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Sample records for abnormal gene dosage

  1. Gene dosage methods as diagnostic tools for the identification of chromosome abnormalities.

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    Gouas, L; Goumy, C; Véronèse, L; Tchirkov, A; Vago, P

    2008-09-01

    Cytogenetics is the part of genetics that deals with chromosomes, particularly with numerical and structural chromosome abnormalities, and their implications in congenital or acquired genetic disorders. Standard karyotyping, successfully used for the last 50 years in investigating the chromosome etiology in patients with infertility, fetal abnormalities and congenital disorders, is constrained by the limits of microscopic resolution and is not suited for the detection of subtle chromosome abnormalities. The ability to detect submicroscopic chromosomal rearrangements that lead to copy-number changes has escalated progressively in recent years with the advent of molecular cytogenetic techniques. Here, we review various gene dosage methods such as FISH, PCR-based approaches (MLPA, QF-PCR, QMPSF and real time PCR), CGH and array-CGH, that can be used for the identification and delineation of copy-number changes for diagnostic purposes. Besides comparing their relative strength and weakness, we will discuss the impact that these detection methods have on our understanding of copy number variations in the human genome and their implications in genetic counseling. PMID:18513889

  2. Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.

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    Marine Douaud

    Full Text Available Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans.

  3. Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.

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    Douaud, Marine; Feve, Katia; Pituello, Fabienne; Gourichon, David; Boitard, Simon; Leguern, Eric; Coquerelle, Gérard; Vieaud, Agathe; Batini, Cesira; Naquet, Robert; Vignal, Alain; Tixier-Boichard, Michèle; Pitel, Frédérique

    2011-01-01

    Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans. PMID:22046416

  4. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  5. Gene expression dosage regulation in an allopolyploid fish.

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    I Matos

    Full Text Available How allopolyploids are able not only to cope but profit from their condition is a question that remains elusive, but is of great importance within the context of successful allopolyploid evolution. One outstanding example of successful allopolyploidy is the endemic Iberian cyprinid Squalius alburnoides. Previously, based on the evaluation of a few genes, it was reported that the transcription levels between diploid and triploid S. alburnoides were similar. If this phenomenon occurs on a full genomic scale, a wide functional ''diploidization'' could be related to the success of these polyploids. We generated RNA-seq data from whole juvenile fish and from adult livers, to perform the first comparative quantitative transcriptomic analysis between diploid and triploid individuals of a vertebrate allopolyploid. Together with an assay to estimate relative expression per cell, it was possible to infer the relative sizes of transcriptomes. This showed that diploid and triploid S. alburnoides hybrids have similar liver transcriptome sizes. This in turn made it valid to directly compare the S. alburnoides RNA-seq transcript data sets and obtain a profile of dosage responses across the S. alburnoides transcriptome. We found that 64% of transcripts in juveniles' samples and 44% in liver samples differed less than twofold between diploid and triploid hybrids (similar expression. Yet, respectively 29% and 15% of transcripts presented accurate dosage compensation (PAA/PA expression ratio of 1 instead of 1.5. Therefore, an exact functional diploidization of the triploid genome does not occur, but a significant down regulation of gene expression in triploids was observed. However, for those genes with similar expression levels between diploids and triploids, expression is not globally strictly proportional to gene dosage nor is it set to a perfect diploid level. This quantitative expression flexibility may be a strong contributor to overcome the genomic shock

  6. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method.

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    Makanae, Koji; Kintaka, Reiko; Makino, Takashi; Kitano, Hiroaki; Moriya, Hisao

    2013-02-01

    Gene overexpression beyond a permissible limit causes defects in cellular functions. However, the permissible limits of most genes are unclear. Previously, we developed a genetic method designated genetic tug-of-war (gTOW) to measure the copy number limit of overexpression of a target gene. In the current study, we applied gTOW to the analysis of all protein-coding genes in the budding yeast Saccharomyces cerevisiae. We showed that the yeast cellular system was robust against an increase in the copy number by up to 100 copies in >80% of the genes. After frameshift and segmentation analyses, we isolated 115 dosage-sensitive genes (DSGs) with copy number limits of 10 or less. DSGs contained a significant number of genes involved in cytoskeletal organization and intracellular transport. DSGs tended to be highly expressed and to encode protein complex members. We demonstrated that the protein burden caused the dosage sensitivity of highly expressed genes using a gTOW experiment in which the open reading frame was replaced with GFP. Dosage sensitivities of some DSGs were rescued by the simultaneous increase in the copy numbers of partner genes, indicating that stoichiometric imbalances among complexes cause dosage sensitivity. The results obtained in this study will provide basic knowledge about the physiology of chromosomal abnormalities and the evolution of chromosomal composition. PMID:23275495

  7. Noise reduction facilitated by dosage compensation in gene networks

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    Peng, Weilin; Song, Ruijie; Acar, Murat

    2016-01-01

    Genetic noise together with genome duplication and volume changes during cell cycle are significant contributors to cell-to-cell heterogeneity. How can cells buffer the effects of these unavoidable epigenetic and genetic variations on phenotypes that are sensitive to such variations? Here we show that a simple network motif that is essential for network-dosage compensation can reduce the effects of extrinsic noise on the network output. Using natural and synthetic gene networks with and without the network motif, we measure gene network activity in single yeast cells and find that the activity of the compensated network is significantly lower in noise compared with the non-compensated network. A mathematical analysis provides intuitive insights into these results and a novel stochastic model tracking cell-volume and cell-cycle predicts the experimental results. Our work implies that noise is a selectable trait tunable by evolution. PMID:27694830

  8. The importance of MDR1 gene polymorphisms for tacrolimus dosage.

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    Kravljaca, Milica; Perovic, Vladimir; Pravica, Vera; Brkovic, Voin; Milinkovic, Marija; Lausevic, Mirjana; Naumovic, Radomir

    2016-02-15

    Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation. PMID:26705892

  9. Dosage effects of Waxy gene on the structures and properties of corn starch.

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    Yangcheng, Hanyu; Blanco, Michael; Gardner, Candice; Li, Xuehong; Jane, Jay-Lin

    2016-09-20

    The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DPstarch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch. PMID:27261752

  10. Subfunctionalization reduces the fitness cost of gene duplication in humans by buffering dosage imbalances

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    Fernández Ariel

    2011-12-01

    Full Text Available Abstract Background Driven essentially by random genetic drift, subfunctionalization has been identified as a possible non-adaptive mechanism for the retention of duplicate genes in small-population species, where widespread deleterious mutations are likely to cause complementary loss of subfunctions across gene copies. Through subfunctionalization, duplicates become indispensable to maintain the functional requirements of the ancestral locus. Yet, gene duplication produces a dosage imbalance in the encoded proteins and thus, as investigated in this paper, subfunctionalization must be subject to the selective forces arising from the fitness bottleneck introduced by the duplication event. Results We show that, while arising from random drift, subfunctionalization must be inescapably subject to selective forces, since the diversification of expression patterns across paralogs mitigates duplication-related dosage imbalances in the concentrations of encoded proteins. Dosage imbalance effects become paramount when proteins rely on obligatory associations to maintain their structural integrity, and are expected to be weaker when protein complexation is ephemeral or adventitious. To establish the buffering effect of subfunctionalization on selection pressure, we determine the packing quality of encoded proteins, an established indicator of dosage sensitivity, and correlate this parameter with the extent of paralog segregation in humans, using species with larger population -and more efficient selection- as controls. Conclusions Recognizing the role of subfunctionalization as a dosage-imbalance buffer in gene duplication events enabled us to reconcile its mechanistic nonadaptive origin with its adaptive role as an enabler of the evolution of genetic redundancy. This constructive role was established in this paper by proving the following assertion: If subfunctionalization is indeed adaptive, its effect on paralog segregation should scale with the dosage

  11. Exon dosage analysis of parkin gene in Chinese sporadic Parkinson's disease.

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    Guo, Ji-Feng; Dong, Xiao-Li; Xu, Qian; Li, Nan; Yan, Xin-Xiang; Xia, Kun; Tang, Bei-Sha

    2015-09-14

    Parkin gene mutations are by far the most common mutations in both familial Parkinson's disease (PD) and sporadic PD. Approximately, 50% of parkin mutations is exon dosage mutations (i.e., deletions and duplications of entire exons). Here, we first established a MLPA assay for quick detection of parkin exon rearrangements. Then, we studied parkin exon dosage mutations in 755 Chinese sporadic PDdisease patients using the established MLPA assay. We found that there were 25 (3.3%) patients with exon dosage alterations including deletions and duplications, 20 (11.4%) patients with exon rearrangements in 178 early-onset patients, and 5 (0.86%) patients with exon rearrangement mutations in 579 later-onset patients. The percentage of individuals with parkin dosage mutations is more than 33% when the age at onset is less than 30 years old, but less than 7% when the age at onset is more than 30. In these mutations, deletion is the main mutational style, especially in exon 2-5. Our results indicated that exon dosage mutations in parkin gene might be the main cause for sporadic PD, especially in EOP. PMID:26240990

  12. Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes.

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    Thompson, Ammon; Zakon, Harold H; Kirkpatrick, Mark

    2016-02-01

    Dosage-balance selection preserves functionally redundant duplicates (paralogs) at the optimum for their combined expression. Here we present a model of the dynamics of duplicate genes coevolving under dosage-balance selection. We call this the compensatory drift model. Results show that even when strong dosage-balance selection constrains total expression to the optimum, expression of each duplicate can diverge by drift from its original level. The rate of divergence slows as the strength of stabilizing selection, the size of the mutation effect, and/or the size of the population increases. We show that dosage-balance selection impedes neofunctionalization early after duplication but can later facilitate it. We fit this model to data from sodium channel duplicates in 10 families of teleost fish; these include two convergent lineages of electric fish in which one of the duplicates neofunctionalized. Using the model, we estimated the strength of dosage-balance selection for these genes. The results indicate that functionally redundant paralogs still may undergo radical functional changes after a prolonged period of compensatory drift.

  13. Importance of gene dosage in controlling dendritic arbor formation during development.

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    Copf, Tijana

    2015-09-01

    Proper dendrite morphology is crucial for normal nervous system functioning. While a number of genes have been implicated in dendrite morphogenesis in both invertebrates and mammals, it remains unclear how developing dendrites respond to changes in gene dosage and what type of patterns their responses may follow. To understand this, I review here evidence from the recent literature, focusing on the genetic studies performed in the Drosophila larval dendritic arborization class IV neuron, an excellent cell type to understand dendrite morphogenesis. I summarize how class IV arbors change morphology in response to developmental fluctuations in the expression levels of 47 genes, studied by means of genetic manipulations such as loss-of-function and gain-of-function, and for which sufficient information is available. I find that arbors can respond to changing gene dosage in several distinct ways, each characterized by a singular dose-response curve. Interestingly, in 72% of cases arbors are sensitive, and thus adjust their morphology, in response to both decreases and increases in the expression of a given gene, indicating that dendrite morphogenesis is a process particularly sensitive to gene dosage. By summarizing the parallels between Drosophila and mammals, I show that many Drosophila dendrite morphogenesis genes have orthologs in mammals, and that some of these are associated with mammalian dendrite outgrowth and human neurodevelopmental disorders. One notable disease-related molecule is kinase Dyrk1A, thought to be a causative factor in Down syndrome. Both increases and decreases in Dyrk1A gene dosage lead to impaired dendrite morphogenesis, which may contribute to Down syndrome pathoetiology. PMID:26108333

  14. Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos

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    Mathur Sachin

    2010-01-01

    Full Text Available Abstract Background Considerable progress has been made in our understanding of sex determination and dosage compensation mechanisms in model organisms such as C. elegans, Drosophila and M. musculus. Strikingly, the mechanism involved in sex determination and dosage compensation are very different among these three model organisms. Birds present yet another situation where the heterogametic sex is the female. Sex determination is still poorly understood in birds and few key determinants have so far been identified. In contrast to most other species, dosage compensation of bird sex chromosomal genes appears rather ineffective. Results By comparing microarrays from microdissected primitive streak from single chicken embryos, we identified a large number of genes differentially expressed between male and female embryos at a very early stage (Hamburger and Hamilton stage 4, long before any sexual differentiation occurs. Most of these genes are located on the Z chromosome, which indicates that dosage compensation is ineffective in early chicken embryos. Gene ontology analyses, using an enhanced annotation tool for Affymetrix probesets of the chicken genome developed in our laboratory (called Manteia, show that among these male-biased genes found on the Z chromosome, more than 20 genes play a role in sex differentiation. Conclusions These results corroborate previous studies demonstrating the rather inefficient dosage compensation for Z chromosome in birds and show that this sexual dimorphism in gene regulation is observed long before the onset of sexual differentiation. These data also suggest a potential role of non-compensated Z-linked genes in somatic sex differentiation in birds.

  15. Rapid optimization of gene dosage in E. coli using DIAL strains

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    Cheung Sherine

    2011-07-01

    Full Text Available Abstract Background Engineers frequently vary design parameters to optimize the behaviour of a system. However, synthetic biologists lack the tools to rapidly explore a critical design parameter, gene expression level, and have no means of systematically varying the dosage of an entire genetic circuit. As a step toward overcoming this shortfall, we have developed a technology that enables the same plasmid to be maintained at different copy numbers in a set of closely related cells. This provides a rapid method for exploring gene or cassette dosage effects. Results We engineered two sets of strains to constitutively provide a trans-acting replication factor, either Pi of the R6K plasmid or RepA of the ColE2 plasmid, at different doses. Each DIAL (different allele strain supports the replication of a corresponding plasmid at a constant level between 1 and 250 copies per cell. The plasmids exhibit cell-to-cell variability comparable to other popular replicons, but with improved stability. Since the origins are orthogonal, both replication factors can be incorporated into the same cell. We demonstrate the utility of these strains by rapidly assessing the optimal expression level of a model biosynthetic pathway for violecein. Conclusions The DIAL strains can rapidly optimize single gene expression levels, help balance expression of functionally coupled genetic elements, improve investigation of gene and circuit dosage effects, and enable faster development of metabolic pathways.

  16. Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes

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    Teichert, M.; Eijgelsheim, M.; Uitterlinden, A.G.; Buhre, P.N.; Hofman, A.; Smet, P.A. de; Visser, L.E.; Stricker, B.H.C.

    2011-01-01

    BACKGROUND: Genome-wide association studies (GWAS) on warfarin and acenocoumarol showed that interindividual dosage variation is mainly associated with single nucleotide polymorphisms (SNPs) in VKORC1 and to a lesser extent in CYP2C9 and CYP4F2. For phenprocoumon dosage, the genes encoding CYP3A4 an

  17. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.

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    Duffy, Supipi; Fam, Hok Khim; Wang, Yi Kan; Styles, Erin B; Kim, Jung-Hyun; Ang, J Sidney; Singh, Tejomayee; Larionov, Vladimir; Shah, Sohrab P; Andrews, Brenda; Boerkoel, Cornelius F; Hieter, Philip

    2016-09-01

    Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1 Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID:27551064

  18. [Cytogenetic abnormalities and gene mutations in myeloid leukemia].

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    Kato, Naoko; Kitamura, Toshio

    2009-10-01

    Myeloid leukemia is a clinically and genetically heterogeneous disease. Cytogenetic studies have revealed specific chromosomal abnormalities, such as translocations, and inversions. Fusion proteins derived from these abnormalities were identified in various subtypes of leukemia. Because most of these fusion proteins were not sufficient to induce leukemia by themselves in mouse models, additional oncogenic events have been thought to be necessary for leukemogenesis. Recently, a hypothesis called "two-hit model" for leukemia has been proposed. Two broad classes of mutations that proliferative or survival advantage of hematopoietic progenitors and impaired differentiation are required for inducing leukemia. In this article, we summarize some typical chromosomal abnormalities or gene mutations associated with myeloid leukemia on the basis of this hypothesis.

  19. Analysis of SRY Gene in 8 Cases of Sex Abnormality

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    王慧; 腾云; 田虹; 陈燕; 杨真荣; 唐艳平

    2004-01-01

    In order to investigate the relationship between sex dysplasia and sex-determining region Y (SRY) gene, 8 patients with sexual abnormality were analyzed by cytogenetic and molecular genetic methods. Fluorescence in situ hybridization (FISH) using PY3.4, X alpha satellite, and SRY probes was performed in each case to analyze the sex chromosome translocation and gene translocation. SRY gene was amplified by polymerase chain reaction (PCR) and its mutation was detected by direct sequencing. The results showed that among 8 patients, 5 were positive for SRY and the remaining negative for SRY. In the patients positive for SRY genes, 3 presented testes and the left 2streak ovaries. In the patients negative for SRY, only one case presented testes, while 2 ovaries.Direct sequencing demonstrated that all SRY genes were normal in the patients positive for SRY genes. FISH technique demonstrated that SRY genes translocated from Ypter to Xpter in 2 46,XX phenotypic males positive for SRY genes. It was concluded that SRY gene is strongly involved in.male sex determination, while a sequence of other genes may be taken into account in sexual development.

  20. Gene dosage imbalance during DNA replication controls bacterial cell-fate decision

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    Igoshin, Oleg

    Genes encoding proteins in a common regulatory network are frequently located close to one another on the chromosome to facilitate co-regulation or couple gene expression to growth rate. Contrasting with these observations, here we demonstrate a functional role for the arrangement of Bacillus subtilis sporulation network genes on opposite sides of the chromosome. We show that the arrangement of two sporulation network genes, one located close to the origin, the other close to the terminus leads to a transient gene dosage imbalance during chromosome replication. This imbalance is detected by the sporulation network to produce cell-cycle coordinated pulses of the sporulation master regulator Spo0A~P. This pulsed response allows cells to decide between sporulation and continued vegetative growth during each cell-cycle spent in starvation. Furthermore, changes in DNA replication and cell-cycle parameters with decreased growth rate in starvation conditions enable cells to indirectly detect starvation without the need for evaluating specific metabolites. The simplicity of the uncovered coordination mechanism and starvation sensing suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings. This work is supported by National Science Foundation Grants MCB-1244135, EAGER-1450867, MCB-1244423, NIH NIGMS Grant R01 GM088428 and HHMI International Student Fellowship.

  1. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans.

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    Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

    2016-09-01

    Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function.

  2. Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice

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    Donald R. Love

    2013-03-01

    Full Text Available The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.

  3. Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage.

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    Souchet, Benoit; Guedj, Fayçal; Sahún, Ignasi; Duchon, Arnaud; Daubigney, Fabrice; Badel, Anne; Yanagawa, Yuchio; Barallobre, Maria Jose; Dierssen, Mara; Yu, Eugene; Herault, Yann; Arbones, Mariona; Janel, Nathalie; Créau, Nicole; Delabar, Jean Maurice

    2014-09-01

    Cognitive deficits in Down syndrome (DS) have been linked to increased synaptic inhibition, leading to an imbalance of excitation/inhibition (E/I). Various mouse models and studies from human brains have implicated an HSA21 gene, the serine/threonine kinase DYRK1A, as a candidate for inducing cognitive dysfunction. Here, consequences of alterations in Dyrk1a dosage were assessed in mouse models with varying copy numbers of Dyrk1a: mBACtgDyrk1a, Ts65Dn and Dp(16)1Yey (with 3 gene copies) and Dyrk1a(+/-) (one functional copy). Molecular (i.e. immunoblotting/immunohistochemistry) and behavioral analyses (e.g., rotarod, Morris water maze, Y-maze) were performed in mBACtgDyrk1a mice. Increased expression of DYRK1A in mBACtgDyrk1a induced molecular alterations in synaptic plasticity pathways, particularly expression changes in GABAergic and glutaminergic related proteins. Similar alterations were observed in models with partial trisomy of MMU16, Ts65Dn and Dp(16)1Yey, and were reversed in the Dyrk1a(+/-) model. Dyrk1a overexpression produced an increased number and signal intensity of GAD67 positive neurons, indicating enhanced inhibition pathways in three different models: mBACtgDyrk1a, hYACtgDyrk1a and Dp(16)1Yey. Functionally, Dyrk1a overexpression protected mice from PTZ-induced seizures related to GABAergic neuron plasticity. Our study shows that DYRK1A overexpression affects pathways involved in synaptogenesis and synaptic plasticity and influences E/I balance toward inhibition. Inhibition of DYRK1A activity offers a therapeutic target for DS, but its inhibition/activation may also be relevant for other psychiatric diseases with E/I balance alterations.

  4. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

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    Zodwa Dlamini

    2015-11-01

    Full Text Available Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.

  5. Direct evaluation of the effect of gene dosage on secretion of protein from yeast Pichia pastoris by expressing EGFP.

    Science.gov (United States)

    Liu, Hailong; Qin, Yufeng; Huang, Yuankai; Chen, Yaosheng; Cong, Peiqing; He, Zuyong

    2014-02-28

    Increasing the gene copy number has been commonly used to enhance the protein expression level in the yeast Pichia pastoris. However, this method has been shown to be effective up to a certain gene copy number, and a further increase of gene dosage can result in a decrease of expression level. Evidences indicate the gene dosage effect is product-dependent, which needs to be determined when expressing a new protein. Here, we describe a direct detection of the gene dosage effect on protein secretion through expressing the enhanced green fluorescent protein (EGFP) gene under the direction of the α-factor preprosequence in a panel of yeast clones carrying increasing copies of the EGFP gene (from one to six copies). Directly examined under fluorescence microscopy, we found relatively lower levels of EGFP were secreted into the culture medium at one copy and two copies, substantial improvement of secretion appeared at three copies, plateau happened at four and five copies, and an apparent decrease of secretion happened at six copies. The secretion of EGFP being limiting at four and five copies was due to abundant intracellular accumulation of proteins, observed from the fluorescence image of yeast and confirmed by western blotting, which significantly activated the unfolded protein response indicated by the up-regulation of the BiP (the KAR2 gene product) and the protein disulfide isomerase. This study implies that tagging a reporter like GFP to a specific protein would facilitate a direct and rapid determination of the optimal gene copy number for high-yield expression. PMID:24225373

  6. Perk gene dosage regulates glucose homeostasis by modulating pancreatic β-cell functions.

    Directory of Open Access Journals (Sweden)

    Rong Wang

    Full Text Available Insulin synthesis and cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in either aspect leads to development of diabetes. PERK (EIF2AK3 loss of function mutations in humans and mice exhibit permanent neonatal diabetes that is characterized by insufficient β-cell mass and reduced proinsulin trafficking and insulin secretion. Unexpectedly, we found that Perk heterozygous mice displayed lower blood glucose levels.Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. In addition, modulation of Perk dosage specifically in β-cells showed that the glucose homeostasis phenotype of Perk heterozygous mice is determined by reduced expression of PERK in the β-cells.We found that Perk heterozygous mice first exhibited enhanced insulin synthesis and secretion during neonatal and juvenile development followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These differences are not likely to entail the well-known function of PERK to regulate the ER stress response in cultured cells as several markers for ER stress were not differentially expressed in Perk heterozygous mice.In addition to the essential functions of PERK in β-cells as revealed by severely diabetic phenotype in humans and mice completely deficient for PERK, reducing Perk gene expression by half showed that intermediate levels of PERK have a profound impact on β-cell functions and glucose homeostasis. These results suggest that an optimal level of PERK expression is necessary to balance several parameters of β-cell function and growth in order to achieve normoglycemia.

  7. Gene dosage as a relevant mechanism contributing to the determination of ovarian function in Turner syndrome

    Science.gov (United States)

    Castronovo, Chiara; Rossetti, Raffaella; Rusconi, Daniela; Recalcati, Maria P.; Cacciatore, Chiara; Beccaria, Elena; Calcaterra, Valeria; Invernizzi, Pietro; Larizza, Daniela; Finelli, Palma; Persani, Luca

    2014-01-01

    array-CGH analysis and confirmed by real-time quantitative PCR, including a BMP15 gene duplication at Xp11.22, a deletion interrupting the PAPPA gene at 9q33.1, and an intragenic duplication involving the PDE8A gene at 15q25.3. LIMITATIONS, REASONS FOR CAUTION This is a pilot study on a relatively small sample size and confirmation in larger TS cohorts may be required. The ovarian tissue could not be studied in any patients and in a subgroup of patients, the mosaicism was estimated in tissues of different embryonic origin. WIDER IMPLICATIONS OF THE FINDINGS The combined determination of X chromosome mosaicism by molecular and molecular-cytogenetic techniques may become useful for the prediction of SM in TS. The detection of CNVs in both X-linked and autosomal ovary-related genes further suggests gene dosage as a relevant mechanism contributing to the ovarian phenotype of TS patients. These CNVs may pinpoint novel candidates relevant to female fertility and generate further insights into the mechanisms contributing to ovarian function. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Telethon Foundation (grant no: GGP09126 to L.P.), the Italian Ministry of the University and Research (grant number: 2006065999 to P.F.) and a Ministry of Health grant ‘Ricerca Corrente’ to IRCCS Istituto Auxologico Italiano (grant number: 08C704-2006). The authors have no conflict of interest to declare. PMID:24324027

  8. Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities

    Directory of Open Access Journals (Sweden)

    Panos eRoussos

    2014-01-01

    Full Text Available Given that the genetic risk for schizophrenia is highly polygenic and the effect sizes, even for rare or de novo events, are modest at best, it has been suggested that multiple biological pathways are likely to be involved in the etiopathogenesis of the disease. Most efforts in understanding the cellular basis of schizophrenia have followed a neuron-centric approach, focusing on alterations in neurotransmitter systems and synapse cytoarchitecture. However, multiple lines of evidence coming from genetics and systems biology approaches suggest that apart from neurons, oligodendrocytes and potentially other glia are affected from schizophrenia risk loci. Neurobiological abnormalities linked with genetic association signal could identify abnormalities that are more likely to be primary, versus environmentally-induced changes or downstream events. Here, we summarize genetic data that support the involvement of oligodendrocytes in schizophrenia, providing additional evidence for a causal role with the disease. Given the undeniable evidence of both neuronal and glial abnormalities in schizophrenia, we propose a neuro-glial model that invokes abnormalities at the node of Ranvier as a functional unit in the etiopathogenesis of the disease.

  9. The structure and expression of normal and abnormal globin genes

    NARCIS (Netherlands)

    Bernards, R.A.; Flavell, R.A.; Grosveld, G.C.; Grosveld, F.G.; Kooter, J.M.; Boer, E. de

    1979-01-01

    Most mammalian genes are present as a single copy per haploid genome and hence comprise only about one part in 10⁶ of the total nuclear DNA. This fact impeded work on single-copy genes, but recently recombinant DNA technology and sensitive gene mapping has led to the elucidation of the structure of

  10. Effects of aberrant Pax6 gene dosage on mouse corneal pathophysiology and corneal epithelial homeostasis.

    Directory of Open Access Journals (Sweden)

    Richard L Mort

    Full Text Available Altered dosage of the transcription factor PAX6 causes multiple human eye pathophysiologies. PAX6⁺/⁻ heterozygotes suffer from aniridia and aniridia-related keratopathy (ARK, a corneal deterioration that probably involves a limbal epithelial stem cell (LESC deficiency. Heterozygous Pax6(+/Sey-Neu (Pax6⁺/⁻ mice recapitulate the human disease and are a good model of ARK. Corneal pathologies also occur in other mouse Pax6 mutants and in PAX77(Tg/- transgenics, which over-express Pax6 and model human PAX6 duplication.We used electron microscopy to investigate ocular defects in Pax6⁺/⁻ heterozygotes (low Pax6 levels and PAX77(Tg/- transgenics (high Pax6 levels. As well as the well-documented epithelial defects, aberrant Pax6 dosage had profound effects on the corneal stroma and endothelium in both genotypes, including cellular vacuolation, similar to that reported for human macular corneal dystrophy. We used mosaic expression of an X-linked LacZ transgene in X-inactivation mosaic female (XLacZ(Tg/- mice to investigate corneal epithelial maintenance by LESC clones in Pax6⁺/⁻ and PAX77(Tg/- mosaic mice. PAX77(Tg/- mosaics, over-expressing Pax6, produced normal corneal epithelial radial striped patterns (despite other corneal defects, suggesting that centripetal cell movement was unaffected. Moderately disrupted patterns in Pax6⁺/⁻ mosaics were corrected by introducing the PAX77 transgene (in Pax6⁺/⁻, PAX77(Tg/- mosaics. Pax6(Leca4/+, XLacZ(Tg/- mosaic mice (heterozygous for the Pax6(Leca4 missense mutation showed more severely disrupted mosaic patterns. Corrected corneal epithelial stripe numbers (an indirect estimate of active LESC clone numbers declined with age (between 15 and 30 weeks in wild-type XLacZ(Tg/- mosaics. In contrast, corrected stripe numbers were already low at 15 weeks in Pax6⁺/⁻ and PAX77(Tg/- mosaic corneas, suggesting Pax6 under- and over-expression both affect LESC clones.Pax6⁺/⁻ and PAX77(Tg

  11. Linezolid Resistance in Staphylococcus aureus: Gene Dosage Effect, Stability, Fitness Costs, and Cross-Resistances▿

    OpenAIRE

    Besier, Silke; Ludwig, Albrecht; Zander, Johannes; Brade, Volker; Wichelhaus, Thomas A.

    2008-01-01

    Linezolid resistance in Staphylococcus aureus is typically associated with mutations in the 23S rRNA gene. Here we show that the accumulation of a single point mutation, G2576T, in the different copies of this gene causes stepwise increases in resistance, impairment of the biological fitness, and cross-resistance to quinupristin-dalfopristin and chloramphenicol.

  12. Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome.

    Science.gov (United States)

    Scarisbrick, Julia J; Woolford, Alison J; Calonje, Eduardo; Photiou, Andrew; Ferreira, Sylvia; Orchard, Guy; Russell-Jones, Robin; Whittaker, Sean J

    2002-03-01

    There are few data on the molecular pathogenesis of cutaneous T cell lymphomas. A recent allelotyping study by our group identified frequent allelic loss on 9p, 10q, and 17p including losses on 9p21 in 16% of patients with mycosis fungoides and 46% with Sezary syndrome. The P15 and P16 genes are intricately linked on 9p21 and can be inactivated in melanoma and non-Hodgkin's lymphoma. We have therefore studied 76 patients with either mycosis fungoides or Sezary syndrome for abnormalities of these genes. DNA samples were analyzed for loss of heterozygosity, homozygous deletion, intragenic mutations, and promoter methylation. In addition P15 and P16 protein expression was assessed. Microsatellite analysis was informative in 73 of 76 cases: allelic loss on 9p21 was identified in 18 patients (25%), including 12 of 57 with mycosis fungoides (21%) and six of 16 with Sezary syndrome (37%). Single strand conformation polymorphism analysis of the entire coding regions of both genes did not identify any mutations, although two polymorphisms were identified including C613A, which has not previously been described. P15 and P16 gene promoter methylation was found in 45% and 29% of patients, respectively. Furthermore aberrant P15 protein expression was detected in 85% of patients analyzed with P15 gene abnormalities and abnormal P16 expression in 59% with P16 gene abnormalities. These abnormalities were not dependent on cutaneous stage of disease. This study suggests that abnormalities of the P15 and P16 genes are common in both early and advanced stages of mycosis fungoides and Sezary syndrome and that these genes may be inactivated by allelic loss and aberrant promoter methylation.

  13. Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Nielsen, Mette Gilling

    Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...

  14. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation. PMID:27631008

  15. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  16. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  17. Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

    DEFF Research Database (Denmark)

    Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

    2009-01-01

    Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named...

  18. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy

    NARCIS (Netherlands)

    Friedman, J. I.; Vrijenhoek, T.; Markx, S.; Janssen, I. M.; Van der Vliet, W. A.; Faas, B. H. W.; Knoers, N. V.; Cahn, W.; Kahn, R. S.; Edelmann, L.; Davis, K. L.; Silverman, J. M.; Brunner, H. G.; Van Kessel, A. Geurts; Wijmenga, C.; Ophoff, R. A.; Veltman, J. A.

