Showing papers by "French Institute of Health and Medical Research published in 1992"
TL;DR: Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD.
3,489 citations
TL;DR: The effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women are studied.
Abstract: Background. Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. Methods. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [±SD] age, 84±6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 μg (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Results. Among the women who completed the 18-month study, the number of hip fra...
2,714 citations
TL;DR: It is reported that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction than in controls, especially among subjects with low body-mass index and low plasma levels of ApoB.
Abstract: Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.
1,965 citations
TL;DR: Evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension is obtained, association of AGT molecular variants with the disease is demonstrated, and significant differences in plasma concentrations of angiotENSinogen among hypertensive subjects with different AGT genotypes are found.
1,827 citations
TL;DR: This paper provides a tutorial introduction to numerical cognition, with a review of essential findings and current points of debate, and proposes a triple-code model, which assumes that numbers are mentally manipulated in an arabic, verbal or analogical magnitude code depending on the requested mental operation.
1,744 citations
TL;DR: A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families.
Abstract: A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families. Statistical linkage analysis placed 813 of the markers into 23 linkage groups corresponding to the 22 autosomes and the X chromosome; 605 show a heterozygosity above 0.7 and 553 could be ordered with odds ratios above 1,000:1. The distance spanned corresponds to ∼90% of the estimated length of the human genome.
1,742 citations
TL;DR: It is demonstrated that cooperation between GM-CSF and tumour necrosis factor-α (TNF-α) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors.
Abstract: Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin (Langerhans cells) and mucosa, and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their site of maturation and the conditions that direct their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the outgrowth of dendritic cells from mouse peripheral blood. Here we extend this finding to man and demonstrate that cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder.
1,568 citations
TL;DR: Caffeine is the most widely consumed central-nervous-system stimulant as discussed by the authors, however, its psychostimulant action on man is often subtle and not very easy to detect.
1,320 citations
TL;DR: This model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of - 0.237, and predicts the impact of step reductions of follicles numbers on the prospective span of menstrual life was predicted.
Abstract: Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of -0.237. The change occurred when numbers had fallen to the critical figure of 25,000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at approximately 51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years.(ABSTRACT TRUNCATED AT 250 WORDS)
1,219 citations
Journal Article•
TL;DR: A combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism.
Abstract: The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)
1,196 citations
TL;DR: Brain activation was assessed in the temporal, parietal and frontal multi-modal association areas that constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.
Abstract: We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing The activation paradigm included three tasks In the reference task, subjects were asked to detect rising pitch within a series of pure tones In the phonological task, they had to monitor the sequential phonemic organization of non-words In the lexico-semantic task, they monitored concrete nouns according to semantic criteria We found highly significant and different patterns of activation Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language
TL;DR: It is shown that unstable RAR-RXR heterodimers were formed in solution, and that C-terminal sequences and the DNA-binding domains of both receptors were required for efficient formation of stable heterodIMers on response elements.
TL;DR: It is reported that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4- T cell death process, with the biochemical and ultrastructural features of apoptosis.
Abstract: In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.
TL;DR: A complex array of combinatorial effects is beginning to emerge which may account for the pleiotropic effects of retinoids.
TL;DR: Sickness behavior refers to the nonspecific symptoms (anorexia, depressed activity, loss of interest in usual activities, disappearance of body-care activities) that accompany the response to infection.
TL;DR: Basic data is provided suggesting that there is a tendency to maintain the body in the most economical position in terms of muscle fatigue and vertebral strain and the way in which these loads vary when the spinal curves and the pelvic slope change is described.
