghrelin is a hormone that increases food intake in rodents and humans. If circulating ghrelin participates in the adaptive response to weight loss, its levels should rise with dieting. Because ghrelin is produced primarily by the stomach, weight loss after gastric bypass surgery may be accompanied by impaired ghrelin secretion. METHODS: We determined the 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in 13 obese subjects before and after a six-month dietary program for weight loss. The 24-hour ghrelin profiles were also determined in 5 subjects who had lost weight after gastric bypass and 10 normal-weight controls; 5 of the 13 obese subjects who participated in the dietary program were matched to the subjects in the gastric-bypass group and served as obese controls. RESULTS: Plasma ghrelin levels rose sharply shortly before and fell shortly after every meal. A diet-induced weight loss of 17 percent of initial body weight was associated with a 24 percent increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, despite a 36 percent weight loss after gastric bypass, the area under the curve for the ghrelin profile in the gastric-bypass group was 77 percent lower than in normal-weight controls (P
Published:
May 22, 2002
Title:
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model
Authors:
Mukherjee, P.; El-Abbadi, M. M.; Kasperzyk, J. L.; Ranes, M. K.; Seyfried, T. N.
Abstract:
Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30-40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal x day(-1), respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers.
Published:
May 19, 2002
Title:
In Bid to Improve Nutrition, Schools Expel Soda and Chips
Authors:
Egan, Timothy
Abstract:
Published:
May 19, 2002
Title:
The proto-oncogene c-myc in hematopoietic development and leukemogenesis
Authors:
Hoffman, Barbara; Amanullah, Arshad; Shafarenko, Marianna; Liebermann, Dan A.
Abstract:
The proto-oncogene c-myc has been shown to play a pivotal role in cell cycle regulation, metabolism, apoptosis, differentiation, cell adhesion, and tumorigenesis, and participates in regulating hematopoietic homeostasis. It is a transcription regulator that is part of an extensive network of interacting factors. Most probably, different biological responses are elicited by different overlapping subsets of c-Myc target genes, both induced and suppressed. Results obtained from studies employing mouse models are consistent with the need for at least one, and possibly two, mutations in addition to deregulated c-myc for malignant tumor formation. Repression of c-myc is required for terminal differentiation of many cell types, including hematopoietic cells. It has been shown that deregulated expression of c-myc in both M1 myeloid leukemic cells and normal myeloid cells derived from murine bone marrow, not only blocked terminal differentiation and its associated growth arrest, but also induced apoptosis, which is dependent on the Fas/CD95 pathway. There is evidence to suggest that the CD95/Fas death receptor pathway is an integral part of the apoptotic response associated with the end of the normal terminal myeloid differentiation program, and that deregulated c-myc expression can activate this signaling pathway prematurely. The ability of egr-1 to promote terminal myeloid differentiation when co-expressed with c-myc, and of c-fos to partially abrogate the block imparted by deregulated c-myc on myeloid differentiation, make these two genes candidate tumor suppressors. Several different transcription factors have been implicated in the down-regulation of c-myc expression during differentiation, including C/EBPalpha, CTCF, BLIMP-1, and RFX1. Alterations in the expression and/or function of these transcription factors, or of the c-Myc and Max interacting proteins, such as MM-1 and Mxi1, can influence the neoplastic process. Understanding how c-Myc controls cellular phenotypes, including the leukemic phenotype, should provide novel tools for designing drugs to promote differentiation and/or apoptosis of leukemic cells.
Published:
May 12, 2002
Title:
Variability in conversion of β-carotene to vitamin A in men as measured by using a double-tracer study design
Authors:
Hickenbottom, Sabrina J.; Follett, Jennifer R.; Lin, Yumei; Dueker, Stephen R.; Burri, Betty J.; Neidlinger, Terry R.; Clifford, Andrew J.
Abstract:
ABSTRACT. Background: The vitamin A activity of β-carotene is variable and surprisingly low in women. The reasons for this are not well understood. The vitamin
Published:
April 30, 2002
Title:
Intra- and interspecific variation in primate gene expression patterns
Authors:
Enard, Wolfgang; Khaitovich, Philipp; Klose, Joachim; Zöllner, Sebastian; Heissig, Florian; Giavalisco, Patrick; Nieselt-Struwe, Kay; Muchmore, Elaine; Varki, Ajit; Ravid, Rivka; Doxiadis, Gaby M.; Bontrop, Ronald E.; Pääbo, Svante
Abstract:
Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.
