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Interindividual Variation (interindividual + variation)
Kinds of Interindividual Variation Selected AbstractsDoes pregnancy affect swimming performance of female Mosquitofish, Gambusia affinis?FUNCTIONAL ECOLOGY, Issue 3 2002I. Plaut Summary 1.,The cost of reproduction due to limiting of the reproductive female's locomotion capability has been suggested many times, but has rarely been directly examined, especially in fishes. Here, the effect of pregnancy on swimming performance in the viviparous Mosquitofish, Gambusia affinis, was studied. 2.,Eight females of G. affinis were isolated, each in a separate aquarium, and critical swimming speed (Ucrit), body mass (BM) and cross-section area were measured every 5 days from the beginning of the pregnancy until 2,4 days after parturition. 3.,Swimming kinematics (tail beat frequency and amplitude) was measured in non-pregnant and pregnant females at different swimming speeds. 4.,BM increased during pregnancy from 0·47 ± 0·13 g to 0·72 ± 0·19 g, and the cross-section area also increased during pregnancy from 0·21 ± 0·06 cm2 to 0·32 ± 0·07 cm2. Ucrit decreased from 25·0 ± 1·3 cm s,1 before pregnancy to 20·1 ± 1·5 cm s,1 just before parturition, and returned to 24·7 ± 1·4 cm s,1 2,4 days after parturition. Interindividual variation was repeatable and reflects real differences among individuals. 5.,Swimming kinematics was not affected by pregnancy. 6.,The results suggest that reductions in Ucrit are probably because of aerobic constraints and not necessarily due to hydrodynamic changes resulting from changing in body form or plasticity. Moreover, the reduction in Ucrit is, potentially, a ,cost of reproduction' owing to decrease in the ability to gain food during pregnancy in G. affinis females. [source] Interindividual variation of serum haloperidol concentrations in Japanese patients , clinical considerations on steady-state serum level,dose ratiosJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2003E. Yukawa Summary Objective:, Marked interpatient variability in haloperidol (HAL) level,dose (L/D) ratios makes it difficult to use the administered dose for predicting serum concentrations. Objective:, To investigate the effect of dose, age, total body weight and co-medication on steady-state HAL L/D ratios. Method:, Retrospective analysis of dose and HAL blood level data from 168 patients. Results:, The HAL L/D ratio decreased curvilinearly with increasing daily dose of HAL. The patients treated with concomitant antiparkinsonian drugs showed a mean HAL L/D ratio that was 24·9% higher than those without antiparkinsonian drugs. The patients treated with concomitant antiepileptic drugs showed a mean HAL L/D ratio that was 27·2% lower than those without antiepileptic drugs. The mean HAL L/D ratio of patients treated with concomitant CYP2D6 substrates was not significantly different from those without CYP2D6 substrates. Conclusion:, There is a wide interindividual variability in blood levels of HAL in patients given the same dose. Routine monitoring of HAL serum level is useful, especially in patients who require associated antiepileptic and/or antiparkinsonian medication. [source] Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009J. Mark Cline Abstract Soy isoflavones are phytoestrogenic components of dietary soy, which are widely consumed for their potential health benefits. Soy isoflavones appear to decrease breast and endometrial cancer risk in human observational studies, but paradoxically stimulate growth of breast cancer cells in culture and uterine enlargement in rodents. We have shown that these compounds are not estrogenic in cynomolgus monkeys even at relatively high doses, but that they reduce estrogen-induced proliferative responses of the breast and endometrium. This effect may be mediated through estrogen receptor interactions and/or modulation of endogenous estrogen metabolism. Interindividual variation in isoflavone absorption and metabolism contributes to the degree of estrogen antagonistic effect. Our recent studies have also shown that individual isoflavone metabolites such as glyceollins may have unique selective estrogen receptor modulator-like activity, acting as tissue-specific antagonists without agonist activity. Rodent studies and human epidemiologic data suggest that timing of exposure and dose relative to endogenous estrogen concentrations are important determinants of effect, and studies of dietary soy on breast development and pubertal maturation are under way. Because soy isoflavones are both abundant in standard monkey chow diets and widely available as dietary supplements for human beings, these findings have broad relevance to the health of human and nonhuman primates. Am. J. Primatol. 71:722,731, 2009. © 2009 Wiley-Liss, Inc. [source] Environmental and ontogenetic constraints on developmental stability in the spatangoid sea urchin Echinocardium (Echinoidea)BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 2 2006THOMAS SAUCEDE Spatangoid irregular sea urchins are detritivorous benthic organisms particularly prone to variations of environment, and their mode of growth and plate morphology make them an appropriate model to assess the effects of environmental variations. Two populations of Echinocardium flavescens were sampled in two sites of the Norwegian coast characterized by contrasted environmental conditions. Different morphological descriptors (plate areas, interlandmarks distances, overall size, and shape of the posterior ambulacra) were used to appraise interindividual variations, and fluctuating asymmetry. The comparisons were carried out using classical