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Phenotype

Distribution by Scientific Domains
Medical Sciences49%
Life Sciences45%
Chemistry2%
7 Other Domains4%
Distribution within Medical Sciences
Immunology8%
Allergy & Clinical Immunology4%
68 Other Subdomains56%

Kinds of Phenotype

  • abnormal phenotype
  • activated phenotype
  • adaptive phenotype
  • adult phenotype
  • advantageous phenotype
  • aggressive phenotype
  • aging phenotype
  • alcohol-related phenotype
  • allergic phenotype
  • altered phenotype
  • alternative phenotype
  • angiogenic phenotype
  • antigen phenotype
  • asthma phenotype
  • asthmatic phenotype
  • atopic phenotype
  • atopy phenotype
  • atypical phenotype
  • autoimmune phenotype
  • b-cell phenotype
  • basal-like phenotype
  • behavioral phenotype
  • behavioural phenotype
  • benign phenotype
  • biochemical phenotype
  • biological phenotype
  • bleeding phenotype
  • bmd phenotype
  • cancer phenotype
  • cardiac phenotype
  • cardiovascular phenotype
  • cartilage phenotype
  • cell phenotype
  • cellular phenotype
  • characteristic phenotype
  • chondrocyte phenotype
  • clinical phenotype
  • cognitive phenotype
  • common phenotype
  • complex phenotype
  • consumption phenotype
  • contractile phenotype
  • cpg island methylator phenotype
  • cytokine phenotype
  • cytotoxic phenotype
    		•
  • dc phenotype
  • deficiency phenotype
  • depressive phenotype
  • developmental phenotype
  • different clinical phenotype
  • different disease phenotype
  • different phenotype
  • differentiated phenotype
  • disease phenotype
  • distinct phenotype
  • distinctive phenotype
  • diverse phenotype
  • dwarf phenotype
  • dystrophy phenotype
  • e phenotype
  • effector phenotype
  • epithelial phenotype
  • extreme phenotype
  • female phenotype
  • fibroblast phenotype
  • floral phenotype
  • functional phenotype
  • gc phenotype
  • growth phenotype
  • heterogeneous phenotype
  • hla phenotype
  • host phenotype
  • human phenotype
  • immunological phenotype
  • individual phenotype
  • inflammatory phenotype
  • intermediate phenotype
  • intestinal phenotype
  • invasive phenotype
  • island methylator phenotype
  • knockout phenotype
  • language phenotype
  • lethal phenotype
  • limb phenotype
  • lipoprotein phenotype
  • loss-of-function phenotype
  • lymphocyte phenotype
  • major phenotype
  • male phenotype
  • malignant phenotype
    		•
  • many phenotype
  • maternal phenotype
  • mature phenotype
  • mdr phenotype
  • memory phenotype
  • mesenchymal phenotype
  • metabolic phenotype
  • metastatic phenotype
  • methylator phenotype
  • migratory phenotype
  • mild clinical phenotype
  • mild phenotype
  • milder phenotype
  • molecular phenotype
  • morphological phenotype
  • motor phenotype
  • mouse phenotype
  • multidrug resistance phenotype
  • multiple phenotype
  • muscle phenotype
  • mutant phenotype
  • mutator phenotype
  • negative phenotype
  • neoplastic phenotype
  • neuronal phenotype
  • neurotransmitter phenotype
  • new phenotype
  • normal phenotype
  • novel phenotype
  • obese phenotype
  • offspring phenotype
  • oncogenic phenotype
  • opposite phenotype
  • osteoblastic phenotype
  • other phenotype
  • overt phenotype
  • parental phenotype
  • particular phenotype
  • pathological phenotype
  • patient phenotype
  • physiological phenotype
  • pigmentary phenotype
  • pigmentation phenotype
  • placental phenotype
  • plant phenotype
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  • pleiotropic phenotype
  • proinflammatory phenotype
  • proliferative phenotype
  • quantitative phenotype
  • rapd phenotype
  • rare phenotype
  • reactive phenotype
  • regulatory phenotype
  • relate phenotype
  • reproductive phenotype
  • rer phenotype
  • resistance phenotype
  • resistant phenotype
  • response phenotype
  • resulting phenotype
  • same phenotype
  • senescence phenotype
  • several phenotype
  • severe clinical phenotype
  • severe phenotype
  • similar phenotype
  • skeletal phenotype
  • skin phenotype
  • specific phenotype
  • surface phenotype
  • syndrome phenotype
  • synthetic phenotype
  • th1 phenotype
  • th2 phenotype
  • tissue phenotype
  • tumor phenotype
  • tumorigenic phenotype
  • unique phenotype
  • unusual phenotype
  • variable phenotype
  • various phenotype
  • viral phenotype
  • virulence phenotype
  • wheezing phenotype
  • white phenotype
  • wild-type phenotype

    • Terms modified by Phenotype

  • phenotype analysis
  • phenotype association
  • phenotype change
  • phenotype characteristic
    		•
  • phenotype consistent
  • phenotype correlation
  • phenotype development
  • phenotype difference
    		•
  • phenotype frequency
  • phenotype marker
  • phenotype matching
  • phenotype relationships
    		•
  • phenotype similar
  • phenotype studies