Published:
April 11, 2002
Title:
Protein consumption and bone mineral density in the elderly : the Rancho Bernardo Study
Authors:
Promislow, Joanne H. E.; Goodman-Gruen, Deborah; Slymen, Donald J.; Barrett-Connor, Elizabeth
Abstract:
The role of dietary protein in osteoporosis is unclear, with previous studies having suggested both protection and harm. The associations of total, animal, and vegetable protein with bone mineral density (BMD) and the variations in these associations with calcium intake were studied in a community-dwelling cohort of 572 women and 388 men aged 55-92 years (Rancho Bernardo, California). Multiple linear regression analyses adjusted for standard osteoporosis covariates showed a positive association between animal protein consumption, assessed by food frequency questionnaires in 1988-1992, and BMD, measured 4 years later. This association was statistically significant in women. For every 15-g/day increase in animal protein intake, BMD increased by 0.016 g/cm2 at the hip (p = 0.005), 0.012 g/cm2 at the femoral neck (p = 0.02), 0.015 g/cm2 at the spine (p = 0.08), and 0.010 g/cm2 for the total body (p = 0.04). Conversely, a negative association between vegetable protein and BMD was observed in both sexes. Some suggestion of effect modification by calcium was seen in women, with increasing protein consumption appearing to be more beneficial for women with lower calcium intakes, but evidence for this interaction was not consistently strong. This study supports a protective role for dietary animal protein in the skeletal health of elderly women.
Published:
March 31, 2002
Title:
The paradoxical nature of hunter-gatherer diets: Meat-based, yet non-atherogenic
Authors:
Cordain, Loren; Eaton, Stanley; Brand-Miller, Jennie; Mann, Neil; Hill, Kim
Abstract:
Field studies of twentieth century hunter-gathers (HG) showed them to be generally free of the signs and symptoms of cardiovascular disease (CVD). Consequently, the characterization of HG diets may have important implications in designing therapeutic diets that reduce the risk for CVD in Westernized societies. Based upon limited ethnographic data (n=58 HG societies) and a single quantitative dietary study, it has been commonly inferred that gathered plant foods provided the dominant energy source in HG diets. In this review we have analyzed the 13 known quantitative dietary studies of HG and demonstrate that animal food actually provided the dominant (65%) energy source, while gathered plant foods comprised the remainder (35%). This data is consistent with a more recent, comprehensive review of the entire ethnographic data (n=229 HG societies) that showed the mean subsistence dependence upon gathered plant foods was 32%, whereas it was 68% for animal foods. Other evidence, including isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid gut size, low activity levels of certain enzymes, and optimal foraging data all point toward a long history of meat-based diets in our species. Because increasing meat consumption in Western diets is frequently associated with increased risk for CVD mortality, it is seemingly paradoxical that HG societies, who consume the majority of their energy from animal food, have been shown to be relatively free of the signs and symptoms of CVD. The high reliance upon animal-based foods would not have necessarily elicited unfavorable blood lipid profiles because of the hypolipidemic effects of high dietary protein (19-35% energy) and the relatively low level of dietary carbohydrate (22-40% energy). Although fat intake (28-58% energy) would have been similar to or higher than that found in Western diets, it is likely that important qualitative differences in fat intake, including relatively high levels of MUFA and PUFA and a lower omega-6/omega-3 fatty acid ratio, would have served to inhibit the development of CVD. Other dietary characteristics including high intakes of antioxidants, fiber, vitamins and phytochemicals along with a low salt intake may have operated synergistically with lifestyle characteristics (more exercise, less stress and no smoking) to further deter the development of CVD.
Published:
March 31, 2002
Title:
Dopamine may be 'hyper' with respect to noradrenaline metabolism, but 'hypo' with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder
Authors:
Oades, Robert D.
