SEARCH · Search PubMed

Results for “CONSTITUTION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed2001

Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1.

The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor alpha. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1.

Animals↗

PubMed2003

Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor.

Through a multiplex promoter spanning 218 kb, the phase II UDP-glucuronosyltransferase 1A (UGT1) gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. The orphan nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were originally identified as sensors able to respond to numerous environmentally derived foreign compounds (xenobiotics) to promote detoxification by phase I cytochrome P450 genes. In this report, we show that both receptors can induce specific UGT1A isoforms including those involved in estrogen, thyroxin, bilirubin, and carcinogen metabolism. Transgenic mice expressing a constitutively active form of human PXR show markedly increased UGT activity toward steroid, heme, and carcinogens, enhanced bilirubin clearance, as well as massively increased steroid clearance. The ability of PXR and constitutive androstane receptor and their ligands to transduce both the phase I and phase II adaptive hepatic response defines a unique transcriptional interface that bridges the ingestion and metabolism of environmental compounds to body physiology.

Animals↗

PubMed2001

Social mobility and constitutional and political preferences in Northern Ireland.

During the past thirty years Catholics in Northern Ireland have experienced unprecedented upward social mobility. Some commentators have suggested that this has led Catholics not merely to adopt the lifestyles of the middle class but also to modify their constitutional preferences, leading to a decline in nationalism. In this paper I examine the relationship between social mobility, on the one hand, and, on the other, both constitutional preferences and political (left or right wing) preferences among Catholics and Protestants in Northern Ireland, using survey data collected in 1996. There is no evidence that Catholics' constitutional preferences are related to their mobility experiences.

Choice Behavior↗

PubMed1987

Adapting the environment to people with disabilities: constitutional issues in Canada.

Many problems experienced by people with disabilities can be ascribed to the effects of a disabling environment rather than personal deficiencies. Adapting the environment to make it less handicapping therefore has become a significant item on agenda of reforms sought by people with disabilities, but pursuit of this objective has wider legal, political and constitutional implications. Canada is one country in which all of these avenues have been explored in order to achieve progress in this sphere. This article, based on interviews with key informants, reports the constitutional and historical background to the Canadian experience and identifies various problems that have been encountered by the organisation and persons who have sought to secure appropriate changes. It is argued that this particular example, founded on a hard-won clarification of rights and entitlements under the Constitution, may offer a more promising way forward than alternative approaches focused on legislative or administrative regulations.

Canada↗

PubMed1991

Effects of body constitution and age on maximum pacing rate of activity-modulated rate responsive pacemakers.

UNLABELLED: The pacing rate of activity-modulated pacemakers is triggered by vibrations running through the body. Whether the body constitution predicts maximum pacing rate and may facilitate rate response programming was studied in 16 patients with Activitrax pacemakers. Rate response parameters were programmed to a fixed setting in VVIR/VOOR mode (lower pacing rate 60 ppm, upper pacing rate 125-130 ppm, activity threshold medium/7). Body vibrations were induced by a treadmill exercise test with increasing speed. Maximum pacing rates were measured at the stage of symptom-limited tolerance. Exercise tests with a duration of 7.3 +/- 2.9 minutes resulted in a maximum pacing rate of 98 +/- 22 ppm ranging from 60-122 ppm. Maximum pacing rates did not differ between male (n = 10; 102 +/- 21 ppm) and female (n = 6; 92 +/- 24 ppm). Correlations between maximum pacing rates and body constitutional factors were not significant with r = -0.15 (weight), r = 0.39 (height), r = 0.07 (body surface area), and r = -0.27 (skin-fold thickness). The correlations with body mass index (r = -0.53) and age (r = -0.53) were initially significant, but not after Bonferroni-Simes-Hommel correction. The age-dependent relationship may be caused by the shorter exercise duration of older patients indicated by the correlation between exercise duration and maximum pacing rate (r = 0.77), as well as with age (r = -0.73). CONCLUSIONS: body constitution did not modify body vibrations and did not allow prediction of maximum pacing rates; therefore, it is no aid for the programming of rate response parameters.