    • Selected Abstracts

    Different Gene Expressions on the Left and the Right: A Genotype/Phenotype Mismatch in Need of Attention

    ANNALS OF HUMAN GENETICS, Issue 1 2008
    Ursula Mittwoch
    Summary Discordance in monozygotic twins has traditionally been explained in terms of environmental influences. A recent investigation has found a difference in epigenetic markers in older but not in younger twins. However, phenotypic differences that depend on an individual's postnatal life style do not address the problem of discordance in congenital malformations, or the reason why malformations are frequently unilateral, often with a preference for one or the other side. One such condition, cleft lip with or without cleft palate, which is preferentially expressed on the left, is a multifactorial condition, that is caused by a failure of the critical timing necessary for different groups of cells to meet and develop into a normal face. This process is dependent on cell proliferation and migration, which are energy-dependent, while the additional requirement for apoptosis to allow cell fusion suggests the involvement of mitochondria. Recent progress in two separate areas of research could lead to a better understanding of the problem of facial clefts: (1) the recognition of an interaction between gene products and mitochondria in the aetiology of neurodegenerative diseases and (2) the discovery of an increasing number of genes, including transcription factors, growth factors and members of the TGF-, signalling family, that are differentially expressed on the left and right side, thus pointing to a difference in their micro-environment. These findings emphasize the importance of investigating the activity of candidate genes for complex developmental processes separately on the left and right sides. Data presented in this review suggest that differential growth rates may lead to an inversion of laterality. A method is described to test for a possible mitochondrial difference between left and right sides, using a mouse model with cleft lip. [source]

    SEXUAL SELECTION AND INTERACTING PHENOTYPES IN EXPERIMENTAL EVOLUTION: A STUDY OF DROSOPHILA PSEUDOOBSCURA MATING BEHAVIOR

    EVOLUTION, Issue 7 2008
    Leonardo D. Bacigalupe
    Sexual selection requires social interactions, particularly between the sexes. When trait expression is influenced by social interactions, such traits are called interacting phenotypes and only recently have the evolutionary consequences of interacting phenotypes been considered. Here we investigated how variation in relative fitness, or the opportunity for sexual selection, affected the evolutionary trajectories of interacting phenotypes. We used experimentally evolved populations of the naturally promiscuous Drosophila pseudoobscura, in which the numbers of potential interactions between the sexes, and therefore relative fitness, were manipulated by altering natural levels of female promiscuity. We considered two different mating interactions between the sexes: mating speed and copulation duration. We investigated the evolutionary trajectories of means and (co)variances (P) and also the influence of genetic drift on the evolutionary response of these interactions. Our sexual selection treatments did not affect the means of either mating speed or copulation duration, but they did affect P. We found that the means of both traits differed among replicates within each selection treatment whereas the Ps did not. Changes as a consequence of genetic drift were excluded. Our results show that although variable potential strengths of sexual interactions influence the evolution of interacting phenotypes, the influence may be nonlinear. [source]

    FEMALE SOLDIER BEETLES DISPLAY A FLEXIBLE PREFERENCE FOR SELECTIVELY FAVORED MALE PHENOTYPES

    EVOLUTION, Issue 5 2005
    Denson Kelly Mclain
    Abstract In Georgia (USA) the soldier beetle, Chauliognathus pennsylvanicus (Coleoptera; Cantharidae), exhibits clinal variation in the length of the spot on its elytron. This suggests that the viability of phenotypes varies by habitat. Evidence of viability selection comes from within-site changes in the spot length distribution across a breeding season. When males with spots of intermediate length became less frequent, they became disproportionately less likely to mate, consistent with either a loss of vigor among remaining males or female rejection of disfavored phenotypes. Persistent, daily courtship by males provides females with the opportunity to track changes in male phenotype frequency and to exercise choice for phenotypes favored under natural selection. A laboratory experiment in which the frequency of one spot morph (long) or the other (short) was increased from 25% to 75% over a period of 30 days revealed that females possess a flexible preference that leads them to prefer whichever spot type has become more common over time. A haploid genetic model demonstrates that a flexible female preference for the locally favored male phenotype can be selected for when different viability alleles, genetically correlated with the male trait, are favored in different habitats that are linked by gene flow. Thus, migration between different kinds of habitat patches of a metapopulation could maintain the variation in male quality. This variation favors female choice for any trait that is directly or indirectly favored by natural selection. Such choice imparts positive frequency-dependent selection that could rapidly fix traits pleiotropically linked to viability. Rapid fixation would cause differentiation between populations of colonizing species as females exercise choice for mates favored under new ecological conditions. [source]

    Temperature and pyoverdine-mediated iron acquisition control surface motility of Pseudomonas putida

    ENVIRONMENTAL MICROBIOLOGY, Issue 7 2007
    Miguel A. Matilla
    Summary Pseudomonas putida KT2440 is unable to swarm at its common temperature of growth in the laboratory (30°C) but exhibits surface motility similar to swarming patterns in other Pseudomonas between 18°C and 28°C. These motile cells show differentiation, consisting on elongation and the presence of surface appendages. Analysis of a collection of mutants to define the molecular determinants of this type of surface movement in KT2440 shows that while type IV pili and lipopolysaccharide O-antigen are requisites flagella are not. Although surface motility of flagellar mutants was macroscopically undistinguishable from that of the wild type, microscopy analysis revealed that these mutants move using a distinct mechanism to that of the wild-type strain. Mutants either in the siderophore pyoverdine (ppsD) or in the FpvA siderophore receptor were also unable to spread on surfaces. Motility in the ppsD strain was totally restored with pyoverdine and partially with the wild-type ppsD allele. Phenotype of the fpvA strain was not complemented by this siderophore. We discuss that iron influences surface motility and that it can be an environmental cue for swarming-like movement in P. putida. This study constitutes the first report assigning an important role to pyoverdine iron acquisition in en masse bacterial surface movement. [source]