fluctuating asymmetry (FA) methods, as well as Procrustean approaches. The population suspected to be less influenced by anthropic activities exhibits lower levels of FA for the size parameters (plate surfaces, interlandmarks distances, and centroid size) than the population located in a polluted area. Conversely, it shows higher FA values for the shape parameters (landmarks configuration). Interindividual variations appear to be correlated to FA. Variations are orientated according to the main growth axis of the ambulacra, and their intensity is stronger in the large posterior plates, which are also the youngest. These results are discussed with respect to architectural constraints involved in the sea urchin growth. © 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 165,177. [source] Neuromotor development from 5 to 18 years.DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2001Part 1: timed performance Timed performance in specific motor tasks is an essential component of a neurological examination applied to children with motor dysfunctions. This article provides centile curves describing normal developmental course and interindividual variation of timed performances of non-disabled children from 5 to 18 years. In a cross-sectional study (n=662) the following motor tasks were investigated: repetitive finger movements, hand and foot movements, alternating hand and foot movements, sequential finger movements, pegboard, and dynamic and static balance. Intraobserver, interobserver, and test-retest reliability for timed measurements were moderate to high. Timed performances improved throughout the entire prepubertal period, but differed among various motor tasks with respect to increase in speed and when the,adolescent plateau' was reached. Centile curves of timed performance displayed large interindividual variation for all motor tasks. At no age were clinically relevant sex differences noted, nor did socioeconomic status significantly correlate with timed performance. Our results demonstrate that timed motor performances between 5 and 18 years are characterized by a long-lasting developmental change and a large interindividual variation. Therefore, a well standardized test instrument, and age-specific standards for motor performances are necessary preconditions for a reliable assessment of motor competence in school-age children. [source] Prediction of polymorphic N -acetylation of new drug candidates by correlation with human NAT1 and NAT2DRUG DEVELOPMENT RESEARCH, Issue 1 2002Katalin Jemnitz Abstract Due to interindividual variation in N -acetyltransferase 2 (NAT2) activity, pharmaceutical companies face the problem of polymorphic metabolism in drugs that are metabolized mainly or exclusively by this enzyme. An in vitro method has been developed to predict in vivo polymorphic N -acetylation at an early stage of drug development. Two new type 5H-2,3-benzodiazepine derivatives, Nerisopam (NER) with anxiolytic activity and GYKI47261 with antiepileptic activity, are metabolized mainly by N -acetylation in the rat and human. The selectivity of human N -acetyltransferases (NAT1,2) to form the acetylated metabolites has been investigated by correlation analysis. Twelve human liver samples were characterized for NAT1 and NAT2 phenotype based on their enzyme activity toward two selective NAT1 (p -aminobenzoic acid, PABA; p -aminosalicylic acid, PAS) and two selective NAT2 (sulfamethazine, SMZ; procainamide, PROC) substrates. Significant correlation was found between enzyme activities NAT1PABA/NAT1PAS and NAT2SMZ/NAT2PROC, respectively, and no correlation was observed comparing enzyme activities toward NAT1PABA/NAT2PROC. Enzyme activities using NER and GYKI 47261 as substrates were compared to activities obtained with NAT1 and NAT2 selective substrates, and the correlation coefficients were calculated. Good correlation was established between the rates of acetylation of the two drugs and that of the NAT2 selective substrate (NER/NAT2SMZ, r2=0.91, GYKI 47261/NAT2SMZ, r2=0.91). In contrast, no correlation was found between the rate of conjugation of the drugs and that of NAT1 selective substrate (NER/NAT1PABA, r2=0.022, GYKI 47261/NAT1PABA, r2=0.0004), suggesting polymorphic in vivo metabolism, since both drugs are acetylated preferably by NAT2. According to our results, correlation analysis based on in vitro acetylation activity may be used to predict in vivo polymorphic metabolism. Drug Dev. Res. 56:17,22, 2002. © 2002 Wiley-Liss, Inc. [source] Daily jaw muscle activity in freely moving rats measured with radio-telemetryEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2007Nobuhiko Kawai The jaw muscle activity of rats has been investigated for specific tasks. However, the daily jaw muscle use remains unclear. The purpose of the present study was to examine daily jaw muscle activity, and its variability over time, in the rat (n = 12) by the use of radio-telemetry. A telemetric device was implanted for the continuous recording of masseter muscle and digastric muscle activity. Daily muscle use was characterized by calculating the total time that each muscle was active (duty time), the number of bursts, and the average length of bursts. All parameters were estimated for activities exceeding various levels (5,90%) of the day's peak activity. Daily muscle use remained constant for 4 wk. At the low-activity level, the duty time and burst number of the digastric muscle were significantly (P < 0.01) higher than those of the masseter muscle, whereas the opposite was true at the high-activity level (P < 0.05). No significant intermuscular correlation was observed between the number of bursts