    2008-01-01

    A homozygous mutation of the CNTNAP2 gene has been associated with a syndrome of focal epilepsy, mental retardation, language regression and other neuropsychiatric problems in children of the Old Order Amish community. Here we report genomic rearrangements resulting in haploinsufficiency of the CNTN

  19. Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.

    Directory of Open Access Journals (Sweden)

    Ingrid Medina-Martinez

    Full Text Available We investigated the role of tumor copy number (CN-altered genome (CN-AG in the carcinogenesis of cervical cancer (CC, especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16-positive CCs were investigated with microarrays-31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1±8.9. Tumors were classified as low (mean = 0.5±0.6, n = 11, medium (mean = 5.4±2.4, n = 10, or high (mean = 19.2±6.6, n = 10 CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance, including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p0.38, p<0.01, Spearman test. Therefore, inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be useful for CC treatment. However, whether they are indispensable for tumor growth remains to be demonstrated.

  20. Feeding a high dosage of zinc oxide affects suppressor of cytokine gene expression in Salmonella Typhimurium infected piglets.

    Science.gov (United States)

    Schulte, Jasper N; Brockmann, Gudrun A; Kreuzer-Redmer, Susanne

    2016-10-01

    Suppressor of cytokine signaling (SOCS) proteins play an important role in the regulation of the immune response by inhibiting cytokines. Here we investigated the effects of zinc oxide fed at three different dosages (LZN=57ppm, MZN=167ppm, HZN=2425ppm) to weaned piglets that were or were not orally infected with Salmonella enterica serovar Typhimurium DT 104. We detected higher expression of SOCS3 six days after weaning for all analyzed piglets, regardless of the infection or the zinc feeding, suggesting a stress induced immune response. Whereas, SOCS1 showed only higher transcript amounts in S. Typhimurium infected piglets, especially the LZN group. This might indicate an infection regulating effect of zinc oxide in the infection model. After 42days of infection, the expression of SOCS2, SOCS4, and SOCS7 was increased only in animals fed the highest concentrations of zinc oxide, while non-infected piglets at the age of 56days showed no regulation for these genes. The up-regulation of SOCS genes in the mesenteric lymph nodes of piglets fed a diet with a very high concentration of zinc over 6 weeks suggests that such treatments may impair the immune response. PMID:27496737

  1. An Investigation of Voice Quality in Individuals with Inherited Elastin Gene Abnormalities

    Science.gov (United States)

    Watts, Christopher R.; Awan, Shaheen N.; Marler, Jeffrey A.

    2008-01-01

    The human elastin gene (ELN) is responsible for the generation of elastic fibres in the extracellular matrix of connective tissue throughout the body, including the vocal folds. Individuals with Supravalvular aortic stenosis (SVAS) and Williams syndrome (WS) lack one normal ELN allele due to heterozygous ELN abnormalities, resulting in a…

  2. Sonic Hedgehog: A Good Gene Gone Bad? Detection and Treatment of Genetic Abnormalities.

    Science.gov (United States)

    Yaich, Lauren E.

    2001-01-01

    Presents a case of a baby born with the genetic condition holoprosencephaly in which students explore the "Sonic hedgehog" gene, signal transduction, and the ethics of body and tissue donation. Presents a two-part assignment that features students writing an informed consent document that explains the science behind this congenital abnormality,…

  3. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris.

    Science.gov (United States)

    Hohenblum, Hubertus; Gasser, Brigitte; Maurer, Michael; Borth, Nicole; Mattanovich, Diethard

    2004-02-20

    The expression of heterologous proteins may exert severe stress on the host cells at different levels. Depending on the specific features of the product, different steps may be rate-limiting. For the secretion of recombinant proteins from yeast cells, folding and disulfide bond formation were identified as rate-limiting in several cases and the induction of the chaperone BiP (binding protein) is described. During the development of Pichia pastoris strains secreting human trypsinogen, a severe limitation of the amount of secreted product was identified. Strains using either the AOX1 or the GAP promoter were compared at different gene copy numbers. With the constitutive GAP promoter, no effect on the expression level was observed, whereas with the inducible AOX1 promoter an increase of the copy number above two resulted in a decrease of expression. To identify whether part of the product remained in the cells, lysates were fractionated and significant amounts of the product were identified in the insoluble fraction containing the endoplasmic reticulum, while the soluble cytosolic fraction contained product only in clones using the GAP promoter. An increase of BiP was observed upon induction of expression, indicating that the intracellular product fraction exerts an unfolded protein response in the host cells. A strain using the GAP promoter was grown both on glucose and methanol and trypsinogen was identified in the insoluble fractions of both cultures, but only in the soluble fraction of the glucose grown cultures, indicating that the amounts and distribution of intracellularly retained product depends on the culture conditions, especially the carbon source. PMID:14755554

  4. Gene dosage of the transcription factor Fingerin (bHLHA9) affects digit development and links syndactyly to ectrodactyly.

    Science.gov (United States)

    Schatz, Omri; Langer, Erez; Ben-Arie, Nissim

    2014-10-15

    Distal limb deformities are congenital malformations with phenotypic variability, genetic heterogeneity and complex inheritance. Among these, split-hand/foot malformation is an ectrodactyly with missing central fingers, yielding a lobster claw-like hand, which when combined with long-bone deficiency is defined as split-hand/foot malformation and long-bone deficiency (SHFLD) that is genetically heterogeneous. Copy number variation (CNV) consisting of 17p13.3 duplication was identified in unrelated pedigrees, underlying SHFLD3 (OMIM 612576). Although the transcription factor Fingerin (bHLHA9) is the only complete gene in the critical region, its biological role is not yet known and there are no data supporting its involvement in mammalian limb development. We have generated knockout mice in which only the entire coding region of Fingerin was deleted, and indeed found that most null mice display some limb defects. These include various levels of simple asymmetrical syndactyly, characterized by webbed fingers, generated by incomplete separation of soft, but not skeletal, tissues between forelimb digits 2 and 3. As expected, hand pads of Fingerin null embryos exhibited reduced apoptosis between digital rays 2 and 3. This defect was shown to cause syndactyly when the same limbs were grown ex vivo following the apoptosis assay. Extrapolating from mouse data, we suggest that Fingerin loss-of-function in humans may underlie MSSD syndactyly (OMIM 609432), which was mapped to the same locus. Taken together, Fingerin gene dosage links two different congenital limb malformations, syndactyly and ectrodactyly, which were previously postulated to share a common etiology. These results add limb disorders to the growing list of diseases resulting from CNV. PMID:24852374

  5. Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis

    International Nuclear Information System (INIS)

    The gene coding for plasminogen has been compared with several abnormal genes from Japanese patients by the polymerase chain reaction and DNA sequence analysis. Two types of abnormal genes coding for plasminogen were identified in these patients. In the type I mutation, a guanosine in GCT coding for Ala-601 near the active-site histidine was replaced by an adenosine resulting in ACT coding for threonine. This mutation was also shown by the loss of a cleavage site for Fnu4HI endonuclease, a restriction enzyme that recognizes GCTGC but not ACTGC. In the type II mutation, a guanosine in GTC coding for Val-355 was replaced by a thymidine resulting in TTC coding for phenylalanine. This change was readily shown by digestion with Ava II endonuclease, a restriction enzyme that recognized GGTCC and not GTTCC. The type I mutation has been found to be identical to a plasminogen variant identified in Japanese patients by amino acid sequence analysis and also detected by isoelectric focusing, whereas the type II mutation is a unique amino acid substitution in the connecting region between the third and fourth kringles in plasminogen. DNA sequence analysis also revealed that the abnormal genes carry several silent nucleotide substitutions located primarily within introns and 5' and 3' flanking regions

  6. Radiation dosage

    International Nuclear Information System (INIS)

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

  7. Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice.

    Science.gov (United States)

    Yajima, Hiroshi; Kawakami, Kiyoshi

    2016-08-01

    Muscle regeneration is an important process for skeletal muscle growth and recovery. Repair of muscle damage is exquisitely programmed by cellular mechanisms inherent in myogenic stem cells, also known as muscle satellite cells. We demonstrated previously the involvement of homeobox transcription factors, SIX1, SIX4 and SIX5, in the coordinated proliferation and differentiation of isolated satellite cells in vitro. However, their roles in adult muscle regeneration in vivo remain elusive. To investigate SIX4 and SIX5 functions during muscle regeneration, we introduced knockout alleles of Six4 and Six5 into an animal model of Duchenne Muscular Dystrophy (DMD), mdx (Dmd(mdx) /Y) mice, characterized by frequent degeneration-regeneration cycles in muscles. A lower number of small myofibers, higher number of thick ones and lower serum creatine kinase and lactate dehydrogenase activities were noted in 50-week-old Six4(+/-) 5(+/-) Dmd(mdx) /Y mice than Dmd(mdx) /Y mice, indicating improvement of dystrophic phenotypes of Dmd(mdx) /Y mice. Higher proportions of cells positive for MYOD1 and MYOG (markers of regenerating myonuclei) and SIX1 (a marker of regenerating myoblasts and newly regenerated myofibers) in 12-week-old Six4(+/-) 5(+/-) Dmd(mdx) /Y mice suggested enhanced regeneration, compared with Dmd(mdx) /Y mice. Although grip strength was comparable in Six4(+/-) 5(+/-) Dmd(mdx) /Y and Dmd(mdx) /Y mice, treadmill exercise did not induce muscle weakness in Six4(+/-) 5(+/-) Dmd(mdx) /Y mice, suggesting higher regeneration capacity. In addition, Six4(+/-) 5(+/-) Dmd(mdx) /Y mice showed 33.8% extension of life span. The results indicated that low Six4 and Six5 gene dosage improved dystrophic phenotypes of Dmd(mdx) /Y mice by enhancing muscle regeneration, and suggested that SIX4 and SIX5 are potentially useful de novo targets in therapeutic applications against muscle disorders, including DMD. PMID:27224259

  8. Exon Dosage Variations in Brazilian Patients with Parkinson’s Disease: Analysis of SNCA, PARKIN, PINK1 and DJ-1 Genes

    OpenAIRE

    Karla Cristina Vasconcelos Moura; Mário Campos Junior; Ana Lúcia Zuma de Rosso; Denise Hack Nicaretta; João Santos Pereira; Delson José Silva; Cíntia Barros Santos-Rebouças; Márcia Mattos Gonçalves Pimentel

    2012-01-01

    Parkinson’s disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson’s disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson’s disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PA...

  9. Enhancement of lipase r27RCL production in Pichia pastoris by regulating gene dosage and co-expression with chaperone protein disulfide isomerase.

    Science.gov (United States)

    Sha, Chong; Yu, Xiao-Wei; Lin, Nai-Xin; Zhang, Meng; Xu, Yan

    2013-12-10

    Pichia pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, but there is still a large room of improvement for this expression system. Two factors drastically influence the lipase r27RCL production from Rhizopus chinensis CCTCC M201021, which are gene dosage and protein folding in the endoplasmic reticulum (ER). Regarding the effect of gene dosage, the enzyme activity for recombinant strain with three copies lipase gene was 1.95-fold higher than that for recombinant strain with only one copy lipase gene. In addition, the lipase production was further improved by co-expression with chaperone PDI involved in the disulfide bond formation in the ER. Overall, the maximum enzyme activity reached 355U/mL by the recombinant strain with one copy chaperone gene PDI plus five copies lipase gene proRCL in shaking flasks, which was 2.74-fold higher than that for the control strain with only one copy lipase gene. Overall, co-expression with PDI vastly increased the capacity for processing proteins of ER in P. pastoris. PMID:24315648

  10. Dosage Effect of Zinc Glycine Chelate on Zinc Metabolism and Gene Expression of Zinc Transporter in Intestinal Segments on Rat.

    Science.gov (United States)

    Huang, Danping; Hu, Qiaoling; Fang, Shenglin; Feng, Jie

    2016-06-01

    Zinc plays an essential role in various fundamental biological processes. The focus of this research was to investigate the dosage effect of zinc glycine chelate (Zn-Gly) on zinc metabolism and the gene expression of zinc transporters in intestinal segments. A total of 30 4-week-old SD rats were randomized into five treatment groups. The basal diets for each group were supplemented with gradient levels of Zn (0, 30, 60, 90, and 180 mg/kg) from Zn-Gly. After 1-week experiment, the results showed that serum and hepatic zinc concentration were elevated linearly with supplemental Zn levels from 0 to 180 mg Zn/kg. Serum Cu-Zn SOD activities resulted in a significant (P < 0.01) quadratic response and reached the peak when fed 60 mg Zn/kg. There were linear responses to the addition of Zn-Gly from 0 to 180 mg Zn/kg on Cu-Zn SOD and AKP activities in the liver. In the duodenum, MT1 mRNA was upregulated with the increasing dietary Zn-Gly levels and reached the peak of 180 mg Zn/kg (P < 0.05). Zip4 mRNA expression was downregulated with the increasing zinc levels (P < 0.05) in both duodenum and jejunum. In the jejunum, Zip5 mRNA expression in 60 mg Zn/kg was higher compared with other groups (P < 0.05). ZnT1 mRNA in duodenum was numerically increased with the rising levels of zinc content and was significantly higher (P < 0.05) with 180 mg Zn/kg. In the duodenum, adding 60 or 90 mg Zn/kg increased PepT1 expression, but in the jejunum, 60 mg Zn/kg did not differ from 0 added Zn. In summary, there is a dose-dependent effect of dietary Zn-Gly on serum and hepatic zinc levels and the activities of Cu-Zn SOD and AKP on rats. Dietary Zn-Gly has a certain effect on MT1, Zip4, Zip5, and ZnT1 expression, which expressed differently in intestinal segments with different levels of Zn-Gly load. Besides, Zn-Gly also could regulate PepT1 expression in intestinal segments.

  11. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    Science.gov (United States)

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  12. Relationship between abnormality of FHIT gene and EBV infection in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Ping Xiao; Cheng-Bo Han; Xiao-Yun Mao; Jin-Yi Li; Lei Xu; Chang-Shan Ren; Yan Xin

    2005-01-01

    AIM: To examine the aberrant expression of fragile histidine triad (FHIT) gene and protein in gastric cancer, and to evaluate the role of FHIT gene and the relationship between FHIT gene and EBV infection in gastric carcinogenesis.METHODS: FHIT transcripts were detected by nested RT PCR in 30 cases of gastric cancer and their products were sequenced. FHIT protein was detected by Western blot.EBV infection was detected by PCR method in 50 cases of gastric cancer.RESULTS: The wild type transcripts were detected in all 30 matched normal tissues of gastric cancer. Aberrant transcripts were found in 11/30 (36.7%) gastric cancerous tissues. Sequencing analysis of the aberrant fragments found an RT-PCR product missing exons 5-7 in one case of gastric cancer, and another product missing exons 4-7. Four of ten (40.0%) cases of primary gastric cancer showed absent or decreased expression of FHIT protein as compared with their matched normal tissues. EBV was detected in 5/50 (10%) gastric cancers, among which 4/5 (80%) had aberrant transcripts of FHIT gene. CONCLUSION: Loss of FHIT gene or FHIT protein p1ays an important role in carcinogenesis, development and progression of gastric cancer. EBV infection might influence carcinogenesis of gastric cancer by inducing the abnormality of FHIT gene.

  13. Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings

    OpenAIRE

    Croonen, Ellen A; Nillesen, Willy M.; Stuurman, Kyra E; Oudesluijs, Gretel; van de Laar, Ingrid M B M; Martens, Liesbeth; Ockeloen, Charlotte; Mathijssen, Inge B.; Schepens, Marga; Ruiterkamp-Versteeg, Martina; Scheffer, Hans; Faas, Brigitte H. W.; Van Der Burgt, Ineke; Helger G Yntema

    2013-01-01

    In recent studies on prenatal testing for Noonan syndrome (NS) in fetuses with an increased nuchal translucency (NT) and a normal karyotype, mutations have been reported in 9–16% of cases. In this study, DNA of 75 fetuses with a normal karyotype and abnormal ultrasound findings was tested in a diagnostic setting for mutations in (a subset of) the four most commonly mutated NS genes. A de novo mutation in either PTPN11, KRAS or RAF1 was detected in 13 fetuses (17.3%). Ultrasound findings were ...

  14. Tobacco mosaic virus 126-kDa protein increases the susceptibility of Nicotiana tabacum to other viruses and its dosage affects virus-induced gene silencing.

    Science.gov (United States)

    Harries, Phillip A; Palanichelvam, Karuppaiah; Bhat, Sumana; Nelson, Richard S

    2008-12-01

    The Tobacco mosaic virus (TMV) 126-kDa protein is a suppressor of RNA silencing previously shown to delay the silencing of transgenes in Nicotiana tabacum and N. benthamiana. Here, we demonstrate that expression of a 126-kDa protein-green fluorescent protein (GFP) fusion (126-GFP) in N. tabacum increases susceptibility to a broad assortment of viruses, including Alfalfa mosaic virus, Brome mosaic virus, Tobacco rattle virus (TRV), and Potato virus X. Given its ability to enhance TRV infection in tobacco, we tested the effect of 126-GFP expression on TRV-mediated virus-induced gene silencing (VIGS) and demonstrate that this protein can enhance silencing phenotypes. To explain these results, we examined the poorly understood effect of suppressor dosage on the VIGS response and demonstrated that enhanced VIGS corresponds to the presence of low levels of suppressor protein. A mutant version of the 126-kDa protein, inhibited in its ability to suppress silencing, had a minimal effect on VIGS, suggesting that the suppressor activity of the 126-kDa protein is indeed responsible for the observed dosage effects. These findings illustrate the sensitivity of host plants to relatively small changes in suppressor dosage and have implications for those interested in enhancing silencing phenotypes in tobacco and other species through VIGS. PMID:18986250

  15. Combined cardiological and neurological abnormalities due to filamin A gene mutation

    Science.gov (United States)

    de Wit, Marie Claire Y.; de Coo, Irenaeus F. M.; Lequin, Maarten H.; Halley, Dicky J. J.; Roos-Hesselink, Jolien W.

    2010-01-01

    Background Cardiac defects can be the presenting symptom in patients with mutations in the X-linked gene FLNA. Dysfunction of this gene is associated with cardiac abnormalities, especially in the left ventricular outflow tract, but can also cause a congenital malformation of the cerebral cortex. We noticed that some patients diagnosed at the neurogenetics clinic had first presented to a cardiologist, suggesting that earlier recognition may be possible if the diagnosis is suspected. Methods and results From the Erasmus MC cerebral malformations database 24 patients were identified with cerebral bilateral periventricular nodular heterotopia (PNH) without other cerebral cortical malformations. In six of these patients, a pathogenic mutation in FLNA was present. In five a cardiac defect was also found in the outflow tract. Four had presented to a cardiologist before the cerebral abnormalities were diagnosed. Conclusions The cardiological phenotype typically consists of aortic or mitral regurgitation, coarctation of the aorta or other left-sided cardiac malformations. Most patients in this category will not have a FLNA mutation, but the presence of neurological complaints, hyperlaxity of the skin or joints and/or a family history with similar cardiac or neurological problems in a possibly X-linked pattern may alert the clinician to the possibility of a FLNA mutation. PMID:20730588

  16. Expression of a begomoviral DNAβ gene in transgenic Nicotiana plants induced abnormal cell division

    Institute of Scientific and Technical Information of China (English)

    CUI Xiao-feng; LI Yun-qin; HU Dong-wei; ZHOU Xue-ping

    2005-01-01

    An increasing number of monopartite begomoviruses are being identified that a satellite molecule (DNAβ) is required to induce typical symptoms in host plants. DNAβ encodes a single gene (termed βC1) encoded in the complementary-sense. We have produced transgenic Nicotiana benthamiana and N. tabacum plants expressing theβC1 gene of a DNAβ associated with Tomato yellow leaf curl China virus (TYLCCNV), under the control of the Cauliflower mosaic virus 35S promoter. Transgenic plants expressing βC1 showed severe developmental abnormalities in both species. Microscopic analysis of sections of both transgenic and non-transgenic N. tabacum leaves showed abnormal outgrowths of transgenic N. tabacum to be due to disorganized cell division (hyperplasia) of spongy and palisade parenchyma. Immuno-gold labeling of sections with a polyclonal antibody against the βC1 protein showed that the βC1 protein accumulated in the nuclei of cells. The possible biological function of the βC1 protein was discussed.

  17. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method

    OpenAIRE

    Makanae, Koji; Kintaka, Reiko; Makino, Takashi; Kitano, Hiroaki; Moriya, Hisao

    2013-01-01

    Gene overexpression beyond a permissible limit causes defects in cellular functions. However, the permissible limits of most genes are unclear. Previously, we developed a genetic method designated genetic tug-of-war (gTOW) to measure the copy number limit of overexpression of a target gene. In the current study, we applied gTOW to the analysis of all protein-coding genes in the budding yeast Saccharomyces cerevisiae. We showed that the yeast cellular system was robust against an increase in t...

  18. X-Chromosome dosage compensation.

    Science.gov (United States)

    Meyer, Barbara J

    2005-01-01

    In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the

  19. Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia.

    Science.gov (United States)

    Cheng, Chin; Chiu, Hsien-Jane; Loh, El-Wui; Chan, Chin-Hong; Hwu, Tzong-Ming; Liu, Yun-Ru; Lan, Tsuo-Hung

    2012-01-10

    Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes. PMID:22037178

  20. CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior.

    Science.gov (United States)

    Frints, Suzanna G M; Marynen, Peter; Hartmann, Dieter; Fryns, Jean-Pierre; Steyaert, Jean; Schachner, Melitta; Rolf, Bettina; Craessaerts, Katleen; Snellinx, An; Hollanders, Karen; D'Hooge, Rudi; De Deyn, Peter P; Froyen, Guy

    2003-07-01

    Investigation of MR patients with 3p aberrations led to the identification of the translocation breakpoint in intron five of the neural Cell Adhesion L1-Like (CALL or CHL1) gene in a man with non-specific mental retardation and 46,Y, t(X;3)(p22.1;p26.3). The Xp breakpoint does not seem to affect a known or predicted gene. Moreover, a fusion transcript with the CALL gene could not be detected and no mutations were identified on the second allele. CALL is highly expressed in the central and peripheral nervous system, like the mouse ortholog 'close homolog to L1' (Chl1). Chl1 expression levels in the hippocampus of Chl1(+/-) mice were half of those obtained in wild-type littermates, reflecting a gene dosage effect. Timm staining and synaptophysin immunohistochemistry of the hippocampus showed focal groups of ectopic mossy fiber synapses in the lateral CA3 region, outside the trajectory of the infra-pyramidal mossy fiber bundle in Chl1(-/-) and Chl1(+/-) mice. Behavioral assessment demonstrated mild alterations in the Chl1(-/-) animals. In the probe trial of the Morris Water Maze test, Chl1(-/-) mice displayed an altered exploratory pattern. In addition, these mice were significantly more sociable and less aggressive as demonstrated in social exploration tests. The Chl1(+/-) mice showed a phenotypic spectrum ranging from wild-type to knockout behavior. We hypothesize that a 50% reduction of CALL expression in the developing brain results in cognitive deficits. This suggests that the CALL gene at 3p26.3 is a prime candidate for an autosomal form of mental retardation. So far, mutation analysis of the CALL gene in patients with non-specific MR did not reveal any disease-associated mutations.

  1. Gene-Dosage-Dependent Association of DYRK1A with the Cytoskeleton in the Brain and Lymphocytes of Down Syndrome Patients

    OpenAIRE

    Dowjat, Karol; Adayev, Tatyana; KaczmarskiPhD, Wojciech; Wegiel, Jerzy; Hwang, Yu-Wen

    2012-01-01

    The triplication of the DYRK1A gene encoding proline-directed serine/threonine kinase and located in the critical region of Down syndrome (DS) has been implicated in cognitive deficits and intellectual disability of individuals with DS. We investigated the effect of abnormal levels of this kinase on the cytoskeleton in brain and peripheral tissues of DS subjects. In DS tissues, the predictable ≈1.5-fold enhancement of the levels of DYRK1A protein was demonstrated. An association of DYRK1A wit...

  2. An altered antioxidant balance occurs in Down syndrome fetal organs: implications for the "gene dosage effect" hypothesis.

    Science.gov (United States)

    de Haan, J B; Susil, B; Pritchard, M; Kola, I

    2003-01-01

    Down syndrome (DS) is the congenital birth defect responsible for the greatest number of individuals with mental retardation. It arises due to trisomy of human chromosome 21 (HSA21) or part thereof. To date there have been limited studies of HSA21 gene expression in trisomy 21 conceptuses. In this study we investigate the expression of the HSA21 antioxidant gene, Cu/Zn-superoxide dismutase-1 (SOD1) in various organs of control and DS aborted conceptuses. We show that SOD1 mRNA levels are elevated in DS brain, lung, heart and thymus. DS livers show decreased SOD1 mRNA expression compared with controls. Since non-HSA21 antioxidant genes are reported to be concomitantly upregulated in certain DS tissues, we examined the expression of glutathione peroxidase-1 (GPX1) in control and DS fetal organs. Interestingly, GPX1 expression was unchanged in the majority of DS organs and decreased in DS livers. We examined the SOD1 to GPX1 mRNA ratio in individual organs, as both enzymes form part of the body's defense against oxidative stress, and because a disproportionate increase of SOD1 to GPX1 results in noxious hydroxyl radical damage. All organs investigated show an approximately 2-fold increase in the SOD1 to GPX1 mRNA ratio. We propose that it is the altered antioxidant ratio that contributes to certain aspects of the DS phenotype.

  3. Developmental abnormalities and differential expression of genes induced in oil and dispersant exposed Menidia beryllina embryos.

    Science.gov (United States)

    Adeyemo, Olanike K; Kroll, Kevin J; Denslow, Nancy D

    2015-11-01

    Exposure of fish embryos to relatively low concentrations of oil has been implicated in sub-lethal toxicity. The objective of this study was to determine the effects of the exposure of Menidia beryllina embryos at 30-48h post-fertilization to the water accommodated fractions of oil (WAF, 200ppm, v/v), dispersants (20ppm, v/v, Corexit 9500 or 9527), and mixtures of oil and each of the dispersants to produce chemically enhanced water accommodated fractions (CEWAFs) over a 72-hour period. The polyaromatic hydrocarbon (PAH) and benzene, toluene, ethylene and xylene (BTEX) constituents of the 5X concentrated exposure solutions (control, WAF, dispersants and CEWAFs) were determined and those of the 1× exposures were derived using a dilution factor. PAH, BTEX and low molecular weight PAH constituents greater than 1ppb were observed in WAF and the dispersants, but at much higher levels in CEWAFs. The WAF and CEWAFs post-weathering were diluted at 1:5 (200ml WAF/CEWAF: 800ml 25ppt saltwater) for embryo exposures. Mortality, heartbeat, embryo normalcy, abnormality types and severities were recorded. The qPCR assay was used to quantify abundances of transcripts of target genes for sexual differentiation and sex determination (StAR, dmrt-1, amh, cyp19b, vtg and chg-L,), growth regulation (ghr) and stress response (cyp1a and Hsp90); and gapdh served as the housekeeping gene. Temperature was 21±1.5°C throughout the experimental period, while mortality was low and not significantly different (p=0.68) among treatments. Heartbeat was significantly different (0.0034) with the lowest heartbeats recorded in Corexit 9500 (67.5beats/min) and 9527 (67.1beats/min) exposed embryos compared with controls (82.7beats/min). Significantly more treated embryos were in a state of deterioration, with significantly more embryos presenting arrested tissue differentiation compared with controls (p=0.021). Exposure to WAF, dispersants and CEWAF induced aberrant expression of all the genes, with

  4. Deoxyribonucleic acid initiation mutation dnaB252 is suppressed by elevated dnaC+ gene dosage.

    OpenAIRE

    Sclafani, R A; Wechsler, J A

    1981-01-01

    The Escherichia coli dnaB252 allele is the only dnaB mutation which confers a deoxyribonucleic acid initiation-defective phenotype on the cell. The presence of a multicopy hybrid plasmid containing the dnaC+ gene in a dnaB252 strain completely suppressed the temperature-sensitive phenotype. It is suggested that at high temperature the dnaB252 protein has a lowered affinity for dnaC protein, and that the formation of a dnaB-dnaC complex is mandatory for initiation.

  5. Disruption of the mouse Jhy gene causes abnormal ciliary microtubule patterning and juvenile hydrocephalus.

    Science.gov (United States)

    Appelbe, Oliver K; Bollman, Bryan; Attarwala, Ali; Triebes, Lindy A; Muniz-Talavera, Hilmarie; Curry, Daniel J; Schmidt, Jennifer V

    2013-10-01

    Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, affects one of every 1000 children born today, making it one of the most common human developmental disorders. Genetic causes of hydrocephalus are poorly understood in humans, but animal models suggest a broad genetic program underlying the regulation of CSF balance. In this study, the random integration of a transgene into the mouse genome led to the development of an early onset and rapidly progressive hydrocephalus. Juvenile hydrocephalus transgenic mice (Jhy(lacZ)) inherit communicating hydrocephalus in an autosomal recessive fashion with dilation of the lateral ventricles observed as early as postnatal day 1.5. Ventricular dilation increases in severity over time, becoming fatal at 4-8 weeks of age. The ependymal cilia lining the lateral ventricles are morphologically abnormal and reduced in number in Jhy(lacZ/lacZ) brains, and ultrastructural analysis revealed disorganization of the expected 9+2 microtubule pattern. Rather, the majority of Jhy(lacZ/lacZ) cilia develop axonemes with 9+0 or 8+2 microtubule structures. Disruption of an unstudied gene, 4931429I11Rik (now named Jhy) appears to underlie the hydrocephalus of Jhy(lacZ/lacZ) mice, and the Jhy transcript and protein are decreased in Jhy(lacZ/lacZ) mice. Partial phenotypic rescue was achieved in Jhy(lacZ/lacZ) mice by the introduction of a bacterial artificial chromosome (BAC) carrying 60-70% of the JHY protein coding sequence. Jhy is evolutionarily conserved from humans to basal vertebrates, but the predicted JHY protein lacks identifiable functional domains. Ongoing studies are directed at uncovering the physiological function of JHY and its role in CSF homeostasis. PMID:23906841

  6. A novel SYBR-based duplex qPCR for the detection of gene dosage: detection of an APC large deletion in a familial adenomatous polyposis patient with an unusual phenotype

    Directory of Open Access Journals (Sweden)

    Torrezan Giovana

    2012-07-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is a hereditary colorectal cancer syndrome caused by a loss of function of the APC gene. Large deletions in APC are a common cause of FAP; despite the existence of a variety of gene dosage detection methodologies, most are labor intensive and time and resource consuming. Methods We describe a new duplex qPCR method for gene dosage analysis based on the coamplification of a target and a reference gene in a SYBR Green reaction, followed by a comparison of the ratio between the target and the reference peaks of the melting curve for the test (patient and control samples. The reliability of the described duplex qPCR was validated for several genes (APC, HPRT1, ATM, PTEN and BRCA1. Results Using this novel gene dosage method, we have identified an APC gene deletion in a FAP patient undergoing genetic testing. Comparative genomic hybridization based on microarrays (aCGH was used to confirm and map the extent of the deletion, revealing a 5.2 MB rearrangement (5q21.3-q22.3 encompassing the entire APC and 19 additional genes. Conclusion The novel assay accurately detected losses and gains of one copy of the target sequences, representing a reliable and flexible alternative to other gene dosage techniques. In addition, we described a FAP patient harboring a gross deletion at 5q21.3-q22.3 with an unusual phenotype of the absence of mental impairment and dysmorphic features.

  7. THE ROLE OF IGF-1 GENE EXPRESSION ABNORMALITY IN PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

    Institute of Scientific and Technical Information of China (English)

    李剑波; 汪承亚; 陈家伟; 李晓璐; 冯振卿; 马洪太

    2002-01-01

    Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P <0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P <0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P <0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P <0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ~ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ~(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P <0. 001; amplitude ofevokedpotential: r = 0. 716, P <0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P < 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.