    Migrating Partial Seizures in Infancy: Expanding the Phenotype of a Rare Seizure Syndrome

    EPILEPSIA, Issue 4 2005
    Eric Marsh
    Summary:,Purpose: The constellation of early-onset, unprovoked, alternating electroclinical seizures and neurodevelopmental devastation was first described by Coppola et al. We report six new patients and the prospect of a more optimistic developmental outcome. Methods: Retrospective chart reviews were performed on six infants evaluated at the Children's Hospital of Philadelphia (five patients) and at Hershey Medical Center (one patient) who had electroclinically alternating seizures before age 6 months of age. Electroclinical characteristics and long-term follow-up were recorded. Results: All had unprovoked, early-onset (range, 1 day to 3 months; mean, 25 days) intractable electroclinical seizures that alternated between the two hemispheres. Each patient underwent comprehensive brain imaging and neurometabolic workups, which were unrevealing. In all patients, subsequently intractable partial seizures developed and often a progressive decline of head circumference percentile occurred with age. Three demonstrated severe developmental delay and hypotonia. All survived, and 7-year follow-up on one patient was quite favorable. Conclusions: Our patients satisfied the seven major diagnostic criteria first described by Coppola et al. The prognosis of this rare neonatal-onset epilepsy syndrome from the original description and subsequent case reports was very poor, with 28% mortality, and the majority of survivors were profoundly retarded and nonambulatory. Our patient data validate the diagnostic criteria of this syndrome and further quantify a previously described observation of progressive decline of head circumference percentiles with age. Our data also suggest that the prognosis of this syndrome, although poor, is not as uniformly grim as the cases reported previously in the literature. [source]

    Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007
    Juan-Manuel Sancho
    Abstract Background and aim:,Only 20,30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph,) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial. Patients and methods:,From 1996 to 2006, 33 patients 55 yr with Ph, ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year. Results:,Median (range) age was 65 yr (56,77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%,57%) and 46% (22%,70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022,0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05). Conclusions:,The prognosis of elderly Ph, ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability. [source]

    Phenotype and function of neonatal DC

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009
    Fabienne Willems
    Abstract Newborns face complex physical and immunological changes before and after birth. Although the uterus is a sterile environment for the fetus, it also contains non-self material from the mother. Birth involves the transition from the sterile intra-uterine environment to an environment rich in microbes and requires rapid induction of appropriate responses to control these microbes. In this review we focus on the similarities and differences of human and murine neonatal DC and their reaction to various stimuli. A better understanding of the newborn immune system , in particular, the DC,T-cell interaction , will be beneficial for the development of improved strategies to prevent or treat infections in this vulnerable population and prepare the immune system to cope with allergens and tumors later in life. [source]

    Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007
    Line Lundfald
    Abstract The ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator. [source]

    Phenotype and Function of Somatic Primary Afferent Nociceptive Neurones with C-, A,- or A,/,-Fibres

    EXPERIMENTAL PHYSIOLOGY, Issue 2 2002
    S. N. Lawson
    Nociceptive dorsal root ganglion (DRG) neurones have fibres that conduct in the C, A, and A,/, conduction velocity range. The properties of nociceptive compared with non-nociceptive somatic afferent dorsal root ganglion neurones appear to fall into two patterns, A and B. Pattern A properties of nociceptive neurones, the more common type, include longer action potential duration and slower maximum rate of fibre firing, as well as a greater expression of substance P and calcitonin gene-related peptide immunoreactivity. The values of pattern A properties appear to be graded according to the conduction velocity group (C, A, or A,/,) of the fibres. The most pronounced forms of A-type properties are expressed by nociceptive neurones with C-fibres, and these become less pronounced in nociceptive neurones with A,-fibres and least pronounced in those with A,/, fibres (C > A, > A,/,). Some of these properties are also expressed in a less extreme but similarly graded manner through C, A, and A,/, groups of non-nociceptive low threshold mechanoreceptive (LTM) neurone. The less common pattern B properties of nociceptive neurones have similar values in C-, A,- and A,/,-fibre nociceptive neurones but these clearly differ from LTM units with C-, A,- and A,/,-fibre conduction velocities. These features of nociceptive neurones include consistently larger action potential overshoots and longer after-hyperpolarisation durations in nociceptive than in LTM neurones. [source]

    Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development

    GENES, CHROMOSOMES AND CANCER, Issue 6 2008
    Kim Loh
    Bone morphogenic proteins (BMPs) are members of the TGFB growth factor superfamily with well-described functions in bone formation. Although disrupted BMP signalling in tumor development has more recently been investigated, a role for BMP3 in colorectal cancer (CRC) has remained largely unexplored. The aim of this study was to investigate BMP3 disruption in CRCs in relation to both the traditional and serrated pathways of tumor progression. BMP3 was down-regulated as assessed by real-time PCR in 50 of 56 primary tumors (89%). Bisulfite sequencing of the putative promoter revealed extensive hypermethylation in the cell line HT29, in which expression could be restored by treatment with a methyltransferase inhibitor. Aberrant hypermethylation was observed in 33/60 (55%) tumors and was highly correlated with microsatellite instability (P < 0.01), the CpG Island Methylator Phenotype (P < 0.01), BRAF oncogene mutation (P < 0.01), and proximal location (P < 0.001). Methylation was also frequently observed in serrated and traditional adenomatous polyps (22/29, 76%). Re-introduction of BMP3 into cell lines revealed marked growth suppression supporting the functional relevance of this alteration in colorectal tumor development. This study provides molecular and functional data supporting the importance of BMP3 silencing as an early and frequent event in colorectal tumors progressing via the serrated and traditional pathways. © 2008 Wiley-Liss, Inc. [source]

    Analysis of genotypic and phenotypic clinical cut-off levels for ritonavir-boosted saquinavir

    HIV MEDICINE, Issue 2 2006
    A Hill
    There is a need for new, clinically relevant interpretation algorithms for genotypic and phenotypic resistance for ritonavir-boosted saquinavir (SQV/r) at the current approved dosage [1000/100 mg twice a day (bid)]. Clinical cut-off levels, which correlate baseline measures of resistance with HIV RNA responses in large cohorts or clinical trials, are the ideal reference for developing such algorithms. Cut-off levels previously developed for unboosted saquinavir may no longer apply, as the plasma drug levels with SQV/r are significantly higher and may be able partially to overcome protease inhibitor-resistant HIV. Clinical cut-off levels for SQV/r, assessed in several cohort studies and clinical trials, also suggest that multiple genotypic mutations are required for complete loss of virological response. For phenotypic analysis of resistance, saquinavir cut-off levels 10,11-fold higher than the wild-type IC50 have best distinguished responders from non-responders in cohort studies. Using Virtual Phenotype, a 12.3-fold upper cut-off level was determined from analysis of large cohort databases. These genotypic and phenotypic algorithms need to be validated in larger prospective studies. [source]

    Monocytes in the rat: Phenotype and function during acute allograft rejection

    IMMUNOLOGICAL REVIEWS, Issue 1 2001
    Birte Steiniger
    Summary: Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through post-capillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-vascularized allografts and chronic allograft rejection. It is very likely that they also contribute to acute allograft destruction. So far it has been impossible to distinguish the function of monocytes from that of macrophages, because cell phenotypes and their alterations upon activation are ill-defined. We have thus begun to characterize the ex vivo phenotype and function of rat monocytes in the normal state and during renal allograft rejection. Monocytes are recovered from both the central and the marginal blood pool by perfusing either the recipient's circulation or the allograft vasculature. Rat monocytes have a unique surface phenotype. During allograft rejection or after infusion of interferon-, they up-regulate class II MHC molecules, CD161 (NKR-P1A), CD62L and CD8, while CD4 and CD43 are down-modulated. Activated perfusate monocytes exert increased in vitro cytotoxicity against tumour targets, which differs from that of NK cells. We speculate that activated monocytes contribute to kidney allograft destruction by directly damaging endothelial cells or by promoting intravascular coagulation. [source]

    Cognitive Impairment Improves the Predictive Validity of the Phenotype of Frailty for Adverse Health Outcomes: The Three-City Study

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2009
    José Alberto Ávila-Funes MD
    OBJECTIVES: To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes. DESIGN: Four-year longitudinal study. SETTING: The French Three-City Study. PARTICIPANTS: Six thousand thirty community-dwelling persons aged 65 to 95. MEASUREMENTS: Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Subjects meeting one or two criteria were prefrail and those meeting none as nonfrail. The lowest quartile in the Mini-Mental State Examination (MMSE) and the Isaacs Set Test (IST) was used to identify subjects with cognitive impairment. The predictive validity of frailty for incident disability, hospitalization, dementia, and death was calculated first for frailty subgroups and then rerun after stratification according to the presence or absence of cognitive impairment. RESULTS: Four hundred twenty-one individuals (7%) met frailty criteria. Cognitive impairment was present in 10%, 12%, and 22% of the nonfrail, prefrail, and frail subjects, respectively. Those classified as frail scored lower on the MMSE and IST than those classified as prefrail and nonfrail. After adjustment, frail persons with cognitive impairment were significantly more likely to develop disability in activities of daily living (ADLs) and instrumental ADLs over the following 4 years. The risk of incident mobility disability and hospitalization was marginally greater. Incident dementia was greater in the groups with cognitive impairment irrespective of their frailty status. Conversely, frailty was not a significant predictor of mortality. CONCLUSION: Cognitive impairment improves the predictive validity of the operational definition of frailty, because it increases the risk of adverse health outcomes in this particular subgroup of the elderly population. [source]

    Leptin, Bone Mass, and the Thrifty Phenotype,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004
    Mark W Hamrick PhD
    First page of article [source]