of the masseter and digastric muscles, but the interindividual variation of both muscles changed, depending on the level of activation. These findings suggest that the masseter muscle and the digastric muscle show a differential active pattern, depending on the activity level. [source] Changes in the bucco-lingual thickness of the mandibular alveolar process and skeletal bone mineral density in dentate women: a 5-yr prospective studyEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2005Grethe Jonasson After tooth extraction there is a great interindividual variation in the remodelling pattern of the alveolar process in edentulous areas, with some individuals losing little bone and others undergoing extensive resorption. However, little is known about possible longitudinal changes in the dentate region of the alveolar process of adults and if these are related to alterations in the skeletal bone mineral density (BMD). In a prospective study, on two occasions, 5-yr apart, the BMD of 117 women was determined in the distal forearm by using dual-energy X-ray absorptiometry, and the bucco-lingual thickness of the mandibular alveolar process was measured on dental casts by using a dial calliper. A decrease in the mean alveolar thickness, exceeding a cut-off value of 0.1 mm, was found in 60% of the women and an increase was found in 3% of the individuals. This decrease was 0.22 ± 0.20 mm in the posterior region and 0.16 ± 0.19 mm in the anterior region. The changes in alveolar thickness in the posterior region were significantly correlated to the BMD changes both on the mid-crestal level site and on the cervical level site. We conclude that the bucco-lingual thickness decreases with age in the dentate alveolar process, possibly owing to periosteal resorption related to skeletal bone loss. [source] Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdalaGENES, BRAIN AND BEHAVIOR, Issue 6 2008H. Yamasue Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders. [source] LPL polymorphism predicts stroke risk in menGENETIC EPIDEMIOLOGY, Issue 3 2002Alanna C. Morrison Abstract Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE ,2- and ,4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23,15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24,5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors. Genet. Epidemiol. 22:233,242, 2002. © 2002 Wiley-Liss, Inc. [source] Progress in understanding the biology of the human mutagen LINE-1,,HUMAN MUTATION, Issue 6 2007Daria V. Babushok Abstract Long interspersed nucleotide element (LINE)-1 retrotransposon (L1) has emerged as the largest contributor to mammalian genome mass, responsible for over 35% of the human genome. Differences in the number and activity levels of L1s contribute to interindividual variation in humans, both by affecting an individual's likelihood of acquiring new L1-mediated mutations, as well as by differentially modifying gene expression. Here, we report on recent progress in understanding L1 biology, with a focus on mechanisms of L1-mediated disease. We discuss known details of L1 lifecycle, including L1 structure, transcriptional regulation, and the mechanisms of translation and retrotransposition. Current views on cell type specificity, timing, and control of retrotransposition are put forth. Finally, we discuss the role of L1 as a mutagen, using the latest findings in L1 biology to illuminate molecular mechanisms of L1-mediated gene disruption. Hum Mutat 28(6), 527,539, 2007. Published 2007 Wiley-Liss, Inc. [source] Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2003*Article first published online: 11 DEC 200, Michel Bourin Abstract Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive, compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old,old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive,compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright © 2002 John Wiley & Sons, Ltd. [source] No evidence for association of the TP53 12139 and the BAX,248 polymorphisms with endemic pemphigus foliaceus (fogo selvagem)INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2006K. F. Köhler Summary Pemphigus foliaceus (PF) is an autoimmune bullous epidermal disease, characterized by autoantibodies specific to the desmosomal protein desmoglein 1 (dsg1) and by acantholysis, the rupture of the cellular junctions among keratinocytes. Known also as fogo selvagem (wild fire) in Brazil, the disease has distinct epidemiological characteristics, being endemic in certain regions of South America. It is a multifactorial (complex) disease, with oligo- or polygenic disease susceptibility. In view of the previously reported evidences of a role for apoptosis dysregulation in pemphigus pathogenesis, we hypothesized that genetic variants of molecules participating in apoptosis may contribute to interindividual variation of susceptibility to PF. The TP53 12139(G,C) and the BAX,248(G,A) single nucleotide polymorphisms (SNP) were analysed in a genetic association study. The allelic, genotypic and allele carrier frequencies for these SNPs did not differ statistically between the patient and the control groups, for both the Euro- and the Afro-Brazilian population strata. The results of this study lead us to conclude that, although the TP53 and BAX alleles analysed differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere with the development of the disease. [source] Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administrationINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2001Shigeru Satoh Abstract Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. Methods: The blood concentration,time curve was studied in 10 