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Title:
Changes in Body Composition during Androgen Deprivation Therapy for Prostate Cancer
Authors:
Smith, Matthew R.; Finkelstein, Joel S.; McGovern, Francis J.; Zietman, Anthony L.; Fallon, Mary Anne; Schoenfeld, David A.; Kantoff, Philip W.
Abstract:
The aim of this study was to determine the effects of initial treatment with a GnRH agonist on body composition in asymptomatic men with nonmetastatic prostate
Published:
January 31, 2002
Title:
Diet-heart disease hypothesis is wishful thinking
Authors:
Ravnskov, Uffe
Abstract:
Published:
January 25, 2002
Title:
Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey
Authors:
Kaufman, David W.; Kelly, Judith P.; Rosenberg, Lynn; Anderson, Theresa E.; Mitchell, Allen A.
Abstract:
CONTEXT: Data on the range of prescription and over-the-counter drug use in the United States are not available. OBJECTIVE: To provide recent population-based information on use of all medications, including prescription and over-the-counter drugs, vitamins and minerals, and herbal preparations/natural supplements in the United States. DESIGN, SETTING, AND PARTICIPANTS: Ongoing telephone survey of a random sample of the noninstitutionalized US population in the 48 continental states and the District of Columbia; data analyzed here were collected from February 1998 through December 1999. MAIN OUTCOME MEASURE: Use of medications, by type, during the preceding week, compared by demographic characteristics. RESULTS: Among 2590 participants aged at least 18 years, 81% used at least 1 medication in the preceding week; 50% took at least 1 prescription drug; and 7% took 5 or more. The highest overall prevalence of medication use was among women aged at least 65 years, of whom 12% took at least 10 medications and 23% took at least 5 prescription drugs. Herbals/supplements were taken by 14% of the population. Among prescription drug users, 16% also took an herbal/supplement; the rate of concurrent use was highest for fluoxetine users, at 22%. Reasons for drug use varied widely, with hypertension and headache mentioned most often (9% for each). Vitamins/minerals were frequently used for nonspecific reasons such as "health" (35%); herbals/supplements were also most commonly used for "health" (16%). CONCLUSIONS: In any given week, most US adults take at least 1 medication, and many take multiple agents. The substantial overlap between use of prescription medications and herbals/supplements raises concern about unintended interactions. Documentation of usage patterns can provide a basis for improving the safety of medication use.
Published:
January 15, 2002
Title:
New evidence for the use of root foods in pre-agrarian subsistence recovered from the late Mesolithic site at Halsskov, Denmark
Authors:
Kubiak-Martens, Lucy
Abstract:
Roots and tubers, together with other plant storage organs such as rhizomes, bulbs, corms, etc. are known to be a source of human food. Until very recently, however, remains of root foods were rarely identified from archaeological contexts in temperate Europe. New evidence for the use of root foods has been recently recovered from the early Ertebølle settlement at Halsskov in Denmark. Remains included charred bulbs of Allium cf. ursinum and tubers of Conopodium majus. They were accompanied by charred remains of parenchymatous tissues derived from underground parts of other plants. All parenchymatous remains were recovered from features that could be interpreted as pit-cooking depressions. A minimum of two periods of root food gathering can be assumed, spring to early summer and autumn. The presence of charred seeds of Nuphar pumilum suggests that either the seeds or rhizomes (or both) were use as food.
Published:
January 5, 2002
Title:
Genomic Divergence Between Human and Chimpanzee Estimated from Large-Scale Alignments of Genomic Sequences
Authors:
Chen, F.-C.; Vallender, E. J.; Wang, H.; Tzeng, C.-S.; Li, W.-H.
Abstract:
Abstract. To study the genomic divergence between human and chimpanzee, large-scale genomic sequence alignments were performed. The genomic sequences of human
Published:
November 30, 2001
Title:
Monocyte Differentiation to Macrophage Requires Interferon Regulatory Factor 7
Authors:
Lu, Runqing; Pitha, Paula M.
Abstract:
Interferon regulatory factors are a growing family of transcription factor that have been implicated in cellular events such as cell-growth regulation, antiviral defense, and development of the immune system. Interferon regulatory factor 7 (IRF-7) is expressed predominantly in lymphoid tissues and has been studied extensively in the context of viral infection and the induction of interferon and cytokine gene expression. In this paper, the involvement of IRF-7 in monocyte differentiation was examined in U937, HL60, and human primary macrophages. We report the induction of IRF-7 expression by 12-O-tetradecanoylphorbol-13-acetate in U937 and HL60 cells and demonstrate that this induction is essential for the monocyte differentiation to macrophages. We show that the monocyte differentiation is inhibited in cells expressing a dominant negative IRF-7 mutant, as evidenced by decreased expression of two macrophage-differentiation markers, CD11b and CD11c, and impaired phagocytic activity. In addition, we demonstrate that overexpression of IRF-7 is sufficient to trigger monocyte differentiation and to induce cell cycle arrest. The identification of IRF-7 as a key regulator in monocyte differentiation suggests a novel function of IRF-7 in innate immunity.