  8. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    Science.gov (United States)

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

  9. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    Science.gov (United States)

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies. PMID:24736736

  10. Targeted Disruption of the LAMA3 Gene in Mice Reveals Abnormalities in Survival and Late Stage Differentiation of Epithelial Cells

    OpenAIRE

    Ryan, Maureen C.; Lee, Keesook; Miyashita, Yuko; Carter, William G.

    1999-01-01

    Laminin 5 regulates anchorage and motility of epithelial cells through integrins α6β4 and α3β1, respectively. We used targeted disruption of the LAMA3 gene, which encodes the α3 subunit of laminin 5 and other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in neonatal lethality, consistent with removal of all α3-laminin isoforms from epithelial B...

  11. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

    Science.gov (United States)

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; de Leeuw, Nicole; de Vries, Bert B A; Esko, Tõnu; Fernandez, Bridget A; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, R Frank; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S; Sanlaville, Damien; Van Haelst, Mieke M; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; de Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S; Elliott, Paul; Faas, Brigitte H W; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Helas, Géraldine Joly; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V A M; Koolen, David A; Kroisel, Peter M; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; MacDermot, Kay D; Magnusson, Pall; Marshall, Christian; Mathieu-Dramard, Michèle; McCarthy, Mark I; Meitinger, Thomas; Mencarelli, Maria Antonietta; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Ndiaye, Ndeye Coumba; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Ramelli, Gian Paolo; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J; Touraine, Renaud; Vallée, Louis; van Binsbergen, Ellen; Van der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-van Silfhout, Anneke T; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W; Stefansson, Kari; Blakemore, Alexandra I F; Beckmann, Jacques S; Froguel, Philippe

    2011-10-01

    Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies

  12. Genetic basis for dosage sensitivity in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Isabelle M Henry

    2007-04-01

    Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

  13. Abnormal immunity and gene mutation in patients with severe hepatitis-B

    Institute of Scientific and Technical Information of China (English)

    Jing-Yan Wang; Pei Liu

    2003-01-01

    AIM: To evaluate the abnormal immunity and gene mutation at precore 1896 site in patients with severe hepatitis-B.METHODS: This study included 23 patients with severe hepatitis-B, 22 patients with acute hepatitis-B and 20 controls.Mutation at precore 1896 site of HBV gene was confirmed with restriction fragment length polymorphism (RFLP) analysis.Cytokines including TNF-α, IFN-y, IL-6, and IL-8 were measured with ELISA, and T subgroups were detected with alkaline phosphatase anti alkaline phosphatase (APAAP) technique.RESULTS: In patients with severe hepatitis-B, the infective rate of HBV mutant strain was 52.5% (12/23), and only one patient with acute hepatitis-B was infected with the mutant strain. The percentage of CD8+ T lymphocyte was obviously lower (0.16±0.02%) and the ratio of CD4+/CD8+ was obviously higher (2.35±0.89) in mutant group than in wildtype group (0.28±0.05% and 1.31±0.18%, respectively,P<0.01 or P<0.05). The levels of cytokines in patients with severe hepatitis-B were higher (TNF-α 359.0±17.2 ng/L, IFNγ 234.7±16.5 ng/L, IL-6 347.5±31.3 ng/L, IL-8 181.1±19.6ng/L) than those in acute hepatitis-B (TNF-α 220.6±8.9ng/L, IFN-γ 174.9±12.0 ng/L, IL-6 285.8±16.5 ng/L, IL-8118.4±5.1 ng/L, P<0.01 or 0.05). In patients with severe hepatitis-B, the levels of IFN-γ and IL-6 were higher in mutant group (273.4±26.6 ng/L, 387.7±32.5 ng/L) than in wild-type group (207.8±12.8 ng/L, 300.9±16.3 ng/L). The mortality of patients infected with HBV mutant strain was higher (100%)than that with wild-type (0.9%).CONCLUSION: In severe hepatitis-B, the infective rate of HBV mutant strain was high. The mutant strain induces more severe immune disorders in host, resulting in the activation of lymphocyte and release of cytokines. HBV DNA mutates easily in response to the altered immunity. Ultimately liver damage is more prominent.

  14. Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells.

    Science.gov (United States)

    Ryan, M C; Lee, K; Miyashita, Y; Carter, W G

    1999-06-14

    Laminin 5 regulates anchorage and motility of epithelial cells through integrins alpha6beta4 and alpha3beta1, respectively. We used targeted disruption of the LAMA3 gene, which encodes the alpha3 subunit of laminin 5 and other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in neonatal lethality, consistent with removal of all alpha3-laminin isoforms from epithelial BMs. Alterations in three different cellular functions were identified. First, using a novel tissue adhesion assay, we found that the mutant BM could not induce stable adhesion by integrin alpha6beta4, consistent with the presence of junctional blisters and abnormal hemidesmosomes. In the absence of laminin 5 function, we were able to detect a new ligand for integrin alpha3beta1 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin alpha3beta1 to interact with an alternative ligand. Second, we identified a survival defect in mutant epithelial cells that could be rescued by exogenous laminin 5, collagen, or an antibody against integrin alpha6beta4, suggesting that signaling through beta1 or beta4 integrins is sufficient for survival. Third, we detected abnormalities in ameloblast differentiation in developing mutant incisors indicating that events downstream of adhesion are affected in mutant animals. These results indicate that laminin 5 has an important role in regulating tissue organization, gene expression, and survival of epithelium. PMID:10366601

  15. Differential gene expression profile associated with the abnormality of bone marrow mesenchymal stem cells in aplastic anemia.

    Directory of Open Access Journals (Sweden)

    Jianping Li

    Full Text Available Aplastic anemia (AA is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs. In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA.

  16. Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

    International Nuclear Information System (INIS)

    Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed

  17. Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

    Directory of Open Access Journals (Sweden)

    Mariëlle I Gallegos Ruiz

    Full Text Available BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%, which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008, survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04. Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

  18. Natural history of chronic myelomonocytic leukemia: gene sequencing identifies multiple clonal molecular abnormalities associated with rapid progression to acute myeloid leukemia

    OpenAIRE

    Xiang, Zhifu; Kaur, Varinder; Aburiziq, Ibrahim K; Mehta, Paulette; Emanuel, Peter; Schichman, Steven A.

    2014-01-01

    Key Clinical Message Gene panel sequencing in a CMML patient without any detectable genetic abnormality by conventional genetic studies identified four concurrent somatic mutations in three genes. Gene panel mutation analysis is a rapidly emerging clinical tool to demonstrate the clonality in hematologic malignancies, and to identify the potential targets for therapy.

  19. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  20. Deletion of the msdS/AfmsdC gene induces abnormal polarity and septation in Aspergillus fumigatus.

    Science.gov (United States)

    Li, Yanjie; Zhang, Lei; Wang, Depeng; Zhou, Hui; Ouyang, Haomiao; Ming, Jia; Jin, Cheng

    2008-07-01

    alpha-Mannosidases play an important role in the processing of mannose-containing glycans in eukaryotes. A deficiency in alpha-mannosidase is lethal in humans and cattle. In contrast to mammals, Saccharomyces cerevisiae does not require the endoplasmic reticulum alpha-mannosidase gene for growth. However, little is known of the consequence of loss of function of class I alpha-mannosidases in filamentous fungi. In this study, the msdS/AfmsdC gene was identified to encode 1,2-alpha-mannosidase MsdS in Aspergillus fumigatus. Soluble MsdS expressed in Escherichia coli was characterized as a typical class I alpha-mannosidase. The msdS gene was deleted by replacement of the msdS gene with a pyrG gene. Although the mutant showed a defect in N-glycan processing, as well as a reduction of cell wall components and a reduced ability of conidiation, it appeared that the rate of hyphal growth was not affected. Morphology analysis revealed abnormal polarity and septation at the stages of germination, hyphal growth and conidiation. Although the mechanism by which the N-glycan processing affects polarity and septation is unclear, our results show that msdS is involved in polarity and septation in A. fumigatus. PMID:18599824

  1. Normal and abnormal mechanisms of gene splicing and relevance to inherited skin diseases

    OpenAIRE

    Wessagowit, Vesarat; Nalla, Vijay K.; Rogan, Peter K; McGrath, John A

    2005-01-01

    The process of excising introns from pre-mRNA complexes is directed by specific genomic DNA sequences at intron—exon borders known as splice sites. These regions contain well-conserved motifs which allow the splicing process to proceed in a regulated and structured manner. However, as well as conventional splicing, several genes have the inherent capacity to undergo alternative splicing, thus allowing synthesis of multiple gene transcripts, perhaps with different functional properties. Within...

  2. Silencing abnormal wing disc gene of the Asian citrus psyllid, Diaphorina citri disrupts adult wing development and increases nymph mortality.

    Science.gov (United States)

    El-Shesheny, Ibrahim; Hajeri, Subhas; El-Hawary, Ibrahim; Gowda, Siddarame; Killiny, Nabil

    2013-01-01

    Huanglongbing (HLB) causes considerable economic losses to citrus industries worldwide. Its management depends on controlling of the Asian citrus Psyllid (ACP), the vector of the bacterium, Candidatus Liberibacter asiaticus (CLas), the causal agent of HLB. Silencing genes by RNA interference (RNAi) is a promising tool to explore gene functions as well as control pests. In the current study, abnormal wing disc (awd) gene associated with wing development in insects is used to interfere with the flight of psyllids. Our study showed that transcription of awd is development-dependent and the highest level was found in the last instar (5(th)) of the nymphal stage. Micro-application (topical application) of dsRNA to 5(th) instar of nymphs caused significant nymphal mortality and adult wing-malformation. These adverse effects in ACP were positively correlated with the amounts of dsRNA used. A qRT-PCR analysis confirmed the dsRNA-mediated transcriptional down-regulation of the awd gene. Significant down-regulation was required to induce a wing-malformed phenotype. No effect was found when dsRNA-gfp was used, indicating the specific effect of dsRNA-awd. Our findings suggest a role for awd in ACP wing development and metamorphosis. awd could serve as a potential target for insect management either via direct application of dsRNA or by producing transgenic plants expressing dsRNA-awd. These strategies will help to mitigate HLB by controlling ACP.

  3. Silencing abnormal wing disc gene of the Asian citrus psyllid, Diaphorina citri disrupts adult wing development and increases nymph mortality.

    Directory of Open Access Journals (Sweden)

    Ibrahim El-Shesheny

    Full Text Available Huanglongbing (HLB causes considerable economic losses to citrus industries worldwide. Its management depends on controlling of the Asian citrus Psyllid (ACP, the vector of the bacterium, Candidatus Liberibacter asiaticus (CLas, the causal agent of HLB. Silencing genes by RNA interference (RNAi is a promising tool to explore gene functions as well as control pests. In the current study, abnormal wing disc (awd gene associated with wing development in insects is used to interfere with the flight of psyllids. Our study showed that transcription of awd is development-dependent and the highest level was found in the last instar (5(th of the nymphal stage. Micro-application (topical application of dsRNA to 5(th instar of nymphs caused significant nymphal mortality and adult wing-malformation. These adverse effects in ACP were positively correlated with the amounts of dsRNA used. A qRT-PCR analysis confirmed the dsRNA-mediated transcriptional down-regulation of the awd gene. Significant down-regulation was required to induce a wing-malformed phenotype. No effect was found when dsRNA-gfp was used, indicating the specific effect of dsRNA-awd. Our findings suggest a role for awd in ACP wing development and metamorphosis. awd could serve as a potential target for insect management either via direct application of dsRNA or by producing transgenic plants expressing dsRNA-awd. These strategies will help to mitigate HLB by controlling ACP.

  4. Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA Leu(UUR)Gene

    International Nuclear Information System (INIS)

    An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and 123I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8±3.7 vs 11.0±1.6 mm, p0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA Leu(UUR) gene. (author)

  5. Adeno-Associated Virus Serotype-9 Microdystrophin Gene Therapy Ameliorates Electrocardiographic Abnormalities in mdx Mice

    OpenAIRE

    Bostick, Brian; Yue, Yongping; Lai, Yi; Long, Chun; Li, Dejia; Duan, Dongsheng

    2008-01-01

    Adeno-associated virus (AAV)-mediated microdystrophin gene therapy holds great promise for treating Duchenne muscular dystrophy (DMD). Previous studies have revealed excellent skeletal muscle protection. Cardiac muscle is also compromised in DMD patients. Here we show that a single intravenous injection of AAV serotype-9 (AAV-9) microdystrophin vector efficiently transduced the entire heart in neonatal mdx mice, a dystrophin-deficient mouse DMD model. Furthermore, microdystrophin therapy norm...

  6. Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.

    Science.gov (United States)

    Bargal, Ruth; Cormier-Daire, Valerie; Ben-Neriah, Ziva; Le Merrer, Martine; Sosna, Jacob; Melki, Judith; Zangen, David H; Smithson, Sarah F; Borochowitz, Zvi; Belostotsky, Ruth; Raas-Rothschild, Annick

    2009-01-01

    The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.(1) Using a homozygosity mapping strategy, we located a candidate region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the candidate region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene(6). We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk. PMID:19110212

  7. Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

    Science.gov (United States)

    Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

    1999-01-01

    Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

  8. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes.

    Science.gov (United States)

    Froyen, Guy; Van Esch, Hilde; Bauters, Marijke; Hollanders, Karen; Frints, Suzanna G M; Vermeesch, Joris R; Devriendt, Koen; Fryns, Jean-Pierre; Marynen, Peter

    2007-10-01

    A tiling X-chromosome-specific genomic array with a theoretical resolution of 80 kb was developed to screen patients with idiopathic mental retardation (MR) for submicroscopic copy number differences. Four patients with aberrations previously detected at lower resolution were first analyzed. This facilitated delineation of the location and extent of the aberration at high resolution and subsequently, more precise genotype-phenotype analyses. A cohort of 108 patients was screened, 57 of which were suspected of X-linked mental retardation (XLMR), 26 were probands of brother pairs, and 25 were sporadic cases. A total of 15 copy number changes in 14 patients (13%) were detected, which included two deletions and 13 duplications ranging from 0.1 to 2.7 Mb. The aberrations are associated with the phenotype in five patients (4.6%), based on the following criteria: de novo aberration; involvement of a known or candidate X-linked nonsyndromic(syndromic) MR (MRX(S)) gene; segregation with the disease in the family; absence in control individuals; and skewed X-inactivation in carrier females. These include deletions that contain the MRX(S) genes CDKL5, OPHN1, and CASK, and duplications harboring CDKL5, NXF5, MECP2, and GDI1. In addition, seven imbalances were apparent novel polymorphic regions because they do not fulfill the proposed criteria. Taken together, our data strongly suggest that not only deletions but also duplications on the X chromosome contribute to the phenotype more often than expected, supporting the increased gene dosage mechanism for deregulation of normal cognitive development.

  9. γA gene repeats polymorphism for the analysis of haplotypes of abnormal hemoglobins

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2014-09-01

    Full Text Available Aim of this study was to analyze γ A gene repeat polymorphism for the analysis of haplotypes of hemoglobin (Hb variants such as Hb S, Hb D-Punjab, Hb O-Arab. Sickle cell cases had mainly Benin and Arab/Indian haplotype. We found three different haplotypes among Hb S, Hb O Arab and Hb D-Punjab cases. We named these three variants as Anatolian-1 and Anatolian-2 and Asian. Our data revealed that Hb O Arab may arise twice one from Asia and the other from Europe.

  10. Abnormal desmin protein in myofibrillar myopathies caused by desmin gene mutations.

    Science.gov (United States)

    Li, M; Dalakas, M C

    2001-04-01

    Muscle proteins were extracted in various sodium dodecyl sulfate buffers from 6 patients with myofibrillar myopathy (MFM) and previously identified with mutations in the desmin gene (desmin myopathy; DesM), 6 with MFM without mutations, and 14 disease controls to search for alterations in biochemistry and solubility of mutated desmin filaments. In the 1% posthigh-speed pellet fraction, desmin was detected with immunoblots only in DesM and not the other MFM. We conclude that mutant desmin forms insoluble aggregates that are specific for the DesM and can be detected with Western blots.

  11. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  12. Abnormal neural behaviors of neonatal rat due to hyperthermia and low dosage of cigarette exposure during pregnancy%高温与低剂量香烟联合致仔鼠的神经行为异常

    Institute of Scientific and Technical Information of China (English)

    任太芳; 邢智峰; 丰慧根; 李延兰; 杨保胜

    2005-01-01

    BACKGROUND: Neural behavior is a sensitive parameter for predicting abnormal central nervous growth that is resulted from multiple factors. Therefore this study was designed to explore the influence of hypothermia and cigarette smoke exposure during pregnancy on neural behavioral growth of neonatal rats.OBJECTIVE: To study the influence of hypothermia and cigarette smoke exposure on neural behavioral growth of neonatal rats.DESIGN: Randomized case control study based on experimental animals. SETTING: Obstetric and Gynecological Department , Third Affiliated Hospital of Xinxiang Medical College; Cytobiological Department of Xinxiang Medical College.MATERIALS: Totally 270 healthy unpregnant SD rats were obtained, including 180 males with body mass of 190- 210 g, and 90 female rats with body mass of 225-275 g. Rats were raised with granulated feed and drinking water routinely in room of 25 ℃ with natural sunlight. Male and female rats in estrus were put in the same cage overnight in proportion of 2: 1, pregnancy was confirmed if vaginal bolt was observed the following morning. Totally 160 pregnant rats were obtained and randomly divided into 16 groups that were exposed to hyperthermia, cigarette smoke or their combination and by this way, earlier reflex, learning and memory of neonatal rats were observed after natural delivery,INTERVENTIONS: From the second day of pregnancy, rats in 37 ℃, 41 ℃,42 ℃ hyperthermia combining cigarette group received subcutaneous injection of 1 mL smoke hydrotrope every other day, while rats in 25 ℃ control group and 37 ℃, 41 ℃, 42 ℃ single hyperthemia groupwere given 2.0 mL double distilled water every day for totally 7 times. From the pregnancy of 10 days, pregnant rats were put into incubator, and rats anus temperature should be kept respectively at(37 ±0.5) ℃, (41 ±0.5)℃, (42 ±0.5)℃in the 37 ℃, 41 ℃, 42 ℃ of single hyperthemia groups and the temperature should last for 2.0 minutes; nats of 37 ℃, 41

  13. Overexpression of the CmACS-3 gene in melon causes abnormal pollen development.

    Science.gov (United States)

    Zhang, H; Luan, F

    2015-01-01

    Sexual diversity expressed by the Curcurbitaceae family is a primary example of developmental plasticity in plants. Most melon genotypes are andromonoecious, where an initial phase of male flowers is followed by a mixture of bisexual and male flowers. Over-expression of the CmACS-3 gene in melon plants showed an increased number of flower buds, and increased femaleness as demonstrated by a larger number bisexual buds. Transformation of CmACS-3 in melons showed earlier development of and an increased number of bisexual buds that matured to anthesis but also increased the rate of development of the bisexual buds to maturity. Field studies showed that CmACS-3-overexpressing melons had earlier mature bisexual flowers, earlier fruit set, and an increased number of fruits set on closely spaced nodes on the main stem.

  14. Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA {sup Leu(UUR)}Gene

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Hiroshi [Hyogo Medical Center for Adults, Akashi (Japan); Shiotani, Hideyuki

    1999-11-01

    An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8{+-}3.7 vs 11.0{+-}1.6 mm, p<0.001) than those without the mutation. Fractional shortening was lower in diabetic patients with the mutation than those without it (30.7{+-}7.0 vs 42.5{+-}6.6, p<0.001). MIBG uptake on the delayed MIBG image was significantly lower in diabetic patients with the mutation than in those without the mutation (mean value of the heart to mediastinum ratio: 1.6{+-}0.2 vs 2.0{+-}0.4, p>0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA {sup Leu(UUR)} gene. (author)

  15. Regulatory mechanisms for abnormal expression of the human breast cancer specific gene 1 in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    LU; Aiping; LI; Qing; LIU; Jingwen

    2006-01-01

    Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally isolated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3' end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5'-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter activity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5' flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory sequences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.

  16. Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

    Science.gov (United States)

    Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

    2016-01-30

    Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. PMID:26435258

  17. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs.

    OpenAIRE

    Nakamura, T.(International Center for Elementary Particle Physics and Department of Physics, The University of Tokyo, Tokyo, Japan); Alder, H; Y. Gu; R. Prasad; Canaani, O; Kamada, N; Gale, R P; Lange, B; Crist, W M; Nowell, P C

    1993-01-01

    Chromosome translocations involving band 11q23 are associated with human acute leukemias. These translocations fuse the ALL-1 gene, homolog of Drosophila trithorax and located at chromosome band 11q23, to genes from a variety of chromosomes. We cloned and sequenced cDNAs derived from transcripts of the AF-4 and AF-9 genes involved in the most common chromosome abnormalities, t(4:11)(q21:q23) and t(9:11)(p22:q23), respectively. Sequence analysis indicates high homology between the AF-9 gene pr...

  18. Individuals With Normal GLA Gene Sequence May Present Abnormally Spliced Alpha-Galactosidase mRNA Transcripts

    Directory of Open Access Journals (Sweden)

    Ferreira

    2015-12-01

    Full Text Available Background Deficient lysosomal α-galactosidase activity leads to intracellular accumulation of globotriaosylceramide (Gb3, which is the pathologic hallmark of Fabry disease (FD. There are over 750 pathogenic variants identified in the α-galactosidase gene (GLA. In rare patients, the cause of α-galactosidase deficiency is the overexpression of a GLA transcript with a cryptic exon in intron 4, which is physiologically present at trace levels. Objectives We aim to report abnormally spliced alpha-galactosidase mRNA transcripts found with a cDNA-based GLA genotyping protocol performed in 482 patients. Patients and Methods Genomic DNA and total RNA specimens were obtained from peripheral blood leukocytes of patients with premature stroke prospectively enrolled in the PORTYSTROKE study, or of patients with possible clinical manifestations of FD who have been referred for molecular diagnostic workup. Results Approximately 20% of the patients expressed alternatively spliced transcripts of GLA mRNA involving exon 3. We additionally report that such non-canonical transcripts are physiologically expressed at trace levels in healthy individuals, and that their expression in leukocytes markedly increased in blood samples kept at room-temperature for 48 hours before RNA extraction. Conclusions Production of alternatively spliced GLA transcripts might be involved in the regulation of GLA gene expression, and its deregulated overexpression, particularly if restricted to specific cells or tissues, might be the cause of organ-limited Gb3 pathology. Elucidation of the molecular mechanisms underlying the production of the non-canonical GLA transcripts warrants further investigation, as it may contribute important new data to the understanding of the molecular pathology of FD and Gb3-related disorders.

  19. Molecular basis of antithrombin deficiency in four Japanese patients with antithrombin gene abnormalities including two novel mutations.

    Science.gov (United States)

    Kyotani, Mayu; Okumura, Kaoru; Takagi, Akira; Murate, Takashi; Yamamoto, Koji; Matsushita, Tadashi; Sugimura, Motoi; Kanayama, Naohiro; Kobayashi, Takao; Saito, Hidehiko; Kojima, Tetsuhito

    2007-08-01

    We analyzed the antithrombin (AT) gene in four unrelated Japanese patients with an AT deficiency, and individually identified four distinct mutations in the heterozygous state. There were two novel mutations, 2417delT leading to a frameshift with a premature termination at amino acid -3 (FS-3Stop) and C2640T resulting in a missense mutation (Ala59Val). Previously reported mutations, T5342C (Ser116Pro) and T72C (Met-32Thr), were also found in the other two patients. To understand the molecular basis responsible for the AT deficiency in these patients, in vitro expression experiments were performed using HEK293 cells transfected with either wild type or respective mutant AT expression vector. We found that -3Stop-AT and -32Thr-AT were not secreted into the culture media, whereas 116Pro-AT and 59Val-AT were secreted normally. We further studied the heparin cofactor activity and the binding to heparin of each recombinant AT molecule. Ser116Pro mutation significantly impaired the binding affinity to heparin resulting in a reduced heparin cofactor activity. In contrast, we found that Ala59Val mutant AT unexpectedly showed a normal affinity to heparin, but severely impaired the heparin cofactor activity. Our findings suggested that FS-3Stop and Met-32Thr mutations are responsible for type I AT deficiency, whereas Ser116Pro and Ala59Val mutations contribute to type II AT deficiency, confirming that there were diverse molecular mechanisms of AT deficiency depend upon discrete AT gene abnormalities as reported previously.

  20. Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

    Science.gov (United States)

    Abrass, C K; Berfield, A K; Ryan, M C; Carter, W G; Hansen, K M

    2006-09-01

    Mice with targeted disruption of the lama3 gene, which encodes the alpha3 chain of laminin-5 (alpha3beta3gamma2, 332), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans. These animals also develop abnormalities in glomerulogenesis. In both wild-type and mutant animals (lama3(-/-)), podocytes secrete glomerular basement membrane and develop foot processes. Endothelial cells migrate into this scaffolding and secrete a layer of basement membrane that fuses with the one formed by the podocyte. In lama3(-/-) animals, glomerular maturation arrests at this stage. Endothelial cells do not attenuate, develop fenestrae, or form typical lumens, and mesangial cells (MCs) were not identified. LN alpha3 subunit (LAMA3) protein was identified in the basement membrane adjacent to glomerular endothelial cells (GEnCs) in normal rats and mice. In developing rat glomeruli, the LAMA3 subunit was first detectable in the early capillary loop stage, which corresponds to the stage at which maturation arrest was observed in the mutant mice. Lama3 mRNA and protein were identified in isolated rat and mouse glomeruli and cultured rat GEnCs, but not MC. These data document expression of LAMA3 in glomeruli and support a critical role for it in GEnC differentiation. Furthermore, LAMA3 chain expression and/or another product of endothelial cells are required for MC migration into the developing glomerulus. PMID:16850021

  1. Dosage compensation is less effective in birds than in mammals

    Directory of Open Access Journals (Sweden)

    Itoh Yuichiro

    2007-03-01

    Full Text Available Abstract Background In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X-linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in which females (ZW and males (ZZ differ in the number of Z chromosomes. Results Using microarray analysis, we compared the male:female ratio of expression of sets of Z-linked and autosomal genes in two bird species, zebra finch and chicken, and in two mammalian species, mouse and human. Male:female ratios of expression were significantly higher for Z genes than for autosomal genes in several finch and chicken tissues. In contrast, in mouse and human the male:female ratio of expression of X-linked genes is quite similar to that of autosomal genes, indicating effective dosage compensation even in humans, in which a significant percentage of genes escape X-inactivation. Conclusion Birds represent an unprecedented case in which genes on one sex chromosome are expressed on average at constitutively higher levels in one sex compared with the other. Sex-chromosome dosage compensation is surprisingly ineffective in birds, suggesting that some genomes can do without effective sex-specific sex-chromosome dosage compensation mechanisms.

  2. Screening of sarcomere gene mutations in young athletes with abnormal findings in electrocardiography: identification of a MYH7 mutation and MYBPC3 mutations.

    Science.gov (United States)

    Kadota, Chika; Arimura, Takuro; Hayashi, Takeharu; Naruse, Taeko K; Kawai, Sachio; Kimura, Akinori

    2015-10-01

    There is an overlap between the physiological cardiac remodeling associated with training in athletes, the so-called athlete's heart, and mild forms of hypertrophic cardiomyopathy (HCM), the most common hereditary cardiac disease. HCM is often accompanied by unfavorable outcomes including a sudden cardiac death in the adolescents. Because one of the initial signs of HCM is abnormality in electrocardiogram (ECG), athletes may need to monitor for ECG findings to prevent any unfavorable outcomes. HCM is caused by mutations in genes for sarcomere proteins, but there is no report on the systematic screening of gene mutations in athletes. One hundred and two genetically unrelated young Japanese athletes with abnormal ECG findings were the subjects for the analysis of four sarcomere genes, MYH7, MYBPC3, TNNT2 and TNNI3. We found that 5 out of 102 (4.9%) athletes carried mutations: a heterozygous MYH7 Glu935Lys mutation, a heterozygous MYBPC3 Arg160Trp mutation and another heterozygous MYBPC3 Thr1046Met mutation, all of which had been reported as HCM-associated mutations, in 1, 2 and 2 subjects, respectively. This is the first study of systematic screening of sarcomere gene mutations in a cohort of athletes with abnormal ECG, demonstrating the presence of sarcomere gene mutations in the athlete's heart. PMID:26178432

  3. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  4. Copy number variants and rasopathies: germline KRAS duplication in a patient with syndrome including pigmentation abnormalities.

    Science.gov (United States)

    Gilbert-Dussardier, Brigitte; Briand-Suleau, Audrey; Laurendeau, Ingrid; Bilan, Frédéric; Cavé, Hélène; Verloes, Alain; Vidaud, Michel; Vidaud, Dominique; Pasmant, Eric

    2016-01-01

    RAS/MAPK pathway germline mutations were described in Rasopathies, a class of rare genetic syndromes combining facial abnormalities, heart defects, short stature, skin and genital abnormalities, and mental retardation. The majority of the mutations identified in the Rasopathies are point mutations which increase RAS/MAPK pathway signaling. Duplications encompassing RAS/MAPK pathway genes (PTPN11, RAF1, MEK2, or SHOC2) were more rarely described. Here we report, a syndromic familial case of a 12p duplication encompassing the dosage sensitive gene KRAS, whose phenotype overlapped with rasopathies. The patient was referred because of a history of mild learning disabilities, small size, facial dysmorphy, and pigmentation abnormalities (café-au-lait and achromic spots, and axillar lentigines). This phenotype was reminiscent of rasopathies. No mutation was identified in the most common genes associated with Noonan, cardio-facio-cutaneous, Legius, and Costello syndromes, as well as neurofibromatosis type 1. The patient constitutional DNA exhibited a ~10.5 Mb duplication at 12p, including the KRAS gene. The index case's mother carried the same chromosome abnormality and also showed development delay with short stature, and numerous café-au-lait spots. Duplication of the KRAS gene may participate in the propositus phenotype, in particular of the specific pigmentation abnormalities. Array-CGH or some other assessment of gene/exon CNVs of RAS/MAPK pathway genes should be considered in the evaluation of individuals with rasopathies. PMID:27450488

  5. DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome

    Science.gov (United States)

    Duchon, Arnaud; Herault, Yann

    2016-01-01

    Down syndrome (DS) is one of the leading causes of intellectual disability, and patients with DS face various health issues, including learning and memory deficits, congenital heart disease, Alzheimer’s disease (AD), leukemia, and cancer, leading to huge medical and social costs. Remarkable advances on DS research have been made in improving cognitive function in mouse models for future therapeutic approaches in patients. Among the different approaches, DYRK1A inhibitors have emerged as promising therapeutics to reduce DS cognitive deficits. DYRK1A is a dual-specificity kinase that is overexpressed in DS and plays a key role in neurogenesis, outgrowth of axons and dendrites, neuronal trafficking and aging. Its pivotal role in the DS phenotype makes it a prime target for the development of therapeutics. Recently, disruption of DYRK1A has been found in Autosomal Dominant Mental Retardation 7 (MRD7), resulting in severe mental deficiency. Recent advances in the development of kinase inhibitors are expected, in the near future, to remove DS from the list of incurable diseases, providing certain conditions such as drug dosage and correct timing for the optimum long-term treatment. In addition the exact molecular and cellular mechanisms that are targeted by the inhibition of DYRK1A are still to be discovered. PMID:27375444

  6. DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome.

    Science.gov (United States)

    Duchon, Arnaud; Herault, Yann

    2016-01-01

    Down syndrome (DS) is one of the leading causes of intellectual disability, and patients with DS face various health issues, including learning and memory deficits, congenital heart disease, Alzheimer's disease (AD), leukemia, and cancer, leading to huge medical and social costs. Remarkable advances on DS research have been made in improving cognitive function in mouse models for future therapeutic approaches in patients. Among the different approaches, DYRK1A inhibitors have emerged as promising therapeutics to reduce DS cognitive deficits. DYRK1A is a dual-specificity kinase that is overexpressed in DS and plays a key role in neurogenesis, outgrowth of axons and dendrites, neuronal trafficking and aging. Its pivotal role in the DS phenotype makes it a prime target for the development of therapeutics. Recently, disruption of DYRK1A has been found in Autosomal Dominant Mental Retardation 7 (MRD7), resulting in severe mental deficiency. Recent advances in the development of kinase inhibitors are expected, in the near future, to remove DS from the list of incurable diseases, providing certain conditions such as drug dosage and correct timing for the optimum long-term treatment. In addition the exact molecular and cellular mechanisms that are targeted by the inhibition of DYRK1A are still to be discovered. PMID:27375444

  7. Over-expression of a grape stilbene synthase gene in tomato induces parthenocarpy and causes abnormal pollen development.