Aging↗

PubMed2003

Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor.

We previously demonstrated that multidrug resistance protein 3 (Mrp3/ABCC3) is induced in rat liver by phenobarbital (PB) and several other microsomal enzyme inducers that induce cytochrome P450 2B (CYP2B). CYP2B is induced by constitutive androstane receptor (CAR)-retinoid X receptor (RXR) heterodimer binding to a phenobarbital-responsive promoter element in the CYP2B promoter. Hepatic mRNA levels of CYP2B and Mrp3 were measured in three models of altered CAR activity to determine whether CAR is also involved in the induction of Mrp3. In Wistar Kyoto rats, where males express higher CAR protein levels than females, the induction of CYP2B1/2 was significantly higher in males than in females by PB, diallyl sulfide, and trans-stilbene oxide but not oltipraz. Mrp3 was induced by each of these treatments, but in contrast to CYP2B1/2, to a similar magnitude in males and females. In male hepatocyte-specific RXRalpha-/- mice, CYP2B10 was not induced by diallyl sulfide or oltipraz but remained inducible by PB and trans-stilbene oxide after considering the decrease in basal CYP2B10 expression. Mrp3, however, was induced by PB, diallyl sulfide, trans-stilbene oxide and oltipraz in both wild-type and RXRalpha-/- mice. Additionally, constitutive expression of Mrp3 was significantly reduced in RXRalpha-/- mice. In CAR-/- mice, the robust induction of CYP2B10 by PB was completely absent. However, Mrp3 was equally induced both in wild-type and CAR-/- mice by PB. These data clearly demonstrate that induction of hepatic Mrp3 by PB and other microsomal enzyme inducers is CAR-independent and implies a role for RXRalpha in the constitutive expression of Mrp3.

Animals↗

PubMed2003

Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter.

CYP2C19 is an important human drug-metabolizing enzyme that metabolizes a number of clinically used drugs including the antiulcer drug omeprazole, the anxiolytic drug diazepam, the beta-blocker propranolol, the antimalarial drug proguanil, certain antidepressants and barbiturates, and the prototype substrate S-mephenytoin. Previous studies show that compounds such as rifampicin and dexamethasone induce CYP2C19 both in vivo in humans and in vitro in human hepatocytes. This study examines the transcriptional regulation of CYP2C19. Analysis of the CYP2C19 promoter revealed a single constitutive androstane receptor (CAR) binding site (CAR-RE; -1891/-1876 bp) and a glucocorticoid-responsive element (GRE; -1750/-1736 bp). Gel-shift assays showed that CAR-RE binds CAR and pregnane X receptor (PXR). Cotransfection with hCAR, mCAR, or hPXR in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -1891-bp CAR-RE abolished up-regulation. Expression with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells. Androstenol repressed the mCAR-mediated constitutive activation of the CYP2C19 promoter in HepG2 cells, whereas the potent mCAR ligand 1,4-bis[2-3,5-dichloropyridyloxyl)] benzene derepressed this response. Rifampicin produced a modest increase in promoter activity in cells cotransfected with hPXR. Dexamethasone activated the -2.7-kb CYP2C19 promoter constructs in HepG2 cells only in the presence of cotransfected glucocorticoid receptor (GR), whereas the GR antagonist mifepristone inhibits this response. Mutation of the GRE abolishes dexamethasone activation. This is the first study to identify nuclear receptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drugs.

Aryl Hydrocarbon Hydroxylases↗

PubMed2004

The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29.

Many cytochrome P450 isoforms are known to be drug-inducible. The anticonvulsant phenytoin has been reported to be an inducer of human CYP2B6, CYP3A4, and murine CYP2C29. However, the molecular mechanism mediating phenytoin induction remains unclear. Herein, we used in vivo and in vitro gene reporter assays of the Cyp2c29 promoter to delineate the phenytoin-response activity to a phenytoin-responsive module located at -1371 kb upstream of the Cyp2c29 translation start site. The phenytoin-responsive module, consisting of two motifs of two imperfect direct repeat hexamers spaced by four nucleotides and a putative CCAAT/enhancer-binding protein-binding site, mediated luciferase reporter induction by phenytoin in mouse livers in vivo and was activated by CAR in HepG2 cells. Hepatic CYP2C29 mRNA was induced by phenytoin in wild-type but not in CAR-null mice, indicating that constitutive active or androstane receptor (CAR) regulates phenytoin-induced transcription of the Cyp2c29 gene. Furthermore, the constitutive levels of CYP2C29 mRNA were reduced approximately 77-fold in CAR-null mice compared with those in the wild-type mice, suggesting that CAR may also regulate the constitutive expression of the Cyp2c29 gene either directly or indirectly.

Active Transport, Cell Nucleus↗

PubMed2005

Association between tumor necrosis factor-alpha gene polymorphism and Sasang constitution in cerebral infarction.

During the last decade, a growing corpus of evidence has indicated an important role of cytokines in the development of brain damage following cerebral ischemia. Tumor necrosis factor-alpha (TNF-alpha), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, we examined whether promoter region polymorphism in the TNF-alpha gene at position -308 affects the odds of cerebral infarction (CI) and whether genetic risk is enhanced by Sasang constitutional classification. Two hundred and twelve CI patients and 610 healthy controls were genotyped and determined according to Sasang constitutional classification. A significant decrease was found for the TNF-alpha A allele in CI patients compared with controls (p = 0.033, odds ratio, OR: 0.622). However, there was no significant association between TNF-alpha polymorphism and Sasang constitution in CI patients. Our finding suggests that TNF-alpha promoter region polymorphism is responsible for susceptibility to CI in Koreans.

Adult↗

PubMed1976

Constitution and body proportions in different strains of rats. A study of race formation in breeding isolates.

(1) There are considerable differences in body constitution in different strains of rats, ranging from very robust to very gracile forms. The differences are greater in the larger males than in the smaller females. (2)Craniofacial and postcranial proportions of the trunk in domesticated strains of rats differ either uniformly or mosaically from the wild form. (3)Nasal shape differs greatly in rats ranging from extreme leptorrhine to extreme platyrrhine forms, giving a total range greater than in human populations. (4)Fisher 344 rats have long tails and extremities and Buffalo and GRL short tails and extremities. (5)Wistar and ACI rats have longer tails than wild rats but do not differ significantly from wild rats in the relative length of their other extremities. (6)The relationship between tail and extremity length is under genetic control which is concordant in Fisher, Buffalo and GRL rats, but discordant in the Lewis, Wistar and ACI strains. (7)There is no connection between relative extremity length and total body constitution since short-limbed strains occupy both the highest (Buffalo) and lowest (GRL) levels o f robusticity, and strains that do not differ in relative extremity length from wild rats differ greatly from each other in constitutional type (Wistar and ACI). (8)Differences of relative extremity length and nasal shape in rats have their parallels in human populations. But in human populations they follow Allen's ecological "rule" and can be duplicated experimentally. In rats here used, however, they do not result from any known ecological pressures, but from the genetic factors acting in breeding isolates.

Animals↗

PubMed2001

Conservation of signaling pathways of xenobiotic-sensing orphan nuclear receptors, chicken xenobiotic receptor, constitutive androstane receptor, and pregnane X receptor, from birds to humans.