    Female Premenopausal Fracture Risk Is Associated With Gc Phenotype,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004
    Anna Lis Lauridsen
    Abstract The phenotype of the vitamin D binding and macrophage activating protein, Gc, is a predictor of premenopausal bone fracture risk, possibly mediated through activation of osteoclasts. This was concluded from a study on 595 Danish perimenopausal women 45-58 years of age (30,040 person years). Introduction: The multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, or vitamin D binding protein (DBP), has two functions with relation to bone tissue: it is the major carrier protein of vitamin D in the circulation, and deglycosylation converts it into a very potent macrophage- and osteoclast-activating factor (Gc-MAF). There are several phenotypes of Gc, and in this study, we examined the relation between Gc phenotype and bone fragility. Materials and Methods: By isoelectric focusing we identified the Gc phenotype of 595 white recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS) and identified three groups: Gc1-1 (n = 323), Gc1-2 (n = 230), and Gc2-2 (n = 42). Differences between the three groups were examined with respect to number of fractures before enrollment, BMC and BMD, and various biochemical and clinical parameters, including the concentration of Gc measured by immunonephelometry and the concentration of the macrophage marker soluble CD163 measured by ELISA. Results and Conclusions: The risk of having at least one premenopausal bone fracture (total number of women with fracture = 179) differed significantly (p = 0.017) in women with phenotype Gc1-1 (110/323 = 0.34), Gc1-2 (63/230 = 0.27), and Gc2-2 (6/42 = 0.14). The differences were even more striking (p = 0.005) for fractures caused by low-energy traumas. Using logistic regression, we found the relative risk of premenopausal fracture to be 0.32 (0.13-0.80) in Gc2-2 compared with Gc1-1. We propose that the Gc phenotypes cause differences in osteoclast activity, a theory supported by our finding of lower levels of Gc and of soluble CD163 in women with Gc2-2 compared with Gc1-1. [source]

    Localization of the Gene Causing the Osteopetrotic Phenotype in the Incisors Absent (Ia) Rat on Chromosome 10q32.1,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2004
    Liesbeth van Wesenbeeck
    Abstract The incisors absent rat is an osteopetrotic animal model. Segregation analysis in 37 affected animals from an outcross enabled us to assign the disease causing gene to a 4.7-cM interval on rat chromosome 10q32.1. Further analysis of the genes mapped in this region will provide more insight into the underlying pathogenesis. Introduction: Many of the insights into the factors that regulate the differentiation and activation of osteoclasts are gained from different spontaneous and genetically induced osteopetrotic animal models. The osteopetrotic incisors absent (ia) rat exhibits a generalized skeletal sclerosis and a delay of tooth eruption. Although the ia rat has well been studied phenotypically, the genetic defect still remains unknown. Material and Methods: To map the ia locus, we outcrossed the inbred ia strain with the inbred strain Brown Norway. Intercrossing F1 animals produced the F2 generation. Thirty-one mutant F2 animals and six mutant F4 animals were available for segregation analysis. Results: Segregation analysis enabled us to assign the disease causing gene to rat chromosome 10q32.1. Homozygosity for the ia allele was obtained for two of the markers analyzed (D10Rat18 and D10Rat84). Key recombinations delineate a candidate region of 4.7 cM flanked by the markers D10Rat99 and D10Rat17. Conclusion: We have delineated a 4.7-cM region on rat chromosome 10q32.1 in which the gene responsible for the osteopetrotic phenotype of the ia rat is located. Although the sequence of this chromosomal region is not complete, over 140 known or putative genes have already been assigned to this region. Among these, several candidate genes with a putative role in osteoclast functioning can be identified. However, at this point, it cannot be excluded that one of the genes with a currently unknown function is involved in the pathogenesis of the ia rat. Further analysis of the genes mapped in this region will provide us more insight into the pathogenesis of this osteopetrotic animal model. [source]

    Idiopathic Hyperphosphatasia and TNFRSF11B Mutations: Relationships Between Phenotype and Genotype,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003
    Belinda Chong
    Abstract Homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin, were found in affected members from six of nine families with idiopathic hyperphosphatasia. The severity of the phenotype was related to the predicted effects of the mutations on osteoprotegerin function. Introduction: Idiopathic hyperphosphatasia (IH) is a rare high bone turnover congenital bone disease in which affected children are normal at birth but develop progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and deafness. There is, however, considerable phenotypic variation from presentation in infancy with severe progressive deformity through to presentation in late childhood with minimal deformity. Two recent reports have linked idiopathic hyperphosphatasia with deletion of, or mutation in, the TNFRSF11B gene that encodes osteoprotegerin (OPG), an important paracrine modulator of RANKL-mediated bone resorption. Materials and Methods: We studied subjects with a clinical diagnosis of IH and unaffected family members from nine unrelated families. Clinical, biochemical, and radiographic data were collected, and genomic DNA examined for mutations in TNFRSF11B. The relationship between the mutations, their predicted effects on OPG function, and the phenotype were then examined. Results: Of the nine families studied, affected subjects from six were homozygous for novel mutations in TNFRSF11B. Their parents were heterozygous, consistent with autosomal recessive inheritance. Four of the six mutations occurred in the cysteine-rich ligand-binding domain and are predicted to disrupt binding of OPG to RANKL. Missense mutations in the cysteine residues, predicted to cause major disruption to the ligand-binding region, were associated with a severe phenotype (deformity developing before 18 months age and severe disability), as was a large deletion mutation. Non-cysteine missense mutations in the ligand-binding domain were associated with an intermediate phenotype (deformity recognized around the age of 5 years and an increased rate of long bone fracture). An insertion/deletion mutation at the C-terminal end of the protein was associated with the mildest phenotype. Conclusion: Mutations in TNFRSF11B account for the majority of, but not all, cases of IH, and there are distinct genotype-phenotype relationships. [source]