    Science.gov (United States)

    Ingrosso, Ilaria; Bonsegna, Stefania; De Domenico, Stefania; Laddomada, Barbara; Blando, Federica; Santino, Angelo; Giovinazzo, Giovanna

    2011-10-01

    A novel strategy to induce parthenocarpy in tomato fruits by the induction of resveratrol biosynthesis in flower tissues was exploited. Two transgenic tomato lines were considered: a higher resveratrol-producing (35SS) line, constitutively expressing a grape stilbene synthase cDNA, and a lower resveratrol-producing (LoxS) line, expressing stilbene synthase under a fruit-specific promoter. The expression of the stilbene synthase gene affected flavonoid metabolism in a different manner in the transgenic lines, and in one of these, the 35SS line, resulted in complete male sterility. Resveratrol was synthesised either in 35SS or LoxS tomato flowers, at an even higher extent (about 8-10 times) in the former line. We further investigated whether stilbene synthase expression may have resulted in impaired naringenin accumulation during flower development. In the 35SS flowers, naringenin was significantly impaired by about 50%, probably due to metabolic competition. Conversely, the amount of glycosylated flavonols increased in transgenic flowers, thereby excluding the diminished production of flavonols as a reason for parthenocarpy in tomato. We further investigated whether resveratrol synthesis may have resulted changes to pollen structure. Microscopic observations revealed the presence of few and abnormal flake-like pollen grains in 35SS flowers with no germination capability. Finally, the analysis of coumaric and ferulic acids, the precursors of lignin and sporopollenin biosynthesis, revealed significant depletion of these compounds, therefore suggesting an impairment in structural compounds as a reason for pollen ablation. These overall outcomes, to the best of our knowledge, reveal for the first time the major role displayed by resveratrol synthesis on parthenocarpy in tomato fruits. PMID:21843947

  8. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  9. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  10. Cytogenetic abnormalities and genomic copy number variations in EPO (7q22) and SEC-61(7p11) genes in primary myelodysplastic syndromes.

    Science.gov (United States)

    Mohanty, Purvi; Korgaonkar, Seema; Shanmukhaiah, Chandrakala; Ghosh, Kanjaksha; Vundinti, Babu Rao

    2016-07-01

    Myelodysplastic syndromes (MDSs) are heterogeneous clonal haematopoeitic stem cell disorders characterized by ineffective haematopoeisis, cytopenias and risk of progression to AML. We studied 150 MDS patients for cytogenetic aberrations and 60 patients with normal karyotype and 40 patients harboring cytogenetic abnormalities for copy number variations (CNVs). Cytogenetic abnormalities were detected in 46% of patients with a majority of patients harboring abnormalities of chromosome 7 and del (20q) at frequencies of 16% and 12% respectively. We explored the potential of quantitative multiplex PCR assay of short fluorescent fragments (QMPSF) to identify CNVs and correlated the findings with cytogenetic data and disease prognosis. CNVs (n=31) were detected in 28.3% of karyotypically normal and 23% patients with abnormal karyotype. Genetic losses or deletions (n=26) were more frequent than duplications (n=5). EPO (7q22) and SEC-61(7p11) emerged as new candidate genes susceptible to genetic losses with 57.7% deletions identified in regions on chromosome 7. The CNVs correlated with International Prognostic Scoring System (IPSS) intermediate disease risk group. Our integrative cytogenetic and copy number variation study suggests that abnormalities of chromosome 7 are predominant in Indian population and that they may play a secondary role in disease progression and should be evaluated further for asserting their clinical significance and influence on disease prognosis. PMID:27282568

  11. Dosage regulation of the active X chromosome in human triploid cells.

    Directory of Open Access Journals (Sweden)

    Xinxian Deng

    2009-12-01

    Full Text Available In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence-based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s. To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81-0.84 in triploid cells with one active X and higher (1.32-1.4 in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset ( approximately 7% of genes had expression levels apparently proportional to the number of autosomal sets.

  12. Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene

    NARCIS (Netherlands)

    E. Nof; B. Belhassen; M. Arad; Z.A. Bhuiyan; C. Antzelevitch; R. Rosso; R. Fogelman; D. Luria; D. El-Ani; M.M.A.M. Mannens; S. Viskin; M. Eldar; A.A.M. Wilde; M. Glikson

    2011-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phen

  13. A homozygous balanced reciprocal translocation suggests LINC00237 as a candidate gene for MOMO (macrosomia, obesity, macrocephaly, and ocular abnormalities) syndrome.

    Science.gov (United States)

    Vu, Phi Yen; Toutain, Jérôme; Cappellen, David; Delrue, Marie-Ange; Daoud, Hussein; El Moneim, Azza Abd; Barat, Pascal; Montaubin, Orianne; Bonnet, Françoise; Dai, Zong Qi; Philippe, Christophe; Tran, Cong Toai; Rooryck, Caroline; Arveiler, Benoît; Saura, Robert; Briault, Sylvain; Lacombe, Didier; Taine, Laurence

    2012-11-01

    Macrosomia, obesity, macrocephaly, and ocular abnormalities syndrome (MOMO syndrome) has been reported in only four patients to date. In these sporadic cases, no chromosomal or molecular abnormality has been identified thus far. Here, we report on the clinical, cytogenetic, and molecular findings in a child of healthy consanguineous parents suffering from MOMO syndrome. Conventional karyotyping revealed an inherited homozygous balanced reciprocal translocation (16;20)(q21;p11.2). Uniparental disomy testing showed bi-parental inheritance for both derivative chromosomes 16 and 20. The patient's oligonucleotide array-comparative genomic hybridization profile revealed no abnormality. From the homozygous balanced reciprocal translocation (16;20)(q21;p11.2), a positional cloning strategy, designed to narrow 16q21 and 20p11.2 breakpoints, revealed the disruption of a novel gene located at 20p11.23. This gene is now named LINC00237, according to the HUGO (Human Genome Organization) nomenclature. The gene apparently leads to the production of a non-coding RNA. We established that LINC00237 was expressed in lymphocytes of control individuals while normal transcripts were absent in lymphocytes of our MOMO patient. LINC00237 was not ubiquitously expressed in control tissues, but it was notably highly expressed in the brain. Our results suggested autosomal recessive inheritance of MOMO syndrome. LINC00237 could play a role in the pathogenesis of this syndrome and could provide new insights into hyperphagia-related obesity and intellectual disability.

  14. Comparison of gene expression profiles and responses to zinc chloride among inter- and intraspecific hybrids with growth abnormalities in wheat and its relatives.

    Science.gov (United States)

    Takamatsu, Kiyofumi; Iehisa, Julio C M; Nishijima, Ryo; Takumi, Shigeo

    2015-07-01

    Hybrid necrosis is a well-known reproductive isolation mechanism in plant species, and an autoimmune response is generally considered to trigger hybrid necrosis through epistatic interaction between disease resistance-related genes in hybrids. In common wheat, the complementary Ne1 and Ne2 genes control hybrid necrosis, defined as type I necrosis. Two other types of hybrid necrosis (type II and type III) have been observed in interspecific hybrids between tetraploid wheat and Aegilops tauschii. Another type of hybrid necrosis, defined here as type IV necrosis, has been reported in F1 hybrids between Triticum urartu and some accessions of Triticum monococcum ssp. aegilopoides. In types I, III and IV, cell death occurs gradually starting in older tissues, whereas type II necrosis symptoms occur only under low temperature. To compare comprehensive gene expression patterns of hybrids showing growth abnormalities, transcriptome analysis of type I and type IV necrosis was performed using a wheat 38k oligo-DNA microarray. Defense-related genes including many WRKY transcription factor genes were dramatically up-regulated in plants showing type I and type IV necrosis, similarly to other known hybrid abnormalities, suggesting an association with an autoimmune response. Reactive oxygen species generation and necrotic cell death were effectively inhibited by ZnCl2 treatment in types I, III and IV necrosis, suggesting a significant association of Ca(2+) influx in upstream signaling of necrotic cell death in wheat hybrid necrosis. PMID:26081164

  15. Antipsychotics dosage and antiparkinsonian prescriptions

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    Gasquet Isabelle

    2007-09-01

    Full Text Available Abstract Background To study the link between the dosage of several antipsychotics and the prescription of antiparkinsonians in an observational study. Methods In the context of a national naturalistic prospective observational study, a database containing all the prescriptions from 100 French psychiatrists during the year 2002 was analysed. The inclusion criteria were a diagnosis of schizophrenia or schizoaffective disorder and age over 18. The mean dosage of antipsychotics with and without antiparkinsonians was compared. Since there were multiple prescriptions for a given subject, generalised mixed linear models were also used to study the link between antiparkinsonian prescription and antipsychotic dosage. Results antiparkinsonians were prescribed to 32,9% of the patients. Two groups of antipsychotics were observed relating to differences in dosage when an antiparkinsonian was co prescribed or not : a first group, where the mean dosage was higher with antiparkinsonians (risperidone, amisulpride and haloperidol and a second group (clozapine, olanzapine, in which antiparkinsonian co prescription was not related to the dosage of antipsychotics. Conclusion As a conclusion, it can be said that it is important to consider the dosage and the type of antipsychotic in the treatment of patients suffering of schizophrenia, because neurological side effects are frequent and can impair quality of life. Moreover the prescription of antiparkinsonians can lead to different side effects such anticholinergic effects.

  16. Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis

    Science.gov (United States)

    Nevarez, Lisette; Pogue, Robert; Krakow, Deborah; Cohn, Daniel H.

    2016-01-01

    The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses. PMID:27622494

  17. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs.

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    Minh T N Le

    2011-09-01

    Full Text Available MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA-target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis.

  18. DYRK1A (Dual-Specificity Tyrosine-Phosphorylated and -Regulated Kinase 1A: A Gene with Dosage Effect During Development and Neurogenesis

    Directory of Open Access Journals (Sweden)

    M. Dierssen

    2006-01-01

    Full Text Available DYRKs (dual-specificity tyrosine-regulated kinases are an emerging family of evolutionarily conserved dual-specificity kinases that play key roles in cell proliferation, survival, and development. The research in the last years suggests a relevant conserved function during neuronal development, related to proliferation and/or differentiation for DYRK1A. It is expressed in neural progenitor cells and has been proposed to participate in the signaling mechanisms that regulate dendrite differentiation. In Drosophila, disruption of the homolog minibrain gene results in flies with reduced neuroblast proliferation, decreased numbers of central brain neurons, and learning/memory deficits. Knockout DYRK1A mice are embryonic lethal, and heterozygotes show decreased viability and region-specific reductions in brain size. In humans, DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with Down syndrome. The large number of protein interaction and putative substrates described for DYRK1A suggest multiple pathways and functions to be involved in its developmental function. This review focuses on the functional role that DYRK1A plays in brain development.

  19. Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition.

    Science.gov (United States)

    McGrath, J A; Gatalica, B; Li, K; Dunnill, M G; McMillan, J R; Christiano, A M; Eady, R A; Uitto, J

    1996-06-01

    Junctional epidermolysis bullosa is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Previously, mutations in this condition have been described in the three genes for the anchoring filament protein laminin 5 (LAMA3, LAMB3, and LAMC2), in the gene encoding the hemidesmosome-associated beta4 integrin (ITGB4), and in the gene for the hemidesmosomal protein type XVII collagen (COL17A1/BPAG2). In this study, we report a patient with a form of junctional epidermolysis bullosa with skin fragility and dental anomalies who is a compound heterozygote for a novel combination of mutations, ie, a glycine substitution mutation in one allele and an internal duplication in the other allele of COL17A1. The patient also has two offspring, both of whom have inherited the glycine substitution mutation, whereas the other COL17A1 allele is normal. The latter individuals show no evidence of skin fragility but have marked dental abnormalities with enamel hypoplasia and pitting. The clinical phenotype of junctional epidermolysis bullosa in the proband in this family probably arises due to a combination of the glycine substitution and the internal duplication in COL17A1, whereas the dental abnormalities of her offspring may be the result of the glycine substitution in COL17A1 alone, resulting in this dominantly inherited clinical phenotype. PMID:8669466

  20. Abnormal promoter methylation of multiple genes in the malignant transformed PEP2D cells induced by alpha particles exposure

    Institute of Scientific and Technical Information of China (English)

    LiP; SuiJL

    2002-01-01

    The 5' promoter regions of some genes contain CpG-rich areas,known as CpG islands,Methylation of the cytosine in these dinuleotides has important regulatory effects on gene expression.The functional significance of promoter hypermethylation would play the same roles in carcinogenesis as gene mutations.The promoter methylations p14ARF,p16INK4a,MGMT,GSTP1,BUB3 and DAPK genes were analyzed with methylation specific PCR(MSP) in the transformed human bronchial epithelial cells(BEP2D) induced by α-particles.The results indicated that p14ARF gene was not methylated in BEP2D cells,but was methylated in the malignant transformed BERP35T-1 cells,and the level of its transcription was depressed remarkable in the latter.However p16INK4a gene,which shares two exons with p14ARF gene,was not methylated.MGMT gene was methylated in both BEP2D and BERP35T-1.DAPK gene was partially methylated in BEP2D cells and methylated completely in BERP35T1.GSTP1 was not methylated in BEP2D cells and was methylated partly in BERP35T-1.BUB3 gene was not methylated in BEP2D as well as BERP35T1 cells and was further proved by sequencing analysis.

  1. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  2. Isolation and sequencing of doublesex/male abnormal 3 (DM related transcription factor (Dmrt genes from the Asian toad Bufo gargarizans (Cantor, 1842

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    Wen Chen

    2007-01-01

    Full Text Available The doublesex/male abnormal 3 (dsx/mab-3 or DM domain gene family involved in sexual development encodes putative transcription factors including a DNA-binding homology motif, the DM domain. We used highly degenerate primers to clone and sequence seven distinct DM related transcription factor (Dmrt genes from the Asian toad (Bufo gargarizans Cantor, 1842. A database search for the cloned sequences revealed the following percentage identity with the homologous Dmrt genes of the human: BgDmrt1 = 97%, BgDmrt2 = 97%, three isoforms of BgDmrt3 (BgDmrt3a = 93%, BgDmrt3b = 95%, BgDmrt3c = 100% and two isoforms of BgDmrt5 (BgDmrt5 = 97%, BgDmrt5 = 91%. Based on DM domain amino acid sequence similarities we constructed a phylogenetic tree which grouped vertebrate and invertebrate Dmrt genes into seven distinct subfamilies. The DM domains of both human and the newly-discovered Bufo gargarizans genes contained two conserved zinc-chelating sites (CCHC and HCCC, except BgDmrt3b, which contained the CCRC and HCCC sites.

  3. Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and Alters Movement Pattern in Zebrafish.

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    Ashok Aspatwar

    Full Text Available Carbonic anhydrase related proteins (CARPs X and XI are highly conserved across species and are predominantly expressed in neural tissues. The biological role of these proteins is still an enigma. Ray-finned fish have lost the CA11 gene, but instead possess two co-orthologs of CA10. We analyzed the expression pattern of zebrafish ca10a and ca10b genes during embryonic development and in different adult tissues, and studied 61 CARP X/XI-like sequences to evaluate their phylogenetic relationship. Sequence analysis of zebrafish ca10a and ca10b reveals strongly predicted signal peptides, N-glycosylation sites, and a potential disulfide, all of which are conserved, suggesting that all of CARP X and XI are secretory proteins and potentially dimeric. RT-qPCR showed that zebrafish ca10a and ca10b genes are expressed in the brain and several other tissues throughout the development of zebrafish. Antisense morpholino mediated knockdown of ca10a and ca10b showed developmental delay with a high rate of mortality in larvae. Zebrafish morphants showed curved body, pericardial edema, and abnormalities in the head and eye, and there was increased apoptotic cell death in the brain region. Swim pattern showed abnormal movement in morphant zebrafish larvae compared to the wild type larvae. The developmental phenotypes of the ca10a and ca10b morphants were confirmed by inactivating these genes with the CRISPR/Cas9 system. In conclusion, we introduce a novel zebrafish model to investigate the mechanisms of CARP Xa and CARP Xb functions. Our data indicate that CARP Xa and CARP Xb have important roles in zebrafish development and suppression of ca10a and ca10b expression in zebrafish larvae leads to a movement disorder.

  4. Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies.

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    Bin Zhang

    Full Text Available Cornelia de Lange syndrome (CdLS, a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B. Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B(-/- mice. While Pds5A(-/- and Pds5B(-/- mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A(-/- or Pds5B(-/- mice. We further identified a functional missense mutation (R1292Q in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS.

  5. Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse

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    Soper Jessica

    2007-07-01

    Full Text Available Abstract Background Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition. Methods Gestational d18.0 uteri (n = 4 were collected from pregnant wild-type and cyclooxygenase-1 knockout mice. Part of the uterus was used for frozen sections and RNA was isolated from the remainder. Microarray analysis was performed at the Indiana University School of Medicine Genomic Core and analyzed using the Microarray Data Portal. Northern analysis was performed to confirm microarray data and the genes localized in the gravid uterus by in situ hybridization. Results We identified 277 genes that are abnormally expressed in the gravid d18.0 cyclooxygenase-1 knockout mouse. Nine of these genes are also regulated in the normal murine uterus during the last half of gestation. Many of these genes are involved in the immune response, consistent with an important role of the immune system in parturition. Expression of 4 of these genes; arginase I, IgJ, Tnfrsf9 and troponin; was confirmed by Northern analysis to be mis-regulated during pregnancy in the knockout mouse. In situ hybridization of these genes demonstrated a similar location in the gravid wild-type and Cox-1 knockout mouse uteri. Conclusion To our knowledge, this is the first work to demonstrate the uterine location of these 4 genes in the mouse during late pregnancy. There are several putative transcription factor binding sites that are shared by many of the 9 genes identified here including; estrogen and

  6. Cystic fibrosis transmembrane conductance regulator (CFTR gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies

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    Rahul Gajbhiye

    2016-01-01

    Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T, four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD. The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.

  7. Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies

    Science.gov (United States)

    Gajbhiye, Rahul; Kadam, Kaushiki; Khole, Aalok; Gaikwad, Avinash; Kadam, Seema; Shah, Rupin; Kumaraswamy, Rangaswamy; Khole, Vrinda

    2016-01-01

    Background & objectives: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. Methods: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings. PMID:27488005

  8. Gene Expression Profile Reveals Abnormalities of Multiple Signaling Pathways in Mesenchymal Stem Cell Derived from Patients with Systemic Lupus Erythematosus

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    Yu Tang

    2012-01-01

    Full Text Available We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs between systemic lupus erythematosus (SLE and normal controls by means of cDNA microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our results showed there were a total of 1, 905 genes which were differentially expressed by BMMSCs derived from SLE patients, of which, 652 genes were upregulated and 1, 253 were downregulated. Gene ontology (GO analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis exhibited that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction, and TGF-β pathway. The high protein level of BMP-5 and low expression of Id-1 indicated that there might be dysregulation in BMP/TGF-β signaling pathway. The expression of Id-1 in SLE BMMSCs was reversely correlated with serum TNF-α levels. The protein level of cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK signaling pathway was activated in BMMSCs from SLE patients via phosphorylation of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE patients was also found disordered. Our results suggested that there were distinguished differences of BMMSCs between SLE patients and normal controls.

  9. [Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer].

    Science.gov (United States)

    Kuznetsova, E S; Zinovieva, O L; Oparina, N Yu; Prokofjeva, M M; Spirin, P V; Favorskaya, I A; Zborovskaya, I B; Lisitsyn, N A; Prassolov, V S; Mashkova, T D

    2016-01-01

    Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

  10. Mutants of bacteriophage T4 deficient in the ability to induce nuclear disruption: shutoff of host DNA and protein synthesis gene dosage experiments, identification of a restrictive host, and possible biological significance.

    Science.gov (United States)

    Snustad, D P; Bursch, C J; Parson, K A; Hefeneider, S H

    1976-04-01

    The shutoff of host DNA synthesis is delayed until about 8 to 10 min after infection when Escherichia coli B/5 cells were infected with bacteriophage T4 mutants deficient in the ability to induce nuclear disruption (ndd mutants). The host DNA synthesized after infection with ndd mutants is stable in the absence of T4 endonucleases II and IV, but is unstable in the presence of these nucleases. Host protein synthesis, as indicated by the inducibility of beta-galactosidase and sodium dodecyl sulfate-polyacrylamide gel patterns of isoptopically labeled proteins synthesize after infection, is shut off normally in ndd-infected cells, even in the absence of host DNA degradation. The Cal Tech wild-type strain of E. coli CT447 was found to restrict growth of the ndd mutants. Since T4D+ also has a very low efficiency of plating on CT447, we have isolated a nitrosoguanidine-induced derivative of CT447 which yields a high T4D+ efficiency of plating while still restricting the ndd mutants. Using this derivative, CT447 T4 plq+ (for T4 plaque+), we have shown that hos DNA degradation and shutoff of host DNA synthesis occur after infection with either ndd98 X 5 (shutoff delayed) or T4D+ (shutoff normal) with approximately the same kinetics as in E. coli strain B/5. Nuclear disruption occurs after infection of CT447 with ndd+ phage, but not after infection with ndd- phage. The rate of DNA synthesis after infection of CT447 T4 plq+ with ndd98 X 5 is about 75% of the rate observed after infection with T4D+ while the burst size of ndd98 X 5 is only 3.5% of that of T4D+. The results of gene dosage experiments using the ndd restrictive host C5447 suggest that the ndd gene product is required in stoichiometric amounts. The observation by thin-section electron microscopy of two distinct pools of DNA, one apparently phage DNA and the other host DNA, in cells infected with nuclear disruption may be a compartmentalization mechanism which separates the pathways of host DNA degradation and

  11. Differential Gene Expression Profile Associated with the Abnormality of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

    OpenAIRE

    Li, Jianping; Yang, Shaoguang; Lu, Shihong; Zhao, Hui; Feng, Jianming; Li, Wenqian; Ma, Fengxia; Ren, Qian; Liu, Bin; Zhang, Lei; Zheng, Yizhou; Han, Zhong Chao

    2012-01-01

    Aplastic anemia (AA) is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs) and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs). In the present study, we comprehensively compared the biological features and gene expression profile...

  12. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities.

    Science.gov (United States)

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roberts, Roland G

    2010-07-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin alpha2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study, we describe a patient with a heterozygous de novo deletion of a approximately 2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles. As these symptoms are a subset of those observed in disorders of dystroglycan glycosylation (muscle-eye-brain disease and Warker-Warburg syndrome), we assess the likely contribution to her phenotype of her heterogosity for a null mutation of DAG1. We also show that the transcriptional compensation observed in the Dag1(+/-) mouse is not observed in the patient. Although we cannot show that haploinsufficiency of DAG1 is the sole cause of this patient's myopathy and white matter changes, this case serves to constrain our ideas of the severity of the phenotypic consequences of heterozygosity for null DAG1 mutations. PMID:20234391

  13.  Possible gene dosage effect of glutathione-S-transferases on atopic asthma: Using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers

    DEFF Research Database (Denmark)

    Andersen, Charlotte Brasch; Christiansen, Lene; Tan, Qihua;

    2004-01-01

    Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. As oxidative stress is a key component of inflammation, variations in genes involved in antioxidant defense could therefore be likely candidates for asthma. Three enzymes from the superfamily glutathione......-S-transferase (GST) involved in the antioxidant defense were tested for association to asthma using 246 Danish atopic families in a family-based transmission disequilibrium test (TDT) design. A real-time PCR assay for relative quantification of gene copy number of GSTM1 and GSTT1 was developed. The assay made...... it possible to distinguish individuals with zero, one, and two copies and thereby to investigate whether the GST genes influenced susceptibility to asthma in a dose-dependent manner. We found that asthmatic patients with two copies of GSTM1 were significantly underrepresented (p

  14. Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.

    Science.gov (United States)

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Kao, Yu-Chien; Agaram, Narasimhan P; Antonescu, Cristina R

    2016-10-01

    SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc. PMID:27218413

  15. Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

    Science.gov (United States)

    Song, Tianbin; Nie, Binbin; Ma, Ensen; Che, Jing; Sun, Shilong; Wang, Yuli; Shan, Baoci; Liu, Yawu; Luo, Senlin; Ma, Guolin; Li, Kefeng

    2015-05-01

    Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

  16. Status of dosage compensation of X chromosome in bovine genome.

    Science.gov (United States)

    Ka, Sojeong; Ahn, Hyeonju; Seo, Minseok; Kim, Heebal; Kim, Jin Nam; Lee, Hyun-Jeong

    2016-08-01

    Dosage compensation system with X chromosome upregulation and inactivation have evolved to overcome the genetic imbalance between sex chromosomes in both male and female of mammals. Although recent development of chromosome-wide technologies has allowed us to test X upregulation, discrete data processing and analysis methods draw disparate conclusions. A series of expression studies revealed status of dosage compensation in some species belonging to monotremes, marsupials, rodents and primates. However, X upregulation in the Artiodactyla order including cattle have not been studied yet. In this study, we surveyed the genome-wide transcriptional upregulation in X chromosome in cattle RNA-seq data using different gene filtration methods. Overall examination of RNA-seq data revealed that X chromosome in the pituitary gland expressed more genes than in other peripheral tissues, which was consistent with the previous results observed in human and mouse. When analyzed with globally expressed genes, a median X:A expression ratio was 0.94. The ratio of 1-to-1 ortholog genes between chicken and mammals, however, showed considerable reduction to 0.68. These results indicate that status of dosage compensation for cattle is not deviated from those found in rodents and primate, and this is consistent with the evolutionary history of cattle.

  17. Dosage compensation of the sex chromosomes and autosomes.

    Science.gov (United States)

    Disteche, Christine M

    2016-08-01

    Males are XY and females are XX in most mammalian species. Other species such as birds have a different sex chromosome make-up: ZZ in males and ZW in females. In both types of organisms one of the sex chromosomes, Y or W, has degenerated due to lack of recombination with its respective homolog X or Z. Since autosomes are present in two copies in diploid organisms the heterogametic sex has become a natural "aneuploid" with haploinsufficiency for X- or Z-linked genes. Specific mechanisms have evolved to restore a balance between critical gene products throughout the genome and between males and females. Some of these mechanisms were co-opted from and/or added to compensatory processes that alleviate autosomal aneuploidy. Surprisingly, several modes of dosage compensation have evolved. In this review we will consider the evidence for dosage compensation and the molecular mechanisms implicated.

  18. Dosage compensation, the origin and the afterlife of sex chromosomes.

    Science.gov (United States)

    Larsson, Jan; Meller, Victoria H

    2006-01-01

    Over the past 100 years Drosophila has been developed into an outstanding model system for the study of evolutionary processes. A fascinating aspect of evolution is the differentiation of sex chromosomes. Organisms with highly differentiated sex chromosomes, such as the mammalian X and Y, must compensate for the imbalance in gene dosage that this creates. The need to adjust the expression of sex-linked genes is a potent force driving the rise of regulatory mechanisms that act on an entire chromosome. This review will contrast the process of dosage compensation in Drosophila with the divergent strategies adopted by other model organisms. While the machinery of sex chromosome compensation is different in each instance, all share the ability to direct chromatin modifications to an entire chromosome. This review will also explore the idea that chromosome-targeting systems are sometimes adapted for other purposes. This appears the likely source of a chromosome-wide targeting system displayed by the Drosophila fourth chromosome.

  19. A brief history of dosage compensation

    Indian Academy of Sciences (India)

    Stanley M. Gartler

    2014-08-01

    In 1914, H. J. Muller postulated the origin of the Y chromosome as having resulted from restricted recombination between homologous sex chromosomes in the male and the accumulation of deleterious mutations. This evolutionary process leads to dosage compensation. This article lays out a brief history of dosage compensation in genetics.

  20. Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart

    DEFF Research Database (Denmark)

    Hertz, C L; Christiansen, S L; Ferrero-Miliani, Laura;

    2016-01-01

    -two cases had non-diagnostic structural cardiac abnormalities and 20 cases, diagnosed with a cardiomyopathy post-mortem (ARVC = 14, HCM = 6), served as comparators. Fifteen (29 %) of the deceased individuals with non-diagnostic findings had variants with likely functional effects based on conservation......BACKGROUND: In sudden, unexpected, non-traumatic death in young individuals, structural abnormalities of the heart are frequently identified at autopsy. However, the findings may be unspecific and cause of death may remain unclear. A significant proportion of these cases are most likely caused...... with non-diagnostic structural abnormalities of the heart. METHODS AND RESULTS: We screened 72 suspected SCD cases (

  1. Estimated Radiation Dosage on Mars

    Science.gov (United States)

    2002-01-01

    This global map of Mars shows the estimated radiation dosages from cosmic rays reaching the surface, a serious health concern for any future human exploration of the planet.The estimates are based on cosmic-radiation measurements by the Mars radiation environment experiment, an instrument on NASA's Mars 2000 Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have the lowest levels of cosmic radiation are where the elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than we have on Earth.The colors in the map refer to the estimated annual dose equivalent in rems, a unit of radiation dose. The range is generally from 10 rems(color-coded dark blue) to 20 rems (color coded dark red). Radiation exposure for astronauts on the International Space Station in Earth orbit is typically equivalent to an annualized rate of 20 to 40 rems.NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center, Houston. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  2. Advances in solid dosage form manufacturing technology.

    Science.gov (United States)

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation. PMID:17855217

  3. ON THE SELECTION OF DRUGS DOSAGE REGIMEN

    Directory of Open Access Journals (Sweden)

    E. N. Bochanova

    2015-09-01

    Full Text Available A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.

  4. ON THE SELECTION OF DRUGS DOSAGE REGIMEN

    OpenAIRE

    E. N. Bochanova

    2015-01-01

    A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.

  5. Large-scale population study of human cell lines indicates that dosage compensation is virtually complete.

    Directory of Open Access Journals (Sweden)

    Colette M Johnston

    2008-01-01

    Full Text Available X chromosome inactivation in female mammals results in dosage compensation of X-linked gene products between the sexes. In humans there is evidence that a substantial proportion of genes escape from silencing. We have carried out a large-scale analysis of gene expression in lymphoblastoid cell lines from four human populations to determine the extent to which escape from X chromosome inactivation disrupts dosage compensation. We conclude that dosage compensation is virtually complete. Overall expression from the X chromosome is only slightly higher in females and can largely be accounted for by elevated female expression of approximately 5% of X-linked genes. We suggest that the potential contribution of escape from X chromosome inactivation to phenotypic differences between the sexes is more limited than previously believed.

  6. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.

    Science.gov (United States)

    Butterfield, D Allan; Poon, H Fai

    2005-10-01

    The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels. PMID:16026957

  7. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  8. Urine - abnormal color

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  9. Abnormalities in structure and expression of the retinoblastoma gene in small cell lung cancer cell lines and xenografts in nude mice

    DEFF Research Database (Denmark)

    Rygaard, K; Sorenson, G D; Pettengill, O S;

    1990-01-01

    The putative retinoblastoma gene (Rb) is a tumor suppressor gene which is believed to cause retinoblastomas when both alleles are inactivated, leading to lack of the encoded Mr 110,000-116,000 phosphoprotein. Inactivation of the Rb gene has also been found in several other tumor types, including...

  10. Molecular Characterisation of Structural Chromosomal Abnormalities Associated with Congenital Disorders

    OpenAIRE

    Mansouri, Mahmoud R.