Chicken xenobiotic receptor, pregnane X receptor, and constitutive androstane receptor are orphan nuclear receptors that have recently been discovered to regulate drug- and steroid-mediated induction of hepatic cytochromes P450 (CYP). This induction is part of an adaptive response involving numerous genes to exposure to drugs and chemicals and has major clinical and toxicological implications. Here we report experiments in the chicken hepatoma cell line LMH that suggest evolutionary conservation of the signaling pathways triggered by pregnane X receptor, constitutive androstane receptor, and chicken xenobiotic receptor. Thus, the phenobarbital-inducible enhancer units of the mouse Cyp2b10, rat CYP2B2, and human CYP2B6 genes were activated in reporter gene assays by the same compounds that activate the chicken CYP2H1 phenobarbital-inducible enhancer units. Chicken xenobiotic receptor, pregnane X receptor, and constitutive androstane receptor all bound to the CYP2H1 phenobarbital-inducible enhancer units in gel-shift experiments. In CV-1 cell transactivation assays, mammalian pregnane X receptors activate the chicken phenobarbital-inducible enhancer units to the same extent as does chicken xenobiotic receptor, each receptor maintaining its species-specific ligand spectrum. To assess the reported role of protein phosphorylation in drug-mediated induction, we treated LMH cells with okadaic acid and observed increased mRNA of delta-aminolevulinate synthase and CYP2H1 whereas expression of CYP3A37 was decreased. The effects of okadaic acid and other modifiers of protein phosphorylation in LMH cells are comparable to those seen on CYP2Bs and CYP3As in mammalian primary hepatocyte cultures. These results indicate that closely related nuclear receptors, transcription factors, and signaling pathways are mediating the transcriptional activation of multiple genes by xenobiotics in chicken, rodents, and man.

Animals↗

PubMed2005

On theoretical principles of constitution typology.

Constitution typology is thought of as a classification that is based on a few fundamental properties of the organism. These properties steadily distinguish individuals and permit the prediction of manifold secondary (external) features of types. At the transition from one constitutional type to another, concordant changes of trait values are determined by the respective changes of general causal factors. Theoretically, external constitution typology should be constructed on the basis of trait concordant "dynamics" under the change of fundamental factors at the individual level. Therefore, it does not depend on statistical relations characterizing population level. Causal factors and their influences on traits are impossible to be correctly and uniquely determined on the basis of population statistics relations. Causal factors do not coincide with the statistical ones of multivariate biometric analysis; equally, trait regression dependencies on statistical factors do not coincide with the causal influences.

Biometry↗

PubMed1987

Constitutional delay of growth and pubertal development: growth hormone secretory pattern and possible therapy.

Constitutional delay of growth and pubertal development is a frequent cause of short stature. These children have a significant retardation of skeletal age and delayed sexual development. They generally maintain a normal growth curve and tend to attain normal adult height. Although children with constitutional delay of growth are believed to have no medical or endocrine abnormality to explain their short stature, some controversy regarding their growth hormone secretory status has recently surfaced; some authors have reported low growth hormone levels to provocative stimuli and decreased growth hormone secretion during sleep, as well as low somatomedin C values in some children with constitutional delay of growth. Others, however, have found the growth hormone secretory status to be normal and similar to that of a control population. The implications of these findings, particularly in regard to possible forms of therapy, are discussed in some detail.

Adolescent↗

PubMedDate not supplied

[Comparative evaluation of the hormonal changes in alimentaro-constitutional and hypothalamic obesity].

A study was made of change in hormone secretion in 243 patients with alimentary-constitutional and hypothalamic obesity. Activation of the somatostatin mechanism, a decrease in somatotropic and thyrotropic function of the hypophysis, an increment of corticotropin, beta-lipotropin and vasopressin levels in the blood, disturbance of circadian fluctuations of hormone secretion, an increase in insulin and C-peptide secretion, a decrease in glucagon secretion and triiodothyronine and cortisol levels in the blood, activation of the renin-aldosterone system and cortisol secretion rate were equally expressed both in alimentary-constitutional and primary hypothalamic obesity. The central mechanisms of the regulation of endocrine functions were incorporated in a pathological process even in alimentary-constitutional obesity. Disorders of the hypothalamic regulation lay in the basis of both types of obesity.