    Ascorbic Acid Induces Collagenase-1 in Human Periodontal Ligament Cells but Not in MC3T3-E1 Osteoblast-Like Cells: Potential Association Between Collagenase Expression and Changes in Alkaline Phosphatase Phenotype,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003
    Momotoshi Shiga
    Abstract Ascorbic acid (AA) enhances osteoblastic differentiation by increasing collagen accumulation, which in turn, results in increased alkaline phosphatase (AP) expression in some osteogenic cells. However, in other cells, including human periodontal ligament (PDL) cells, additional osteoinductive agents are required for this response. To understand the potential basis for the maintenance of the AP phenotype of PDL cells exposed to AA, we examined the modulation of the tissue-degrading matrix metalloproteinases (MMPs) and their inhibitors by AA in short-term cell cultures. Early passage PDL cells in serum-free medium were exposed to AA for 5 days. The samples were analyzed for MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), AP, collagen I(,1), and osteocalcin. We found that AA dose-dependently increased the expression of collagenase-1, and minimally TIMP-1, but not stromelysin-1 or TIMP-2. Additionally, AA caused substantial increases in levels of type I collagen. AA was unable to increase AP activity or osteocalcin messenger RNA in PDL cells. However, the cells retained the ability to show a significantly greater AP expression in high- versus low-density cultures, and increased osteocalcin as well as AP levels when cultured in the presence of dexamethasone. Moreover, in cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied by a repression of collagenase-1 expression. In contrast to PDL cells, AA did not induce collagenase but produced a significant increase in AP expression in MC3T3-E1 cells. These findings provide the first evidence that AA, by modulating both collagen and collagenase-1 expression in PDL cells, most likely contributes to a net matrix remodeling response in these cells. Furthermore, the relationship between changes in collagenase expression and alterations in AP activity in PDL and MC3T3-E1 cells suggests a potential role for collagenase in modulating the AP phenotype of cells with osteoblastic potential. [source]

    Study of the Nonresorptive Phenotype of Osteoclast-like Cells from Patients with Malignant Osteopetrosis: A New Approach to Investigating Pathogenesis

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2000
    Adrienne M. Flanagan
    Abstract Osteopetrosis manifests as failure of osteoclastic bone resorption. The cause of the disease lies either in the hematopoietic lineage or in the bone marrow stromal microenvironment. It has not been possible to define the cell type involved in the various forms of the human disease because of the inability to form human osteoclasts in vitro. Using the recently described method for generating human osteoclasts from peripheral blood in coculture with rat osteoblastic UMR 106 cells, we demonstrate that a defect lies in the mature osteoclast-like cells in four cases of this disease. Control and osteopetrotic cocultures generated large numbers of osteoclast-like cells (calcitonin and vitronectin receptor positive, and F-actin ring,positive cells) with similar morphology. Bone resorption did not occur in three of the four osteopetrotic cultures. In case 1, in which bone resorption was identified, the area of resorption was negligible compared with the number of osteoclast-like cells in the culture and was detected only by scanning electron microscopy. In contrast, up to 20% of the bone surface in controls was resorbed. The normal and osteopetrotic osteoclast-like cells had a similar phenotype except that two of the osteopetrotic cases did not express CD44 and two expressed CD44 weakly, whereas CD44 was strongly expressed in the controls. This study shows that it is possible to reproduce in vitro the pathological features of human osteopetrosis, and the assay provides a means of acquiring a greater understanding of the pathogenesis of human osteopetrosis. (J Bone Miner Res 2000;15:352,360) [source]

    Not All hERG Pore Domain Mutations Have a Severe Phenotype: G584S Has an Inactivation Gating Defect with Mild Phenotype Compared to G572S, Which Has a Dominant Negative Trafficking Defect and a Severe Phenotype

    JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2009
    JING TING ZHAO Ph.D.
    Introduction: Mutations in the pore domain of the human ether-a-go-go- related gene (hERG) potassium channel are associated with higher risk of sudden death. However, in many kindreds clinical presentation is variable, making it hard to predict risk. We hypothesized that in vitro phenotyping of the intrinsic severity of individual mutations can assist with risk stratification. Methods and Results: We analyzed 2 hERG pore domain mutations, G572S and G584S. Similar to 90% of hERG missense mutations, G572S-hERG subunits did not traffic to the plasma membrane but could coassemble with WT subunits and resulted in a dominant negative suppression of hERG current density. The G584S-hERG subunits traffic normally but have abnormal inactivation gating. Computer models of human ventricular myocyte action potentials (AP), incorporating Markov models of the hERG mutants, indicate that G572S-hERG channels would cause more severe AP prolongation than that seen with G584S-hERG channels. Conclusions: hERG-G572S and -G584S are 2 pore domain mutations that involve the same change in sidechain but have very different in vitro phenotypes; G572S causes a dominant negative trafficking defect, whereas G584S is the first hERG missense mutation where the cause of disease can be exclusively attributed to enhanced inactivation. The G572S mutation is intrinsically more severe than the G584S mutation, consistent with the overall clinical presentation in the 2 small kindreds studied here. Further investigation, involving a larger number of cohorts, to test the hypothesis that in vitro phenotyping of the intrinsic severity of a given mutation will assist with risk stratification is therefore warranted. [source]