    2006-01-01

    Chromosomal abnormalities are defined as changes in the chromosome structure and fall in one of two categories. The first category is numerical alterations while the second category consists of structural abnormalities. Structural chromosomal abnormalities do not always interrupt genes in order to cause disease. They can also affect gene expression by separating a gene and its promoter element from distant regulatory elements. We have used characterisation of structural chromosomal abnormalit...

  11. Housing under abnormal light-dark cycles attenuates day/night expression rhythms of the clock genes Per1, Per2, and Bmal1 in the amygdala and hippocampus of mice.

    Science.gov (United States)

    Moriya, Shunpei; Tahara, Yu; Sasaki, Hiroyuki; Ishigooka, Jun; Shibata, Shigenobu

    2015-10-01

    Although the results of previous studies have suggested that disruptions in circadian rhythms are involved in the pathogenesis of depression, no studies have examined the interaction of clock gene expression deficit and depression state. In this study, we examined clock gene expression levels and depressive-like behavior in mice housed under 3.5h light, 3.5h dark (T = 7) conditions to investigate the association between clock gene expression and depressive state. C57BL/6J mice were housed under a T = 24 cycle (12h light, 12h dark) or a T = 7 cycle and clock gene expression levels in the hippocampus and the amygdala were measured by real-time RT-PCR. Depressive state was evaluated by the forced swim test (FST). Although circadian rhythms of Per1 and Per2 clock gene expression in the hippocampus and amygdala were still detected under T = 7 conditions, rhythmicity and expression levels of both significantly decreased. Mice housed with a T = 7 cycle showed increased immobile time in the FST than those with a T = 24 cycle. The present results suggest that the presence of a depressive state around the early active phase of activity may be related to impairment of rhythmicity and expression levels of Per1 and Per2 genes under abnormal light-dark conditions.

  12. Abnormal mineralization of the Ts65Dn Down syndrome mouse appendicular skeleton begins during embryonic development in a Dyrk1a-independent manner.

    Science.gov (United States)

    Blazek, Joshua D; Malik, Ahmed M; Tischbein, Maeve; Arbones, Maria L; Moore, Clara S; Roper, Randall J

    2015-05-01

    The relationship between gene dosage imbalance and phenotypes associated with Trisomy 21, including the etiology of abnormal bone phenotypes linked to Down syndrome (DS), is not well understood. The Ts65Dn mouse model for DS exhibits appendicular skeletal defects during adolescence and adulthood but the developmental and genetic origin of these phenotypes remains unclear. It is hypothesized that the postnatal Ts65Dn skeletal phenotype originates during embryonic development and results from an increased Dyrk1a gene copy number, a gene hypothesized to play a critical role in many DS phenotypes. Ts65Dn embryos exhibit a lower percent bone volume in the E17.5 femur when compared to euploid embryos. Concomitant with gene copy number, qPCR analysis revealed a  ~1.5 fold increase in Dyrk1a transcript levels in the Ts65Dn E17.5 embryonic femur as compared to euploid. Returning Dyrk1a copy number to euploid levels in Ts65Dn, Dyrk1a(+/-) embryos did not correct the trisomic skeletal phenotype but did return Dyrk1a gene transcript levels to normal. The size and protein expression patterns of the cartilage template during embryonic bone development appear to be unaffected at E14.5 and E17.5 in trisomic embryos. Taken together, these data suggest that the dosage imbalance of genes other than Dyrk1a is involved in the development of the prenatal bone phenotype in Ts65Dn embryos. PMID:25556111

  13. International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

    Science.gov (United States)

    Yildiz, Ismail; Sagliker, Yahya; Demirhan, Osman; Tunc, Erdal; Inandiklioglu, Nihal; Tasdemir, Deniz; Acharya, Vidya; Zhang, Ling; Golea, Ovidia; Sabry, Alaa; Ookalkar, Dhananjay S; Capusa, Cristina; Radulescu, Dana; Garneata, Liliana; Mircescu, Gabriel; Ben Maiz, Hedi; Chen, Cheng Hsu; Prado Rome, Jorge; Benzegoutta, Mansour; Paylar, Nuray; Eyuboglu, Kamil; Karatepe, Ersin; Esenturk, Mustafa; Yavascan, Onder; Grzegorzevska, Alicza; Shilo, Valery; Mazdeh, Mitra Mahdavi; Francesco, Ramos Carillo; Gouda, Zaghloul; Adam, Siddik Momin; Emir, Idris; Ocal, Faith; Usta, Erol; Kiralp, Necati; Sagliker, Cemal; Ozkaynak, Piril Sagliker; Sagliker, Hasan Sabit; Bassuoni, Mahmoud; Sekin, Oktay

    2012-01-01

    Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS. PMID:22200434

  14. Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal

    NARCIS (Netherlands)

    Postma, A. V.; Alders, M.; Sylva, M.; Bilardo, C. M.; Pajkrt, E.; van Rijn, R. R.; Schulte-Merker, S.; Bulk, S.; Stefanovic, S.; Ilgun, A.; Barnett, P.; Mannens, M. M. A. M.; Moorman, A. F. M.; Oostra, R. J.; van Maarle, M. C.

    2014-01-01

    Background The T gene (brachyury gene) is the founding member of the T-box family of transcription factors and is vital for the formation and differentiation of the mesoderm and the axial development of all vertebrates. Results We report here on four patients from three consanguineous families exhib

  15. Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal

    NARCIS (Netherlands)

    Postma, A V; Alders, M; Sylva, M; Bilardo, C M; Pajkrt, E; van Rijn, R R; Schulte-Merker, S; Bulk, S; Stefanovic, S; Ilgun, A; Barnett, P; Mannens, M M A M; Moorman, A F M; Oostra, R J; van Maarle, M C

    2014-01-01

    BACKGROUND: The T gene (brachyury gene) is the founding member of the T-box family of transcription factors and is vital for the formation and differentiation of the mesoderm and the axial development of all vertebrates. RESULTS: We report here on four patients from three consanguineous families exh

  16. Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

    Science.gov (United States)

    Okamoto, Y; Chaves, A; Chen, J; Kelley, R; Jones, K; Weed, H G; Gardner, K L; Gangi, L; Yamaguchi, M; Klomkleaw, W; Nakayama, T; Hamlin, R L; Carnes, C; Altschuld, R; Bauer, J; Hai, T

    2001-08-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function. PMID:11485922

  17. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities

    OpenAIRE

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N.; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roland G. Roberts

    2010-01-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin α2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study...

  18. Heterozygous deletion of a 2-megabase region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities

    OpenAIRE

    Roland G Roberts; Frost, Amy R; Boehm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise

    2010-01-01

    Abstract Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin ?2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN, FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been report...

  19. Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

    Directory of Open Access Journals (Sweden)

    Erica Larschan

    Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

  20. Higher unit dosage of psychotropic drugs.

    Science.gov (United States)

    Burrell, C D

    1975-12-01

    The realities of the marketplace dictate that pharmaceutical companies seek to develop higher unit dosage forms. Technical problems not infrequently hinder such development. In low doses once-a-day medication with psychotropics is possible and practical. The potential for adverse reactions frequently renders it desirable to divide higher daily doses into two separate doses, one given in the morning and the other in the evening. PMID:1233527

  1. Estimated Maximal Safe Dosages of Tumescent Lidocaine

    OpenAIRE

    Klein, Jeffrey A.; Jeske, Daniel R.

    2016-01-01

    BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses wer...

  2. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes.

    Science.gov (United States)

    Li, Wen; Wang, Xianming; Fan, Wenxia; Zhao, Ping; Chan, Yau-Chi; Chen, Shen; Zhang, Shiqiang; Guo, Xiangpeng; Zhang, Ya; Li, Yanhua; Cai, Jinglei; Qin, Dajiang; Li, Xingyan; Yang, Jiayin; Peng, Tianran; Zychlinski, Daniela; Hoffmann, Dirk; Zhang, Ruosi; Deng, Kang; Ng, Kwong-Man; Menten, Bjorn; Zhong, Mei; Wu, Jiayan; Li, Zhiyuan; Chen, Yonglong; Schambach, Axel; Tse, Hung-Fat; Pei, Duanqing; Esteban, Miguel A

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation. PMID:21949351

  3. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes.

    Science.gov (United States)

    Li, Wen; Wang, Xianming; Fan, Wenxia; Zhao, Ping; Chan, Yau-Chi; Chen, Shen; Zhang, Shiqiang; Guo, Xiangpeng; Zhang, Ya; Li, Yanhua; Cai, Jinglei; Qin, Dajiang; Li, Xingyan; Yang, Jiayin; Peng, Tianran; Zychlinski, Daniela; Hoffmann, Dirk; Zhang, Ruosi; Deng, Kang; Ng, Kwong-Man; Menten, Bjorn; Zhong, Mei; Wu, Jiayan; Li, Zhiyuan; Chen, Yonglong; Schambach, Axel; Tse, Hung-Fat; Pei, Duanqing; Esteban, Miguel A

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.

  4. Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke [Teikyo Univ. School of Medicine, Tokyo (Japan)] [and others

    1997-01-20

    We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,de1(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient. 16 refs., 4 figs.

  5. Incomplete sex chromosome dosage compensation in the Indian meal moth, Plodia interpunctella, based on de novo transcriptome assembly.

    Science.gov (United States)

    Harrison, Peter W; Mank, Judith E; Wedell, Nina

    2012-01-01

    Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global dosage compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide dosage compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of dosage compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome dosage compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global dosage compensation, although more species will need to be sampled to confirm this assertion.

  6. : MAP6 dosage controls cognitive abilities

    OpenAIRE

    Volle, Julien; Brocard, Jacques,; Saoud, Mohamed; Gory-Faure, Sylvie; Brunelin, Jérôme; Andrieux, Annie; Suaud-Chagny, Marie-Françoise

    2012-01-01

    International audience Background: STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP null mice. Methods : Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (He...

  7. Research progress of the abnormal expression of Sox genes in breast cancer%Sox基因的异常表达与乳腺癌研究的进展

    Institute of Scientific and Technical Information of China (English)

    石静; 章佳新

    2014-01-01

    Sox基因家族是一类SRY相关基因构成的基因家族,编码一系列Sox家族的转录因子.Sox基因在个体发育过程中参与了性别决定和分化、神经发育、软骨形成等多种发育过程.近年研究者发现,Sox基因的异常表达与乳腺癌的发生、发展有一定关系,如Sox2、Sox4的过表达与乳腺癌的发生相关;Sox7和Sox17在乳腺癌中可作为抑癌基因,其表达下调可激活Wnt/β-catenin信号通路,与乳腺癌的发生发展有一定关系.%Sox gene family is composed of a class of SRY gene,encoding a series of transcription factors.In the ontogeny,sox genes involved in a variety of development,such as sex determination and differentiation,neural development,cartilage formation.In recent years,researchers found that the abnormal expression of sox gene was related with the development of breast cancer,such as,the overexpression of Sox2 and Sox4 was related with breast cancer; Sox7 and Sox17 in breast cancer could act as tumor suppressor gene,the downregulation of which could activate Wnt/β-catenin signaling pathway.

  8. Chromosomal Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

  9. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  10. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome.

    Science.gov (United States)

    Shi, Jianhua; Zhang, Tianyi; Zhou, Chunlei; Chohan, Muhammad Omar; Gu, Xiaosong; Wegiel, Jerzy; Zhou, Jianhua; Hwang, Yu-Wen; Iqbal, Khalid; Grundke-Iqbal, Inge; Gong, Cheng-Xin; Liu, Fei

    2008-10-17

    Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.

  11. Abnormal protein aggregationand neurodegenerativediseases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Abnormal protein aggregation or amyloid is the major cause ofmany neurodegenerative disorders. The present review focuses on the correlation between sequence and structure features of proteins related to the diseases and abnormal protein aggregation. Recent progress has improved our knowledge on understand-ing the mechanism of amyloid formation. We suggest a nucleation model for ordered protein aggregation, which can also explain pathogenesis mechanisms of these neurodegenerative diseases in vivo.

  12. Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

    OpenAIRE

    Okamoto, Yoshichika; Chaves, Alysia; Chen, Jingchun; Kelley, Robert; Jones, Keith; Weed, Harrison G.; Gardner, Kevin L.; Gangi, Lisa; Yamaguchi, Mamoru; Klomkleaw, Wuthichai; Nakayama, Tomohiro; HAMLIN, Robert L.; Carnes, Cynthia; Altschuld, Ruth; Bauer, John

    2001-01-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the α-myosin heavy chain promoter have atrial enlargement, and a...

  13. SEMISOLID DOSAGE FORM OF PHENYTOIN SODIUM

    Directory of Open Access Journals (Sweden)

    Maiada M Almousilly

    2012-11-01

    Full Text Available Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse skin was higher from the water soluble base (10% w/w compared to other ointment bases, the difference was highly significant (P< 0.05.

  14. SEMISOLID DOSAGE FORM OF PHENYTOIN SODIUM

    OpenAIRE

    Maiada M Almousilly; Loay K. Abdulrahman; Sadiq H. Alshmesawy; Fatima A. Tawfiq

    2012-01-01

    Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse ...

  15. Foreign matter identification from solid dosage forms

    DEFF Research Database (Denmark)

    Pekka Pajander, Jari; Haugshøj, Kenneth Brian; Bjørneboe, Kathrine;

    2013-01-01

    was analysed by utilization of different analytical techniques, such as light microscopy (LM), scanning electron microscopy in combination with energy dispersive X-ray microanalysis (SEM/EDX), Fourier transform infrared spectroscopy (FT-IR) and time-of-flight secondary ion mass spectrometry (ToF-SIMS...... confirmation of the identification. However, FT-IR can be used to obtain information on the compounds chemical structure and conformation, and ToF-SIMS provides sensitivity in cases, where the entire solid dosage form is contaminated with foreign matter....

  16. Normal number of CGG repeats in the FMR-1 gene and abnormal incorporation of fibrillin into the extracellular matrix in Lujan Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Greenhaw, G.A.; Stone, C.; Milewicz, D. [Univ. of Texas Health Science Center, Houston, TX (United States)

    1994-09-01

    Lujan syndrome is an X-linked condition that includes mild-to-moderate mental retardation, poor social integration, normal secondary sexual development with normal testicular size, generalized hypotonia, hypernasal voice and dolichostenomelia. Major cardiac complications and lens dislocation have not been reported although severe myopia may occur. All reported cases have had negative cytogenetic screening for fra(X) syndrome but establishing this constellation of findings as a distinctive entity has been difficult. We report 4 males in two sibships with clinical findings consistent with Lujan syndrome, normal karyotypes, negative cytogenetic screening for fra(X) syndrome and a normal number of CGG repeats in the FMR-1 gene. Dermal fibroblasts explanted from one of the affected males were used to study fibrillin synthesis secretion and extracellular matrix incorporation into microfibrils. Cells from the affected individual showed normal synthesis and secretion of fibrillin when compared to control cells, but the fibrillin was not incorporated into the extracellular matrix. These results suggest the presence of a gene on the X chromosome which may play a role in microfibril assembly and when deficient may disrupt the incorporation of fibrillin into microfibrils. This may be important not only in normal body morphogenesis but also in the development/function of the brain. More affected individuals are needed to investigate these findings further.

  17. Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

    Science.gov (United States)

    Banno, Kimihiko; Omori, Sayaka; Hirata, Katsuya; Nawa, Nobutoshi; Nakagawa, Natsuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakuma, Tetsushi; Yamamoto, Takashi; Toki, Tsutomu; Ito, Etsuro; Yamamoto, Toshiyuki; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2016-05-10

    Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. PMID:27134169

  18. The characteristics of novel dosage forms

    Directory of Open Access Journals (Sweden)

    Milić-Aškrabić Jela

    2003-01-01

    Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

  19. Evaluation of new indomethacin dosage forms.

    Science.gov (United States)

    Waller, E S

    1983-01-01

    Indomethacin, an indole derivative nonsteroidal anti-inflammatory drug, has been available since the early 1960s in gelatin capsules. In 1982, a sustained release product, Indocin SR, was marketed. Awaiting marketing approval is a unique controlled release form of indomethacin, Indos. The disposition of indomethacin includes enterohepatic cycling and extensive metabolism to inactive metabolites. Enterohepatic cycling makes interpretation of bioavailability estimates of indomethacin dosage forms difficult. The relationship of indomethacin plasma concentration to therapeutic effects and side effects is inconclusive. It appears in vivo prostaglandin inhibition occurs at very low plasma concentrations that are achievable with all available dosage forms. Indocin SR is a sustained release capsule of indomethacin designed to deliver 25 mg of drug immediately and 50 mg gradually. Absolute bioavailability of the product is 80%. The plasma concentration-time curves do not show good sustained release characteristics; after four hours plasma concentrations resemble those seen with a single dose of regular capsule. The cost compared with Indocin is competitive. Indos is a zero-order release form of indomethacin. It is a unique drug delivery system that shows good controlled release characteristics. Bioavailability is 85%. Both Indocin SR and Indos are apparently therapeutically equivalent to indomethacin capsules. In elderly patients, Indos has been shown to be associated with fewer side effects than Indocin. Both Indocin SR and Indos have the advantage of once or twice daily dosing.

  20. Abnormal expression of VEGF and its gene transcription status as diagnostic indicators in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Yun Shi; Yang Shi; Xuli Yang; Jianrong Chen; Qi Qian; Dengfu Yao; Guangzhou Wu

    2015-01-01

    Objective Angiogenesis is known to be essential for the survival, growth, invasion, and metastasis of lung cancer cells. Vascular endothelial growth factor (VEGF) is an important factor regulating angiogenesis of non-small cell lung cancer (NSCLC); however, its pathologic features and significance are unclear. In this study, the tissue VEGF expression levels and its gene transcriptional status, as well as circulating VEGF levels, were investigated in patients with lung disease.Methods VEGF protein and mRNA expression levels in 38 lung tissue samples were analyzed by immu-nohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Circulating VEGF levels were detected quantitatively by an enzyme linked immuno-sorbent assay. Results The level of VEGF expression was significantly higher in lung cancer tissue than in the corre-sponding paracancerous or non-cancerous tissues. The average level of VEGF-positive staining was 76% in tissue samples from NSCLC patients; the levels were 89% in tissue samples from stage Ⅲ patients and 92% in stage Ⅳ patients. High VEGF expression was also evident in cases with lymph node metastasis (84%), distant metastasis (90%), and lower differentiation degree (89%). VEGF mRNA in cancerous tis-sues was represented predominantly by the VEGF121 and VEGF165 isoforms. Circulating VEGF levels were significantly higher in NSCLC patients [(840 ± 324) pg/mL] than in patients with benign lung diseases [(308 ± 96) pg/mL] or in healthy individuals serving as controls [(252 ± 108) pg/mL]. Conclusion The over-expression of lung VEGF and its gene transcription status should be useful mo-lecular indicators for NSCLC diagnosis.

  1. Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes

    Directory of Open Access Journals (Sweden)

    Pérez-Jurado Luis A

    2011-05-01

    Full Text Available Abstract Background Down syndrome (DS; trisomy 21 is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown. Many different experimental techniques have been applied to analyse the effects of dosage imbalance at the molecular and phenotypical level, however, currently no integrative approach exists that attempts to extract the common information. Results We have performed a statistical meta-analysis from 45 heterogeneous publicly available DS data sets in order to identify consistent dosage effects from these studies. We identified 324 genes with significant genome-wide dosage effects, including well investigated genes like SOD1, APP, RUNX1 and DYRK1A as well as a large proportion of novel genes (N = 62. Furthermore, we characterized these genes using gene ontology, molecular interactions and promoter sequence analysis. In order to judge relevance of the 324 genes for more general cerebral pathologies we used independent publicly available microarry data from brain studies not related with DS and identified a subset of 79 genes with potential impact for neurocognitive processes. All results have been made available through a web server under http://ds-geneminer.molgen.mpg.de/. Conclusions Our study represents a comprehensive integrative analysis of heterogeneous data including genome-wide transcript levels in the domain of trisomy 21. The detected dosage effects build a resource for further studies of DS pathology and the development of new therapies.

  2. Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: Re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach

    Directory of Open Access Journals (Sweden)

    Yamaguchi Toshikazu

    2005-01-01

    lesions in the distal stomach, which had both gastric and intestinal phenotypic mucin, are considered to develop from the tubular proliferative zone with the incomplete type of the intestinal metaplasia and p53 gene abnormality, while a part of them, which had only gastric phenotypic mucin, may derive from the gastric native tubules (non-metaplastic epithelium with p53 gene abnormality.

  3. SOLID DOSAGE FORMS IN UNANI SYSTEM OF MEDICINE: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Shahid S. Chaudhary

    2013-06-01

    Full Text Available Drugs obtained from natural sources are rarely administered or dispensed to patients in their native forms but are formulated into dosage forms. In Unani system of medicine dosage forms are broadly classified into four categories according to their state these are solid dosage forms, semisolid, liquid and gaseous dosage forms. Among them solid dosage forms e.g. Sufoof (powder, Kohal (coryllium, Kushta (calx, Qurs (tablet etc have several advantages over other dosage forms such as higher stability, easy to carry, better patient compliance. The rate of absorption of a formulation depends on the dosage form, route of administration and particle size. Some solid dosage forms like shiyaf (suppository, zarur (dusting powder, noorah (depilatory are used locally to produce their respective actions. But unfortunately some effective and potent dosage forms are neither used nor manufactured and they are near to extinct. Therefore in the present review an effort has been made to summarize the detailed Unani classical literature of solid dosage forms.

  4. [Hair shaft abnormalities].

    Science.gov (United States)

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  5. Neurological abnormalities predict disability

    DEFF Research Database (Denmark)

    Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje;

    2014-01-01

    was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5......, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost...

  6. Abnormal dentin structure in two novel gene mutations [COL1A1, Arg134Cys] and [ADAMTS2, Trp795-to-ter] causing rare type I collagen disorders.

    Science.gov (United States)

    De Coster, P J; Cornelissen, M; De Paepe, A; Martens, L C; Vral, A

    2007-02-01

    Histological and ultrastructural observations of dentin of two patients affected with rare types of type I collagen disorders are presented. In the first case, a homozygous nonsense mutation in ADAMTS2 (substitution of a codon for tryptophan by a stopcodon) causes type VIIC Ehlers-Danlos syndrome (EDS) with multiple tooth agenesis and focal dysplastic dentin defects. In the second case, a missense mutation in COL1A1 (substitution of arginine by cysteine) results in a type I EDS phenotype with clinically normal-appearing dentition. Tooth samples are investigated by using light microscopy (LM), transmission electron microscopy (TEM) and immunostaining for types I and III collagen, and tenascin. These are compared with samples from patients with types III and IV osteogenesis imperfecta (OI) in association with dentinogenesis imperfecta (DI), showing a consistently abnormal appearance of the dentin in all specimens, with variations being primarily those of degree of change. Similarities in histological changes include the alternating presence of normal and severe pathological areas in primary and secondary dentin, the latter being characterized by large canal-like structures in atubular areas. Ultrastructural evidence of pathological dentinogenesis include abnormal distribution, size and organization of collagen fibers, which may also be found in clinically unaffected teeth. The histological and ultrastructural changes seen can be explained on the basis of odontoblast dysfunction which may be secondary to the collagen defect, interfering with different levels of odontoblast cell function and intercellular communication. These observations on (ultra)structural dentin defects associated with the two novel gene mutations are the first ever reported. PMID:17118335

  7. A Novel Large Deletion Encompassing the Whole of the Galactose-1-Phosphate Uridyltransferase (GALT) Gene and Extending into the Adjacent Interleukin 11 Receptor Alpha (IL11RA) Gene Causes Classic Galactosemia Associated with Additional Phenotypic Abnormalities

    OpenAIRE

    Papachristoforou, Rena; Petrou, Petros P.; Sawyer, Hilary; Williams, Maggie; Drousiotou, Anthi

    2013-01-01

    Objective The characterization of a novel large deletion in the galactose-1-phosphate uridyltransferase (GALT) gene accounting for the majority of disease alleles in Cypriot patients with classic galactosemia.

  8. Abnormal Expression of p73 Gene in Adult Acute Lymphoblastic Leukemia%p73基因在成人急性淋巴细胞白血病中表达的研究

    Institute of Scientific and Technical Information of China (English)

    俞罡

    2014-01-01

    目的:研究p73基因在急性淋巴细胞性白血病(ALL)发病机制中的作用及临床意义。方法:收集32例ALL患者及30例正常对照组骨髓样本,DNA和RNA抽提后用RT-PCR检测p73基因的表达、甲基化特异性PCR(MSP)检测p73基因第一外显子甲基化状态,并结合临床资料进行分析。结果:11例p73基因阴性表达,阴性表达率为34.38%,其中9例第一外显子区域均发生甲基化(81.82%);21例p73基因阳性表达,32例ALL患者中,仅1例发生甲基化(4.76%);正常对照组30例,均为p73基因阳性表达,阳性表达率为100%。p73基因的阴性表达与ALL患者的高年龄(≥60岁)、高白细胞数(≥30×109/L)及对治疗时间延长(>4周取得完全缓解)有关。结论:p73基因异常表达与成人ALL的发病机制有关,具有一定的诊断及判断预后的价值;其甲基化可能是p73基因在ALL中表达沉默的主要机制。%Objective:To investigate the effect of p73 gene on pathogenesis of acute lymphoblastic leukemia(ALL)and clinical significance of abnormal expression of p73 gene. Method:Genomic DNA and total RNA were extracted from 32 ALL and 30 normal bone marrow samples. The expression of p73 was evaluated by RT-PCR. The methylation specific PCR(MSP)was performed to examine the methylation status of p73 gene exon. Result:Of 32 ALL samples,11 showed without expression of p73 mRNA,with a negative rate of 34.38%. Normal samples all had expression of p73 gene,with a positive rate of 100%. 9 patients without expression of p73 were found to have methylation of p73 gene,whereas only one of patients with expression of p73 mRNA was found to have methylation. Negative expression of p73 gene was associated with higher age(≥60 years old ),higher leucocyte count(≥30×109/L) and delayed reaction to therapy(patients attained complete remission after 4 weeks). Conclusion:Negative expression of p73 gene probably plays a role in the

  9. [Reexaminations of dosages in Shanghanlun: comparison of the dosages among decoctions, pills and powder formulations].

    Science.gov (United States)

    Suzuki, Tatsuhiko; Endo, Jiro

    2011-01-01

    This paper reveals the dosages of decoctions in Shanghanlun in relation of pills and powder formulations, and obtains following results. At the first examination of the system of weight, while Taohongjing shows three kinds of system of weight; [(1)1liang is equivalent to 14 g. (2) 1liang = 7 g (3) 1liang = 1.4 g], he describes the necessity of the corrective system of weight among the decoctions, the pills and the powder formulations. After Song dynasty, Zhusanfa, which is the method of preparing the decoction by placing powder ingredients of prescriptions in water and simmer, have been mainly adopted. In the term of Zhusanfa, although the whole quantities of prescriptions are written with the ancient weight unit, the notation of the dosage is indicated by the current weight unit, Qian. In Shanghanlun, since the dosage form seems to have been changed from the pills or the powders into the decoction, some of decoctions contain impractical dose for decoction. PMID:21796994

  10. The X factor: X chromosome dosage compensation in the evolutionarily divergent monotremes and marsupials.

    Science.gov (United States)

    Whitworth, Deanne J; Pask, Andrew J

    2016-08-01

    Marsupials and monotremes represent evolutionarily divergent lineages from the majority of extant mammals which are eutherian, or placental, mammals. Monotremes possess multiple X and Y chromosomes that appear to have arisen independently of eutherian and marsupial sex chromosomes. Dosage compensation of X-linked genes occurs in monotremes on a gene-by-gene basis, rather than through chromosome-wide silencing, as is the case in eutherians and marsupials. Specifically, studies in the platypus have shown that for any given X-linked gene, a specific proportion of nuclei within a cell population will silence one locus, with the percentage of cells undergoing inactivation at that locus being highly gene-specific. Hence, it is perhaps not surprising that the expression level of X-linked genes in female platypus is almost double that in males. This is in contrast to the situation in marsupials where one of the two X chromosomes is inactivated in females by the long non-coding RNA RSX, a functional analogue of the eutherian XIST. However, marsupial X chromosome inactivation differs from that seen in eutherians in that it is exclusively the paternal X chromosome that is silenced. In addition, marsupials appear to have globally upregulated X-linked gene expression in both sexes, thus balancing their expression levels with those of the autosomes, a process initially proposed by Ohno in 1967 as being a fundamental component of the X chromosome dosage compensation mechanism but which may not have evolved in eutherians.

  11. Increased STAG2 dosage defines a novel cohesinopathy with intellectual disability and behavioral problems.

    Science.gov (United States)

    Kumar, Raman; Corbett, Mark A; Van Bon, Bregje W M; Gardner, Alison; Woenig, Joshua A; Jolly, Lachlan A; Douglas, Evelyn; Friend, Kathryn; Tan, Chuan; Van Esch, Hilde; Holvoet, Maureen; Raynaud, Martine; Field, Michael; Leffler, Melanie; Budny, Bartłomiej; Wisniewska, Marzena; Badura-Stronka, Magdalena; Latos-Bieleńska, Anna; Batanian, Jacqueline; Rosenfeld, Jill A; Basel-Vanagaite, Lina; Jensen, Corinna; Bienek, Melanie; Froyen, Guy; Ullmann, Reinhard; Hu, Hao; Love, Michael I; Haas, Stefan A; Stankiewicz, Pawel; Cheung, Sau Wai; Baxendale, Anne; Nicholl, Jillian; Thompson, Elizabeth M; Haan, Eric; Kalscheuer, Vera M; Gecz, Jozef

    2015-12-20

    Next generation genomic technologies have made a significant contribution to the understanding of the genetic architecture of human neurodevelopmental disorders. Copy number variants (CNVs) play an important role in the genetics of intellectual disability (ID). For many CNVs, and copy number gains in particular, the responsible dosage-sensitive gene(s) have been hard to identify. We have collected 18 different interstitial microduplications and 1 microtriplication of Xq25. There were 15 affected individuals from 6 different families and 13 singleton cases, 28 affected males in total. The critical overlapping region involved the STAG2 gene, which codes for a subunit of the cohesin complex that regulates cohesion of sister chromatids and gene transcription. We demonstrate that STAG2 is the dosage-sensitive gene within these CNVs, as gains of STAG2 mRNA and protein dysregulate disease-relevant neuronal gene networks in cells derived from affected individuals. We also show that STAG2 gains result in increased expression of OPHN1, a known X-chromosome ID gene. Overall, we define a novel cohesinopathy due to copy number gain of Xq25 and STAG2 in particular.

  12. Abnormal ionization in sonoluminescence

    Institute of Scientific and Technical Information of China (English)

    张文娟; 安宇

    2015-01-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%–70%as the bubble flashes, which is difficult to explain by using previous models.

  13. Ultrasonography of splenic abnormalities

    Institute of Scientific and Technical Information of China (English)

    Ming-Jen Chen; Ming-Jer Huang; Wen-Hsiung Chang; Tsang-En Wang; Horng-Yuan Wang; Cheng-Hsin Chu; Shee-Chan Lin; Shou-Chuan Shih

    2005-01-01

    AIM: This report gives a comprehensive overview of ultrasonography of splenic abnormalities. Certain ultrasonic features are also discussed with pathologic correlation.METHODS: We review the typical ultrasonic characteristics of a wide range of splenic lesions, illustrating them with images obtained in our institution from 2000 to 2003.One hundred and three patients (47 men, 56 women),with a mean age of 54 years (range 9-92 years), were found to have an abnormal ultrasonic pattern of spleen.RESULTS: We describe the ultrasonic features of various splenic lesions such as accessory spleen, splenomegaly,cysts, cavernous hemangiomas, lymphomas, abscesses,metastatic tumors, splenic infarctions, hematomas, and rupture, based on traditional gray-scale and color Doppler sonography.CONCLUSION: Ultrasound is a widely available, noninvasive,and useful means of diagnosing splenic abnormalities. A combination of ultrasonic characteristics and clinical data may provide an accurate diagnosis. If the US appearance alone is not enough, US may also be used to guide biopsy of suspicious lesions.