Published:
November 29, 2001
Title:
[Metabolic complications and neurologic manifestations of vitamin B12 deficiency in children of vegetarian mothers]
Authors:
Smolka, V.; Bekárek, V.; Hlídková, E.; Bucil, J.; Mayerová, D.; Skopková, Z.; Adam, T.; Hrubá, E.; Kozich, V.; Buriánková, L.; Saligová, J.; Buncová, M.; Zeman, J.
Abstract:
BACKGROUND: Serious hematological, metabolic and neurological complications owing to the nutritional deficiency of vitamin B12 may occur in infants of mothers on a strict vegetarian diet. METHODS AND RESULTS: The mother of the first child was a strict vegetarian. She had an elevated urinary methylmalonic acid level and a low concentration of serum vitamin B12. Her 13-month-old daughter was exclusively breast-fed until the age of 9 month and then she was fed only vegetables. Physical examination revealed psychomotoric retardation, apathy, muscular hypotonia, abnormal movements and failure to thrive. Laboratory analysis showed a megaloblastic anaemia, a low level of vitamin B12 and methylmalonic aciduria. MRI of the brain revealed diffuse frontotemporoparietal atrophy and retardation of myelination. After treatment with vitamin B12 supplements, abnormal movements disappeared and development improved, but a mild generalised hypotonia continued. A cranial MRI 9 months after treatment still showed signs of retardation of myelination. The second patient, an 8 month-old male, son of a strict vegetarian mother too, was referred for investigation of psychomotoric retardation, hypotonia, dyskinesia, failure to thrive and microcephaly. He was breast-fed and from 6 month of age he had also received fruit juices. Laboratory analysis revealed megaloblastic anaemia, high methylmalonic aciduria and homocystinuria. The patient's and his mother's serum level of vitamin B12 were low. After treatment with vitamin B12 supplements, biochemical and metabolic markers of disease were normal but there continued a generalised hypotonia, microcephaly and language delay. CONCLUSION: Our observations emphasize the health complications of nutritional cobalamine deficiency and a requirement of clinical, biochemical and metabolic monitoring in infants within strict vegetarian families.
Published:
November 21, 2001
Title:
[Macrocytic anemia and neurological signs due to vitamin B-12 deficiency in a breast-fed infant of a strict vegetarian mother]
Authors:
Fogarasi, A.; Neuwirth, M.; Békési, A.; Bocskai, E.
Abstract:
Vitamin B12 deficiency is a very rare disease of infants and young children in Europe. Authors report a case of a 9.5-month-old infant who was exclusively breast-fed by his vegan mother and developed serious vitamin B12 deficiency in form of neurological regression, repetitive vomiting, drowsiness, dysphagia, obstipation, and tremor. A few days after intramuscular vitamin substitution his abnormal signs improved dramatically, hematological restitution was reached in six weeks. Authors describe the hematological and neurological signs, the diagnostic and differential-diagnostic pitfalls, therapy, prognosis, and prevention of this condition. Beside reviewing the literature they emphasize the importance of early recognition and intervention and the need of an appropriate doctor-parent cooperation in this disease.
Published:
November 17, 2001
Title:
Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer
Authors:
Chen, X.; Thakkar, H.; Tyan, F.; Gim, S.; Robinson, H.; Lee, C.; Pandey, S. K.; Nwokorie, C.; Onwudiwe, N.; Srivastava, R. K.
Abstract:
TRAIL/Apo-2L is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis in cancer cells, but not in normal cells. In nude mice injected with human tumors, TRAIL reduces the size of these tumors without side effects. Akt promotes cell survival and block apoptosis. Some prostate cancer cells express high levels of Akt due to lack of active lipid phosphatase PTEN, a negative regulator of PI-3 kinase pathway, which may be responsible for drug resistance. The objective of this paper is to investigate the intracellular molecules that regulate TRAIL resistance. We have examined caspase-8 activity, BID cleavage, Akt activity, mitochondrial membrane potential (DeltaPsi(m)) and apoptosis in prostate cancer (LNCap, PC-3, PC-3M and DU145) cells treated with or without TRAIL. PC-3, PC-3M and DU145 cells are sensitive to TRAIL, whereas LNCap cells are resistant. LNCap cells express the highest level of constitutively active Akt, which is directly correlated with TRAIL resistance. TRAIL activates caspase-8 in all the cell lines. Downregulation of constitutively active Akt by PI-3 kinase inhibitors (wortmannin and LY-294002), dominant negative Akt or PTEN, renders LNCap cells sensitive to TRAIL. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage. Inhibition of protein synthesis by cycloheximide also causes LNCap cells sensitive to TRAIL. Overexpression of Bcl-2 or Bcl-X(L) inhibits TRAIL-induced DeltaPsi(m) and apoptosis. Overexpression of constitutively active Akt in PC-3M cells (express very low levels of constitutively active Akt) restores TRAIL resistance. These data suggest that elevated Akt activity protects LNCap cells from TRAIL-induced apoptosis, and the PI-3 kinase/Akt pathway may inhibit apoptotic signals by inhibiting processing of BID. Thus, constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.
Published:
September 19, 2001
Title:
[Imbalance of plasma amino acids in patients with autism and subjects with attention deficit/hyperactivity disorder]
Authors:
Zavala, M.; Castejón, H. V.; Ortega, P. A.; Castejón, O. J.; Marcano de Hidalgo, A.; Montiel, N.