Abstract: The standing posture of 17 young men and women were studied using Barycentremeter measurements and full spine radiograph with a single referential system. These procedures provide in vivo measurements of the weight and center of weight supported by each vertebra and the coxofemoral joints. The relationship between the vertebra, the sacrum or the coxofemoral rotation axis and the center of weight they support, is displayed. The moment of the corresponding force may also be assessed. Mean values were computed and the relation with spine sagittal curves and pelvic parameters were studied. The position of the center of weight, in front of or behind the vertebra or the coxofemoral joints, requires an opposing muscle force to ensure mechanical stability. The load exerted on the vertebra cannot be precisely evaluated, but we can describe the way in which these loads vary when the spinal curves and the pelvic slope change. This study provides basic data suggesting that there is a tendency to maintain the body in the most economical position in terms of muscle fatigue and vertebral strain. Individual anatomical shapes and pelvic parameters of the pelvis induce corresponding specific sagittal curves of the spine. This concept is very useful for analysing pathological situations and devising appropriate treatment.
Journal Article•
TL;DR: The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution.
Abstract: The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution. The jackknife is based on the observation of the estimator for subsamples, generally of size n-1, obtained from the original sample. The bootstrap is based on the observation of the estimator on size n samples drawn from the original sample. The two methods are presented, their principle is illustrated through their application to simple examples and to more complex epidemiological problems.
TL;DR: Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding, which suggest that D3 receptor are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons.
Abstract: We have identified 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 100-, 1000-, and 10,000-fold lower at D2, D4, and D1 receptors, respectively. Specific [3H]7-OH-DPAT binding sites, with a Kd of 0.8 nM and a pharmacology similar to those at reference D3 receptors of CHO cells, were identified in rat brain. D3 receptors differ from D2 receptors in brain by their lower abundance (2 orders of magnitude) and distribution, restricted to a few mainly phylogenetically ancient areas--e.g., paleostriatum and archicerebellum--as evidenced by membrane binding are autoradiography studies. Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding. These various features suggest that D3 receptors are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons.
TL;DR: The aim of this study was to demonstrate that goal-directed pointing movements, executed at normal speed to a small visual target, but without vision of the movement, do not rely on preprogrammed commands (open-loop process); by contrast these responses are under the control of a feedback loop, which compares the ongoing response and the goal.
Abstract: 1. The aim of this study was to demonstrate that goal-directed pointing movements, executed at normal speed to a small visual target, but without vision of the movement, do not rely on preprogrammed commands (open-loop process); by contrast these responses are under the control of a feedback loop, which compares the ongoing response and the goal (or its internal representation). When the location of this goal is changed at the onset of the movement, an automatic correction of the path occurs. Modification of the goal was obtained by presenting a target in the peripheral visual field that the subject had to look at and point at as quickly and accurately as possible. When the orienting ocular saccade reached its peak velocity, statistically corresponding to the hand movement onset, the target was suddenly shifted 10 degrees in a random direction. This perturbation was undetected by the subject because of the absence of perception during the saccade. For the compensation to occur, the initial orientation of the movement and also its extent had to be modified. The results revealed 1) a nearly complete compensation of the movement path and a 66- to 80-ms duration lengthening; 2) relatively short reaction times to the perturbations (from 145 to 174 ms, with effective reaction times even 40 ms shorter); 3) nearly identical spatiotemporal movement characteristics to the perturbations, regardless of whether vision of the hand was allowed, suggesting that corrections were subserved by the same mechanisms. 2. The spatiotemporal characteristics of these unconscious corrections were similar to those observed in the classical double-step experiments investigating the intentional modifications of ongoing movements and suggest that they might share some common low-level mechanisms. That is, they could rely on visuokinesthetic feedback loops, which compare the updated information provided by the eye at the end of the saccade and the proprioceptive information of the end point effector (the fingertip here); they could also rely on feed-forward processes detecting the discrepancy between an efference copy of the movement and the new goal; or they could rely on a combination of those two main processes.
TL;DR: The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for the understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.