    Phenotype and chondrogenic differentiation of mesenchymal cells from adipose tissue of different species

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2009
    María José Martínez-Lorenzo
    Abstract Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several mesoderm lineages. They have been isolated from different tissues, such as bone marrow, adult peripheral blood, umbilical cord blood, and adipose tissue. The aim of this study was to analyze the differences in proliferation and phenotype of adipose tissue-derived MSCs from three different species, and to evaluate their capacity to differentiate into chondrocytes in vitro. A comparative study of cultured human, rabbit, and sheep mesenchymal cells from adipose tissue was carried out, and the main morphological parameters, proliferative activity, and expression of surface markers were characterized. Proliferation and flow cytometry data showed species-related differences between animal and human MSCs. Histological staining suggested that rabbit and sheep mesenchymal cells were able to differentiate into chondrocytic lineages. Human mesenchymal cells, though they could also differentiate, accomplished it with more difficulty than animal MSCs. These results could help to explain the differences in the chondrogenic capacity of sheep and rabbit MSCs when they are used as animal models compared to human mesenchymal cells in a clinical assay. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1499,1507, 2009 [source]

    Adipogenic Phenotype of Hepatic Stellate Cells

    ALCOHOLISM, Issue 2005
    Hide Tsukamoto
    Abstract: Transdifferentiation of hepatic stellate cells (HSC) constitutes a major cellular event in the genesis of alcoholic liver fibrosis and cirrhosis and molecular mechanisms underlying this process is incompletely understood. Our laboratory proposed several years ago that HSC quiescence requires the transcriptional program known to be integral to preadipocyte to adipocyte differentiation. In support of the hypothesis, our research demonstrates the expression of adipogenic transcription factors (C/EBPs, PPAR,, SREBP-1c, LXR,) and adipocyte-specific genes (adipsin, resistin) are high in quiescent HSC and depleted in activated HSC. Three gain-of-function approaches have been taken to test this notion: the treatment of activated HSC with the adipocyte differentiation cocktail; ectopic expression of PPAR, or SREBP-1c. All three treatments coordinately upregulate a panel of putative adipogenic transcrition factors and cause morphologic and biochemical reversal of activated HSC to quiescent cells. These findings establish a new conceptual framework for the treatment of liver fibrosis and propose an intriguing notion concerning the plasticity of HSC. [source]

    Suggestive Linkage on Chromosome 1 for a Quantitative Alcohol-Related Phenotype

    ALCOHOLISM, Issue 10 2002
    Danielle M. Dick
    Background Alcohol dependence is a clinically and etiologically heterogeneous disorder. Accordingly, a variety of subtypes of alcohol-dependent individuals have been proposed, and multiple operational definitions of alcohol use, abuse, and dependence have been used in linkage analyses directed toward detecting genes involved in alcohol use and problems. Here, we develop quantitative phenotypes that characterize drinking patterns among both alcoholic and nonalcoholic subjects, and use these phenotypes in subsequent linkage analyses. Methods More than 9000 individuals from alcoholic and control families were administered a semistructured interview and personality questionnaire as part of the initial stage of the Collaborative Study on the Genetics of Alcoholism (COGA). A principal component analysis was conducted on items that captured many of the dimensions of drinking and related behaviors, including aspects of alcohol use, antisocial behavior and affective disturbance when drinking, and personality. Factor scores were computed for all individuals. Nonparametric linkage analyses were conducted on these factor scores, in the initial COGA sample consisting of 987 individuals from 105 extended families, and in a replication sample consisting of 1295 individuals from 157 extended families. Results Three factors were identified, accounting for 68% of the total variance. The most promising regions of linkage appeared for factor 2, on which higher scores indicate a later age of onset of regular drinking and higher harm avoidance. Chromosome 1 yielded consistent evidence of linkage in both samples, with a maximum lod score of 3.3 when the samples were combined for analysis. Consistent suggestion of linkage also was found to chromosome 15. Conclusions Developing novel phenotypes that more accurately model the effect of influential genes may help efforts to detect genes involved in complex disorders. Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage. [source]

    Phenotype of severe hemophilia A and plasma levels of risk factors for thrombosis

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2007
    K. VAN DIJK
    [source]

    Prevalence of Unilateral and Bilateral Deafness in Border Collies and Association with Phenotype

    JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2006
    Simon Platt
    Background:Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. Hypothesis:Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. Animals:A total of 2597 Border Collies from the United Kingdom. Methods:A retrospective study of Border Collies tested, during 1994,2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. Results:The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P= .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P= .007), after adjustment for phenotypic attributes. Conclusions and Clinical Importance: Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease. [source]

    Influence of a Self-Assembling Peptide, RADA16, Compared with Collagen I and Matrigel on the Malignant Phenotype of Human Breast-Cancer Cells in 3D Cultures and in vivo