living-related kidney transplant recipients, aged 18,51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. Results: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0,27.2% for preoperative and 6.4,22.0% for postoperative area under the curve, respectively. Conclusion: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment. [source] Pressure,pain threshold determination in the oral mucosa: validity and reliabilityJOURNAL OF ORAL REHABILITATION, Issue 7 2002T. Ogimoto Fundamental knowledge of pain in the oral mucosa is lacking. We determined the validity and reliability of the pressure,pain threshold (PPT) measurement in the oral mucosa using a newly developed hand-held pressure algometer. Ten dentulous subjects were recruited, and the PPT was measured at the bilateral buccal (on the attached gingiva apical to the midline of the upper first premolars, 3 mm from the mucogingival junction) and the palatal sites (mid-point between the bilateral upper first molars). The PPT linearly increased with an increase in load-rate (P < 0·0001). The PPT yielded a high intra-individual stability both for the same-day consecutive trials and weekly sessions. The palatal site revealed a 4- to 4·65-fold greater PPT than the buccal sites (Bonferroni, P < 0·0001), whereas no difference was found between the bilateral buccal sites (P=0·663). Despite a great interindividual variation in the PPT, significant intra-individual correlations were found among the measurement sites. This suggested differences in individual sensitivity to pain in the oral mucosa, which may determine overall pain sensation specific to an individual. A pressure algometer described herein reliably assessed the PPT in the oral mucosa and sensitively discriminated PPT differences at different sites and at different load-rates, suggest-ing the reliability and validity of PPT measure-ments in the oral mucosa for clinical and research investigations. [source] Cytochrome P450-mediated metabolism in the human gut wallJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Kirstin Thelen Abstract Objective Although the human small intestine serves primarily as an absorptive organ for nutrients and water, it also has the ability to metabolise drugs. Interest in the small intestine as a drug-metabolising organ has been increasing since the realisation that it is probably the most important extrahepatic site of drug biotransformation. Key findings Among the metabolising enzymes present in the small intestinal mucosa, the cytochromes P450 (CYPs) are of particular importance, being responsible for the majority of phase I drug metabolism reactions. Many drug interactions involving induction or inhibition of CYP enzymes, in particular CYP3A, have been proposed to occur substantially at the level of the intestine rather than exclusively within the liver, as originally thought. CYP3A and CYP2C represent the major intestinal CYPs, accounting for approximately 80% and 18%, respectively, of total immunoquantified CYPs. CYP2J2 is also consistently expressed in the human gut wall. In the case of CYP1A1, large interindividual variation in the expression levels has been reported. Data for the intestinal expression of the polymorphic CYP2D6 are conflicting. Several other CYPs, including the common hepatic isoform CYP2E1, are expressed in the human small intestine to only a very low extent, if at all. The distribution of most CYP enzymes is not uniform along the human gastrointestinal tract, being generally higher in the proximal regions of the small intestine. Summary This article reviews the current state of knowledge of CYP enzyme expression in human small intestine, the role of the gut wall in CYP-mediated metabolism, and how this metabolism limits the bioavailability of orally administered drugs. Possible interactions between drugs and CYP activity in the small intestine are also discussed. [source] Genetic Repeat Polymorphism in the Regulating Region of CYP2E1: Frequency and Relationship With Enzymatic Activity in AlcoholicsALCOHOLISM, Issue 6 2001E. Plee-Gautier Background: Differences in the regulatory region of the CYP2E1 gene could be responsible for the interindividual variation in the cytochrome P-450 2E1 (CYP2E1) involved in ethanol oxidation. Recently, a polymorphic repeat sequence in the human gene was described between ,2178 and ,1945 base pairs. Its frequency seemed to vary among different ethnic populations, and it was suspected to be related to an increased inducibility to further ethanol intake. In the study reported here, the frequency of this polymorphism was investigated in a white French population. Its relationship with the previously described Pst I/Rsa I or Dra I CYP2E1 polymorphisms, alcoholism, alcoholic liver disease, and inducibility of CYP2E1 by ethanol was examined. Methods: The polymorphic region was characterized by polymerase chain reaction in 103 controls, 148 alcoholic subjects without liver diseases, and 98 others with liver cirrhosis. By using in vivo chlorzoxazone (CHZ) metabolism, CYP2E1 phenotype was assessed in 36 non,ethanol-induced subjects (17 controls and 19 withdrawn alcoholics) and in 14 ethanol-induced subjects (10 controls after ingestion of 0.8 g/kg ethanol and four alcoholics with 100 g of daily intake). This phenotype was expressed as the 6-hydroxy CHZ/CHZ ratio. Results: The rare allele frequency was found to be 1.58% in whites (n= 349). Neither significant association with alcoholism or alcoholic liver diseases, nor relationship with the Pst I/Rsa I polymorphism, was observed. But the Dra I polymorphism was more frequent among the heterozygous subjects when compared with wild-type homozygous ones (p < 0.05). The CYP2E1 phenotype was similar in wild-type homozygotes and in heterozygotes at the constitutive level, as well as after induction with ethanol. Conclusions: Our data suggest that CYP2E1 repeat polymorphism does not seem to constitute a major factor for interindividual differences in CYP2E1 expression and susceptibility to alcohol-related disorders in whites. [source] Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin timeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2004R. Al Dieri Summary., Heparin can be quantified with antifactor Xa and IIa tests (aXa, aIIa) but the anticoagulant power of heparin depends upon plasma properties as well as upon heparin concentrations and thus differs between subjects. Measuring the effect, as with the activated partial thromboplastin time (APTT) therefore is clinically more relevant. Here we investigate the use of the endogenous thrombin potential (ETP) for this purpose. In 12 volunteers 9000 IU of four heparins of different mol. wt distributions were injected. Samples were taken at 11 time points between 0 and 24 h. With the exception of the 0 and 24-h time points, heparin could be demonstrated by its aIIa and aXa activity in virtually all samples. The APTT showed the effect of this heparin in 34% of the samples; the ETP in 80%. This is partly due to the wide margins of the normal values, caused by large interindividual variation [coefficient of variation (CV) approximately 12% for the APTT, approximately 17% for the ETP]. The intraindividual variation is much smaller (CV approximately 4% for the APTT, approximately 5% for the ETP). Relative to the baseline value of the individual, the heparin effect was recognized by the APTT in 55% of the cases and by the ETP in 98%. There were no large differences between the different types of heparin. [source] Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristicsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004K. Vanschoonbeek Summary., The hemostatic activity of plasma is determined by platelet activation and coagulation, which processes are mutually stimulatory. We studied this interaction by measuring the cleavage of fluorescent thrombin substrate in platelet-rich plasma (PRP), using the calibrated thrombogram method. In freshly isolated human plasma, thrombin formation triggered by tissue factor was fully dependent on the presence of platelets. It was abolished by annexin A5, indicating dependence on phosphatidylserine (PS) exposure at activated platelets. Comparison of plasmas from various subjects showed considerable interindividual variation in total amount of thrombin generation, regardless of whether platelets or PS-containing phospholipids were present. Integrin ,IIb,3 antagonists and ADP receptor blockage, but not aspirin, decreased the rate of thrombin generation (thrombin peak level) and extended the time of onset. Platelet inhibition with cAMP-elevating agents decreased the thrombin-forming rate, but surprisingly shortened the onset time. Stimulation of platelets with agonists of Gi/q-coupled receptors and, to a larger extent, with collagen or Ca2+ -ionophore increased the rate of thrombin generation and shortened its onset. In PRP from donors with low and high generation, platelet inhibitors and activators were similarly effective. Taken together, these results indicate that, in tissue factor-triggered PRP, PS exposure on activated platelets regulates both onset and rate of thrombin generation. However, coagulant activity rather than platelet activation determines the total amount of thrombin formed, i.e. the endogenous thrombin potential. Thus, kinetics of thrombin generation in PRP are controlled by platelet inhibitors and agonists, but the process is restricted in amount by the subject-dependent variation in coagulation. [source] The transcriptomics of life-history trade-offs in whitefish species pairs (Coregonus sp.)MOLECULAR ECOLOGY, Issue 7 2008J. ST-CYR Abstract Despite the progress achieved in elucidating the ecological mechanisms of adaptive radiation, there has been little focus on documenting the extent of adaptive differentiation in physiological functions during this process. Moreover, a thorough understanding of the genomic basis underlying phenotypic adaptive divergence is still in its infancy. One important evolutionary process for which causal genetic mechanisms are largely unknown pertains to life-history trade-offs. We analysed patterns of gene transcription in liver tissue of sympatric dwarf and normal whitefish from two natural lakes, as well as from populations reared in controlled environments, using a 16 006-gene cDNA microarray in order to: (i) document the extent of physiological adaptive divergence between sympatric dwarf and normal species pairs, and (ii) explore the molecular mechanisms of differential life history trade-offs between growth and survival potentially involved in their adaptive divergence. In the two natural lakes, 6.45% of significantly transcribed genes showed regulation either in parallel fashion (2.39%) or in different directions (4.06%). Among genes showing parallelism in regulation patterns, we observed a higher proportion of over-expressed genes in dwarf relative to normal whitefish (70.6%). Patterns observed in controlled conditions were also generally congruent with those observed in natural populations. Dwarf whitefish consistently showed significant over-expression of genes potentially associated with survival through enhanced activity (energy metabolism, iron homeostasis, lipid metabolism, detoxification), whereas more genes associated with growth (protein synthesis, cell cycle, cell growth) were generally down-regulated in