Abstract:
INTRODUCTION: Plasma and brain amino acids are influenced by dietary intake. Alterations of plasma amino acid concentrations have been reported in neuropsychiatric disorders. OBJECTIVE: To analyse the plasma amino acid values in subject diagnosed with autism, with attention deficit/hyperactivity disorder (ADHD), and healthy subjects as controls. PATIENTS AND METHODS: Forty subjects affected by autism, 11 with ADHD and 41 healthy subjects (age range 3 18 years old) were included in this study. Peripheral venous blood was obtained in fasting condition, collected in EDTA tubes and centrifuged. Plasma was de proteinised with sulfosalicylic acid. Amino acids were analysed by ion exchange liquid chromatography with an LKB amino acid analyser with sodium citrate elution system and ninhydrin reaction. Results were expressed as mmol/L. RESULTS AND CONCLUSIONS: In both disorders a diminution of phenylalanine and glutamine plasma concentrations was observed beside an increase of glycine. Lysine appeared increased only in autistic subjects. These alterations produce an imbalance with the rest of plasma amino acids competing at the brain blood barrier by the same transport system thus causing alterations in the metabolism and/or transport of amino acids to the brain, altering CNS functions. The phenylalanine decreasing, beside glycine increasing appear to support the hypothesis of a disorder in the inhibitory neurotransmission system, especially in ADHD. The diminution of phenylalanine and the increasing of lysine in autism are suggestive that these two amino acids are metabolically related.
Published:
August 31, 2001
Title:
Norepinephrine is required for the anticonvulsant effect of the ketogenic diet
Authors:
Szot, P.; Weinshenker, D.; Rho, J. M.; Storey, T. W.; Schwartzkroin, P. A.
Abstract:
Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat children with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic system has a role in mediating the anticonvulsant action of the KD, dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine (NE) and Dbh +/- littermates that have normal NE content were fed either a standard rodent chow or the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to myoclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- mice fed normal chow. In contrast, Dbh -/- mice fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed normal chow. These results suggest that an intact, functional noradrenergic nervous system is required for the KD to exert an anticonvulsant effect.
Published:
August 22, 2001
Title:
Is attention-deficit/hyperactivity disorder an energy deficiency syndrome?
Authors:
Todd, R. D.; Botteron, K. N.
Abstract:
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable yet clinically heterogeneous syndrome associated with hypocatecholamine function in subcortical and prefrontal cortical regions and clinical response to medications that enhance catecholamine function. The goal of this article is to present a hypothesis about the etiology of ADHD by synthesizing these findings with recent experiments indicating that activity-dependent neuronal energy consumption is regulated by cortical astrocytes. The scientific literature was searched from 1966 to the present using MEDLINE and relevant key words. Inattention and impulsivity may be related to hypofunctionality of catecholamine projection pathways to prefrontal cortical areas, resulting in decreased neuronal energy availability. This may be mediated by astrocyte catecholamine receptors that normally regulate energy availability during neuronal activation. At least some forms of ADHD may be viewed as cortical, energy-deficit syndromes secondary to catecholamine-mediated hypofunctionality of astrocyte glucose and glycogen metabolism, which provides activity-dependent energy to cortical neurons. Several tests of this hypothesis are proposed.
Published:
July 31, 2001
Title:
α-Amylase expressed in human liver is encoded by the AMY-2B gene identified in tumorous tissues
Authors:
Koyama, Iwao; Komine, Shin-ichi; Iino, Nozomi; Hokari, Shigeru; Igarashi, Seiji; Alpers, David H; Komoda, Tsugikazu
Abstract:
Background: An α-Amylase in human liver is detected with an anti-human salivary amylase antibody, but the enzyme activity is very low. We previously found that the rat liver contained an amylase which differed from the enzyme of mice. In this study, we characterized the human liver amylases biochemically and immunohistochermically. Methods and Results: Although the amylase activity of human liver was much lower than that of rat, protein moiety and sugar chains of the human amylase were identified as similar to the rat liver enzyme with an anti-human salivary amylase antibody and by concanavalin A (Con A) affinity chromatography. Liver amylases from human and rat were the same size, 50 kDa, on Western blot analysis and had the same isoelectric points. The cytoplasm of hepatocytes was moderately stained immunohistochemically with the anti-human salivary amylase antibody. Intrahepatic bile ducts were also stained weak-to-moderately. RT-PCR, with a specific primer for the consensus sequence of human amylases, amplified a single 474-bp product from the human liver total RNA. The PCR product was sequenced and referred to the homology. Thirteen bases in the 434-bp fragment of the human liver amylase differed from the corresponding region of the AMY-1 gene transcript and the deduced amino acid sequence differed at five residues. The human liver amylase cDNA sequence was identical to the corresponding cDNA of the AMY-2B, which was known to expressed in tumorous tissues. In situ hybridization revealed the expression of AMY-2B mRNA in non-tumorous human liver. Conclusions: The present results suggest the possibility that a novel amylase detected in tumorous tissues and encoded by the AMY-2B gene is a liver-specific amylase expressed in the human liver.
Published:
July 4, 2001
Title:
Age-related changes in cells and tissues due to advanced glycation end products (AGEs)
Authors:
Kasper, Michael; Funk, Richard H. W.
Abstract:
Advanced glycation end products (AGEs) formed by nonenzymatic glycation and oxidation of proteins accumulate during normal aging and at accelerated rate during the course of diabetes. They play a role in the pathogenesis of several other chronic diseases such as Alzheimer's disease, arthritis, atherosclerosis, pulmonary fibrosis and renal failure. AGE-formation changes the chemical and biological properties of proteins inside and outside of the cell. Binding to specific cell surface receptors induces activation of cellular signaling pathways leading to cellular dysfunction and cell death. AGEs are inducible by oxidative stress and induce oxidative stress. Subject of current studies of cell biologists is the intracellular processing of AGEs, which is accompanied by changes of the endolysosomal compartment.
Published:
May 31, 2001
Title:
Effects of Novel Polymorphisms in the RAGE Gene on Transcriptional Regulation and Their Association With Diabetic Retinopathy
Authors:
Hudson, Barry I.; Stickland, Max H.; Futers, T. Simon; Grant, Peter J.
Abstract:
Interactions between advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the vascular complications in diabetes. We have identified eight novel polymorphisms, of which the −1420 (GGT)n, −1393 G/T, −1390 G/T, and −1202 G/A were in the overlapping PBX2 3′ untranslated region (UTR), and the −429 T/C (66.5% TT, 33.5% TC/CC), −407 to –345 deletion (99% I, 1% I/D, 0% D), −374 T/A (66.4% TT, 33.6% TA/AA), and +20 T/A were in the RAGE promoter. To evaluate the effects on transcriptional activity, we measured chloramphenicol acetyl transferase (CAT) reporter gene expression, driven by variants of the –738 to +49 RAGE gene fragment containing the four polymorphisms identified close to the transcriptional start site. The –429 C, −374 A, and 63-bp deletion alleles resulted in a mean increase of CAT expression of twofold (P < 0.0001), threefold (P < 0.001), and fourfold (P < 0.05), respectively, with the –374 T and A alleles yielding highly differential binding of nuclear protein extract from both monocyte- and hepatocyte-derived cell lines. The prevalence of the functional polymorphisms were investigated in subjects with type 2 diabetes (106 with and 109 without retinopathy), with the –429 C allele showing an increase in the retinopathy group (P
Published:
May 31, 2001
Title:
Novel biomarkers of the metabolism of caffeic acid derivatives in vivo
Authors:
Rechner, A. R.; Spencer, J. P.; Kuhnle, G.; Hahn, U.; Rice-Evans, C. A.
Abstract:
The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism.
Published:
May 31, 2001
Title:
Peroxidation of linoleic acid and its relation to aging and age dependent diseases
Authors:
Spiteller, G.
Abstract:
Cell proliferation, cell injury and aging are connected with changes in the cell membrane structure. Apparently these changes activate, in mammalian as well as in plant cells, lipases which liberate polyunsaturated fatty acids (PUFAs). PUFAs are the substrates for lipoxygenases which convert them to corresponding hydroperoxides (LOOHs). Lipoxygenases commit suicide by releasing iron ions. LOOHs react with iron ions to generate radicals. Thus, a nonenzymic lipid peroxidation process (LPO) is induced. It is speculated that the change from enzymic to nonenzymic LPO is connected with the switch from apoptosis to necrosis and that LOOHs produced in enzymic reactions are degraded specifically to signal compounds which induce physiological responses, while nonenzymic reactions seem to induce generation of reactive oxygen species, cell death and age related diseases. Enzymic and nonenzymic LPO processes concern all PUFAs not only arachidonic acid. The main PUFA in mammals is linoleic acid. Since these products serve signalling functions, different degradation paths of linoleic-hydroperoxides are described in detail and the physiological properties of LPO products are discussed in relation to aging and age related diseases.
Published:
May 30, 2001
Title:
Unique morphology of the human eye and its adaptive meaning: comparative studies on external morphology of the primate eye
Authors:
Kobayashi, Hiromi; Kohshima, Shiro
Abstract:
In order to clarify the morphological uniqueness of the human eye and to obtain cues to understanding its adaptive significance, we compared the external morphology of the primate eye by measuring nearly half of all extant primate species. The results clearly showed exceptional features of the human eye: (1) the exposed white sclera is void of any pigmentation, (2) humans possess the largest ratio of exposed sclera in the eye outline, and (3) the eye outline is extraordinarily elongated in the horizontal direction. The close correlation of the parameters reflecting (2) and (3) with habitat type or body size of the species examined suggested that these two features are adaptations for extending the visual field by eyeball movement, especially in the horizontal direction. Comparison of eye coloration and facial coloration around the eye suggested that the dark coloration of exposed sclera of nonhuman primates is an adaptation to camouflage the gaze direction against other individuals and/or predators, and that the white sclera of the human eye is an adaptation to enhance the gaze signal. The uniqueness of human eye morphology among primates illustrates the remarkable difference between human and other primates in the ability to communicate using gaze signals.
Published:
April 30, 2001
Title:
Out of Africa: origins of the Taenia tapeworms in humans.
Authors:
Hoberg, E. P.; Alkire, N. L.; de Queiroz, A.; Jones, A.