Abstract: Cellular proteins associated with immunodeficiency viruses were identified by determination of the amino acid sequence of the proteins and peptides present in sucrose density gradient-purified human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus (SIV). beta 2 microglobulin (beta 2m) and the alpha and beta chains of human lymphocyte antigen (HLA) DR were present in virus preparations at one-fifth the concentration of Gag on a molar basis. Antisera to HLA DR, beta 2 m, as well as HLA class I precipitated intact viral particles, suggesting that these cellular proteins were physically associated with the surface of the virus. Antisera to class I, beta 2m, and HLA DR also inhibited infection of cultured cells by both HIV-1 and SIV. The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for our understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.
TL;DR: In this article, a linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset.
Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM.
TL;DR: It is demonstrated in this work that the TP53 gene is an informative model with which to study the molecular mechanisms of mutagenesis in the human genome.
Abstract: More than 350 independent point mutations of the TP53 gene, found in a wide variety of human cancers, were compiled and analysed. From this study, we confirm the presence of four hot-spot regions which colocalize with some highly conserved domains of the protein. We also define a new hot-spot region which is observed predominantly in lung tumors. Analysis of the mutational events suggests the direct involvement of environmental carcinogens in lung tumors and hepatocarcinomas, and spontaneous mutagenesis generating essentially CpG transitions in most of the remaining ones. Furthermore, we demonstrate in this work that the TP53 gene is an informative model with which to study the molecular mechanisms of mutagenesis in the human genome.
TL;DR: It is suggested that this bacterium isolated from Mediterranean seawater near a petroleum refinery be assigned to a new genus, at least temporarily, because of the impossibility of finding a single most closely related species.
Abstract: On the basis of phenotypical characteristics and analysis of 16S rRNA sequence, a new species belonging to a new genus is described, and the name Marinobacter hydrocarbonoclasticus is proposed. This organism, isolated from Mediterranean seawater near a petroleum refinery, is a gram-negative, aerobic, rod-shaped bacterium. It grows at NaCl concentrations of 0.08 to 3.5 M and uses various hydrocarbons as the sole source of carbon and energy. Its DNA has a guanine-plus-cytosine content of 52.7 mol%. The 16S rRNA analysis shows a clear affiliation between M. hydrocarbonoclasticus and the gamma group of the phylum Proteobacteria. A close phylogenetic relationship appears among the species Marinomonas vaga, Oceanospirillum linum, Halomonas elongata, and Pseudomonas aeruginosa. Because of the impossibility of finding a single most closely related species, we suggest that this bacterium be assigned to a new genus, at least temporarily. The possibility of a revision of this status when new data appear is, however, not excluded. The type strain is M. hydrocarbonoclasticus SP.17 (= ATCC 49840).
TL;DR: Study of MPL expression by PCR analysis indicated that MPL is expressed at a low level in a large number of cells of hematopoietic origin and that the two types of mRNAs (P and K) were always found to be coexpressed.
Abstract: We have cloned the human homolog of the v-mpl oncogene transduced in the myeloproliferative leukemia retrovirus, which presents striking homologies with members of the hematopoietin receptor superfamily. We obtained two types of clones, MPLP and MPLK, which had the same 5' extremity but differed at their 3' ends. The resulting deduced polypeptides are composed of a common extracellular domain with a putative signal sequence and a common transmembrane domain, but they differ in their cytoplasmic domain after a stretch of 9 common amino acids. The extracellular domain of MPL contains the consensus sequences described for the members of the hematopoietin receptor superfamily. In addition, as for murine interleukin 3 and human and murine granulocyte-macrophage colony-stimulating factor type beta receptors, this domain can be divided into two subunits. An additional motif specific for MPL could be displayed by hydrophobic cluster analysis in the first subdomain. When RNAs from various hematopoietic cell lines were analyzed by Northern blot, MPL was detected only in the human erythroleukemia (HEL) cell line as a major 3.7-kilobase (kb) mRNA (MPLP) and a minor 2.8-kb mRNA (MPLK). However, study of MPL expression by PCR analysis indicated that MPL is expressed at a low level in a large number of cells of hematopoietic origin and that the two types of mRNAs (P and K) were always found to be coexpressed.