Adrenal Cortex↗

PubMed1979

[Special hormone-determined constitutional types in women from the anthropological viewpoint].

The question is examined, whether in females hormonal determined constitution types are present which would require a different dosage of the estrogen respectively gestagen portion in the compound of ovulation inhibitors. Various aspects of constitution biology as well as of hormone physiology connected with this question are discussed in detail. Provided that a coherence between the hormonal balance and the constitutional type would be present, ovulation inhibitors could be dosed for the estrogen respectively gestagen portion. However, until now such a coherence could not be proved convincingly.

Androgens↗

PubMed1997

[Formation of individual somatotype parameters and features of constitutional organization in 7-12-year-old boys (longitudinal)].

Individual somatotype parameters and peculiarities of constitution in 7-12 years boys were evaluated in the present investigation. The age range studied was shown to be divided on 3 stages. Regular growth processes with the prevalence of "infantal" proportions occur at the age of 7-9. Signs of definite constitutional type are expressed yet insufficiently. The age of 10-11 is transitional which shows in delay of muscle growth. At the age of 11-12 prepubescent sets in, during which features of constitution types and appropriate somatotype parameters are distinctly manifested.

Aging↗

PubMed1998

Heat-shock proteins in axoplasm: high constitutive levels and transfer of inducible isoforms from glia.

To characterize heat-shock proteins (HSPs) of the 70-kDa family in the crayfish medial giant axon (MGA), we analyzed axoplasmic proteins separately from proteins of the glial sheath. Several different molecular weight isoforms of constitutive HSP 70s that were detected on immunoblots were approximately 1-3% of the total protein in the axoplasm of MGAs. To investigate inducible HSPs, MGAs were heat shocked in vitro or in vivo, then the axon was bathed in radiolabeled amino acid for 4 hours. After either heat-shock treatment, protein synthesis in the glial sheath was decreased compared with that of control axons, and newly synthesized proteins of 72 kDa, 84 kDa, and 87 kDa appeared in both the axoplasm and the sheath. Because these radiolabeled proteins were present in MGAs only after heat-shock treatments, we interpreted the newly synthesized proteins of 72 kDa, 84 kDa, and 87 kDa to be inducible HSPs. Furthermore, the 72-kDa radiolabeled band in heat-shocked axoplasm and glial sheath samples comigrated with a band possessing HSP 70 immunoreactivity. The amount of heat-induced proteins in axoplasm samples was greater after a 2-hour heat shock than after a 1-hour heat shock. These data indicate that MGA axoplasm contains relatively high levels of constitutive HSP 70s and that, after heat shock, MGA axoplasm obtains inducible HSPs of 72 kDa, 84 kDa, and 87 kDa from the glial sheath. These constitutive and inducible HSPs may help MGAs maintain essential structures and functions following acute heat shock.

Action Potentials↗

PubMed1999

ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells.

Overexpression of the growth factor receptor ErbB-2/Her2/Neu has been implicated in the development of non-small-cell lung cancer. We have reported that the transformation of human lung epithelial cells by c-erbB-2 also requires an active ErbB-1 (EGF receptor) and the autocrine production of its ligand, TGF-alpha. In this report, we demonstrate that STAT 3 is constitutively activated in these cells by the TGF-alpha-stimulated ErbB-1/-2 heterodimer complex. STAT 3 activation was confirmed by mobility shift assays and nuclear localization. ErbB-1 was required, but not sufficient for the TGF-alpha-induced activation of STATs. Inhibition of ErbB-2 kinase activity by tyrphostin AG825 prevented the constitutive activation of STAT 3 in the TGF-alpha-producing, ErbB-1 expressing cell line. Our results demonstrate a requirement for ErbB-2 kinase activity to establish constitutive STAT 3 activation resulting from an autocrine ErbB-1/ TGF-alpha loop. Int. J. Cancer 83:564-570, 1999. Published 1999 Wiley-Liss, Inc.

Benzothiazoles↗