Abstract:
Phylogenetic and divergence date analyses indicate that the occurrence of Taenia tapeworms in humans pre-dates the development of agriculture, animal husbandry and domestication of cattle (Bos spp.) or swine (Sus scrofa). Taeniid tapeworms in Africa twice independently colonized hominids and the genus Homo prior to the origin of modern humans. Dietary and behavioural shifts, from herbivory to scavenging and carnivory, as early Homo entered the carnivore guild in the Pliocene/Pleistocene, were drivers for host switching by tapeworms to hominids from carnivores including hyaenids and felids. Parasitological data provide a unique means of elucidating the historical ecology, foraging behaviour and food habits of hominids during the diversification of Homo spp.
Published:
April 21, 2001
Title:
Similarities of prostate and breast cancer: Evolution, diet, and estrogens
Authors:
Coffey, Donald S
Abstract:
Environment determines the risk of both prostate and breast cancer, and this risk can vary >10-fold. In contrast, no risk exists for human seminal vesicle cancer demonstrating tissue specificity. There is also species specificity, because there is no risk for prostate cancer in any other aging mammal except the dog. A study of evolution indicates that the prostate and breast appeared at the same time 65 million years ago with the development of mammals. All male mammals have a prostate; however, the seminal vesicles are variable and are determined by the diet so that species primarily eating meat do not have seminal vesicles. The exception is the human, who has seminal vesicles and consumes meat, although this is a recent dietary change. Human lineage departed from other higher primates 8 million years ago. The closest existing primate to humans is the bonobo (pigmy chimpanzee), which does not eat meat but exists primarily on a high fruit and fresh vegetable diet. Homo sapiens evolved only about 150,000 years ago, and only in the last 10% of that time (10 to 15 thousand years ago) did humans and dogs dramatically alter their diets. This is the time when humans domesticated the dog, bred animals, grew crops, and cooked, processed, and stored meats and vegetables. All current epidemiologic evidence and suggestions for preventing prostate and breast cancer in humans indicates that we should return to the original diets under which our ancestors evolved. The recent development of the Western-type diet is associated with breast and prostate cancer throughout the world. It is believed that the exposure to and metabolism of estrogens, and the dietary intake of phytoestrogens, combined with fat intake, obesity, and burned food processing may all be related to hormonal carcinogenesis and oxidative DNA damage. An explanatory model is proposed.
Published:
March 31, 2001
Title:
Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis
Authors:
Ludwig, D. S.; Peterson, K. E.; Gortmaker, S. L.
Abstract:
BACKGROUND: The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks. Our aim was to examine this relation. METHODS: We enrolled 548 ethnically diverse schoolchildren (age 11.7 years, SD 0.8) from public schools in four Massachusetts communities, and studied them prospectively for 19 months from October, 1995, to May, 1997. We examined the association between baseline and change in consumption of sugar-sweetened drinks (the independent variables), and difference in measures of obesity, with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools. FINDINGS: For each additional serving of sugar-sweetened drink consumed, both body mass index (BMI) (mean 0.24 kg/m2; 95% CI 0.10-0.39; p=0.03) and frequency of obesity (odds ratio 1.60; 95% CI 1.14-2.24; p=0.02) increased after adjustment for anthropometric, demographic, dietary, and lifestyle variables. Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI (mean 0.18 kg/m2 for each daily serving; 95% CI 0.09-0.27; p=0.02). INTERPRETATION: Consumption of sugar-sweetened drinks is associated with obesity in children.
Published:
February 16, 2001
Title:
Fibrinolytic parameters and insulin resistance in young survivors of myocardial infarction with heterozygous familial hypercholesterolemia
Authors:
Sebestjen, M.; Zegura, B.; Guzic-Salobir, B.; Keber, I.
Abstract:
A characteristic feature of patients with heterozygous familial hypercholesterolemia (FH) is the premature occurrence of coronary artery disease because of elevated LDL cholesterol levels. Hyperinsulinemia and insulin resistance, important characteristics of the cardiovascular dysmetabolic syndrome (CDS), were found to be associated with coronary artery disease in FH subjects, as in the general population. We investigated whether hypofibrinolysis, as part of CDS, is independently associated with symptomatic coronary artery disease in these high-risk patients. Clinical examination (body mass index, waist circumference, blood pressure) and blood analysis (plasma tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen and activity, fibrinogen, serum lipids and lipoproteins, fasting glucose and insulin) were carried out in 39 male patients with heterozygous FH (aged 46.6 +/- 8.8 years). Insulin resistance was calculated using the homeostasis model assessment (HOMA) mathematical model. Thirteen of the patients had suffered a myocardial infarction (MI) 5 to 8 years ago (aged 47.8 +/- 6.1 years) and 26 were free of coronary artery disease (aged 45.9 +/- 9.9 years). There was no difference in total and LDL cholesterol between the two groups. Patients with previous myocardial infarction had significantly higher levels of insulin, insulin resistance, triglycerides, t-PA antigen, PAI-1 antigen and activity, and significantly lower values of HDL cholesterol. Other widely recognised risk factors for coronary artery disease, such as smoking, systolic and diastolic blood pressure, obesity and age, did not differ significantly between the groups. In the logistic regression model, PAI-1 antigen, as a marker of hypofibrinolysis, emerged as an independent risk factor for the occurrence of myocardial infarction (odds ratio 1.55; p = 0.02). In summary our results suggest that the impairment of fibrinolytic activity resulting from elevated levels of PAI-1 antigen and activity and t-PA antigen is an independent variable in CDS associated with the premature occurrence of myocardial infarction in male patients with FH.