TL;DR: The deduced amino-acid sequence of the receptor yields a hydropathy profile characteristic of receptors with seven putative transmembrane regions, which indicates that the ADH receptor is a member of the superfamily of G-protein-coupled receptors.
Abstract: ANTIDIURESIS, the recovery of water from the lumen of the renal collecting tubule, is regulated by the hypothalamic release of antidiuretic hormone (ADH), which binds to specific receptors on renal collecting tubule cells, stimulates adenylyl cyclase and promotes the cyclic AMP-mediated incorporation of water pores into the luminal surface of these cells'1–3. We report here the isolation of the human ADH receptor gene using a genomic expression cloning approach4. The gene was used to clone the complementary DNA from a human renal library. The deduced amino-acid sequence of the receptor yields a hydropathy profile characteristic of receptors with seven putative transmembrane regions. This and the comparison with other cloned receptors indicates that the ADH receptor is a member of the superfamily of G-protein-coupled receptors.
University of Toronto1, National University of La Plata2, French Institute of Health and Medical Research3, International Agency for Research on Cancer4, University of British Columbia5, Israel Ministry of Health6, University of Melbourne7, National University of Singapore8, University of California, San Francisco9, University of Southern California10, University of Minnesota11, University of Utah12, Harvard University13, Stanford University14
TL;DR: This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum and estimates that risk of colorectal cancer in the U.S. population could be reduced about 31% by an average increase in fiber intake from food sources of about 13 g/d.
Abstract: BACKGROUND Colorectal cancer is a major public health problem in both North America and western Europe, and incidence and mortality rates are rapidly increasing in many previously low-risk countries. It has been hypothesized that increased intakes of fiber, vitamin C, and beta carotene could decrease the risk of colorectal cancer. PURPOSE The objective of this study was to examine the effects of fiber, vitamin C, and beta-carotene intakes on colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. The study was designed to estimate risks in the pooled data, to test the consistency of the associations across the studies, and to examine interactions of the effects of the nutrients with cancer site, sex, and age. METHODS Original data records for 5287 case subjects with colorectal cancer and 10,470 control subjects without disease were combined. Logistic regression analysis was used to estimate relative risks and confidence intervals for intakes of fiber, vitamin C, and beta carotene, with the effects of study, sex, and age group being adjusted by stratification. RESULTS Risk decreased as fiber intake increased; relative risks were 0.79, 0.69, 0.63, and 0.53 for the four highest quintiles of intake compared with the lowest quintile (trend, P < .0001). The inverse association with fiber is seen in 12 of the 13 studies and is similar in magnitude for left- and right-sided colon and rectal cancers, for men and for women, and for different age groups. In contrast, after adjustment for fiber intake, only weak inverse associations are seen for the intakes of vitamin C and beta carotene. CONCLUSION This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum. IMPLICATIONS If causality is assumed, we estimate that risk of colorectal cancer in the U.S. population could be reduced about 31% (50,000 cases annually) by an average increase in fiber intake from food sources of about 13 g/d, corresponding to an average increase of about 70%.
TL;DR: The results indicate that HCV infect blood mononuclear cells, thus suggesting that this cellular tropism may play a role in HCV infection.
TL;DR: The most striking is a decrease of frequency with numerical magnitude, with local increases for reference numerals such as 10, 12, 15, 20, 50 or 100, which reveals the frequent confound of two experimental variables: numerical magnitude and numeral frequency.
TL;DR: Results suggest a feedback inhibition of NMDA receptors by NO under physiological condition and Pretreatment with hemoglobil potentiated NMDA-induced effects, demonstrating that endogenous NO modulatesNMDA receptors.
TL;DR: The characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients suggest that MyLRAR may interfere in a dominant manner with both MyL and RAR functions.
Abstract: Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions.