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Interindividual Differences (interindividual + difference)
Selected AbstractsRelationship Between Interindividual Differences and Physiological Indexes of Acute Stress in RatsJOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 4 2005Mitsuo Nagane We used in vivo microdialysis to examine interindividual differences in the effects of acute immobilization stress and diazepam treatment on monoamine turnover in the hippocampus of male rats as an index of stress. Immobilization significantly increased the concentrations of 3,4-dihydroxyphenyl-aceticacid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). This effect was attenuated by injection of diazepam, Interindividual differences in reactivity to stressors caused differential changes in different metabolic products of monoamines. In our study, stress-induced changes in DOPAC levels were relatively great, and there was a similar change in the concentration of HVA. We conclude that at least 2 indexes of stress should be measured to take into account interindividual differences in the changes in stress indexes. [source] Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus MacaquesCHILD DEVELOPMENT, Issue 4 2009Pier Francesco Ferrari The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the 1st month of life. The results show that infants who imitate facial gestures display more developed skills in goal-directed movements (reaching,grasping and fine hand motor control) than nonimitators. These differences might reflect, at least in part, the differential maturation of motor chains in the parietal and motor cortices, which partly overlap with those of the mirror neuron system. Thus, neonatal imitation appears to be a predictor of future neurobehavioral development. [source] Relationship Between Interindividual Differences and Physiological Indexes of Acute Stress in RatsJOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 4 2005Mitsuo Nagane We used in vivo microdialysis to examine interindividual differences in the effects of acute immobilization stress and diazepam treatment on monoamine turnover in the hippocampus of male rats as an index of stress. Immobilization significantly increased the concentrations of 3,4-dihydroxyphenyl-aceticacid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). This effect was attenuated by injection of diazepam, Interindividual differences in reactivity to stressors caused differential changes in different metabolic products of monoamines. In our study, stress-induced changes in DOPAC levels were relatively great, and there was a similar change in the concentration of HVA. We conclude that at least 2 indexes of stress should be measured to take into account interindividual differences in the changes in stress indexes. [source] Heterogeneity in lipopolysaccharide responsiveness of endothelial cells identified by gene expression profiling: role of transcription factorsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006G. C. Beck Summary Interindividual differences of endothelial cells in response to endotoxins might contribute to the diversity in clinical outcome among septic patients. The present study was conducted to test the hypothesis that endothelial cells (EC) with high and low proinflammatory potential exist and to dissect the molecular basis underlying this phenomenon. Thirty human umbilical vein endothelial cell (HUVEC) lines were stimulated for 24 h with lipopolysaccharide (LPS) and screened for interleukin (IL)-8 production. Based on IL-8 production five low and five high producers, tentatively called types I and II responders, respectively, were selected for genome-wide gene expression profiling. From the 74 genes that were modulated by LPS in all type II responders, 33 genes were not influenced in type I responders. Among the 41 genes that were increased in both responders, 17 were expressed significantly stronger in type II responders. Apart from IL-8, significant differences in the expression of proinflammatory related genes between types I and II responders were found for adhesion molecules [intercellular adhesion molecule (ICAM-1), E-selectin)], chemokines [monocyte chemoattractant protein (MCP-1), granulocyte chemotactic protein (GCP-2)], cytokines (IL-6) and the transcription factor CCAAT/enhancer binding protein-delta (C/EBP-,). Type I responders also displayed a low response towards tumour necrosis factor (TNF)-,. In general, maximal activation of nuclear factor (NF)-,B was achieved in type I responders at higher concentrations of LPS compared to type II responders. In the present study we demonstrate that LPS-mediated gene expression differs quantitatively and qualitatively in types I and II responders. Our results suggest a pivotal role for common transcription factors as a low inflammatory response was also observed after TNF-, stimulation. Further studies are required to elucidate the relevance of these findings in terms of clinical outcome in septic patients. [source] Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1, concentration in uninvolved skin of patients with chronic irritant contact dermatitisCONTACT DERMATITIS, Issue 5 2008Cindy M. DeJongh Background:, Interleukin (IL)-1, and its receptor antagonist IL-1ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1,, IL-1ra, and IL-1,, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. Objective:, We studied the association between the polymorphisms IL1A -889 (C,T) and IL1B -31 (T,C) and the concentration of IL-1, and IL-1ra in the stratum corneum (SC). Method:, In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A -889 and IL1B -31 polymorphisms and determined the amount of IL-1, and IL-1ra on tape strips obtained from uninvolved skin of the volar forearm. Results:, The SC IL-1, concentration was 23% and 47% lower in subjects with IL1A -889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B -31 C/C genotype, the IL-1, concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1ra/IL-1, increased twofold in IL1A -889 C/T genotype and threefold in T/T genotype compared with wild type. Conclusions:, We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin. [source] An in vivo model to evaluate the efficacy of barrier creams on the level of skin penetration of chemicalsCONTACT DERMATITIS, Issue 1 2006Alexa Teichmann The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin. In the present study, a method was developed to investigate the effectiveness of reservoir closure by different formulations. Patent Blue V in water was used as a model penetrant. Its penetration, with and without barrier cream treatment, was analyzed by tape stripping in combination with UV/VIS spectroscopic measurements. The investigations showed that the stratum corneum represents a reservoir for topically applied Patent Blue V in water. Furthermore, the barrier investigations showed that vaseline and bees wax form a 100% barrier on the skin surface. The third barrier cream, containing waxes and surfactant, only partially showed a protective effect against the penetration of Patent Blue V in water. Strong interindividual differences were observed for this barrier product. In conclusion, it was assumed that the application of barrier creams cannot replace other protective measures and should be maximally used to inhibit low-grade irritants or in combination with other protectants or in body areas where other protective measures are not applicable. [source] Early recognition of newborn goat kids by their mother: II.DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2003Auditory recognition, evidence of an individual acoustic signature in the neonate Abstract The vocal recognition of newborn kids by their mother at 2 days postpartum and the possible existence of interindividual differences in the voice structure of newborn kids were investigated in two separate studies. The ability of goats to discriminate between the bleats of their own versus an alien kid was tested at 2 days postpartum in mothers being prevented access to visual and olfactory cues from the young. Goats spent significantly more time on the side of the enclosure from which their own kid was bleating, looked in its direction for longer, and responded more frequently to the bleats of their own than to those of the alien kid (p,<,0.05). In the second study, the sonograms of 13 kids, studied from Days 1 to 5, showed significant interindividual differences for the five variables taken into account and on each of the 5 days (duration of bleat, fundamental frequency, peak frequency, and numbers of segments and of harmonics). The potential for individual coding ranged between 1.1 and 4.1, indicating that for some variables variations between individuals were greater than intraindividual variations. Furthermore, when considering the five parameters together, the discriminating scores showed an average of 95% in the 78 combinations of any 2 kids for any given day. Finally, some significant intraindividual differences also were found between days, suggesting ontogenic changes in the characteristics of the kid's voice in early life. Therefore, mother goats are likely to recognize the vocalizations of their 48-hr-old kids, as they show sufficient interindividual variability to allow the existence of individual vocal signatures, even though some of the characteristics of the bleats change rapidly over time. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 311,320, 2003. [source] Big Five personality development in adolescence and adulthoodEUROPEAN JOURNAL OF PERSONALITY, Issue 1 2007Susan J. T. Branje Abstract The present article examines Big Five personality development across adolescence and middle adulthood. Two adolescents and their fathers and mothers from 285 Dutch families rated their own and their family members' personality. Using accelerated longitudinal growth curve analyses, mean level change in Big Five factors was estimated. For boys, Extraversion and Openness decreased and for girls, Extraversion, Agreeableness, Conscientiousness, and Openness increased. Whereas mothers' Emotional Stability and Conscientiousness increased, fathers' Extraversion, Agreeableness, and Emotional Stability decreased. Differences in self- and other-reported personality change were found, as well as interindividual differences in personality change. Results confirm that personality change is possible across the life course but these changes are not similar for all individuals and depend on the type of observer. Copyright © 2006 John Wiley & Sons, Ltd. [source] Individual differences in socioaffective skills influence the neural bases of fear processing: The case of alexithymiaHUMAN BRAIN MAPPING, Issue 10 2010Lydia Pouga Abstract Being exposed to fear signals makes us feel threatened and prompts us to prepare an adaptive response. In our previous studies, we suggested that amygdala (AMG) and premotor cortex (PM) play a role in the preparation of the observers' motor response required by the situation. The present experiment aimed at assessing how interindividual differences in alexithymia,a personality trait associated with deficits in emotional reactivity and regulation,influence the neural network associated with the perception of fear. Using fMRI, we scanned 34 healthy subjects while they were passively observing fearful body expressions. Applying a dimensional approach, we performed correlation analyses between fear-related brain areas and alexithymia scores among all participants. Using a categorical approach, we conducted a between-group comparison (13 high vs. 12 low-alexithymia subjects). Our results were threefold. First, the right AMG activity in response to fearful stimuli was negatively correlated with the level of difficulty to identify emotions. Second, PM activity was linked to reduced subjective emotional reactivity. Third, the between-group comparison revealed greater activity in anterior cingulate cortex (ACC) for high than low-alexithymia scorers. Moreover, the relationship between ACC and PM was in opposite direction in individuals with high (negative link) and low (positive link) alexithymia. Therefore, compared to our previous findings, we hereby further reveal how ACC interacts with PM to sustain self-regulation of one's own emotional state in response to threatening social signals. Moreover, this neural mechanism could account for the description of the "cold-blooded" personality of individuals with alexithymia. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] The evolution of problem and social competence behaviors during toddlerhood: A prospective population-based cohort surveyINFANT MENTAL HEALTH JOURNAL, Issue 1 2007Raymond H. Baillargeon Research in developmental psychopathology has long been preoccupied with rather broad categories of behavior, but we know little about the specific behaviors that comprise these categories. The objective of this study was to: (a) estimate the prevalence of problem and social competence behaviors in the general population of children at 17 months of age, and (b) describe the continuity and discontinuity in the degree to which children exhibit these behaviors between 17 and 29 months of age. The results show that frequent problem behaviors are not typical of children under two years of age. Further, the results suggest that it is possible to distinguish between different types of problem behaviors before two years of age. In addition, the results show that gender differences in some problem behaviors are already present before two years of age, and increase in magnitude during toddlerhood. Finally, the results show that interindividual differences in problem behaviors observed before two years of age are stable. The predictive accuracy of frequent problem behaviors in children at 17 months of age was limited, however, with often a majority of toddlers not behaving this way a year later. Overall, our results suggest that toddlerhood represents a critical period when behavioral and emotional problems of potentially clinical significance emerge. Pediatricians should routinely ask parents to report the frequency of their young children's problem behaviors during child health supervision visits so that children whose frequent problem behaviors persist over time can be identified and possibly referred for treatment. [source] Ethnic skin types: are there differences in skin structure and function?,INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2006A. V. Rawlings Synopsis People of skin of colour comprise the majority of the world's population and Asian subjects comprise more than half of the total population of the earth. Even so, the literature on the characteristics of the subjects with skin of colour is limited. Several groups over the past decades have attempted to decipher the underlying differences in skin structure and function in different ethnic skin types. However, most of these studies have been of small scale and in some studies interindividual differences in skin quality overwhelm any racial differences. There has been a recent call for more studies to address genetic together with phenotypic differences among different racial groups and in this respect several large-scale studies have been conducted recently. The most obvious ethnic skin difference relates to skin colour which is dominated by the presence of melanin. The photoprotection derived from this polymer influences the rate of the skin aging changes between the different racial groups. However, all racial groups are eventually subjected to the photoaging process. Generally Caucasians have an earlier onset and greater skin wrinkling and sagging signs than other skin types and in general increased pigmentary problems are seen in skin of colour although one large study reported that East Asians living in the U.S.A. had the least pigment spots. Induction of a hyperpigmentary response is thought to be through signaling by the protease-activated receptor-2 which together with its activating protease is increased in the epidermis of subjects with skin of colour. Changes in skin biophysical properties with age demonstrate that the more darkly pigmented subjects retaining younger skin properties compared with the more lightly pigmented groups. However, despite having a more compact stratum corneum (SC) there are conflicting reports on barrier function in these subjects. Nevertheless, upon a chemical or mechanical challenge the SC barrier function is reported to be stronger in subjects with darker skin despite having the reported lowest ceramide levels. One has to remember that barrier function relates to the total architecture of the SC and not just its lipid levels. Asian skin is reported to possess a similar basal transepidermal water loss (TEWL) to Caucasian skin and similar ceramide levels but upon mechanical challenge it has the weakest barrier function. Differences in intercellular cohesion are obviously apparent. In contrast reduced SC natural moisturizing factor levels have been reported compared with Caucasian and African American skin. These differences will contribute to differences in desquamation but few data are available. One recent study has shown reduced epidermal Cathepsin L2 levels in darker skin types which if also occurs in the SC could contribute to the known skin ashing problems these subjects experience. In very general terms as the desquamatory enzymes are extruded with the lamellar granules subjects with lowered SC lipid levels are expected to have lowered desquamatory enzyme levels. Increased pores size, sebum secretion and skin surface microflora occur in Negroid subjects. Equally increased mast cell granule size occurs in these subjects. The frequency of skin sensitivity is quite similar across different racial groups but the stimuli for its induction shows subtle differences. Nevertheless, several studies indicate that Asian skin maybe more sensitive to exogenous chemicals probably due to a thinner SC and higher eccrine gland density. In conclusion, we know more of the biophysical and somatosensory characteristics of ethnic skin types but clearly, there is still more to learn and especially about the inherent underlying biological differences in ethnic skin types. Résumé, Les gens qui ont une peau de couleur représentent la majorité de la population mondiale et les sujets asiatiques en représentent plus de la moitié. Pourtant la littérature consacrée aux caractéristiques de ces sujets est limitée. Plusieurs groupes de travail ont essayé au cours des dernières années de comprendre les différences sous-jacentes de la structure et de la fonction de la peau de différentes ethnies. Maisla plupart de ces études ont été réalisées à petite échelle et dans certains cas les différences observées entre les individus au niveau de la qualité de la peau ne font pas ressortir de différence entre races. Récemment, un besoin d'études reliant les diffèrences génétiques et phénotypiques entre différents groupes raciaux s'est fait sentir et de ce fait beaucoup d'études à grande èchelle ont été entreprises. La différence la plus évidente, entre les peaux ethniques, est leur couleur liée à la présence de la mélanine. La photoprotection induite par ce polymère influence le taux de vieillissement de la peau entre les différents groupes raciaux qui finalement sont tous sujets au processus de photovieillissement. Généralement, les caucasiens ont des signes plus précoces et plus importants de formation de rides et de relâchement de la peau; en général, les problèmes d'augmentation de la pigmentation sont observés sur les peaux de couleur, bien qu'une grande étude ait rapporté que des sujets originaires de l'Asie de l'Est vivant aux U.S.A. avaient le moins de taches pigmentaires. On pense que la réponse d'une induction hyperpigmentaire est due à un signal envoyé par le récepteur 2 activé par une protéase. Le récepteur 2 augmente en même temps que la protéase activatrice dans l'épiderme des sujets ayant une peau de couleur. Les changements dans les propriètés biophysiques de la peau en fonction de l'âge montrent que les sujets qui ont la pigmentation la plus sombre gardent une peau plus jeune par comparaison aux groupes qui possèdent une pigmentation moins forte. Toutefois, bien qu'ayant un stratum corneum plus compact, il existe des rapports divergents sur la fonction barrière de ces sujets. Dans le cas d'agression chimique ou mécanique, la fonction barrière du stratum corneum est considérée plus forte chez les sujets à peau plus foncée, malgré leurs taux plus faibles encéramide. On doit garder à l'esprit que la fonction barrière du stratum corneum dépend de toute son architecture et pas seulement de sa teneur en lipides. On considère que la peau asiatique à unePIE (TEWL) basale similaire à la peau caucasienne, ainsi que des taux en céramides comparables, mais on constate que dans le cas d'agression mécanique, elle possède un effet barrière le plus faible. Des différences dans la cohésion intercellulaire sont évidentes. A contrario, on a mis en évidence des taux d'hydratation (NMF) plus faibles dans son stratum corneum, comparativement à la peau caucasienne et afro-américaine. Ces différences expliquent les variations au niveau de la desquamation, mais on a très peu de données sur ce sujet. Une étude récente a mis en évidence des taux réduits de Cathepsin L2 dans l'épiderme des types de peau plus sombre, ce qui, si cela se produisait dans le stratum corneum, expliquerait les problèmes biens connus de cendrage de la peau que ces sujets connaissent. En terme très gènéral, étant donné que les enzymes liées à la desquamation sont libérées avec les granules lamellaires, on s'attend à ce que les sujets ayant des taux de lipides faibles dans le stratum corneum aient des taux d'enzymes liés à la desquamation faibles. On constate chez les sujets noirs une augmentation de la taille des pores, de la sécrétion du sébum et de la microflore cutanée. On observe également chez ces sujets une augmentation de la taille des granules mastocellulaires. Le phénomène de peau sensible se retrouve à une fréquence similaire dans les différents groupes raciaux, mais il existe des différences subtiles dans lesstimuli nécessaires pour l'induire. En tout cas, plusieurs études montrent que la peau asiatique est peut-être plus sensible aux produits chimiques exogènes, ce qui probablement est dûà un stratum corneum plus mince et à une densité de glandes eccrines plus élevées. En conclusion, c'est sur les caractéristiques biophysiques et somato-sensorielles des différents types de peaux ethniques que nous en savons plus, mais il est clair qu'il nous reste à comprendre encore beaucoup de choses principalement sur leurs différences biologiques. [source] Relationship Between Interindividual Differences and Physiological Indexes of Acute Stress in RatsJOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 4 2005Mitsuo Nagane We used in vivo microdialysis to examine interindividual differences in the effects of acute immobilization stress and diazepam treatment on monoamine turnover in the hippocampus of male rats as an index of stress. Immobilization significantly increased the concentrations of 3,4-dihydroxyphenyl-aceticacid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). This effect was attenuated by injection of diazepam, Interindividual differences in reactivity to stressors caused differential changes in different metabolic products of monoamines. In our study, stress-induced changes in DOPAC levels were relatively great, and there was a similar change in the concentration of HVA. We conclude that at least 2 indexes of stress should be measured to take into account interindividual differences in the changes in stress indexes. [source] Enzymes involved in the bioconversion of ester-based prodrugsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2006Bianca M. Liederer Abstract Enzymes are essential for the activation of many prodrugs. In this review, the most important enzymes (e.g., paraoxonase, carboxylesterase, acetylcholinesterase, cholinesterase) involved in the bioconversion of ester-based prodrugs will be discussed in terms of their biology and biochemistry. Most of these enzymes fall into the category of hydrolytic enzymes. However, nonhydrolytic enzymes, including cytochrome P450s, can also catalyze the bioconversion of ester prodrugs and thus will be discussed here. Other factors influencing the ability of these enzymes to catalyze the bioconversion of ester-based prodrugs, particularly species and interindividual differences and stereochemical and structural features of the prodrugs, will be discussed. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1177,1195, 2006 [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] Bereitschaftspotential and movement-related potentials: Origin, significance, and application in disorders of human movementMOVEMENT DISORDERS, Issue 5 2007James G. Colebatch MB Abstract The existence of a slow negative wave, the Bereitschaftspotential ("BP"), preceding voluntary movement by 1 second or more was first reported more than 40 years ago. There appears to be considerable interindividual differences, but there is general agreement that the initial negativity actually consists of two distinct phases. Uncertainty remains about many other properties and features of the response, including nomenclature, which makes the existing literature difficult to synthesize. The duration of the premovement negativity raises questions about how and when voluntary movement is initiated. Premovement negativities can also be seen before (predictably) externally paced movement, and these have similarities to the BP. Although lateralized generators exist, it is likely that the majority of the early component of the BP (BP1 or early BP), arises from the anterior supplementary motor area (SMA) and more rostral pre-SMA. The late phase of the BP (BP2 or late BP) is probably generated by activity in both the SMA proper and the contralateral motor cortex. Changes in the BP occur in several movement disorders, notably Parkinson's disease, in which the pattern is consistent with a failure of pre-SMA activation. The presence (or absence) of a clear preceding negativity can also have diagnostic importance for certain movement disorders. © 2007 Movement Disorder Society [source] The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2007Tugba Boyunegmez Tumer 6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, *3A allele frequency was significantly (P < 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1, CYP1A1, GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL. Am. J. Hematol. 82:906,910, 2007. © 2007 Wiley-Liss, Inc. [source] Proteomic profiling of animal models mimicking skeletal muscle disordersPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Philip Doran Abstract Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping. [source] Effects of post-density gradient swim-up on apoptosis signalling in human spermatozoaANDROLOGIA, Issue 2 2010S. Grunewald Summary The inclusion of apoptotic spermatozoa during assisted reproductive techniques (ART) may be one reason for suboptimal success rates. The aim of our study was to evaluate the potential of routine semen preparation to eliminate spermatozoa with activated apoptosis signalling. Semen samples from 20 infertility patients scheduled for ART procedures were investigated. Following density gradient centrifugation (DGC) and swim-up, aliquots were taken from each sample to analyse motility, Caspase-3 activation (CP3) and integrity of the mitochondrial membrane potential (MMP) using flow cytometry. Aliquots from the neat semen served as controls. Semen samples of patients contained 53.8 ± 17.7% spermatozoa with disrupted MMP and 51.8 ± 14.9% with active CP3. Preparation by DGC and swim-up resulted in improvement of progressive motility (+43.5%) and reduction of spermatozoa with disrupted MMP (,34.3%) and activated CP3 (,25.7%, P < 0.01). Minimal reduction of spermatozoa with disrupted MMP and active CP3 was 6.0% and 0.7%, maximum reduction was 65.5% (disrupted MMP) and 49.3% (CP3). Semen samples of subfertile patients contain high levels of spermatozoa with activated apoptosis signalling. Although there was a reduction in the majority of the samples, profound interindividual differences in the separation effect demand further development of innovative molecular-based separation methods to deplete apoptotic spermatozoa. [source] Viral reactivation is not related to septic complications after major surgical resections,APMIS, Issue 4 2008T. VOGEL Anastomotic leakage and septic complications are the most important determinants of postoperative outcome after major surgical resections. Malignant diseases and surgical trauma can influence immune responses and the ability to react against infectious factors, such as bacteria and viruses. Comparable immune suppression can cause viral reactivation in transplantation and trauma patients. In this prospective study, patients who underwent major surgical resections for oesophageal or pancreatic cancer were investigated for the potential involvement of viral reactivation in the development of septic complications. 