Abstract:
Noradrenaline: Hechtman (J Psychiat Neurosci 1994;19:193) argued for a role for frontal dopamine (DA) and noradrenaline (NA) in ADHD, where Oades (Prog Neurobiol 1987;29:365) has described lateralised functional impairments. Mechanisms (e.g. via alpha-2 sites) for stimulating low NA activity in ADHD children (J Am Acad Child Adolesc Psychiatry 1997;36:1688) in order to promote interactions with mesocortical DA have been discussed (J Psychopharmacology 1997;11:151; Psychiatr Res 1994;52:305). We described with indicators of overall transmitter metabolism (monoamines, metabolites in 24 h urine samples (Behav Brain Res 1997;88:95)) significantly lower utilisation ratios (MHPG/NA) in ADHD children with respect to healthy controls. Interestingly, a comparison of between catecholamine levels (DA/NA) showed a correlation with the conditioned blocking measure of selective attention recorded at the time of collection. This measure was negatively associated with blocking in controls. These results are consistent with reports of lower DOPEG and increased DOPAC in ADHD urine (J Child Adolesc Psychopharmacol 1996;6:63) and indicate that the relatively hyperactive DA versus NA systems may have functional consequences. Serotonin: the relevance for ADHD of an association of impulsivity with low serotonin (5-HT) metabolism (Behav Brain Sci 1986;9:319) has long been played down. Yet, some symptoms have been related to CSF measures of the metabolite 5-HIAA, and in particular the HVA/5-HIAA ratio has been reported to correlate with ratings of activity (Psychiatr Res 1994;52:305). We find that while urinary measures of 5-HIAA are somewhat higher, the ratio HVA/5-HIAA is markedly lower in ADHD children versus controls. In these ADHD children 5-HIAA levels were negatively related to d-prime measures in a continuous performance task (CPTax), and the HVA/5-HIAA was negatively associated with conditioned blocking. These results suggest a relatively low DA versus 5-HT activity may have functional consequences, albeit in a subgroup of ADHD. This is consistent with drug-induced prolactin changes reported by Verbaten et al. (Eur Child Adolesc Psychiatry 1999;8:30).
Published:
March 9, 2002
Title:
A prospective study of tomato products, lycopene, and prostate cancer risk
Authors:
Giovannucci, Edward; Rimm, Eric B.; Liu, Yan; Stampfer, Meir J.; Willett, Walter C.
Abstract:
BACKGROUND: Some data, including our findings from the Health Professionals Follow-Up Study (HPFS) from 1986 through January 31, 1992, suggest that frequent intake of tomato products or lycopene, a carotenoid from tomatoes, is associated with reduced risk of prostate cancer. Overall, however, the data are inconclusive. We evaluated additional data from the HPFS to determine if the association would persist. METHODS: We ascertained prostate cancer cases from 1986 through January 31, 1998, among 47 365 HPFS participants who completed dietary questionnaires in 1986, 1990, and 1994. We used pooled logistic regression to compute multivariate relative risks (RR) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From 1986 through January 31, 1998, 2481 men in the study developed prostate cancer. Results for the period from 1992 through 1998 confirmed our previous findings---that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84; 95% CI = 0.73 to 0.96; P(trend) =.003); intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77; 95% CI = 0.66 to 0.90; P(trend)
Published:
March 5, 2002
Title:
Advanced Glycation End Products Induce Angiogenesis in Vivo
Authors:
Okamoto, Tamami; Tanaka, Shinya; Stan, Alex C.; Koike, Takao; Kase, Manabu; Makita, Zenji; Sawa, Hirofumi; Nagashima, Kazuo
Abstract:
Advanced glycation end products (AGEs) have been thought to participate in diabetic microangiopathy. However, the effects of AGEs on angiogenesis have so far been mainly examined either in vitro or by using cultured cells. In the present study, we have analyzed whether AGEs induce angiogenesis in vivo by using the chorioallantoic membrane (CAM) assay. The CAM assay was carried out in embryonated hen eggs to determine the effects of AGEs. Following generation of AGEs based on bovine serum albumin (BSA), either AGE–BSA or nonglycated BSA was administered to the CAM and their effects on angiogenesis were assessed, together with an inhibitory effect of an anti-AGE antibody against AGE–BSA-induced angiogenesis. The histological features of AGE-induced vascular lumens were examined by immunohistochemical analysis for Factor VIII and smooth muscle α-actin. AGE–BSA induced angiogenesis in CAM in a dose- and time-dependent manner. AGE-induced angiogenesis on CAM was neutralized by the anti-AGE antibody. Immunohistochemical analysis demonstrated that AGE-induced vascular lumens were devoid of pericytes. Our data demonstrated that AGEs are an angiogenetic factor and that our system of AGE-induced abnormal vessels in CAMs is useful in further investigations of the mechanism of diabetic retinal angiogenesis and can also be used to provide a therapeutic model for diabetic angiopathy.
Published:
February 28, 2002
bottom of page