dwarf relative to normal whitefish. Overall, parallelism in patterns of gene transcription, as well as patterns of interindividual variation across controlled and natural environments, provide strong indirect evidence for the role of selection in the evolution of differential regulation of genes involving a vast array of potentially adaptive physiological processes between dwarf and normal whitefish. Our results also provide a first mechanistic, genomic basis for the observed trade-off in life-history traits distinguishing dwarf and normal whitefish species pairs, wherein enhanced survival via more active swimming, necessary for increased foraging and predator avoidance, engages energetic costs that translate into slower growth rate and reduced fecundity in dwarf relative to normal whitefish. [source] Phenotypic tradeoffs between egg number and egg size in three parasitic anisakid nematodesOIKOS, Issue 10 2007M. Victoria Herreras Phenotypic tradeoffs between number and size of eggs were tested in three component populations of three marine anisakid nematodes: Anisakis simplex, Pseudoterranova decipiens and Contracaecum osculatum. Body and uterine volumes (as proxies of female size), and egg number, mean egg volume and clutch volume (as descriptors of reproductive output) were measured in 50 females of each species. Evidence of a phenotypic tradeoff was detected only in A. simplex; the first time that has been found in a parasite population. Comparison of feasible values inferred from the van Noordwijk and de Jong's model and current data showed that interindividual variation in egg size was narrower than expected in the three populations. Structural constrictions in response to optimal allocation rules might account for this pattern. In P. decipiens and C. osculatum variation in egg size was the lowest and independent of female size, suggesting that the tradeoff is absent, rather than being present but masked by unaccounted variables. Spatial constrictions imposed by uterine size seemed to play an important role determining the emergence of the tradeoffs. So factors accounting for the tradeoff in A. simplex are probably constructional rather than physiological. Individual variability in investment in clutch volume was similar to previous studies but variation in allocation between number and size of eggs was much smaller than that reported previously. Perhaps differences in life-history strategies might explain this because the nematodes studied are either semelparous or short-lived iteroparus organisms whereas previous data derive from long-lived iteroparous ones. Despite the perception that parasites live in resource-rich habitats, the present study indicates that patterns relating number and size of eggs might not differ much from those observed in free-living populations and thus the same range of factors would operate in both types of organisms. [source] Parallel effects of genetic variation in ACE activity in baboons and humansAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2007Jenny Tung Abstract Like humans, savannah baboons (Papio sp.) show heritable interindividual variation in complex physiological phenotypes. One prominent example of such variation involves production of the homeostatic regulator protein angiotensin converting enzyme (ACE), which shows heritable variation in both baboons and humans. In humans, this phenotypic variation is associated with an Alu insertion,deletion polymorphism in the ACE gene, which explains approximately half of the variation in serum ACE activity. We identified a similar Alu insertion,deletion polymorphism in the baboon ACE homologue and measured its frequency in a wild population and a captive population of baboons. We also analyzed the contribution of ACE genotype at this indel to variation in serum ACE activity in the captive population. When conditioned on weight, a known factor affecting ACE activity in humans, age and ACE genotype both accounted for variance in ACE activity; in particular, we identified a significant nonadditive interaction between age and genotype. A model incorporating this interaction effect explained 21.6% of the variation in residual serum ACE activity. Individuals homozygous for the deletion mutation exhibited significantly higher levels of ACE activity than insertion,deletion heterozygotes at younger ages (10,14 years), but showed a trend towards lower levels of ACE activity compared with heterozygotes at older ages (,15 years). These results demonstrate an interesting parallel between the genetic architecture underlying ACE variation in humans and baboons, suggesting that further attention should be paid in humans to the relationship between ACE genetic variation and aging. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc. [source] Variability of Broca's area homologue in African great apes: Implications for language evolutionTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2003Chet C. Sherwood Abstract The cortical circuits subserving neural processing of human language are localized to the inferior frontal operculum and the posterior perisylvian region. Functional language dominance has been related to anatomical asymmetry of Broca's area and the planum temporale. The evolutionary history of these asymmetric patterns, however, remains obscure. Although testing of hypotheses about the evolution of language areas requires comparison to homologous regions in the brains of our closest living relatives, the great apes, to date little is known about normal interindividual variation of these regions in this group. Here we focus on Brodmann's area 44 in African great apes (Pan troglodytes and Gorilla