86 patients (40 oesophageal resections, 27 pancreatic resections, 19 surgical explorations) were included. Viral antigens, viral DNA, antibodies against viral structures (IgG, IgM, IgA) and, in part, viral cultivation were performed for CMV, EBV, HSV1, HSV2, HZV6 and VZV in serum, urine, sputum and swabs from buccal mucosa preoperatively and at postoperative days 1, 3 and 5. Test results were compared with the postoperative outcome (30-day morbidity, in-hospital mortality) and clinical scores (SOFA, TISS). For statistical analyses Student's t -tests and Chi2 -tests were used. The overall complication rate was 19.8% (30-day morbidity) with an in-hospital mortality of 1.2% (1/86 patients). Postoperatively, anti-CMV-IgG titres were significantly reduced (p<0.05) and remained suppressed in patients with septic complications. Anti-CMV-gB-IgG were also reduced, but showed considerable interindividual differences. Anti-CMV-IgA and -IgM did not show significant alterations in the postoperative course. In addition, direct viral detection methods did not support viral reactivation in patients in any of the investigated groups. The reduction of anti-CMV antibodies is likely caused by an immune suppression, specifically by reduced B-cell counts after major surgical interventions. Viral reactivation, however, did not occur in the early postoperative period as a specific risk for septic complications. [source] Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowingARTHRITIS & RHEUMATISM, Issue 2 2009Tapio Videman Objective To examine the allelic diversity of structural, inflammatory, and matrix-modifying gene candidates and their association with disc degeneration. Methods Subjects were 588 men ages 35,70 years. We investigated associations of single-nucleotide polymorphisms in AGC1 and in 12 collagen, 8 interleukin, and 4 matrix metalloproteinase genes with quantitative magnetic resonance imaging measurements of disc desiccation and disc bulging and height narrowing scores, after controlling for age and suspected risk factors. Analyses were performed using QTDT software. P values were derived from 1,000 permutations, and empirical P values for global significance also were applied. Results Twelve of the 99 variants in 25 selected candidate genes provided evidence of association (P < 0.05) with disc signal intensity in the upper and/or lower lumbar regions. Allelic variants of AGC1 (rs1042631; P = 0.001), COL1A1 (rs2075555; P = 0.005), COL9A1 (rs696990; P = 0.00008), and COL11A2 (rs2076311; P = 0.018) genes provided the most significant evidence of association with disc signal intensity. The same variants of AGC1 (P = 0.010) and COL9A1 (P = 0.014), as well as variants in the COL11A1 gene (rs1463035 [P = 0.004]; rs1337185 [P = 0.015]) were also associated with disc bulging, as was AGC1 with disc height narrowing (rs1516797; P = 0.005). In addition, 4 allelic variants in the immunologic candidate genes (rs2071375 in IL1A [P = 0.027]; rs1420100 in IL18RAP [P = 0.005]) were associated with disc signal intensity. Conclusion Genetic variants account for interindividual differences in disc matrix synthesis and degradation. The accuracy of the quantitative disc signal intensity measurements we used likely enhanced our ability to observe these associations. Our findings shed light on possible mechanisms of degeneration and support the view that disc degeneration is a polygenetic condition. [source] Development of the human hypogastric nerve sheath with special reference to the topohistology between the nerve sheath and other prevertebral fascial structuresCLINICAL ANATOMY, Issue 6 2008Yusuke Kinugasa Abstract Semi-serial sections from the lumbosacral region of nine fetuses (8,25 weeks gestation) were examined to clarify the lumbar prevertebral fascial arrangement. The prevertebral fasciae became evident after 12 weeks of age. After 20 weeks of age, the hypogastric nerve (HGN) was sandwiched by two fascial structures; the ventral fascia which seemed to correspond to the mesorectal fascia, whereas the dorsal fascia corresponded to the presacral fascia. These fasciae or the HGN sheaths extended laterally along the ventral aspects of the great vessels and associated lymph follicles. The ventral fascia is, to some extent, fused with the mesocolon descendens on the left side of the body. Notably, the lateral continuation of these two fasciae also sandwiches the left ureter, but not the right ureter, presumably due to modifications by the left-sided fusion fascia. A hypothetical common sheath for the HGN and ureter (i.e., the ureterohypogastric or vesicohypogastric fascia) might thus be an oversimplification. Before retroperitoneal fixation, the morphology of the peritoneal recess along the mesocolon descendens and mesosigmoid suggested interindividual differences in location, shape, and size. Therefore, in adults the ease of surgical separation of the rectum and left-sided colon from the HGN seems to depend on interindividual differences in the development of the embryonic peritoneal recess. On