    MACROMOLECULAR BIOSCIENCE, Issue 5 2009
    Kun Mi
    Abstract Cancer-cell phenotype is not only the result of malignant progression, but also dependent on the microenvironment surrounding them, including influences from the extracellular matrix and its structural properties. We have investigated the influence of the nanofiber matrix of the self-assembling peptide, RADA16, in comparison with collagen I and Matrigel on the malignant phenotype of the human breast-cancer cell, MDA-MB-231, in 3D cultures, including the morphology, survival, proliferation rate, migration potential and the effect of these matrices on the malignancy of the cancer cells in vivo. Our data indicate that these tumor cells change their morphology in response to the different 3D matrix in vitro cultures and the RADA16 self-assembling peptide scaffold mimics an extracellular matrix and could effectively reduce the malignant phenotype of the tumor cells in vitro and in vivo. [source]

    Clinical feature profile of spinocerebellar ataxia type 1,8 predicts genetically defined subtypes

    MOVEMENT DISORDERS, Issue 11 2005
    Matthias Maschke MD
    Abstract An increasing number of genetically defined types of spinocerebellar ataxia (SCA) have been reported in the past decade. Phenotype,genotype correlation studies have suggested a broad overlap between SCA types. The aim of the present study was to identify patterns of clinical features that were likely to distinguish between SCA types and to test the specificity and sensitivity of these signs and symptoms using a Bayesian classifier. In total, 127 patients from 50 families with SCA types 1 to 8 were examined using a worksheet with a panel of 33 symptoms and signs. By computing the probabilities of each trait for each SCA type, we rated the predictive value of each feature for each form of ataxia and then combined the probabilities for the entire panel of traits to construct a Bayesian classifier. Results of this analysis were summarized in a simpler, more operator-based algorithm. Patients with SCA5, SCA6, and SCA8 demonstrated a predominant cerebellar syndrome, whereas patients with SCA1, SCA2, SCA3, SCA4, and SCA7 frequently had clinical features indicating an extracerebellar involvement. The Bayesian classifier predicted the SCA type in 78% of patients with sensitivities between 60 and 100% and specificities between 94 and 98.2%. The highest sensitivity to correctly predict the true SCA type was found for SCA5, SCA7, and SCA8. Sensitivities and specificities found in the present study validate the use of algorithms to help to prioritize specific SCA gene testing, which will help to reduce costs for gene testing. © 2005 Movement Disorder Society [source]

    Phenotype and genotype of Dent's disease in three Chinese boys

    NEPHROLOGY, Issue 2 2009
    PENG LI
    SUMMARY Aim: Dent's disease represents a group of hereditary renal tubular disorders mainly characterized by hypercalciuria, nephrocalcinosis and low molecular weight proteinuria. The majority of patients with Dent's disease were found to carry CLCN5 gene mutations, whereas a small fraction of patients carry OCRL1 gene mutations. Up to date, over 100 patients with Dent's disease have been reported to carry CLCN5 gene mutations, but none in Chinese patients. The purpose of this study was to investigate the phenotypes and genotypes of three Chinese boys with Dent's disease. Methods: Three patients from three unrelated families were studied. Genomic DNA was extracted from peripheral white blood cells using a simple salting out procedure after informed consent. Thirteen pairs of primers were used to amplify all coding exons and exon,intron boundaries of the CLCN5 gene by polymerase chain reaction (PCR). All PCR products were sequenced directly on an autosequencer. Results: Low molecular weight proteinuria and hypercalciuria were found in all patients, nephrocalcinosis in two patients and hypophosphataemia in two patients. Three mutations of the CLCN5 gene were revealed, including R467X, L594fsX595 and R637X. Each mutation was inherited from maternal DNA, respectively. The mutation L594fsX595 was never reported before. Conclusion: Low molecular weight proteinuria and hypercalciuria were the main clinical features of the three Chinese boys with Dent's disease. Our study was the first to demonstrate CLCN5 gene mutations in Chinese patients with Dent's disease and we reported a novel mutation. [source]

    Subtyping of Bacterial Foodborne Pathogens

    NUTRITION REVIEWS, Issue 7 2002
    Martin Wiedmann D.V.M. Ph.D.
    Phenotype-based and DNA-based subtyping methods allow for differentiation of bacterial isolates beyond the species and subspecies level. Bacterial subtyping methods not only have improved our ability to detect and track foodborne disease outbreaks, but also represent tools to track sources of bacterial contamination throughout the food system. The use of subtyping methods furthermore provides an opportunity to better understand the population genetics, epidemiology, and ecology of different foodborne pathogens. The last 5 years have seen tremendous advancement in the development of sensitive, rapid, automated, and increasingly easy-to-use molecular subtyping methods for a variety of different bacterial foodborne pathogens. This review will highlight key aspects of different subtyping methods for bacterial foodborne pathogens and provide examples of their applications in public health, food safety, epidemiology, and population genetics. Molecular subtyping and characterization methods may also facilitate the development of a novel framework for tracking, preventing, and regulating foodborne bacterial diseases, which is based on evolutionary relationships and genetic characteristics rather than traditional species definitions. [source]

    Androgens and Male Predominance of the Brugada Syndrome Phenotype

    PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7p1 2003
    CHARLES ANTZELEVITCH
    No abstract is available for this article. [source]