  14. Lubricants in Pharmaceutical Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Jinjiang Li

    2014-02-01

    Full Text Available Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.

  15. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  16. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms....

  17. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms....

  18. 21 CFR 520.2345 - Tetracycline oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline oral dosage forms. 520.2345 Section 520.2345 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Tetracycline oral dosage forms....

  19. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    Science.gov (United States)

    2012-03-19

    ... Medicine, 21 CFR part 520 is amended as follows: PART 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS 0 1. The... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Pergolide..., 2012. FOR FURTHER INFORMATION CONTACT: Amy L. Omer, Center for Veterinary Medicine (HFV-114), Food...

  20. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Science.gov (United States)

    2011-09-23

    ... to the Center for Veterinary Medicine, 21 CFR part 520 is amended as follows: PART 520--ORAL DOSAGE... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Tylosin... September 23, 2011. FOR FURTHER INFORMATION CONTACT: John K. Harshman, Center for Veterinary Medicine...

  1. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    Science.gov (United States)

    2011-12-16

    ... for Veterinary Medicine, 21 CFR part 520 is amended as follows: ] PART 520--ORAL DOSAGE FORM NEW... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Estriol..., Center for Veterinary Medicine (HFV-116), Food and Drug Administration, 7500 Standish Pl., Rockville,...

  2. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696...

  3. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin...

  4. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....

  5. PTEN dosage is essential for neurofibroma development and malignant transformation.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Dry, Sarah M; Nghiemphu, P Leia; Smith, Kate Barzan; Ao, Yan; Dang, Julie; Lawson, Gregory; Mellinghoff, Ingo K; Mischel, Paul S; Phelps, Michael; Parada, Luis F; Liu, Xin; Sofroniew, Michael V; Eilber, Fritz C; Wu, Hong

    2009-11-17

    Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes. Only K-Ras activation in combination with a single Pten allele deletion led to 100% penetrable development of NF lesions and subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression was found in all murine MPNSTs and a majority of human NF1-associated MPNST lesions, suggesting that PTEN dosage and its controlled signaling pathways are critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT imaging, we demonstrated that FDG can be used to identify the malignant transformation in both murine and human MPNSTs. Our data suggest that combined inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for patients with MPNST.

  6. PTEN dosage is essential for neurofibroma development and malignant transformation.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Dry, Sarah M; Nghiemphu, P Leia; Smith, Kate Barzan; Ao, Yan; Dang, Julie; Lawson, Gregory; Mellinghoff, Ingo K; Mischel, Paul S; Phelps, Michael; Parada, Luis F; Liu, Xin; Sofroniew, Michael V; Eilber, Fritz C; Wu, Hong

    2009-11-17

    Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes. Only K-Ras activation in combination with a single Pten allele deletion led to 100% penetrable development of NF lesions and subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression was found in all murine MPNSTs and a majority of human NF1-associated MPNST lesions, suggesting that PTEN dosage and its controlled signaling pathways are critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT imaging, we demonstrated that FDG can be used to identify the malignant transformation in both murine and human MPNSTs. Our data suggest that combined inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for patients with MPNST. PMID:19846776

  7. HLA dosage effect in narcolepsy with cataplexy.

    Science.gov (United States)

    van der Heide, Astrid; Verduijn, Willem; Haasnoot, Geert W; Drabbels, Jos J M; Lammers, Gert J; Claas, Frans H J

    2015-01-01

    Narcolepsy with cataplexy is a sleep disorder caused by the loss of hypocretin-producing neurons in the hypothalamus. It is tightly associated with a specific human leukocyte antigen (HLA)-allele: HLA-DQB1*06:02. Based on this, an autoimmune process has been hypothesized. A functional HLA-DQ molecule consists of a DQα and a DQβ chain. HLA-DQB1*06:02 (DQβ) has a strong preference for binding to HLA-DQA1*01:02 (DQα), and together they form the functional DQ0602 dimer. A dosage effect would be expected if the HLA-DQ0602 dimer itself is directly involved in the aetiology. An increased expression of the HLA-DQ0602 dimer is expected in individuals homozygous for HLA-DQB1*06:02-DQA1*01:02, but is also hypothesized in individuals heterozygous for HLA-DQB1*06:02 and homozygous for HLA-DQA1*01:02. To study the impact of the expression of the HLA-DQ0602 dimer on narcolepsy susceptibility, 248 Dutch narcolepsy patients and 1272 Dutch control subjects, all of them positive for DQB1*06:02 (heterozygous and homozygous), were HLA-genotyped with attention not only to DQB1 but also to DQA1*01:02. DQB1*06:02-DQA1*01:02 homozygosity was significantly more often seen in patients compared to controls (O.R. 2.29) confirming previous observations. More importantly, a significantly higher prevalence of homozygosity for DQA1*01:02 was found in HLA-DQB1*06:02 heterozygous patients compared to controls (O.R. 2.37, p < 0.001). The latter finding clearly supports a direct role of the HLA-DQ molecule in the development of disease.

  8. Abnormal ionization in sonoluminescence

    Science.gov (United States)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  9. rHuEPO Hyporesponsiveness and Related High Dosages Are Associated with Hyperviscosity in Maintenance Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Mehtap Erkmen Uyar

    2013-01-01

    Full Text Available Objective. Increased viscosity may increase the risk of thrombosis or thromboembolic events. Recombinant human erythropoietin (rHuEPO is the key stone treatment in anemic ESRD patients with the thrombotic limiting side effect. We evaluated the influence of clinical and laboratory findings on plasma viscosity in MHD patients in the present study. Method. After applying exclusion criteria 84 eligible MHD patients were included (30 female, age: years. Results. Patients with high viscosity had longer MHD history, calcium × phosphorus product, and higher rHuEPO requirement (356.4 versus 204.2 U/kg/week, : 0.006. rHuEPO hyporesponsiveness was also more common in hyperviscosity group. According to HD duration, no rHuEPO group had the longest and the low rHuEPO dosage group had the shortest duration. Despite similar Hb levels, 68% of patients in high rHuEPO dosage group; and 38.7% of patients in low rHuEPO dosage group had higher plasma viscosity (: 0.001. Patients with hyperviscosity had higher rHuEPO/Hb levels (: 0.021. Binary logistic regression analyses revealed that rHuEPO hyporesponsiveness was the major determinant of hyperviscosity. Conclusion. We suggest that the hyperviscous state of the hemodialysis patients may arise from the inflammatory situation of long term HD, the calcium-phosphorus mineral abnormalities, rHuEPO hyporesponsiveness, and related high dosage requirements.

  10. Extending the market exclusivity of therapeutic antibodies through dosage patents.

    Science.gov (United States)

    Storz, Ulrich

    2016-07-01

    Dosage patents are one way to extend the market exclusivity of an approved drug beyond the lifetime of the patent that protects the drug as such. Dosage patents may help to compensate the applicant for the long period where the active pharmaceutical ingredient as such is already under patent prosecution, but not on the market yet, due to lengthy development and approval procedures. This situation erodes part of the time the drug is marketed under patent protection. Dosage patents filed at a later date can provide remedy for this problem. Examples of successful and unsuccesful attempts, and the reasons for the respective outcomes, are provided in this article. PMID:27115842

  11. Dosage of boron traces in graphite, uranium and beryllium oxide

    International Nuclear Information System (INIS)

    The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.)

  12. Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Yuichi; Miura, Yoshitaka; Saito, Hidehiko [Toyota Memorial Hospital (Japan)] [and others

    1995-12-01

    T{sub 4}-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 {mu}g/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of {beta}-globin, which is located on chromosome 11, and Duchenne muscular dystropy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/{beta}-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families. 35 refs., 3 figs., 2 tabs.

  13. Dopaminergic system abnormalities Etiopathogenesis of dystonia

    Institute of Scientific and Technical Information of China (English)

    Shuhui Wu; Huifang Shang; Xiaoyi Zou

    2008-01-01

    BACKGROUND: Much research has focused on the close relationship between etiopathogenesis of dystonia and abnormalities of the dopaminergic system. Nevertheless, details of the mechanism are still not clear.OBJECTIVE: To review studies from the past few years about pathogenesis and molecular interactions involved in the relationship between dystonia and abnormalities of the dopaminergic system.RETRIEVAL STRATEGY: Using the key words "dystonia" and "dopamine", PubMed database and SCI databases were searched from January 1990 to December 2005 for relevant English publications. A total of 73 articles were searched and, initially, all articles were selected. Inclusive criteria: studies based on pathogenesis and molecular interactions involved in the relationship between dystonia and abnormalities of the dopaminergic system. Exclusive criteria: duplicated studies. A total of 19 articles were extracted after preliminary screening.LITERATURE EVALUATION: The data sources were the PubMed and SCI databases. The types of articles chosen were reviews and original articles.DATA SYNTHESIS: Metabolism and function of dopamine in the central nervous system: the chemical constitution of dopamine is a single benzene ring. The encephalic regions of dopamine synthesis and their fiber projections comprise four nervous system pathways. One of these pathways is the substantia nigra-striatum dopamine pathway, which is a side-loop of the basal ganglia circuitry that participates in movement control and plays a main role in the adjustment of extracorticospinal tract movement. Dopamine can lead to the facilitation of movement. Dystonia and abnormalities of the dopaminergic system: different modes of dopamine abnormality exist in various forms of dystonia. Abnormalities of the dopaminergic system in several primary dystonias: at present, fifteen gene loci of primary dystonia have been reported (DYT1-DYT15). The relationship between abnormalities of the dopaminergic system and the

  14. Determination of dosage compensation of the mammalian X chromosome by RNA-seq is dependent on analytical approach

    OpenAIRE

    Jue, Nathaniel K.; Murphy, Michael B.; Kasowitz, Seth D; Qureshi, Sohaib M; Obergfell, Craig J; Elsisi, Sahar; Foley, Robert J; O’Neill, Rachel J.; O’Neill, Michael J.

    2013-01-01

    Background An enduring question surrounding sex chromosome evolution is whether effective hemizygosity in the heterogametic sex leads inevitably to dosage compensation of sex-linked genes, and whether this compensation has been observed in a variety of organisms. Incongruence in the conclusions reached in some recent reports has been attributed to different high-throughput approaches to transcriptome analysis. However, recent reports each utilizing RNA-seq to gauge X-linked gene expression re...

  15. A Rare Stapes Abnormality

    Directory of Open Access Journals (Sweden)

    Hala Kanona

    2015-01-01

    Full Text Available The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively.

  16. An overview on various approaches to Gastroretentive dosage forms

    OpenAIRE

    Sarojini, S.; R. Manavalanb

    2012-01-01

    Over the past four decades, gastro retentive dosage forms have recently become a leading methodology in the field of site-specific orally administered controlled release drug delivery system.. Gastroretentive dosage forms have the potential to improve local therapy with an increase of short gastric residence time and unpredictable gastric emptying time and decrease the variation in bioavailability which is unobserved, in other commercially available preparations. With the advent to current sc...

  17. Gene expression profiling of 1p35-36 genes in neuroblastoma.

    Science.gov (United States)

    Janoueix-Lerosey, Isabelle; Novikov, Eugene; Monteiro, Marta; Gruel, Nadège; Schleiermacher, Gudrun; Loriod, Béatrice; Nguyen, Catherine; Delattre, Olivier

    2004-08-01

    Deletion of the chromosome 1p36 region is a frequent abnormality in neuroblastoma. To gain further insights into the role of this alteration in oncogenesis, we have constructed a specific cDNA microarray representing most known genes and ESTs from the 1p35-36 region and analysed the expression profiles of 15 neuroblastoma cell lines and 28 neuroblastoma tumours. Hierarchical clustering using expression levels of 320 cDNAs from 1p35-36 separated localized or 4S cases without 1p deletion from advanced stages and cell lines. Supervised learning classification enabled to predict reliably the status of chromosome 1p according to its expression profile. Around 15% of the genes or ESTs presented a significantly decreased expression in samples with 1p deletion as compared to 1p-normal samples suggesting that 1p deletion results in a gene dosage effect on a subset of genes critical for the development of 1p-deleted neuroblastoma. Several genes presumed to have functions in neural differentiation (CDC42, VAMP3, CLSTN1), signal transduction in neural cells (GNB1) and cell cycle regulation (STMN1, RPA2, RBAF600, FBXO6, MAD2L2) exhibited a decreased expression in samples presenting 1p deletion. The identification of such genes provides baseline information for further studies to elucidate how these genes could individually or collectively play a critical role in neuroblastoma tumorigenesis. PMID:15195138

  18. Abnormal uterine bleeding.

    Science.gov (United States)

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  19. Ictal Cardiac Ryhthym Abnormalities.

    Science.gov (United States)

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  20. Communication and abnormal behaviour.

    Science.gov (United States)

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  1. Communication and abnormal behaviour.

    Science.gov (United States)

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential). PMID:261653

  2. Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

    Directory of Open Access Journals (Sweden)

    Norwood Thomas H

    2006-07-01

    Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

  3. A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

    1996-07-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

  4. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  5. Abnormal pressure in hydrocarbon environments

    Science.gov (United States)

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  6. Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Aydin, Cigdem; Cetin, Zafer; Manguoglu, Ayse Esra; Tayfun, Funda; Clark, Ozden Altiok; Kupesiz, Alphan; Akkaya, Bahar; Karauzum, Sibel Berker

    2016-06-01

    Childhood acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia. Specifically, ALL is a malignant disorder of the lymphoid progenitor cells, with a peak incidence among children aged 2-5 years. The t(12;21)(p13;q22) translocation occurs in 25 % of childhood B cell precursor ALL. In this study, bone marrow samples were obtained from 165 patients with childhood ALL. We analyzed the t(12;21) translocation and other related abnormalities using the fluorescent in situ hybridization (FISH) technique with the ETV6(TEL)/RUNX1(AML1) ES dual color translocation probe. Conventional cytogenetic analyses were also performed. ETV6 and RUNX1 related chromosomal abnormalities were found in 42 (25.5 %) of the 165 patients with childhood ALL. Among these 42 patients, structural changes were detected in 33 (78.6 %) and numerical abnormalities in 9 (21.4 %). The frequency of FISH abnormalities in pediatric ALL cases were as follows: 8.5 % for t(12;21)(p13;q22) ETV6/RUNX1 fusion, 6.0 % for RUNX1 amplification, 3.0 % for tetrasomy/trisomy 21, 1.8 % for ETV6 deletion, 1.21 % for ETV6 deletion with RUNX1 amplification, 1.21 % for ETV6 amplification with RUNX1 amplification, 0.6 % for polyploidy, 0.6 % for RUNX1 deletion, and 0.6 % for diminished ETV6 signal. The most common structural abnormality was the t(12;21) translocation, followed by RUNX1 amplification and ETV6 deletion, while the most commonly observed numerical abnormality was trisomy 21. PMID:27065576

  7. Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution.

    Science.gov (United States)

    Baumgartner, M R; Jansen, G A; Verhoeven, N M; Mooyer, P A; Jakobs, C; Roels, F; Espeel, M; Fourmaintraux, A; Bellet, H; Wanders, R J; Saudubray, J M

    2000-01-01

    We describe an 18-year-old patient with psychomotor retardation and abnormally short metatarsi and metacarpals but no other signs of classic Refsum disease. Molecular analysis of the phytanoyl-coenzyme A hydroxylase gene revealed a homozygous deletion causing a frameshift. Surprisingly, L-pipecolic acid was elevated in plasma, and microscopy of the liver showed a reduced number of peroxisomes per cell and a larger average peroxisome size. These abnormal peroxisomes lacked catalase as did peroxisomes in fibroblasts of this patient. Such generalized peroxisomal abnormalities are not present in classic Refsum disease.

  8. 应用SNPs技术确定C.elegans形成异常习惯化的基因位置%A study of ascertaining the exact gene location where C. elegans form abnormal habituation using SNPs methods

    Institute of Scientific and Technical Information of China (English)

    许锡振; 张桂芳; 赵彦; 濮瀑; 乐卫东

    2009-01-01

    Objective To determine the enact gene location hab-1 ( en308) which effects C elagans abnormal habituation using SNPs methods. Methods (1) To retrieve the SNP markers of Y71A12B which chained at the first autosome the CB4856 (22. 330MU) and SNP markers of C37A5 (22. 330MU) in C. elegans gene bank,its genotype was set to YC/YC,the genotypes of hab-1 (cn308) was set to h/h. (2) By means of Synchronized processing, the size of worms was unified. (3) Wild-type CB4856 male was three-factor hybridized with her-maphroditism cn308. F1 generation were tested by Tap test, recording the distance of response of the worms, statistical processing, screening habituation and retaining the Normal Heterozygote (YC/h) , suboulturing to F2. (4) Then F2 generation were tested by Tap test,C. elegans with slow habitualion were selected, processed by PCR, digested by restriction enzyme , separated target fragment with 2% agarose gel electrophoresis. Results After the first Tap test, the formation of habituation of the wild-type was significantly faster than the cn308. (the average of habituation for Tap stimulation( Moving distance, unit;mm) ,the wild-type' s was (0.414 ±0. 049)mm,cn308 was (0.777 ±0.062)mm, ( = 10.08, P<0.001) ,in the habituation retention test 1 hour later,the habituation of wild-type was found that it retained significantly longer than cn308 (the average of habituation retention, wild-type was (0.307 ±0.041)mm,cn308 was (0. 815 ±0. 054) mm, : = 11.54, P< 0.001). (2) SNP fragments were analyzed, the genetic recombination number between SNP marker of Y71A12B and hab-1 and the genetic recombination number between SNP marker of C37A5 and hab-1 were gathered, observing the phenotype of H non C-type, namely, Ch/h:20, Yh/h:6 ,by reckoning the restructuring proportion it was determined that the distance between hab-1 and SNP marker of Y71A12B was 0. 831MU. The distance between hab-1 and SNP marker of C37A5 was 0. 249MU. So it could be ascertained that hab-1 located between

  9. Curve Fitting And Interpolation Model Applied In Nonel Dosage Detection

    Directory of Open Access Journals (Sweden)

    Jiuling Li

    2013-06-01

    Full Text Available The Curve Fitting and Interpolation Model are applied in Nonel dosage detection in this paper firstly, and the gray of continuous explosive in the Nonel has been forecasted. Although the traditional infrared equipment establishes the relationship of explosive dosage and light intensity, but the forecast accuracy is very low. Therefore, gray prediction models based on curve fitting and interpolation are framed separately, and the deviations from the different models are compared. Simultaneously, combining on the sample library features, the cubic polynomial fitting curve of the higher precision is used to predict grays, and 5mg-28mg Nonel gray values are calculated by MATLAB. Through the predictive values, the dosage detection operations are simplified, and the defect missing rate of the Nonel are reduced. Finally, the quality of Nonel is improved.

  10. Estimation of drug dosage regimens with a pharmacokinetic slide rule.

    Science.gov (United States)

    Straughn, A B; Cruze, C A; Meyer, M C

    1977-02-01

    A pharmacokinetic slide rule to facilitate the computations based on relatively simple pharmacokinetic principles involved in the development of individualized drug dosage regimens is described. The calculations are based on the assumption that the body can be conceived as a one-compartment open model with drug elimination proceeding by apparent first-order kinetics. Examples are presented (1) to illustrate the clinical application of a slide rule to compute the time-course of drug in the body, (2) to calculate steady-state maximum and minimum levels, and accumulation during multiple dosage and (3) to estimate appropriate maintenance doses and intravenous infusion rates. PMID:842548

  11. SPECTROPHOTOMETRIC ESTIMATION OF GEMFIBROZIL IN BULK AND PHARMACEUTICAL DOSAGE FORMS

    Directory of Open Access Journals (Sweden)

    Parikh Vikas C.

    2011-06-01

    Full Text Available A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no interference from any common pharmaceutical additives and excipients. The results of analysis were validated statistically and by recovery studies.

  12. SPECTROPHOTOMETRIC ESTIMATION OF GEMFIBROZIL IN BULK AND PHARMACEUTICAL DOSAGE FORMS

    OpenAIRE

    Parikh Vikas C.; Karkhanis V.V

    2011-01-01

    A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no ...

  13. Visible spectrophotometric determination of valdecoxib in tablet dosage forms

    Directory of Open Access Journals (Sweden)

    Suganthi A

    2006-01-01

    Full Text Available A simple, accurate, rapid, and sensitive visible spectrophotometric method has been developed for the determination of valdecoxib in pure and pharmaceutical dosage forms. The method is based on the reaction of valdecoxib with potassium permanganate to form a bluish green coloured chromogen with an absorption maximum at 610 nm. Beer′s law was obeyed in the range of 5-25 mg/ml. The proposed method has been successfully applied to the analysis of the bulk drug and its dosage forms

  14. Skin - abnormally dark or light

    Science.gov (United States)

    ... ency/article/003242.htm Skin - abnormally dark or light To use the sharing features on this page, ... the hands. The bronze color can range from light to dark (in fair-skinned people) with the ...

  15. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    Science.gov (United States)

    2011-07-12

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new...

  16. Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

    NARCIS (Netherlands)

    Vogt, M; Derendorf, H; Krämer, J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2007-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongl

  17. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    NARCIS (Netherlands)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  18. Quality of 'Climax' blueberries after low dosage electron beam irradiation

    International Nuclear Information System (INIS)

    Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

  19. Whole-body vibration dosage alters leg blood flow.

    NARCIS (Netherlands)

    Lythgo, N.; Eser, P.; Groot, P.C.E. de; Galea, M.

    2009-01-01

    The effect of whole-body vibration dosage on leg blood flow was investigated. Nine healthy young adult males completed a set of 14 random vibration and non-vibration exercise bouts whilst squatting on a Galileo 900 plate. Six vibration frequencies ranging from 5 to 30 Hz (5 Hz increments) were used

  20. 77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

    Science.gov (United States)

    2012-03-19

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs... CONTACT: Lisa M. Troutman, Center for Veterinary Medicine (HFV-116), Food and Drug Administration, 7500... of Food and Drugs and redelegated to the Center for Veterinary Medicine, 21 CFR part 520 is...

  1. 21 CFR 520.1448 - Monensin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... starting line). The loss on drying is not more than 10 percent when dried in vacuum at 60 °C for 2 hours....

  2. Maths anxiety and medication dosage calculation errors: A scoping review.

    Science.gov (United States)

    Williams, Brett; Davis, Samantha

    2016-09-01

    A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. PMID:27589091

  3. Maths anxiety and medication dosage calculation errors: A scoping review.

    Science.gov (United States)

    Williams, Brett; Davis, Samantha

    2016-09-01

    A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety.

  4. 3D nanochannel electroporation for high-throughput cell transfection with high uniformity and dosage control

    Science.gov (United States)

    Chang, Lingqian; Bertani, Paul; Gallego-Perez, Daniel; Yang, Zhaogang; Chen, Feng; Chiang, Chiling; Malkoc, Veysi; Kuang, Tairong; Gao, Keliang; Lee, L. James; Lu, Wu

    2015-12-01

    Of great interest to modern medicine and biomedical research is the ability to inject individual target cells with the desired genes or drug molecules. Some advances in cell electroporation allow for high throughput, high cell viability, or excellent dosage control, yet no platform is available for the combination of all three. In an effort to solve this problem, here we show a ``3D nano-channel electroporation (NEP) chip'' on a silicon platform designed to meet these three criteria. This NEP chip can simultaneously deliver the desired molecules into 40 000 cells per cm2 on the top surface of the device. Each 650 nm pore aligns to a cell and can be used to deliver extremely small biological elements to very large plasmids (>10 kbp). When compared to conventional bulk electroporation (BEP), the NEP chip shows a 20 fold improvement in dosage control and uniformity, while still maintaining high cell viability (>90%) even in cells such as cardiac cells which are characteristically difficult to transfect. This high-throughput 3D NEP system provides an innovative and medically valuable platform with uniform and reliable cellular transfection, allowing for a steady supply of healthy, engineered cells.Of great interest to modern medicine and biomedical research is the ability to inject individual target cells with the desired genes or drug molecules. Some advances in cell electroporation allow for high throughput, high cell viability, or excellent dosage control, yet no platform is available for the combination of all three. In an effort to solve this problem, here we show a ``3D nano-channel electroporation (NEP) chip'' on a silicon platform designed to meet these three criteria. This NEP chip can simultaneously deliver the desired molecules into 40 000 cells per cm2 on the top surface of the device. Each 650 nm pore aligns to a cell and can be used to deliver extremely small biological elements to very large plasmids (>10 kbp). When compared to conventional bulk

  5. Genetic abnormalities associated with acute lymphoblastic leukemia.

    Science.gov (United States)

    Yokota, Takafumi; Kanakura, Yuzuru

    2016-06-01

    Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies. PMID:26991355

  6. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  7. Memetics clarification of abnormal behavior

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: Biological medicine is hard to fully and scientifically explain the etiological factor and pathogenesis of abnormal behaviors; while, researches on philosophy and psychology (including memetics) are beneficial to better understand and explain etiological factor and pathogenesis of abnormal behaviors. At present, the theory of philosophy and psychology is to investigate the entity of abnormal behavior based on the views of memetics.METHODS: Abnormal behavior was researched in this study based on three aspects, including instinctive behavior disorder, poorly social-adapted behavior disorder and mental or body disease associated behavior disorder. Most main viewpoints of memetics were derived from "The Meme Machine", which was written by Susan Blackmore. When questions about abnormal behaviors induced by mental and psychological diseases and conduct disorder of teenagers were discussed, some researching achievements which were summarized by authors previously were added in this study, such as aggressive behaviors, pathologically aggressive behaviors, etc.RESULTS: The abnormal behaviors mainly referred to a part of people's substandard behaviors which were not according with the realistic social environment, culture background and the pathologic behaviors resulted from people's various psychological diseases. According to the theory of "meme", it demonstrated that the relevant behavioral obstacles of various psychological diseases, for example, the unusual behavior of schizophrenia, were caused, because the old meme was destroyed thoroughly but the new meme was unable to establish; psychoneurosis and personality disorder were resulted in hard establishment of meme; the behavioral obstacles which were ill-adapted to society, for example, various additional and homosexual behaviors, were because of the selfish replications and imitations of "additional meme" and "homosexual meme"; various instinct behavioral and congenital intelligent obstacles were not significance

  8. Abnormal expression of PACAP gene in patients with myelodysplastic syndrome%骨髓增生异常综合征患者骨髓细胞中PACAP基因的异常表达

    Institute of Scientific and Technical Information of China (English)

    Stella Aprilia Ika; Zixing Chen; Xiaofei Qi; Hongjie Shen; Jiannong Cen; Yuanyuan Wang

    2009-01-01

    Objective: To explore the expression pattern of PACAP gene in patients with myelodysplastic syndrome (MDS). Methods: The expression pattem of PACAP gene in CD34+ cells from MDS patients was determined by microarray, con-firmed in expanding samples by quantitative real-time PCR in bone marrow mononuclear cells. Results: The transcription of PACAP gene was found significantly down-regulated in patients with MDS in comparison with that in control samples, with a means of 220.1 in MDS-RA and 116.8 in MDS-RAEB (P < 0.05 ). Conclusion: PACAP gene is expressed significantly lower in patients with MDS.

  9. Thyroid abnormality in perimenopausal women with abnormal uterine bleeding

    Directory of Open Access Journals (Sweden)

    Prasanna Byna

    2015-11-01

    Full Text Available Background: AUB is a common but complicated clinical presentation and occurs in 15-20% of women between menarche to menopause and significantly affects the women's health. Women with thyroid dysfunction often have menstrual irregularities, infertility and increased morbidity during pregnancy. The objective of present study is to find the correlation between thyroid disorders and AUB in perimenopausal women attending gynecology OPD. Methods: In the present study, fifty five patients with AUB were included and were evaluated for the cause including thyroid abnormality. Thyroid function tests were done in all patients. Results: Among 55 patients, 12 patients were diagnosed as hypothyroidism and 7 as hyperthyroidism, women with AUB 36 (65.4% were euthyroid. Among 19 women with thyroid abnormality, heavy menstrual bleeding was seen in 8 (42% women, 6 (31.57% had polymenorrhagia, 5 (26.31% had oligomenorrhoea. The frequent menstrual abnormality in women with hypothyroidism (12 women was heavy menstrual bleeding in 5 (41.6% women, 3 (25% had oligomennorhoea, 4 (33.3% had polymenorrhagia. Out of 7 women with hyperthyroidism, 2 (28.57% had oligomenorrhoea, 3 (42.8% had heavy menstrual bleeding, 2 (28.57% had polymenorrhagia. In a total of 55 patients with AUB, 11 (20% had structural abnormalities in uterus and ovaries. 5 (9% had adenomyosis, 3 (5.4% had ovarian cysts, 3 (5.4% had fibroids. Conclusions: It is important to screen all women for thyroid abnormality who are presenting with AUB especially with non-structural causes of AUB. Correction of thyroid abnormalities also relieves AUB. This will avoid unnecessary hormonal treatment and surgery. [Int J Res Med Sci 2015; 3(11.000: 3250-3253

  10. Condensin-driven remodelling of X chromosome topology during dosage compensation

    Science.gov (United States)

    Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

    2015-07-01

    The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using

  11. Chromosome abnormalities in Indonesian patients with short stature

    Directory of Open Access Journals (Sweden)

    Paramayuda Chrysantine

    2012-08-01

    Full Text Available Abstract Background Short stature is associated with several disorders including wide variations of chromosomal disorders and single gene disorders. The objective of this report is to present the cytogenetic findings in Indonesian patients with short stature. Methods G-banding and interphase/metaphase FISH were performed on short stature patients with and without other clinical features who were referred by clinicians all over Indonesia to our laboratory during the year 2003–2009. Results The results of chromosomal analysis of ninety seven patients (mean age: 10.7 years old were collected. The group of patients with other clinical features showed sex chromosome abnormalities in 45% (18/40 and autosomal abnormalities in 10% (4/40, whereas those with short stature only, 42.1% (24/57 had sex chromosome abnormalities and 1.75% (1/57 had autosomal abnormalities. The autosomal chromosomal abnormalities involved mostly subtelomeric regions. Results discrepancies between karyotype and FISH were found in 10 patients, including detection of low-level monosomy X mosaicism in 6 patients with normal karyotype, and detection of mosaic aneuploidy chromosome 18 in 1 patient with 45,XX,rob(13;14(q10;q10. Statistical analysis showed no significant association between the groups and the type of chromosomal abnormalities. Conclusion Chromosome abnormalities account for about 50% of the short stature patients. Wide variations of both sex and autosomal chromosomes abnormalities were detected in the study. Since three out of five patients had autosomal structural abnormalities involving the subtelomeric regions, thus in the future, subtelomeric FISH or even a more sensitive method such as genomic/SNP microarray is needed to confirm deletions of subtelomeric regions of chromosome 9, 11 and 18. Low-level mosaicism in normal karyotype patients indicates interphase FISH need to be routinely carried out in short stature patients as an adjunct to karyotyping.

  12. Cerebral Abnormalities in Adults with Ataxia-Telangiectasia

    OpenAIRE

    Lin, D.D.M.; Barker, P. B.; Lederman, H M; Crawford, T O

    2013-01-01

    Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiecta...

  13. Oral abnormalities in the Ellis-van Creveld syndrome

    Directory of Open Access Journals (Sweden)

    Babaji Prashant

    2010-01-01

    Full Text Available Ellis-van Creveld (EvC syndrome is an autosomal recessive disorder, mainly affecting the ectodermal components such as, enamel, nail, and hair. The gene for EvC syndrome is located on chromosome 4p16. Patients with EvC syndrome characteristically presents with congenitally missing teeth, abnormal frenal attachment, microdontia, and hexadactyly.