Published:
February 14, 2001
Title:
CD36, a Member of the Class B Scavenger Receptor Family, as a Receptor for Advanced Glycation End Products
Authors:
Ohgami, Nobutaka; Nagai, Ryoji; Ikemoto, Mamoru; Arai, Hiroyuki; Kuniyasu, Akihiko; Horiuchi, Seikoh; Nakayama, Hitoshi
Abstract:
Interaction of advanced glycation end products (AGE) with AGE receptors induces several cellular phenomena potentially relating to diabetic complications. Five AGE receptors identified so far are RAGE (receptor for AGE), galectin-3, 80K-H, OST-48, and SRA (macrophage scavengerreceptor class A types I and II). Since SRA is known to belong to the class A scavenger receptor family, and the scavenger receptor collectively represents a family of multiligand lipoprotein receptors, it is possible that CD36, although belonging to the class B scavenger receptor family, can recognize AGE proteins as ligands. This was tested at the cellular level in this study using Chinese hamster ovary (CHO) cells overexpressing human CD36 (CD36-CHO cells). Cellular expression of CD36 was confirmed by immunoblotting and immunofluorescent microscopy using anti-CD36 antibody. Upon incubation at 37 °C, 125I-AGE-bovine serum albumin (AGE-BSA) and 125I-oxidized low density lipoprotein (LDL), an authentic ligand for CD36, were endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CD36-CHO cells, but not wild-type CHO cells. In binding experiments at 4 °C, 125I-AGE-BSA exhibited specific and saturable binding to CD36-CHO cells (K d = 5.6 μg/ml). The endocytic uptake of 125I-AGE-BSA by these cells was inhibited by 50% by oxidized LDL and by 60% by FA6-152, an anti-CD36 antibody inhibiting cellular binding of oxidized LDL. Our results indicate that CD36 expressed by these cells mediates the endocytic uptake and subsequent intracellular degradation of AGE proteins. Since CD36 is one of the major oxidized LDL receptors and is up-regulated in macrophage- and smooth muscle cell-derived foam cells in human atherosclerotic lesions, these results suggest that, like oxidized LDL, AGE proteins generated in situ are recognized by CD36, which might contribute to the pathogenesis of diabetic macrovascular complications.
Published:
February 1, 2001
Title:
Advanced glycation end-products: a review
Authors:
Singh, R.; Barden, A.; Mori, T.; Beilin, L.
Abstract:
Advanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occuring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications. [Diabetologia (2001) 44: 129–146]
Published:
January 31, 2001
Title:
Genomic Divergences between Humans and Other Hominoids and the Effective Population Size of the Common Ancestor of Humans and Chimpanzees
Authors:
Chen, Feng-Chi; Li, Wen-Hsiung
Abstract:
To study the genomic divergences among hominoids and to estimate the effective population size of the common ancestor of humans and chimpanzees, we selected 53 autosomal intergenic nonrepetitive DNA segments from the human genome and sequenced them in a human, a chimpanzee, a gorilla, and an orangutan. The average sequence divergence was only 1.24% ± 0.07% for the human-chimpanzee pair, 1.62% ± 0.08% for the human-gorilla pair, and 1.63% ± 0.08% for the chimpanzee-gorilla pair. These estimates, which were confirmed by additional data from GenBank, are substantially lower than previous ones, which included repetitive sequences and might have been based on less-accurate sequence data. The average sequence divergences between orangutans and humans, chimpanzees, and gorillas were 3.08% ± 0.11%, 3.12% ± 0.11%, and 3.09% ± 0.11%, respectively, which also are substantially lower than previous estimates. The sequence divergences in other regions between hominoids were estimated from extensive data in GenBank and the literature, and Alus showed the highest divergence, followed in order by Y-linked noncoding regions, pseudogenes, autosomal intergenic regions, X-linked noncoding regions, synonymous sites, introns, and nonsynonymous sites. The neighbor-joining tree derived from the concatenated sequence of the 53 segments—24,234 bp in length—supports the Homo-Pan clade with a 100% bootstrap value. However, when each segment is analyzed separately, 22 of the 53 segments (∼42%) give a tree that is incongruent with the species tree, suggesting a large effective population size (Ne) of the common ancestor of Homo and Pan. Indeed, a parsimony analysis of the 53 segments and 37 protein-coding genes leads to an estimate of Ne = 52,000 to 96,000. As this estimate is 5 to 9 times larger than the long-term effective population size of humans (∼10,000) estimated from various genetic polymorphism data, the human lineage apparently had experienced a large reduction in effective population size after its separation from the chimpanzee lineage. Our analysis assumes a molecular clock, which is in fact supported by the sequence data used. Taking the orangutan speciation date as 12 to 16 million years ago, we obtain an estimate of 4.6 to 6.2 million years for the Homo-Pan divergence and an estimate of 6.2 to 8.4 million years for the gorilla speciation date, suggesting that the gorilla lineage branched off 1.6 to 2.2 million years earlier than did the human-chimpanzee divergence.