gorilla). This area corresponds to the pars opercularis of the inferior frontal gyrus (IFG), and has been shown to exhibit both gross and cytoarchitectural asymmetries in humans. We calculated frequencies of sulcal variations and mapped the distribution of cytoarchitectural area 44 to determine whether its boundaries occurred at consistent macrostructural landmarks. A considerable amount of variation was found in the distribution of the inferior frontal sulci among great ape brains. The inferior precentral sulcus in particular was often bifurcated, which made it impossible to determine the posterior boundary of the pars opercularis. In addition, the distribution of Brodmann's area 44 showed very little correspondence to surface anatomy. We conclude that gross morphologic patterns do not offer substantive landmarks for the measurement of Brodmann's area 44 in great apes. Whether or not Broca's area homologue of great apes exhibits humanlike asymmetry can only be resolved through further analyses of microstructural components. Anat Rec Part A 271A:276,285, 2003. © 2003 Wiley-Liss, Inc. [source] Milk composition varies in relation to the presence and abundance of Balantidium coli in the mother in captive rhesus macaques (Macaca mulatta)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 6 2007Katherine Hinde Abstract Primate infants require extensive maternal investment, and lactation is the most expensive aspect of this investment. However, the relationship between maternal condition and milk composition has been largely uninvestigated in primates. To better understand this relationship, I collected mid-lactation milk samples from 46 captive multiparous rhesus macaques (Macaca mulatta) at the Caribbean Primate Research Center, Sabana Seca Field Station, Puerto Rico. The maternal variables assessed were age, weight, weight for crown,rump length (CRL), and presence of parasites. Additionally the analysis included infant age, weight, and sex. Protein concentration in milk showed little interindividual variation, whereas fat had a high variance. Mothers without the lower intestinal parasite Balantidium coli had a significantly higher fat concentration in milk than mothers with B. coli, but other parasite species (Trichuris trichiura and Strongyloides fulleborni) were not associated with milk fat concentration. Females with younger infants had a higher fat concentration in their milk than mothers with older infants; however, the association between B. coli and milk fat remained significant after controlling for infant age. These results, obtained from a well fed captive population, indicate that even small differences among mothers are associated with milk composition. Am. J. Primatol. 69:625,634, 2007. © 2007 Wiley Liss, Inc. [source] Is correction for protein concentration appropriate for protein adduct dosimetry?CANCER SCIENCE, Issue 2 2007Hypothesis, clues from an aflatoxin B1-exposed population Protein adducts are useful biomarkers for assessing exposure, metabolism and risk of carcinogens. Aflatoxin B1,albumin adducts (AAA) and protein carbonyl content (PCC) have long been used for assessing aflatoxin exposure and oxidative stress to proteins, and the quantitative data are almost exclusively expressed per mg protein. Given the large variation in protein concentrations in plasma among populations, this may not be the most appropriate method. The objective was to test the hypothesis that AAA and PCC should be expressed per mL plasma in population studies. AAA and PCC were analyzed among 402 subjects from three regions of China with a gradient in hepatocellular carcinoma (HCC) mortality ranging from 21 to 97 per 100 000. When biomarker values were expressed per mL plasma, the AAA level was significantly associated with plasma PCC (r = 0.262, P < 0.001), and adjusted levels of AAA and PCC paralleled HCC mortalities in the three regions, suggesting a role for aflatoxin-related oxidative stress in hepatocarcinogenesis in this population. In addition, there were statistically significant associations between both protein biomarkers, expressed per mL plasma, and the levels of alanine aminotransferase and aspartate aminotransferase in hepatitis B virus-infected subjects, suggesting roles for aflatoxin exposure, oxidative stress and hepatitis B virus infection in the development of HCC. The present data suggest that interindividual variation in plasma protein concentration may influence the dosimetry and relevant interpretation of protein biomarkers. (Cancer Sci 2007; 98: 140,146) [source] GENOTYPE AND ALLELE FREQUENCIES OF N -ACETYLTRANSFERASE 2 AND GLUTATHIONE S -TRANSFERASE IN THE IRANIAN POPULATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Anahita Torkaman-Boutorabi SUMMARY 1.,Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide interindividual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of the present study was to determine the frequencies of important allelic variants in the N- acetyltransferase 2 (NAT2) and glutathione S- transferase (GST) genes in the Iranian population and compare them with frequencies in other ethnic populations. 2Genotyping was performed in a total of 229 unrelated healthy subjects (119 men, 110 women) for NAT2 and 170 unrelated healthy subjects (89 men, 81 women) for GST from the general Tehran population. A combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was applied for typing of NAT2 polymorphisms. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. 3The frequencies of specific NAT2 alleles were 0.299, 0.314, 0.380, 0.007 and 0.000 for *4 (wild-type), *5 (C481T, M1), *6 (G590A, M2), *7 (G857A, M3) and *14 (G191A, M4), respectively. The most prevalent genotypes were NAT2 *5/*6 (29.70%) and *4/*6 (21.40%). The GSTM1 - and GSTT1 -null alleles were detected in 44.7 and 21.2% of subjects, respectively. 