  14. Relationship between folic acid metabolism-related enzyme gene polymorphism and susceptibility of abnormal pregnancy%叶酸代谢相关酶基因多态性与不良孕产发生易感性的关系

    Institute of Scientific and Technical Information of China (English)

    李茜西; 伍萍芝; 何琳琳; 吕德欣; 傅锦坚

    2015-01-01

    Objective To analyze the relationship between methylenetetrahydrofolate reductase (MTHFR)C677T,A1298C and methionine synthase reductase(MTRR)gene polymorphism with abnormal pregnancy history.Methods 549 normal women (control group)and 300 women with the abnormal pregnancy history(observation group)were taken as the subjects by adopting the case control research method.The oral mucosa epithelial cells were collected for extracting genomic DNA.The MTHFR and MTRR gene polymorphisms were detected by the gene sequencing method.Results The distribution frequency of MTHFR 677TT genotype in the abnormal pregnancy group was significantly increased compared with the control group (10.00% vs.3.46%,χ2 =15.25,P <0.01);the distribution frequency of MTHFR-1298CC genotype in the abnormal pregnancy group was significantly in-creased compared with the control group (11.00 vs.4.01%,χ2 =15.66,P <0.01);the distribution frequency of MTRR A66G gen-otype had no statistical difference between the two groups(χ2 =3.02,P =0.082).The interactive analysis of 2 genes indicated that simultaneous carrying the MTHFR A1298C mutation site and MTRR A66G mutation site increased the possibility of abnormal pregnancy occurrence (OR=1.52,P =0.011).Conclusion MTHFR C677T and A1298C have a certain correlation with female ab-normal pregnancy occurrence.%目的:分析妇女亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C 及甲硫氨酸合成酶还原酶(MTRR)A66G 基因多态性与不良孕产史的关联性。方法采用病例对照研究的方法,以549例正常妇女(对照组)及300例有不良孕产史(观察组)妇女为对象,采集口腔黏膜上皮细胞,提取基因组 DNA,采用基因测序技术,进行 MTHFR 及 MTRR 基因多态性检测。结果MTHFR 677TT 基因型在观察组的分布频率(10.00%)较对照组(3.46%)明显升高(χ2=15.25,P <0.01);MTHFR-1298CC基因型在观察组的分布频率(11.00%)较对照组(4

  15. Knee loading for abnormal gait

    OpenAIRE

    Hutchison, J.; Madsen, D.; Norman, T. L.; -Blaha, J. D.

    2014-01-01

    The purpose of the study was to develop a mathematical model for determining knee loads for abnormal gait. Abnormal gait was defined as a person with varus, i.e. “bowleggedness”, or a person who had an external rotation of the femur (or the inability to internally rotate the femur) which caused an indirect varus in the forward positions of gait. Conditions such as these have been observed clinically to result in increased wear on the medial condyle of total knee replacements. This problem was...

  16. An overview on various approaches to Gastroretentive dosage forms

    Directory of Open Access Journals (Sweden)

    S. Sarojini

    2012-03-01

    Full Text Available Over the past four decades, gastro retentive dosage forms have recently become a leading methodology in the field of site-specific orally administered controlled release drug delivery system.. Gastroretentive dosage forms have the potential to improve local therapy with an increase of short gastric residence time and unpredictable gastric emptying time and decrease the variation in bioavailability which is unobserved, in other commercially available preparations. With the advent to current scientific and patented literature, this review have covered in detail the recent developments of FDDS including the physiological and formulation variables affecting gastric retention, classification, approaches to design single and multiple unit floating systems, formulation aspects and invitro and invivo studies to evaluate the performance.

  17. INDUSTRIAL PROCESS VALIDATION OF TABLET DOSAGE FORM: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Gupta Surbhi

    2012-03-01

    Full Text Available In pharmaceutical organizations, validation is a fundamental segment that supports a company commitment to quality assurance. Validation is a tool of quality assurance which provides confirmation of the quality in equipment systems, manufacturing processes, software and testing methods. Validation assures that products with pre-determined quality characteristics and attributes can be reproduced consistently/reproducibly within the established limits of the manufacturing process operation at the manufacturing site. Validation of the individual steps of the manufacturing processes is called the process validation. Different dosage forms have different validation protocols. Here this article concentrates on the process validation of tablet dosage form, protocol preparation and regulatory basis for process validation in industry. It gives in detail the validation of each step of the manufacturing process of tablets through wet granulation.

  18. Spectrophotometric determination of nateglinide in bulk and tablet dosage forms

    Directory of Open Access Journals (Sweden)

    Jain Suresh

    2009-01-01

    Full Text Available Nateglinide (NTG is available as tablet dosage form in 60 mg and 120 mg strength. In the present study, two simple, reproducible and efficient UV spectrophotometric methods for the estimation of this drug in bulk and pharmaceutical dosage forms have been developed. In method I, methanol-AR was used as solvent, while in method II, Methanol-AR + 10% V/V 3N NaOH was used as reference solvent. In method I, nateglinide shows λmax at 216 nm, which is then shifted to 225.4 nm on increasing the basicity of the reference solvent in method II. The linearity for nateglinide was observed to be statistically in the range of 10-100 μg/ml in method I and 100-1000 μg/ml in method II. Both the methods were validated using ANOVA. The recovery studies confirmed the accuracy of the proposed methods.

  19. Spectrophotometric estimation of roxithromycin in tablet dosage forms

    Directory of Open Access Journals (Sweden)

    Suhagia B

    2006-01-01

    Full Text Available A simple and sensitive spectrophotometric method has been developed for determination of roxithromycin in its pharmaceutical dosage forms. In the proposed method, roxithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone in the presence of ammonium acetate to give a yellow-coloured chromogen with absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml with regression coefficient of 0.9987. No significant difference was found between the proposed method and the reported method when two-tailed t-tests are applied. Various reaction parameters, such as concentration of potassium permanganate and reagent, time required for oxidation and maximum colour intensity, were optimized. The method was validated and can be used successfully to assay roxithromycin in its pharmaceutical dosage form, viz, tablets.

  20. Determination of Azithromycin in pharmaceutical dosage forms by Spectrophotometric method

    Directory of Open Access Journals (Sweden)

    Suhagia B

    2006-01-01

    Full Text Available A simple and sensitive spectrophotometric method has been developed for determination of azithromycin in its pharmaceutical dosage forms. In the proposed method, azithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone, in the presence of ammonium acetate. A yellow coloured chromogen was obtained, having an absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml, with regression coefficient of 0.9978. Various reaction parameters such as concentration of potassium permanganate and reagent, time required for oxidation, and maximum colour intensity were optimized. The method was validated, and can be used successfully to assay azithromycin in its pharmaceutical dosage forms viz. tablets, capsules, and injections.

  1. RFID Tag Helix Antenna Sensors for Wireless Drug Dosage Monitoring.

    Science.gov (United States)

    Huang, Haiyu; Zhao, Peisen; Chen, Pai-Yen; Ren, Yong; Liu, Xuewu; Ferrari, Mauro; Hu, Ye; Akinwande, Deji

    2014-01-01

    Miniaturized helix antennas are integrated with drug reservoirs to function as RFID wireless tag sensors for real-time drug dosage monitoring. The general design procedure of this type of biomedical antenna sensors is proposed based on electromagnetic theory and finite element simulation. A cost effective fabrication process is utilized to encapsulate the antenna sensor within a biocompatible package layer using PDMS material, and at the same time form a drug storage or drug delivery unit inside the sensor. The in vitro experiment on two prototypes of antenna sensor-drug reservoir assembly have shown the ability to monitor the drug dosage by tracking antenna resonant frequency shift from 2.4-2.5-GHz ISM band with realized sensitivity of 1.27 [Formula: see text] for transdermal drug delivery monitoring and 2.76-[Formula: see text] sensitivity for implanted drug delivery monitoring. PMID:27170865

  2. Application of Abnormal Touchdown PCR with High Degeneracy Primer in Amplification of Large-family Genes%高简并引物小温度范围不规则降落PCR在庞大基因家族扩增中的应用

    Institute of Scientific and Technical Information of China (English)

    华慧颖; 王芳; 常重杰; 杜启艳

    2011-01-01

    [目的]探讨高简并性引物扩增庞大基因家族基因的特殊方法.[方法]采用高简并引物对鲤鱼基因组DNA分别进行了常规PCR扩增、常规降落PCR扩增以及优化后的小温度范围不规则跳跃降落PCR扩增.[结果]采用常规PCR仅得1条明显条带,得到的基因较少;采用常规降落PCR仅得到弥散性扩增,无明显条带出现;而采用小温度范围不规则跳跃降落PCR则得到了3条明显条带和多个基因,扩增结果理想.[结论]为庞大基因家族扩增条件的优化与选择提供了理论依据.%[ Objective] The aim was to explore the special methods for amplification of large-family genes by using primers with high degeneracy. [ Method] By using the primers with high degeneracy, conventional PCR, conventional touchdown PCR and the optimized abnormal touchdown PCR were respectively carried out to amplify the genomic DNA of Cyprinus carpio. [ Result ] Only one evident electrophoretic band and a few Sox genes were obtained by using normal PCR; no obvious electrophoretic band but dispersive product was obtained by normal touchdown PCR; ideal result was obtained by the abnormal touchdown PCR that three evident electrophoretic bands and much more Sox genes were amplified. [ Conclusion] The research provided theoretical basis for the optimization and selection of PCR amplification conditions of the large-family genes.

  3. 高简并引物小温度范围不规则降落PCR在庞大基因家族扩增中的应用%Application of Abnormal Touchdown PCR with High Degeneracy Primer in Amplification of Large-Family Genes

    Institute of Scientific and Technical Information of China (English)

    华慧颖; 王芳; 常重杰; 杜启艳

    2011-01-01

    [目的]探讨了高简并性引物扩增庞大基因家族基因的特殊方法.[方法]采用常规高简并引物对鲤鱼基因组DNA分析进行了常规PCR扩增、常规降落PCR扩增以及优化后的小温度范围不规则跳跃降落PCR扩增.[结果]采用PCR仅得1条明显条带,得到的基因较少;采用常规降落PCR法仅得到弥散性扩增,无明显条带出现;而采用小温度范围的不规则跳跃降落PCR则得到了得到了3条明显条带和多个基因,扩增结果理想.[结论]为庞大基因家族扩增条件中的优化与选择提供了理论依据.%[Objective] The aim was to explore the special methods for amplificati,on of large-family genes by using primers with high degeneracy. [Method] By using the primers with high degeneracy, conventional PCR, conventional touchdown PCR and the optimized abnormal touchdown PCR were respectively carried out to amplify the genomic DNA of Cyprinus carpio. [Result] Only one evident electrophoretic band and a few Sox genes were obtained by using normal PCR; no obvious electrophoretic band but dispersive product was obtained by normal touchdown PCR; ideal result was obtained by the abnormal touchdown PCR that three evident electrophoretic bands and much more Sox genes were amplified. [Conclusion] The research provided theoretical basis for the optimization and selection of PCR amplification conditions of the large-family genes.

  4. The chemistry of low dosage clathrate hydrate inhibitors.

    OpenAIRE

    Perrin, A.; Musa, O. M.; STEED, J. W.

    2013-01-01

    This review aims to introduce the chemistry of low dosage inhibitors of clathrate hydrate formation within the context of their role in the oil and gas industry. The review covers both kinetic hydrate inhibitors and anti-agglomerants from the point of view of structure–function relationships, focussing on recent refinements in mechanistic understanding and chemical design, and the consequently evolving and increasingly fine-tuned properties of these fascinating compounds.

  5. MULTIPLE UNIT DOSAGE FORM - PELLET AND PELLETIZATION TECHNIQUES: AN OVERVIEW

    OpenAIRE

    Kumar Vikash; Mishra Santosh Kumar; Lather Amit; Vikas; Singh Ranjit

    2011-01-01

    Pellets have been used in the pharmaceutical industry for more than four decades, with the advent of controlled release technology, that the full impact of the inherent advantages of pellets over single unit dosage forms have been realized, not only has focused on refining and optimizing existing pelletization techniques, but also focused on the development of novel approaches and procedures for manufacturing of pellets. The present review outlines the manufacturing and evaluation of pellets....

  6. Spectrophotometric estimation of roxithromycin in tablet dosage forms

    OpenAIRE

    Suhagia B; Shah S; Rathod I; Patel H; Doshi K; Parmar V

    2006-01-01

    A simple and sensitive spectrophotometric method has been developed for determination of roxithromycin in its pharmaceutical dosage forms. In the proposed method, roxithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone in the presence of ammonium acetate to give a yellow-coloured chromogen with absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml with regression...

  7. Determination of Azithromycin in pharmaceutical dosage forms by Spectrophotometric method

    OpenAIRE

    Suhagia B; Shah S; Rathod I; Patel H; Doshi K

    2006-01-01

    A simple and sensitive spectrophotometric method has been developed for determination of azithromycin in its pharmaceutical dosage forms. In the proposed method, azithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone, in the presence of ammonium acetate. A yellow coloured chromogen was obtained, having an absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml, with ...

  8. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

    Directory of Open Access Journals (Sweden)

    Colin D Meiklejohn

    2011-08-01

    Full Text Available The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

  9. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi

    2013-12-03

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ∼0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (∼0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ∼1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

  10. 3D nanochannel electroporation for high-throughput cell transfection with high uniformity and dosage control.

    Science.gov (United States)

    Chang, Lingqian; Bertani, Paul; Gallego-Perez, Daniel; Yang, Zhaogang; Chen, Feng; Chiang, Chiling; Malkoc, Veysi; Kuang, Tairong; Gao, Keliang; Lee, L James; Lu, Wu

    2016-01-01

    Of great interest to modern medicine and biomedical research is the ability to inject individual target cells with the desired genes or drug molecules. Some advances in cell electroporation allow for high throughput, high cell viability, or excellent dosage control, yet no platform is available for the combination of all three. In an effort to solve this problem, here we show a "3D nano-channel electroporation (NEP) chip" on a silicon platform designed to meet these three criteria. This NEP chip can simultaneously deliver the desired molecules into 40,000 cells per cm(2) on the top surface of the device. Each 650 nm pore aligns to a cell and can be used to deliver extremely small biological elements to very large plasmids (>10 kbp). When compared to conventional bulk electroporation (BEP), the NEP chip shows a 20 fold improvement in dosage control and uniformity, while still maintaining high cell viability (>90%) even in cells such as cardiac cells which are characteristically difficult to transfect. This high-throughput 3D NEP system provides an innovative and medically valuable platform with uniform and reliable cellular transfection, allowing for a steady supply of healthy, engineered cells. PMID:26309218

  11. 3D nanochannel electroporation for high-throughput cell transfection with high uniformity and dosage control.

    Science.gov (United States)

    Chang, Lingqian; Bertani, Paul; Gallego-Perez, Daniel; Yang, Zhaogang; Chen, Feng; Chiang, Chiling; Malkoc, Veysi; Kuang, Tairong; Gao, Keliang; Lee, L James; Lu, Wu

    2016-01-01

    Of great interest to modern medicine and biomedical research is the ability to inject individual target cells with the desired genes or drug molecules. Some advances in cell electroporation allow for high throughput, high cell viability, or excellent dosage control, yet no platform is available for the combination of all three. In an effort to solve this problem, here we show a "3D nano-channel electroporation (NEP) chip" on a silicon platform designed to meet these three criteria. This NEP chip can simultaneously deliver the desired molecules into 40,000 cells per cm(2) on the top surface of the device. Each 650 nm pore aligns to a cell and can be used to deliver extremely small biological elements to very large plasmids (>10 kbp). When compared to conventional bulk electroporation (BEP), the NEP chip shows a 20 fold improvement in dosage control and uniformity, while still maintaining high cell viability (>90%) even in cells such as cardiac cells which are characteristically difficult to transfect. This high-throughput 3D NEP system provides an innovative and medically valuable platform with uniform and reliable cellular transfection, allowing for a steady supply of healthy, engineered cells.

  12. Incidence of legal abortions and congenital abnormalities in Hungary

    International Nuclear Information System (INIS)

    The annual and monthly distributions of congenital abnormalities and pregnancy outcomes as confounding factors were evaluated in Hungary in reflection of the accident at the Chernobyl reactor. The different congenital abnormality entities and the components of fetal radiation syndrome did not show a higher rate after the Chernobyl accident in the data-set of the Hungarian Congenital Abnormality Registry. Among confounding factors, the rate of induced abortions did not increase after the Chernobyl accident in Hungary. In the 9th month after the peak of public concern (May and June, 1986) the rate of livebirths decreased. Three indicator conditions: 15 sentinel anomalies as indicators of germinal dominant gene mutations, Down syndrome as an indicator of germinal numerical and structural chromosomal mutations, and unidentified multiple congenital abnormalities as indicators of germinal dominant gene and chromosomal mutations were selected from the material of the Hungarian Congenital Abnormality Registry. Diagnoses were checked, familial and sporadic cases were separated and only the sporadic cases were evaluated. The analysis of indicator conditions did not reveal any measurable germinal mutagenic effect of the Chernobyl accident in Hungary

  13. Cardiac abnormalities after subarachnoid hemorrhage

    NARCIS (Netherlands)

    Bilt, I.A.C. van der

    2016-01-01

    Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart Syn

  14. Congenital abnormalities in methylmercury poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Gilani, S.H.

    1975-04-01

    This study was undertaken to determine the teratogenic potential of methylmercury on chick embryogenesis. Methylmercuric chloride was dissolved in sodium bicarbonate (0.2%) and administered to the chick embryos at doses ranging from 0.0009 to 0.010 mg per egg. The injections were made at days 2 and 3 on incubation (Groups A and B). All the embryos including controls were examined on the 7th day of incubation. Methylmercury poisoning was observed to be both embryolethal and teratogenic. Within the two groups, embryolethality was higher in Group A. The following congenital abnormalities were observed: exencephaly, shortened and twisted limbs, microphthalmia, shortened and twisted neck, beak abnormalities, everted viscera, reduced body size and hemorrhage all over the body. Exencephaly and limb abnormalities were very common. No differences in the incidence and types of gross abnormalities within both the groups (A and B) were noted. The incidence of malformations among the controls was low. The results of present investigation show that methylmercury poisoning is both embryolethal and teratogenic to early chick embryogenesis. (auth)

  15. Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

    Directory of Open Access Journals (Sweden)

    Nukman Moeloek

    2009-11-01

    Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

  16. 21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms....

  17. The Development of Teaching Efficacy for Drug-Dosage Calculation Instruction: A Nursing Faculty Perspective

    Science.gov (United States)

    Vitale, Gail A.

    2011-01-01

    The purpose of this study was to examine how nursing efficacy for drug-dosage calculation instruction is determined. Medication administration is a critical function of nurses in healthcare settings. An essential component of safe medication administration is accurate drug-dosage calculation, but instruction in drug-dosage calculation methods…

  18. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms....

  19. Application of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene%全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因的克隆鉴定中的应用

    Institute of Scientific and Technical Information of China (English)

    刘晓娣; 张新友; 宋通微; 洪澄英

    2016-01-01

    目的:研究采用全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因鉴定中的应用价值。方法采集12例遗传性纤维蛋白原异常患者及其核心家庭成员外周血检测凝血指标,并提取其基因组DNA进行全基因组外显子测序,分析测序结果,探讨遗传性纤维蛋白原异常的分子机制。结果全基因组外显子测序结果显示:先证者A1、A4以及B2均为FGA基因g.1233G>A突变,A1的妹妹、A4的父亲以及B2的母亲均携带有相同的突变;A2、A7、B4和B5均为FGG基因g.10819G>A突变,家系成员中A2的母亲和外婆、A7的姐姐和女儿、B4的母亲和B5的母亲均携带有相同的突变;A3、A5、A6、B1和B3及其相关亲属共10例携带有FGB基因g.9692A>G突变。先证者及家系主要成员中发生Fg基因突变的成员APTT、PT和TT均明显延长,但Fg活性显著降低。结论遗传性纤维蛋白原异常可由多种Fg基因外显子突变导致,FGB和FGG外显子突变较为常见。%Objective To research the applicative value of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene. Methods Peripheral blood of 12 patients with hereditary fibrinogen abnormality and core family members was collected to detect coagulation index. And genomic DNA was received whole genome exon sequencing. Test results were analyzed to explore molecular mechanism of hereditary fibrinogen abnormality. Results Results of whole genome exon sequencing technology showed probandA1, A4, and B2 all had FGA gene g. 1233G>A mutation. A1’s sister, A4’s father, and B2’s mother carried the same mutation. A2, A7, B4 and B5 all had FGA gene, g.10819G>A mutation. A2’s mother and grandmother, A7’s sister and daughter, B4’s mother and B5’s mother carried the same mutation. A3, A5, A6, B1 and B3 and 10 people in their related family had FGA gene g.9692A>G mutation. In proband and

  20. Correlation between Abnormal Expressions of CD44 Protein and Gene and Lymph Node Metastasis for Human Lung Carcinoma%人肺癌CD44蛋白和基因的异常表达与淋巴结转移的相关性

    Institute of Scientific and Technical Information of China (English)

    张连斌; 孙玉鹗

    2001-01-01

    目的:研究 CD44蛋白和基因在人肺癌组织中的异常表达,以及这种异常表达与淋巴结转移的相关性。方法:应用 SP免疫组织化学染色方法和 RT PCR/Southern方法,研究人肺癌组织中 CD44蛋白和基因的表达,并应用 QTM970计算机图像分析仪,对免疫组织化学染色结果进行定量分析。结果: SP免疫组织化学染色和计算机图像定量分析结果显示,非小细胞肺癌( non small cell lung carcinomas, NSCLCs)组织比癌旁肺组织,有淋巴结转移比无淋巴结转移的非小细胞肺癌组织染色强度深,差异有极显著意义( F=16.67, P< 0.01); RT PCR/Southern杂交结果显示,有淋巴结转移较无淋巴结转移的非小细胞肺癌表达更多的 CD44 mRNA异常转录子(χ 2=12.13, P< 0.01)。结论: CD44蛋白和基因在人非小细胞肺癌中出现异常表达,这种异常表达在人非小细胞肺癌的发展和淋巴结转移中起重要作用。检测 CD44蛋白和基因的表达,可能对判断非小细胞肺癌病人的预后、预测淋巴结的转移趋势 ,具有重要的临床意义。%Objective:The aim of this study was to investigate the abnormal expressions of CD44 protein and gene, relationship between the abnormal expressions of CD44 protein and gene and lymph node metastasis of human lung carcinomas. Methods: SP immunohistochemistry and RT PCR/Southern methods were used to investigate the expressions of CD44 protein and gene of human lung carcinomas. The immunohistochemistry results were quantitatively analyzed with QTM970 computed image analyzer. Results: SP immunohistochemistry results and quantitative analysis revealed that stronger expression of CD44 protein was observed in non small cell lung carcinomas than in para carcinomatous pulmonary tissues, in non small cell lung carcinomas with lymph node metastasis than in non small cell lung carcinomas without lymph node metastasis

  1. 3种微生物诱导的家蚕attacin基因异常表达形式的研究%Abnormal Expression of Silkworm Attacin Gene Induced by 3 Kinds of Microorganisms

    Institute of Scientific and Technical Information of China (English)

    孔卫青; 杨金宏

    2008-01-01

    [Objective] The aim of this research was to study the expression of silkworm attacin gene induced by some different microorganisms. [Method] Three kinds of microorganism, BmNPV, JM109 and Agrobacterium LBA4404, were ingested to silkworm and the expression profile of attacin gene in hemocyte and fat body was detected by semi-quantitative PCR. And subsequently, the PCR products were cloned and sequenced for further analysis. [Result] A specific band, about 800 bp, appeared in fat body of all induced silkworms. As indicated by the results of cloning and sequencing (GenBank accession number: FJ373019), the band was produced because the 2 introns existing in normal expression form were not spliced. Furthermore, when the extended expression sequence was translated into amino acids, the translation stopped earlier by the stop codon TGA at the 5' end of the first intron of the original sequence, leading the loss of attacin C terminus. [Conclusion] There were two splicesomes of attacin gene, which had reference value to study the role of the attacin gene in silkworm immunity.

  2. Radiological appearances of sinonasal abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    El-Beltagi, A.H.; Sobeih, A.A.; Valvoda, M.; Dahniya, M.H.; Badr, S.S

    2002-08-01

    The aim of this pictorial review is to present a variety of abnormalities of the sinonasal cavities to emphasize the diversity of lesions occurring in this region. These include congenital, neoplastic and granulomatous disorders and some allergic and inflammatory lesions with uncommon radiological appearances, as well as expanding lesions of the facial bones or of dental origin with secondary involvement of the related sinus(es). El-Beltagi, A.H. et al. (2002). Clinical Radiology 57, 702-718.

  3. Is Dark Energy Abnormally Weighting?

    OpenAIRE

    Fuzfa, A.; Alimi, J. -M.

    2006-01-01

    We present a new interpretation of dark energy in terms of an \\textit{Abnormally Weighting Energy} (AWE). This means that dark energy does not couple to gravitation in the same way as ordinary matter, yielding a violation of the weak and strong equivalence principles on cosmological scales. The resulting cosmological mechanism accounts for the Hubble diagram of type Ia supernovae in terms of both cosmic acceleration and variation of the gravitational constant while still accounting for the pr...

  4. Research of abnormal changes of APC and DCC gene in the carcinogenesis of colorectal cancer%大肠癌发生发展过程中APC和DCC基因异常改变的研究

    Institute of Scientific and Technical Information of China (English)

    李圆圆; 杨玉秀

    2008-01-01

    Objective To approach the effect of APC gene and DCC gene in the pathogenetie process of eoloreetal cancer,and to offer theoretical evidence to clinical diagnosis and therapy by detecting the expression of APC gene and DCC gene in nor-real cases ,eoloreetal adenoma and colorectal cancer. Methods Tissue samples were collected from 37 cases of eoloreetal canc-er,22 cases of eolorectal adenoma and 12 cases normal controls. Tissue DNA was extracted and APC and DCC gene mutation were detected with PCR -SSCP. Results The mutation rate of APC gene and DCC gene in coloreetal cancer were 37.8% (14/37)and 51.3% (19/37) ,respectively,and the mutation rate of APC gene and DCC gene in colorectal adenoma were 27.3% (6/22)and 22.7% (5/22). None mutation was detected in 12 normal controls. There was some relation between DCC gene mutation and the histological differentiated degree, the lower the histological differentiated degree, the higher mutation rate (P < 0.05). Con-dusion The mutation of APC and DCC hare occurred in the early stage of colorectal cancer and might be the early diagnostic criteria of clinical application.%目的 探讨APC、DCC基因在正常大肠组织、腺瘤及癌组织中的表达情况,分析其相互作用关系,探讨其发病机制,为临床早期诊断和治疗提供实验依据.方法 从37例大肠癌、22例大肠腺瘤以及12例正常对照者的大肠组织中分别提取DNA,应用PCR-SSCP法检测组织中APC、DCC基因突变情况.结果 37例大肠癌组织中APC基因突变率为37.8%(14/37),DCC基因突变率为51.3%(19/37);22例大肠腺瘤组织中APC基因突变率为27.3%(6/22),DCC基因突变率为22.7%(5/22);12例正常组织中APC、DCC基因突变率为0.DCC基因突变与组织分化程度有关,分化程度越低,突变率越高(P<0.05).结论 APC及DCC基因突变发生在大肠癌的早期阶段,有可能作为早期诊断指标应用于临床.

  5. Influence of dosage and chemical restraints on feline excretory urography

    OpenAIRE

    R.A. Ajadi; Adetunji, A.; V.O. Omoerah; J.U. Okoh

    2006-01-01

    Three series of trials involving 10 domestic short-haired cats were carried out to determine the influence of dosage of contrast media or type of chemical restraint on feline excretory urography. The 1st series (group A) involved 5 cats sedated with 2.0 mg/kg intramuscular (i.m) injection of 2 % xylazine and receiving 800 mg/kg of 76 % meglumine diatrizoate (urografin). The 2nd series (group B) involved another 5 cats sedated with 2.0 mg/kg (i.m) injection of 2 % xylazine and receiving 1200 m...

  6. Avian sex, sex chromosomes, and dosage compensation in the age of genomics.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2014-04-01

    Comparisons of the sex chromosome systems in birds and mammals are widening our view and deepening our understanding of vertebrate sex chromosome organization, function, and evolution. Birds have a very conserved ZW system of sex determination in which males have two copies of a large, gene-rich Z chromosome, and females have a single Z and a female-specific W chromosome. The avian ZW system is quite the reverse of the well-studied mammalian XY chromosome system, and evolved independently from different autosomal blocs. Despite the different gene content of mammal and bird sex chromosomes, there are many parallels. Genes on the bird Z and the mammal X have both undergone selection for male-advantage functions, and there has been amplification of male-advantage genes and accumulation of LINEs. The bird W and mammal Y have both undergone extensive degradation, but some birds retain early stages and some mammals terminal stages of the process, suggesting that the process is more advanced in mammals. Different sex-determining genes, DMRT1 and SRY, define the ZW and XY systems, but DMRT1 is involved in downstream events in mammals. Birds show strong cell autonomous specification of somatic sex differences in ZZ and ZW tissue, but there is growing evidence for direct X chromosome effects on sexual phenotype in mammals. Dosage compensation in birds appears to be phenotypically and molecularly quite different from X inactivation, being partial and gene-specific, but both systems use tools from the same molecular toolbox and there are some signs that galliform birds represent an early stage in the evolution of a coordinated system.

  7. The Abnormal Choroidal Vessels in Aged Patients

    Institute of Scientific and Technical Information of China (English)

    Shizhou Huang; Feng Wen; Dezheng Wu; Guangwei Luo; Caijiao Liu

    2002-01-01

    Background: To show the abnormal choroidal vessels in aged patients with indocyanine-green angiography (ICGA).Methods: ICGA was performed in 350 patients with TOPCON TRC-50IA fundus camera.The images were recorded and retrospectively reviewed.Results: Five aged patients out of 350 cases were found to have abnormal choroidalvessels. The incidence was 1.43%. The abnormal choroidal vessels showed round- shapet,focal enlargement, abnormal shape and entrance, satellite appearance, and vascularloops. These might be due to congenital abnormality of choroid.Conclusion: ICGA could be used to observe the abnormal choroidal vessels.

  8. Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome

    OpenAIRE

    Meyer-Lindenberg, Andreas; Mervis, Carolyn B.; Sarpal, Deepak; Koch, Paul; Steele, Sonya; Kohn, Philip; Marenco, Stefano; Morris, Colleen A.; Das, Saumitra; Kippenhan, Shane; Mattay, Venkata S.; Weinberger, Daniel R.; Berman, Karen Faith

    2005-01-01

    Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, ...

  9. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  10. Aceclofenac topical dosage forms: in vitro and in vivo characterization.

    Science.gov (United States)

    Dua, Kamal; Pabreja, Kavita; Ramana, Malipeddi Venkata

    2010-12-01

    Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1% (m/m) aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations.

  11. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    Science.gov (United States)

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry. PMID:27194002

  12. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    Science.gov (United States)

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  13. Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders

    Energy Technology Data Exchange (ETDEWEB)

    Aoyama, T.; Furthmayr, H.; Francke, U.; Gasner, C. [Stanford Univ. Medical Center, CA (United States)

    1995-08-28

    Marfan syndrome (MFS), a multisystem autosomal-dominant disorder, is characterized by mutations of the fibrillin-1 (FBN1) gene and by abnormal patterns of synthesis, secretion, and matrix deposition of the fibrillin protein. To determine the sensitivity and specificity of fibrillin protein abnormalities in the diagnosis of MFS, we studied dermal fibroblasts from 57 patients with classical MFS, 15 with equivocal MFS, 8 with single-organ manifestations, and 16 with other connective tissue disorders including homocystinuria and Ehlers-Danlos syndrome. Abnormal fibrillin metabolism was identified in 70 samples that were classified into four different groups based on quantitation of fibrillin synthesis and matrix deposition. Significant correlations were found for phenotypic features including arachnodactyly, striae distensae, cardiovascular manifestations, and fibrillin groups II and IV, which included 70% of the MFS patients. In addition, these two groups were associated with shortened {open_quotes}event-free{close_quotes} survival and more severe cardiovascular complications than groups I and III. The latter included most of the equivocal MFS/single manifestation patients with fibrillin abnormalities. Our results indicate that fibrillin defects at the protein level per se are not specific for MFS, but that the drastically reduced fibrillin deposition, caused by a dominant-negative effect of abnormal fibrillin molecules in individuals defined as groups II and IV, is of prognostic and possibly diagnostic significance. 25 refs., 3 figs., 6 tabs.