Published:
January 31, 2001
Title:
Biased Over- Or Under-Reporting is Characteristic of Individuals Whether Over Time or by Different Assessment Methods
Authors:
Black, ALISON E.; Cole, TIMOTHY J.
Abstract:
Seven studies with repeated measurements of energy intake and/or nitrogen intake were examined to determine whether misreporting is characteristic of some persons or occurs randomly. Four of the studies were validated by doubly labeled water measurements of energy expenditure. Reporting validity was expressed as the ratio of energy intake to energy expenditure. Ratios were consistently below the expected value of 1.0 for some subjects and consistently above 1.0 for others, indicating characteristic reporting validity within subjects. Two year-long studies provided 4 to 12 measurements and a total number of days sufficient to measure individual habitual intake. Subjects mean energy intake to basal metabolic rate (BMR) ratios were <1.35 in 45% and 47% and
Published:
December 31, 2000
Title:
The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects
Authors:
de Roos, Baukje; Caslake, Muriel J; Stalenhoef, Anton FH; Bedford, Dorothy; Demacker, Pierre NM; Katan, Martijn B; Packard, Chris J
Abstract:
Published:
December 31, 2000
Title:
Antioxidants in vegan diet and rheumatic disorders
Authors:
Hänninen, null; Kaartinen, K.; Rauma, A. L.; Nenonen, M.; Törrönen, R.; Häkkinen, A. S.; Adlercreutz, H.; Laakso, J.
Abstract:
Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.
Published:
November 29, 2000
Title:
Bax is a transcriptional target and mediator of c-myc-induced apoptosis
Authors:
Mitchell, K. O.; Ricci, M. S.; Miyashita, T.; Dicker, D. T.; Jin, Z.; Reed, J. C.; El-Deiry, W. S.
Abstract:
The c-Myc oncoprotein is a transcription factor involved in cellular transformation as well as apoptotic cell death. We show here that over-expression of c-Myc delivered by an adenovirus vector up-regulates endogenous proapoptotic bax mRNA and protein expression in human cells. In contrast, the cytotoxic tumor necrosis factor-related apoptosis-inducing ligand induces cell death without up-regulating bax expression. c-Myc/Max heterodimers bind to canonical E-box elements located in the bax promoter region as demonstrated by electrophoretic mobility shift analysis and DNaseI foot-printing assays. Analysis of bax regulatory region mutants suggests a model involving myc-dependent activation as well as relief of repression through distinct E-box elements. c-Myc-null cells are deficient in bax-promoter activation as compared with wild-type c-Myc-expressing cells. Overexpression of c-Myc in serum-starved human or mouse embryonic cells leads to apoptosis which is significantly reduced in the presence of growth factor-containing serum. c-Myc-induced apoptosis appears to be deficient in bax-null as compared with bax-wild-type mouse embryonic fibroblasts. The results suggest that the cell death-promoting gene bax is directly downstream of c-Myc in a pathway leading to apoptosis.
Published:
November 14, 2000
Title:
Alcohol Consumption Raises HDL Cholesterol Levels by Increasing the Transport Rate of Apolipoproteins A-I and A-II
Authors:
De Oliveira e Silva Elizabeth R.; Foster David; McGee Harper Monnie; Seidman Cynthia E.; Smith Jonathan D.; Breslow Jan L.; Brinton Eliot A.
Abstract:
Background—Moderate alcohol intake is associated with lower atherosclerosis risk, presumably due to increased HDL cholesterol (HDL-C) concentrations; however, the metabolic mechanisms of this increase are poorly understood.Methods and Results—We tested the hypothesis that ethanol increases HDL-C by raising transport rates (TRs) of the major HDL apolipoproteins apoA-I and -II. We measured the turnover of these apolipoproteins in vivo in paired studies with and without alcohol consumption in 14 subjects. The fractional catabolic rate (FCR) and TR of radiolabeled apoA-I and -II were determined in the last 2 weeks of a 4-week Western-type metabolic diet, without (control) or with alcohol in isocaloric exchange for carbohydrates. Alcohol was given as vodka in fixed amounts ranging from 0.20 to 0.81 g · kg−1 · d−1 (mean±SD 0.45±0.19) to reflect the usual daily intake of each subject. HDL-C concentrations increased 18% with alcohol compared with the control (Wilcoxon matched-pairs test, P=0.002). The apoA-I concentrations increased by 10% (P=0.048) and apoA-II concentrations increased by 17% (P=0.005) due to higher apoA-I and -II TRs, respectively, whereas the FCR of both apoA-I and -II did not change. The amount of alcohol consumed correlated with the degree of increase in HDL-C (Pearson’s r=0.66, P=0.01) and apoA-I TR (r=0.57, P=0.03). The increase in HDL-C also correlated with the increase in apoA-I TR (r=0.61, P=0.02).Conclusions—Alcohol intake increases HDL-C in a dose-dependent fashion, associated with and possibly caused by an increase in the TR of HDL apolipoproteins apoA-I and -II.