4We found that Iranians resemble Indians with regard to allelic frequencies of the tested variants of NAT2. The predominance of slow (49.36%) and intermediate (41.47%) acetylation status compared with wild-type rapid acetylation status (9.17%) in the study group suggests the significant prevalence of the slow acetylator (SA) phenotypes in the Iranian population. Our data confirmed that Iranians are similar to other Caucasian populations in the frequency of both GSTM1 - and GSTT1 -null alleles. [source] The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: an investigation in healthy Danish twinsCLINICAL ENDOCRINOLOGY, Issue 6 2009Wendy M. Van Der Deure Summary Introduction, Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3, untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective, In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analysed the underlying functional mechanism by performing mRNA stability measurements and analysed the effect of these variants on D1 activity. Methods, Serum thyroid measurements and genotypes of the D1-C785T and D1-A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1-transfected JEG3 cells. Results, Carriers of the D1-785T allele had 3·8% higher FT4 and 14·3% higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0·87% and 1·79%, respectively, of the variation in serum FT4 and rT3. The D1-A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild-type D1 and the two variants. Conclusion, The D1-C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated. [source] Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantationCLINICAL TRANSPLANTATION, Issue 5 2005Xin Zhang Abstract:, Objective:, Tacrolimus is an immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp, encoded by MDR1) play an important role in the absorption and metabolism of tacrolimus. The objective of this study was to evaluate whether or not CYP3A5*1/*3 or MDR1 C3435T polymorphisms are associated with the tacrolimus concentration per dose. Methods:, CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 118 Chinese renal transplant patients receiving tacrolimus. Whole blood trough tacrolimus concentration was measured by enzyme-linked immunosorbent assay and dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 wk, 1 month, and 3 months after transplantation. Results:, The dose-adjusted concentration of CYP3A5*1/*1 and *1/*3 patients was significantly lower than *3/*3 patients (32.8 ± 17.7 and 41.6 ± 15.8 vs. 102.3 ± 51.2 at 1 wk; 33.1 ± 7.5 and 46.4 ± 12.9 vs. 103 ± 47.5 at 1 month; 35.3 ± 20.9 and 59.0 ± 20.6 vs. 150 ± 85.3 at 3 months after transplantation respectively). At 1 wk, 46% of the CYP3A5*1 allele carriers had a tacrolimus concentration lower than 5 ng/mL and 77% lower than 8 ng/mL, whereas 20% of the *3/*3 patients had a concentration higher than 20 ng/mL. There was a mild difference between *1/*1 homozygotes and *1/*3 heterozygotes at 1 and 3 months after transplantation. No difference was found among the MDR1 genotypes. Conclusion:, CYP3A5*1/*3 polymorphisms are associated with tacrolimus pharmacokinetics and dose requirements in renal transplant recipients. Pharmacogenetic methods could be employed prospectively to help initial dose selection and to individualize immunosuppressive therapy. [source] Human breast areolae as scent organs: Morphological data and possible involvement in maternal-neonatal coadaptationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2006Benoist Schaal Abstract In humans, areolar skin glands (AG) enlarge during pregnancy and lactation. Their role in mother-infant interactions may pertain to protective, mechanical, and communicative functions. It was questioned here whether more profuse AG could be related to more optimal adaptation to breastfeeding. A morphological study of the areolae was undertaken between birth and day 3 to assess the number, secretory status, and spatial distribution of AG. These data were related to infants' weight variation, mothers' perception of their infant's behavior at breast, and time between delivery and onset of lactation. AG were seen in virtually all women but with great interindividual variations; their areolar distribution was nonrandom, and about 1/5 of the women had AG giving off a secretion. The AG number was positively related with neonatal weight gain between birth and day 3, and with the mother's perception of infant's latching speed and sucking activity. AG numbers were also positively related with the onset of lactation in first-time mothers. In conclusion, the maternal endowment in AG may contribute to the infants' breastfeeding performance, early growth, and the mother's lactation onset. © 2006 Wiley Periodicals, Inc. Dev Psyshobiol 48: 100,110, 2006. [source] Type I collagen markers in cord serum of appropriate vs. small for gestational age infants born during the second half of pregnancyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2001T. Saarela Background The serum concentration of the N-terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C-terminal telopeptide (ICTP) mirrors its degradation. Design PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate-for-gestational-age (AGA) infants and 98 smal-for-gestational-age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g. Results Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0·700 and 0·692, respectively; P < 0·001 in both). Conclusions The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established. 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