the caudal side of the second sacral segment, fascial structures were restricted along and around the HGN, pelvic splanchnic nerve, and pelvic plexus. The rectal lateral ligament thus seems to represent a kind of migration fascia formed by mechanical stress. Clin. Anat. 21:558,567, 2008. © 2008 Wiley-Liss, Inc. [source] Multiple Inert Gas Elimination Technique For Determining Ventilation/Perfusion Distributions In Rat During Normoxia, Hypoxia And HyperoxiaCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2001V Alfaro SUMMARY 1. The use of the multiple inert gas elimination technique (MIGET) in quantifying ventilation/perfusion distributions (V,A/Q,) in small animals, such as the rat, may cause results to be biased due to haemodilution produced by the large volume of liquid infused intravenously. 2. We tested two methods of administering inert gases in rats using the MIGET: (i) standard continuous intravenous administration of inert gases (method A); and (ii) a new method based on the physicochemical properties of each inert gas (method B). This method included acute simultaneous inert gas administration using three pathways: inhalation, intravenous infusion and rectal infusion. Both MIGET methods were applied to obtain data while breathing three different inspiratory fractions of oxygen (FIO2): normoxia, hypoxia and hyperoxia. 3. Inert gas levels obtained from blood or expired air samples were sufficient for chromatographic measurement, at least during a 2 h period. The V,A/Q, distributions reported using both methods were acceptable for all the physiological conditions studied; therefore, the alternative method used here may be useful in further MIGET studies in rats because haemodilution resulting from continuous intravenous infusion of less-soluble gases can be avoided. 4. Normoxic rats showed lower mean values of the V,A/Q, ratio of ventilation distribution and higher mean values of the V,A/Q, ratio of perfusion distribution with the usual method of inert gas administration (method A). These non-significant differences were observed under almost all physiological conditions studied and they could be caused by haemodilution. Nevertheless, the effect of interindividual differences cannot be discarded. An additional effect of the low haematocrit on cardiovascular changes due to low FIO2, such as pulmonary vasoconstriction or increased cardiac output, may explain the lower dispersion of perfusion distributions found in group A during hypoxia. [source] ORIGINAL ARTICLE: Characteristics of plasma NOx levels in severe sepsis: high interindividual variability and correlation with illness severity, but lack of correlation with cortisol levelsCLINICAL ENDOCRINOLOGY, Issue 3 2010J. T. Ho Summary Objectives, Nitric oxide (NO) concentrations are elevated in sepsis and their vasodilatory action may contribute to the development of hyperdynamic circulatory failure. Hydrocortisone infusion has been reported to reduce nitric oxide metabolite (NOx) concentrations and facilitate vasopressor withdrawal in septic shock. Our aim was to determine whether NOx concentrations relate to (i) protocol-driven vasopressor initiation and withdrawal and (ii) plasma cortisol concentrations, from endogenous and exogenous sources. Demonstration of a relation between NOx, cortisol and vasopressor requirement may provide an impetus towards the study of hydrocortisone-mediated NOx suppression as a tool in sepsis management. Design, A prospective study of 62 patients with severe sepsis admitted to the intensive care unit. Measurements, Plasma NOx, total and free cortisol, and corticosteroid-binding globulin (CBG) concentrations were measured and related to protocol-driven vasopressor use for 7 days following admission. Results, Patients who developed septic shock (n = 35) had higher plasma NOx, total and free cortisol, and lower CBG concentrations than the nonseptic shock group (n = 27). Cortisol, CBG and NOx concentrations correlated with illness severity. Free cortisol, and to a lesser extent total cortisol, but not NOx concentrations, predicted septic shock. NOx concentrations were higher in nonsurvivors, and the concentrations were characteristically stable within individuals but marked interindividual differences were only partly accounted for by illness severity or renal dysfunction. NOx concentrations did not correlate with cortisol, did not relate to vasopressor requirement and did not fall after standard dose hydrocortisone, given for clinical indications. Conclusions, Nitric oxide production increased with sepsis severity but did not correlate with plasma cortisol or vasopressor requirement. NOx levels were not suppressed reproducibly by hydrocortisone. High interindividual variability of NOx levels suggests that absolute NOx levels may not be a suitable target for individualized hydrocortisone therapy. [source] | |||||||||||||||||||||||||||||||