Published:
November 6, 2000
Title:
Adult ADHD: evaluation and treatment in family medicine
Authors:
Searight, H. R.; Burke, J. M.; Rottnek, F.
Abstract:
Attention-deficit/hyperactivity disorder (ADHD) affects 30 to 50 percent of adults who had ADHD in childhood. Accurate diagnosis of ADHD in adults is challenging and requires attention to early development and symptoms of inattention, distractibility, impulsivity and emotional lability. Diagnosis is further complicated by the overlap between the symptoms of adult ADHD and the symptoms of other common psychiatric conditions such as depression and substance abuse. While stimulants are a common treatment for adult patients with ADHD, antidepressants may also be effective. Cognitive-behavioral skills training and psychotherapy are useful adjuncts to pharmacotherapy.
Published:
October 31, 2000
Title:
Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists
Authors:
Myint, T.; Fraser, G. E.; Lindsted, K. D.; Knutsen, S. F.; Hubbard, R. W.; Bennett, H. W.
Abstract:
Meat consumption predicts risk of several chronic diseases. The authors validate the accuracy of meat consumption reported by food frequency questionnaires and the mean of eight 24-hour recalls, using urinary methylhistidine excretion, in 55 Black and 71 White Adventist subjects in Los Angeles and San Diego, California, in 1994-1997. 1-Methylhistidine excretion predicts vegetarian status in Black (p = 0.02) and in White (p = 0.005) subjects. Spearman's correlation coefficients between 1-methylhistidine and estimated meat consumption were usually between 0.4 and 0.6 for both food frequency questionnaires and 24-hour recall data. This is despite the chance collection of dietary recalls and urines from omnivores on meatless days.
Published:
October 14, 2000
Title:
Insulin resistance in patients with depression and its changes during the clinical course of depression: Minimal model analysis
Authors:
Okamura, Fumio; Tashiro, Atsushi; Utumi, Atsushi; Imai, Towako; Suchi, Takatosi; Tamura, Daisaku; Sato, Yoshinori; Suzuki, Susumu; Hongo, Michio
Abstract:
A high proportion of patients with depression develop glucose intolerance accompanied by hyperinsulinemia, suggestive of reduced insulin sensitivity (insulin resistance). The aim of this study was to evaluate insulin sensitivity in patients with depression and its changes during the clinical course of depression. Twenty nondiabetic patients with depression (13 males and 7 females aged 44 ± 14 years; body mass index [BMI] 23.2 ± 2.8 kg/m2) were prospectively studied by the frequently sampled intravenous glucose tolerance test (FSIGT) and the oral glucose tolerance test (OGTT) before and after treatment of depression, and an age-, sex-, and BMI-matched control group (n = 13) was examined once by the FSIGT. Metabolic indices measuring glucose effectiveness at basal insulin (SG) and insulin sensitivity (SI) were derived from minimal model analysis. Each patient was treated by cyclic antidepressants with an 1,800 to 2,200 kcal/d food intake and underwent no exercise therapy. SI was significantly lower in patients before treatment versus control subjects (6.0 ± 2.5 v 13.8 ± 8.6 × 10−5 min−1 · mol−1 · L, P < .01). After treatment of depression, a significant increase in SI (10.7 ± 7.5 × 10−5 min−1 · mol−1 · 1, P
Published:
September 30, 2000
Title:
A Naturalistic Comparison of Clozapine, Risperidone, and Olanzapine in the Treatment of Bipolar Disorder
Authors:
Guille, Constance; Sachs, Gary S.; Ghaemi, S. Nassir
Abstract:
Background: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. Method: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. Results: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. Conclusion: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weightgain effect of novel antipsychotics. (J Clin Psychiatry 2000;61:638–642)
Published:
September 14, 2000
Title:
US public health and the 21st century: diabetes mellitus
Authors:
McKinlay, John; Marceau, Lisa
Abstract:
No one can question the remarkable contribution of US public health to understanding the causes and consequences of illness, disability, and death. However, some commentators question the agenda: the endless pursuit of individual risk factors and the cursory attention to social determinants of disease. We attempt to illustrate some limitations of US public health by focusing on type-2 diabetes (adult-onset non-insulin-dependent diabetes)—an increasingly prevalent but still poorly understood medical condition with devastating complications and implications for quality of life. A more theoretically based multilevel approach to diabetes, outlined for the 21st century, has an almost exclusive downstream curative focus, that ranges from midstream preventive programmes to upstream healthy public policy.
Published:
August 25, 2000
Title:
Obesity and insulin resistance
Authors:
Kahn, Barbara B.; Flier, Jeffrey S.
Abstract:
Published:
August 14, 2000
Title:
The Pharmaceutical Industry — To Whom is It Accountable?
Authors:
Angell, Marcia
Abstract:
The pharmaceutical industry is under mounting scrutiny because of rapidly increasing expenditures for drugs in the United States. Drug expenditures are now the fastest-growing component of health care costs, increasing at the rate of about 15 percent per year.1,2 They account for about 8 percent of health care spending, and at their current rate of increase, they will soon surpass spending for physicians' services and, for many health maintenance organizations (HMOs), the costs of hospitalization. The increase is due both to a greater use of drugs and to higher prices for individual drugs. Patients feel drug costs keenly, because . . .
Published:
June 21, 2000
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