  14. Divergent actions of long noncoding RNAs on X-chromosome remodelling in mammals and Drosophila achieve the same end result: dosage compensation

    Indian Academy of Sciences (India)

    Subhash C. Lakhotia

    2015-12-01

    Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon’s proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast, Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open. Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes. However, the most striking and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X- inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented.

  15. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH SPERM DISORDERS

    OpenAIRE

    L. Y. Pylyp; L. A. Spinenko; V. D. Zukin; N. M. Bilko

    2013-01-01

    Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intrac...

  16. On Regularity of Abnormal Subriemannian Geodesics

    CERN Document Server

    Tan, Kanghai

    2012-01-01

    We prove the smoothness of abnormal minimizers of subriemannian manifolds of step 3 with a nilpotent basis. We prove that rank 2 Carnot groups of step 4 admit no strictly abnormal minimizers. For any subriemannian manifolds of step less than 7, we show all abnormal minimizers have no corner type singularities, which partly generalize the main result of Leonardi-Monti.

  17. Microarray-based analysis for hepatocellular carcinoma: From gene expression profiling to new challenges

    Institute of Scientific and Technical Information of China (English)

    Yutaka Midorikawa; Masatoshi Makuuchi; Wei Tang; Hiroyuki Aburatani

    2007-01-01

    Accumulation of mutations and alterations in the expression of various genes result in carcinogenesis, and the development of microarray technology has enabled us to identify the comprehensive gene expression alterations in oncogenesis. Many studies have applied this technology for hepatocellular carcinoma (HCC), and identified a number of candidate genes useful as biomarkers in cancer staging, prediction of recurrence and prognosis, and treatment selection. Some of these target molecules have been used to develop new serum diagnostic markers and therapeutic targets against HCC to benefit patients. Previously, we compared gene expression profiling data with classification based on clinicopathological features, such as hepatitis viral infection or liver cancer progression. The next era of gene expression analysis will require systematic integration of expression profiles with other types of biological information, such as genomic locus, gene function, and sequence information. We have reported integration between expression profiles and locus information, which is effective in detecting structural genomic abnormalities, such as chromosomal gains and losses, in which we showed that gene expression profiles are subject to chromosomal bias. Furthermore, array-based comparative genomic hybridization analysis and allelic dosage analysis using genotyping arrays for HCC were also reviewed, with comparison of conventional methods.

  18. A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: Cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Rutishauser, J.; Boeni-Schnetzler, M.; Froesch, E.R.; Wichmann, W.; Huisman, T. [Univ. of Zuerich (Switzerland)] [and others

    1996-01-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant of idiopathic central diabetes insipidus. Several different mutations in the human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied nine family members from three generations of an ADNDI pedigree at the clinical, morphological, and molecular levels. AVP concentrations were measured during diagnostic fluid restriction tests. Coronal and sagittal high resolution T1-weighted images of the pituitary were obtained from affected and healthy family members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were close to or below the detection limit in affected individuals. Magnetic resonance imaging studies revealed the characteristic hyperintense ({open_quotes}bright spot{close_quotes}) appearance of the posterior pituitary in two healthy family members. This signal was absent in all four ADNDI patients examined. The coding sequences of AVP and its carrier protein, neurophysin II, were normal in all family members examined. Affected individuals showed a novel single base deletion (G 227) in the translation initiation codon of the AVP-NP II signal peptide on one allele. The mutation in the AVP-NP II leader sequence appears to be responsible for the disease in this kindred, possibly by interfering with protein translocation. The absence of the hyperintense posterior pituitary signal in affected individuals could reflect deficient posterior pituitary function. 56 refs., 4 figs., 3 tabs.

  19. Condensin-mediated chromosome organization and gene regulation

    Directory of Open Access Journals (Sweden)

    Alyssa Christine Lau

    2015-01-01

    Full Text Available In many organisms sexual fate is determined by a chromosome-based method which entails a difference in sex chromosome-linked gene dosage. Consequently, a gene regulatory mechanism called dosage compensation equalizes X-linked gene expression between the sexes. Dosage compensation initiates as cells transition from pluripotency to differentiation. In C. elegans, dosage compensation is achieved by the dosage compensation complex (DCC binding to both X chromosomes in hermaphrodites to downregulate gene expression by two fold. The DCC contains a subcomplex (condensin IDC similar to the evolutionarily conserved condensin complexes which play a fundamental role in chromosome dynamics during mitosis. Therefore, mechanisms related to mitotic chromosome condensation are hypothesized to mediate dosage compensation. Consistent with this hypothesis, monomethylation of histone H4 lysine 20 (H4K20 is increased, whereas acetylation of histone H4 lysine 16 (H4K16 is decreased, both on mitotic chromosomes and on interphase dosage compensated X chromosomes in worms. These observations suggest that interphase dosage compensated X chromosomes maintain some characteristics associated with condensed mitotic chromosome. This chromosome state is stably propagated from one cell generation to the next. In this review we will speculate on how the biochemical activities of condensin can achieve both mitotic chromosome compaction and gene repression.

  20. Ventilation abnormalities in pulmonary embolus

    International Nuclear Information System (INIS)

    The ventilation scans of 11 patients with angiographically-proven PE were reviewed. All patients had one or more lung perfusion defects. The chest roentgenograph was abnormal in 11 of the patients. The ventilation studies were performed in the posterior positron prior to the perfusion lung scan using Xe-133. The ventilation study consists of washin, equilibrium, and washout images. In four patients with normal washin there was retention of the Xe-133 (delayed washout) at the site of the perfusion defect. All had roentgenographic abnormalities. Another pattern was observed at the sites of some perfusion defects in six patients. In these, there was decreased washin at the perfusion defect location. Two patients had both decreased washin and delayed washout. In only one case was the typical ventilation pattern of normal washin and normal washout. The method of retention is unclear, but may be due to decreased clearance of Xe-133 secondary to decreased blood flow in the area or deposition of some fat soluble component left at the site of embolization. The etiology of the reduced washin is unclear, but may be due to reduced surfactant production. This study suggests that more attention must be paid to the ventilation study, where there may be additional clues to the diagnosis of pulmonary embolus

  1. Nanofibrous solid dosage form of living bacteria prepared by electrospinning

    Directory of Open Access Journals (Sweden)

    I. Wagner

    2014-05-01

    Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.

  2. Complex interactions between genes controlling trafficking in primary cilia.

    Science.gov (United States)

    Ocbina, Polloneal Jymmiel R; Eggenschwiler, Jonathan T; Moskowitz, Ivan; Anderson, Kathryn V

    2011-06-01

    Cilia-associated human genetic disorders are striking in the diversity of their abnormalities and their complex inheritance. Inactivation of the retrograde ciliary motor by mutations in DYNC2H1 causes skeletal dysplasias that have strongly variable expressivity. Here we define previously unknown genetic relationships between Dync2h1 and other genes required for ciliary trafficking. Mutations in mouse Dync2h1 disrupt cilia structure, block Sonic hedgehog signaling and cause midgestation lethality. Heterozygosity for Ift172, a gene required for anterograde ciliary trafficking, suppresses cilia phenotypes, Sonic hedgehog signaling defects and early lethality of Dync2h1 homozygotes. Ift122, like Dync2h1, is required for retrograde ciliary trafficking, but reduction of Ift122 gene dosage also suppresses the Dync2h1 phenotype. These genetic interactions illustrate the cell biology underlying ciliopathies and argue that mutations in intraflagellar transport genes cause their phenotypes because of their roles in cilia architecture rather than direct roles in signaling.

  3. Warfarin dosage response related pharmacogenetics in Chinese population.

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    Siyue Li

    Full Text Available OBJECTIVES: As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population. METHODS: 220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes. RESULTS: rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR. CONCLUSIONS: A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

  4. Effects of maternal psychotropic drug dosage on birth outcomes

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    Michielsen LA

    2013-12-01

    Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes

  5. Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

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    Jennifer L Mozeiko

    2014-04-01

    Intensive aphasia treatment has been employed with equivocal results likely due in part to variability in the severity of participants as well as in the parameters that comprise intensity (e.g., session duration. Intensive Language Action Therapy (ILAT; Difrancesco, Pulvermüller, & Mohr, 2012 is an intensive aphasia therapy that has been replicated successfully and also tends to use similar dosage parameters across replication studies (Barthel, Meinzer, Djundja, & Rockstroh, 2008; Kurland, Pulvermüller, Silva, Burke, & Andrianopoulos, 2012; Maher, 2006; Meinzer et al., 2004. Those with more severe aphasia are thought to have the most to gain from ILAT since they could potentially benefit more from the “forced use” aspect than those who have more residual language (Meinzer et al., 2008. Since Pulvermüller and colleagues’ (2001 initial study, several successful replication studies have shown increases on standardized tests, discourse measures or functional communication outcomes. The dosage for these tends to be approximately thirty hours over two weeks or less. If the dosage of ILAT contributes to gains as suggested by evidence from work in our lab (Mozeiko, Myers, & Coelho, 2011, then it is possible that increasing the dosage to sixty hours over four weeks might produce even greater outcomes. The present study employed a modified multiple probe technique (McReynolds & Kearns, 1983 in which ILAT was delivered at a dosage of three hours per day for twenty days. Discourse productivity and naming accuracy were probed daily. In addition, fMRI scanning was performed at four time points throughout the treatment process in order to compare potential language changes to changes in neural activation patterns with each participant acting as his or her own control. These results are expected to contribute to the limited fMRI results from investigations of neural recovery throughout an extended aphasia treatment period. Methods Participants Two participants were

  6. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

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    Daniela Mierla

    2012-06-01

    Full Text Available Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%. The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions.

  7. Dosage of strontium 90 in human bone ashes; Dosage du strontium 90 sans les cendres d'os humain

    Energy Technology Data Exchange (ETDEWEB)

    Patti, F.; Jeanmaire, L. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1964-07-01

    The determination of {sup 90}Sr in bones by dosage of its daughter product {sup 90}Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of {sup 85}Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the {sup 90}Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of {sup 90}Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors) [French] Determination du Sr dans les os par dosage de son produit de filiation {sup 90}Y. Principe du dosage: 1 - Eliminer les ions phosphates par precipitation du calcium et du strontium sous forme d'oxalate en milieu acide. 2 - Reduire la concentration en calcium a un niveau convenable par addition d'un volume determine d'acide nitrique (une seule precipitation est necessaire). Le rendement de precipitation du nitrate de strontium est controle par la mesure de {sup 85}Sr ajoute comme traceur. 3 - Purifier par une precipitation d'hydroxyde d'yttrium. 4 - Extraire a l'equilibre l'{sup 90}Y qui eat compte pour determiner le {sup 90}Sr. En traitant 50 g de cendre, il est possible de deceler de l'ordre de 0,1 pCi de {sup 90}Sr par gramme de calcium. Les 3 avantages de cette technique: 1 - traitement d'une quantite importante de cendres d'os, 2 - emploi d'un faible volume d'acide nitrique (moins de 2 ml/g de cendres), et 3 - les diverses operations ne presentent aucune difficulte.

  8. Abnormal Returns and Contrarian Strategies

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    Ivana Dall'Agnol

    2003-12-01

    Full Text Available We test the hypothesis that strategies which are long on portfolios of looser stocks and short on portfolios of winner stocks generate abnormal returns in Brazil. This type of evidence for the US stock market was interpreted by The Bondt and Thaler (1985 as reflecting systematic evaluation mistakes caused by investors overreaction to news related to the firm performance. We found evidence of contrarian strategies profitability for horizons from 3 months to 3 years in a sample of stock returns from BOVESPA and SOMA from 1986 to 2000. The strategies are more profitable for shorter horizons. Therefore, there was no trace of the momentum effect found by Jagadeesh and Titman (1993 for the same horizons with US data. There are remaing unexplained positive returns for contrarian strategies after accounting for risk, size, and liquidity. We also found that the strategy profitability is reduced after the Real Plan, which suggests that the Brazilian stock market became more efficient after inflation stabilization.

  9. Evaluation of insecticides in different dosages to control cicadas in parica plantations

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    Odineila Martins Monteiro

    2014-07-01

    Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

  10. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of sever von Willebrand disease

    International Nuclear Information System (INIS)

    Severe von Willebrand disease is characterized by undetectable or trace quantities of von Willebrand factor in plasma and tissue stores. The authors have studied the genomic DNA of 10 affected individuals from six families with this disorder using probes from the 5' and 3' ends of the vWF cDNA and with a probe extending from the 5' end into the central region. Southern blots of restriction endonuclease digest and gene dosage analysis measurements carried out with quantitative slot blots of undigested genomic DNA separated these patients into three groups. The first group consisted of a family with complete homozygous deletions of the vWF gene in the four probands. The second group was comprised of a family in which there was a complete heterozygous deletion of the vWF gene in the proband and one asymptomatic parent, suggesting that a different type of genetic abnormality was inherited from the other parent. Thus, the patient appeared to be doubly heterozygous for interacting genetic abnormalities affecting vWF expression. In the third group, no gene deletions could be detected. Alloantibodies developed only in the kindred with homozygous deletions. These techniques should prove useful in identifying carriers of severe von Willebrand disease and also in defining patients predictably at risk of developing alloantibodes to vWF

  11. Lithium treatment and thyroid abnormalities

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    Bocchetta Alberto

    2006-09-01

    autoimmunity do not much differ from those observed in the general population; h hyperthyroidism and thyroid cancer are observed rarely during lithium treatment. Recommendations Thyroid function tests (TSH, free thyroid hormones, specific antibodies, and ultrasonic scanning should be performed prior to starting lithium prophylaxis. A similar panel should be repeated at one year. Thereafter, annual measurements of TSH may be sufficient to prevent overt hypothyroidism. In the presence of raised TSH or thyroid autoimmunity, shorter intervals between assessments are advisable (4–6 months. Measurement of antibodies and ultrasonic scanning may be repeated at 2-to-3-year intervals. The patient must be referred to the endocrinologist if TSH concentrations are repeatedly abnormal, and/or goitre or nodules are detected. Thyroid function abnormalities should not constitute an outright contraindication to lithium treatment, and lithium should not be stopped if a patient develops thyroid abnormalities. Decisions should be made taking into account the evidence that lithium treatment is perhaps the only efficient means of reducing the excessive mortality which is otherwise associated with affective disorders.

  12. Association of Vitamin D Receptor Apa I Gene Polymorphism and Immunological Abnormality in Patients with Vitiligo%白癜风患者维生素D受体Apa I基因多态性及免疫异常的研究

    Institute of Scientific and Technical Information of China (English)

    孙越; 韩菁; 吴瑞勤; 谢匡成; 朱光斗; 施伟民

    2011-01-01

    Objective To investigate the association between vitamin D receptor (VDR) Apa Ⅰ gene polymorphism and immunological abnormality on vitiligo patients. Methods VDR genotypes of 46 vitiligo patients and 50 healthy controls were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). We also measured the levels of immunoglobulin IgG, IgM, IgA and complements C3, C4 and T lymphocyte subpopulations CD3+, CD4+ and CD8+ of peripheral blood. Results ①There was significant difference in genotype distribution of VDR-Apa Ⅰ polymorphisms between vitiligo patients, whose frequency of aa is higher(P<0.05), and normal controls. ② Vitiligo patients with Aa, aa had higher level of IgA than control cases, and the C3 measured in aa genotype showed the same trend (P<0.01). ③ Compared with normal controls,the percentage of CD3+ was significantly lower in vitiligo patients with aa genotype (P<0.05). Conclusion It suggests that VDR is a susceptible gene for involving in vitiligo, and aa is the susceptible genotype·for vitiligo patients. Immunological abnormality may exist in vitiligo patients with aa genotype. Our study also indicates that the pathogenesis of vitiligo might have some connection with VDR gene and immunological abnormality.%目的 探讨白癜风维生素D(VDR)受体Apa I基因多态性及其与免疫异常的关系.方法 采用聚合酶链反应和限制性片段长度多态性方法,对46例白癜风患者和50例健康人的VDR Apa I基因多态性进行分析,以及各基因型与外周血免疫球蛋白IgA、IgM、IgG,补体C3、C4以及T细胞亚群CD3+、CD4+、CD8+之间的关系.结果 ①VDR-Apa I位点的aa基因型在白癜风患者中出现的频率高于正常对照组(P<.05).②Aa、aa基因型组白癜风患者血清免疫球蛋白IgA水平显著低于正常对照组(P<0.05与P<0.01),aa基因型患者补体C3水平显著低于正常对照组(P<0.01).③aa基因型组白癜风患者的CD3+T淋巴细

  13. Transcription factor SP4 is a susceptibility gene for bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Xianjin Zhou

    Full Text Available The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018. To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029, and two of them (rs12673091, rs3735440 were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012 also displayed a significant association. The SNP7 (rs12673091 was therefore significantly associated in all three samples, and shared the same susceptibility allele (A across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these

  14. Influence of dosage and chemical restraints on feline excretory urography

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    R.A. Ajadi

    2006-06-01

    Full Text Available Three series of trials involving 10 domestic short-haired cats were carried out to determine the influence of dosage of contrast media or type of chemical restraint on feline excretory urography. The 1st series (group A involved 5 cats sedated with 2.0 mg/kg intramuscular (i.m injection of 2 % xylazine and receiving 800 mg/kg of 76 % meglumine diatrizoate (urografin. The 2nd series (group B involved another 5 cats sedated with 2.0 mg/kg (i.m injection of 2 % xylazine and receiving 1200 mg/kg of 76% urografin. The 3rd series (group C involved the repeat urography of the group B cats but sedated with 15 mg/kg (i.m injection of 5% ketamine hydrochloride. Ventrodorsal radiographs were obtained immediately, 5, 15 and 40 minutes after the injection of 76 % urografin. Scores were assigned to nephrographic opacification as described in the literature. The heart rates, respiratory rates and rectal temperatures of the cats were also determined before sedation, after sedation, immediately after the injection of 76 % urografin and at 15-minute intervals over a period of 60 minutes. In this study, there were significant differences (P < 0.05 in the nephrographic opacification scores between the group A and group B cats at times 0 and 40 minutes post-administration of urografin. Group A cats had good initial nephrographic opacification which faded later while the nephrographic opacification of group B cats progressively increased. Similarly, nephrographic opacification was significantly (P < 0.05 higher in the xylazine-sedated cats (groups A and B than the ketamine-sedated cats (group C. However, there were no significant differences (P > 0.05 in heart rates, respiratory rates and rectal temperatures between the 3 groups of cats. It was therefore concluded that increasing the dosage of urografin above 800 mg/kg in cats does not provide additional beneficial effects on the nephrograms produced. Xylazine sedation was observed to produce better nephrographic

  15. Association Between Interstitial Lung Abnormalities and All-Cause Mortality

    Science.gov (United States)

    Putman, Rachel K.; Hatabu, Hiroto; Araki, Tetsuro; Gudmundsson, Gunnar; Gao, Wei; Nishino, Mizuki; Okajima, Yuka; Dupuis, Josée; Latourelle, Jeanne C.; Cho, Michael H.; El-Chemaly, Souheil; Coxson, Harvey O.; Celli, Bartolome R.; Fernandez, Isis E.; Zazueta, Oscar E.; Ross, James C.; Harmouche, Rola; Estépar, Raúl San José; Diaz, Alejandro A.; Sigurdsson, Sigurdur; Gudmundsson, Elías F.; Eiríksdottír, Gudny; Aspelund, Thor; Budoff, Matthew J.; Kinney, Gregory L.; Hokanson, John E.; Williams, Michelle C; Murchison, John T.; MacNee, William; Hoffmann, Udo; O’Donnell, Christopher J.; Launer, Lenore J.; Harrris, Tamara B.; Gudnason, Vilmundur; Silverman, Edwin K.; O’Connor, George T.; Washko, George R.; Rosas, Ivan O.; Hunninghake, Gary M.

    2016-01-01

    IMPORTANCE Interstitial lung abnormalities have been associated with decreased six-minute walk distance, diffusion capacity for carbon monoxide and total lung capacity; however to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, POPULATION Prospective cohort studies of 2633 participants from the Framingham Heart Study (FHS) (CT scans obtained 9/08–3/11), 5320 from the Age Gene/Environment Susceptibility (AGES)-Reykjavik (recruited 1/02–2/06), 2068 from COPDGene (recruited 11/07–4/10), and 1670 from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) (between 12/05–12/06). EXPOSURES Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES All cause mortality over approximately 3 to 9 year median follow up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS Interstitial lung abnormalities were present in 177 (7%) of the participants from FHS, 378 (7%) from AGES-Reykjavik, 156 (8%) from COPDGene, and in 157 (9%) from ECLIPSE. Over median follow-up times of ~3–9 years there were more deaths (and a greater absolute rate of mortality) among those with interstitial lung abnormalities compared to those without interstitial lung abnormalities in each cohort; 7% compared to 1% in FHS (6% difference, 95% confidence interval [CI] 2%, 10%), 56% compared to 33% in AGES-Reykjavik (23% difference, 95% CI 18%, 28%), 16% compared to 11% in COPDGene (5% difference, 95% CI −1%, 11%) and 11% compared to 5% in ECLIPSE (6% difference, 95% CI 1%, 11%). After adjustment for covariates, interstitial lung abnormalities were associated with an increase in the risk of death in the FHS (HR=2.7, 95% CI, 1.1–65, P=0.030), AGES-Reykjavik (HR 1.3, 95% CI 1.2–1.4, P<0.001), COPDGene (HR=1.8, 95% CI, 1.1, 2

  16. ABNORMAL CARDIOVASCULAR REFLEXES IN PATIENTS WITH ACHALASIA

    Institute of Scientific and Technical Information of China (English)

    戈峰; 李泽坚; 柯美云

    1994-01-01

    Using 3 non-invasive tests,abnormalities of cardiovascular reflex function were found in 7 of 15 patients with achalasia.Abnormalities of heart rate responses to the Valsalva maneuver,deep breathing ,and standing were moted in patients with autonomic neuropathy defect.The findings are consistent with the hypothesis that an abnormality of vagal function may contribute to the pathogenesis of achalasia.

  17. Do Stock Dividends Generate Abnormal Returns?

    OpenAIRE

    Torgal, Kishan

    2009-01-01

    In this paper I have studied and understood the concepts of stock dividends, stock splits and the announcement effects and the effective day effects by using the standard event studies methodology which measures the significance of the abnormal returns. The previous studies have significant positive abnormal returns. In my results its shown that the as there is some significant abnormal returns which are connected with the announcement and effective day of the stock splits but it changes...

  18. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    OpenAIRE

    Daniela Mierla; Viorica Radoi; Veronica Stoian

    2012-01-01

    Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, ka...

  19. [Renal abnormalities in ankylosing spondylitis].

    Science.gov (United States)

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. PMID:22520483

  20. Sensorial abnormalities: Smell and taste

    Directory of Open Access Journals (Sweden)

    Palheta Neto, Francisco Xavier

    2011-07-01

    Full Text Available Introduction: Taste and smell abnormalities have proven to be an extremely more complex subject than previously regarded. Wide-ranging nosologic entities arise along with smell and taste alterations, and they can be congenital or acquired. Objective: Analyze the main features of smell and taste dysfunctions. Method: Automated databases were used to collect data, by searching keywords like 'alteration', 'smell', and 'taste'. A non-systematic search was also made in scientific printings and medical books. Literature Review: Smell and taste dysfunctions have a vast etiology, the most significant of which are obstructive nasal and sinusal disease, infections of the upper respiratory tract, cranioencephalic trauma, aging, exposure to toxics and some drugs, nasal or intracranial neoplasias, psychiatric and neurological pathologies, iatrogenic disease, idiopathic and congenital causes. A detailed anamnesis, a careful physical examination and supplementary evaluations are important for the diagnosis of these alterations. Conclusion: As a rule, smell and taste dysfunctions occur in a combined way. The early discovery of such dysfunctions can lead to a more efficient treatment, making the progress of diseases causing them retard and the symptoms less severe. In many cases, treating these alterations is not easy and there needs to be a multidisciplinary cooperation among the otorhinolaryngologist, endocrinologist, neurologist, psychiatrist, among others.

  1. Neuronal migration abnormalities and its possible implications for schizophrenia

    Directory of Open Access Journals (Sweden)

    Kenji eTanigaki

    2015-03-01

    Full Text Available Schizophrenia is a complex mental disorder that displays behavioral deficits such as decreased sensory gating, reduced social interaction and working memory deficits. The neurodevelopmental model is one of the widely accepted hypotheses of the etiology of schizophrenia. Subtle developmental abnormalities of the brain which stated long before the onset of clinical symptoms are thought to lead to the emergence of illness. Schizophrenia has strong genetic components but its underlying molecular pathogenesis is still poorly understood. Genetic linkage and association studies have identified several genes involved in neuronal migrations as candidate susceptibility genes for schizophrenia, although their effect size is small. Recent progress in copy number variation studies also has identified much higher risk loci such as 22q11. Based on these genetic findings, we are now able to utilize genetically-defined animal models. Here we summarize the results of neurodevelopmental and behavioral analysis of genetically-defined animal models. Furthermore, animal model experiments have demonstrated that embryonic and perinatal neurodevelopmental insults in neurogenesis and neuronal migrations cause neuronal functional and behavioral deficits in affected adult animals, which are similar to those of schizophrenic patients. However, these findings do not establish causative relationship. Genetically-defined animal models are a critical approach to explore the relationship between neuronal migration abnormalities and behavioral abnormalities relevant to Schizophrenia.

  2. RP-HPLC estimation of risperidone in tablet dosage forms

    Directory of Open Access Journals (Sweden)

    Bladania S

    2008-01-01

    Full Text Available A simple, specific, accurate, and precise reverse phase liquid chromatographic method was developed and validated for the estimation of risperidone in tablet dosage forms. A Phenomenex Gemini C-18, 5 µm column having 250x4.6 mm i.d. in isocratic mode, with mobile phase containing methanol: acetonitrile: 50 mM potassium dihydrogen orthophosphate (80:10:10 v/v was used. The flow rate was 1.3 ml/min and effluents were monitored at 234 nm. Clozapine was used as an internal standard. The retention time of risperidone and clozapine were 2.5 min and 3.3 min, respectively. The method was validated for linearity, accuracy, precision, specificity, limit of quantification, limit of detection, robustness and stability. The limit of detection and limit of quantification for estimation of risperidone was found to be 500 ng/ml and 990 ng/ml, respectively. Recovery of risperidone was found to be in the range of 99.02-101.68%. Proposed method was successfully applied for the quantitative determination of risperidone in tablet formulations.

  3. REFLECTIONS ON QUALITY AND DOSAGE OF PRESCHOOL AND CHILDREN'S DEVELOPMENT.

    Science.gov (United States)

    Votruba-Drzal, Elizabeth; Miller, Portia

    2016-06-01

    This ambitious monograph tackles several important questions related to children's preschool experiences that have relevance for program and policy initiatives at the state and federal levels. The authors' approach is rigorous: they conduct parallel analyses across eight large and diverse studies of preschool children in center care and use meta-analysis to summarize patterns across studies. The study finds nonlinear associations between preschool quality and gains in language and literacy skills, with larger associations in higher versus lower quality classrooms. Results also show that domain-specific measures of preschool quality were more strongly related to children's development than global quality measures. The "dosage" of preschool was likewise important: more years in Head Start predicted larger vocabulary and literacy gains, whereas more time spent on instruction predicted greater literacy and math skills growth. In this commentary, we situate these findings in the broader literature addressing links between preschool experiences and children's development and discuss key takeaways for research, practice, and policy. PMID:27273510

  4. Spectrophotometric determination of diloxanide furoate in its dosage forms.

    Science.gov (United States)

    Al-Ghanam, S M; Belal, F

    2001-09-01

    A simple and sensitive spectrophotometric method has been developed for the determination of diloxanide furoate in its dosage forms. The method is based on the reaction of the drug with potassium permanganate in the presence of sodium hydroxide to produce a bluish green coloured species measurable at 610 nm. The absorbance-concentration plot is linear over the range 2.5-20 microg/ml with correlation coefficient (n = 8) of 0.9998 and minimum detectability of 0.2 microg/ml (6.1 x 10(-7) M). The molar absorptivity was 1.1 x 10(4) l/mol cm. The different experimental parameters affecting the development and stability of the colour were carefully studied and optimised. The proposed method was applied successfully for the determination of diloxanide furoate in its tablet form. The results obtained were in good agreement with those obtained using the official method. The proposed method could be applied to the determination of diloxanide furoate in presence of some co-formulated drugs. The effect of sensitisers and surfactants on the performance of the proposed method was also studied. A proposal of the reaction pathway was presented. PMID:11680811

  5. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  6. a Step Toward Development of Printable Dosage Forms for Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Raijada, Dhara; Genina, Natalja; Fors, Daniela;

    2013-01-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkje...

  7. 21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms....

  8. 75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2010-05-12

    ... parasites that were approved for the pioneer product with 3 years of marketing exclusivity (69 FR 501... HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New... part 524 is amended as follows: PART 524--OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS 0 1....

  9. The abnormal genes of learning and memory in C. elegans and their functions%C.elegans的学习记忆异常基因及其功能的研究

    Institute of Scientific and Technical Information of China (English)

    许锡振; 吴利标; 罗信国; 赵彦; 濮瀑; 朱旭新

    2009-01-01

    目的 探索学习记忆异常基因hab-1(cn308)的功能.方法 1. 在hab-1领域有Y63D3A.6、Y63D3A.7和Y63D3A.8等三个YAC克隆.在基因库里检索Y63D3A.6、Y63D3A.7和Y63D3A.8的cDNA序列,用DNASIS-Mac v3.6软件处理并设计引物,进行PCR.把PCR产物插入pMD~(TM)18-TVector载体,并培养提取Y63D3A.6、Y63D3A.7和Y63D3A.8的目的 DNA,纯化DNA.2.进行rescue实验:把三种YAC克隆(clone)Y63D3A.6、Y63D3A.7和Y63D3A.8的DNA分别与GFP蛋白连接配制融合蛋白.应用OLYMPUSAxiovert S100共聚焦倒置显微镜操作系统,在L4大小的C.elegans生殖腺(gonad)内分别把三种GFP融合蛋白溶液显微注射,发育传代至F1.在F1代选择带有GFP荧光的C.elegans,观察基冈的表达部位,并进行Tap测试,通过观察在哪个YAC克隆把hab-1(cn308)的表现型恢复为野生型来确定hab-1的等位基因.3. DNA测序和同源性检索:hab-1的等位基冈确定以后对cn308进行DNA测序.根据cn308的测序结果与已知的等位基因DNA序列进行Homology search,分析cn308的基因结构,并进行BLSTP homologic search,和其他物种比较目的 基因的功能来阐明hab-1的基因功能.结果 对Y63D3A.6、Y63D3A.7和Y63D3A.8等三种基因表达率进行χ~2检验结果表示差异有显著性(χ~2=26.84,P0.05, P<0.05, there was a significant difference. It showed that although Y63D3A.6, Y63D3A.7 and Y63D3A.8 have linkage with the adjacent location of the first autosomal, expressing rate on the head of C. elegans had no relatedness and had significant differences. It revealed that Y63D3A.7 was expressed strongly on the head of C. elegans, and Tap test proved that Y63D3A.7 rescued hab-1 to wild-type phenotype. The result of DNA sequencing was that hab-1 (cn308) was a missense mutation (GAG→GGG, namely, Glu→Gly ). The result of BLST homologic search showed that Y63D3A.7 was the activity which adjusts mitochondrion complex Ⅰ, it illustrated that hab-1 gene had relations with the function of mitochondrion

  10. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)–deficient mice

    OpenAIRE

    Miettinen, Helena E.; Rayburn, Helen; Krieger, Monty

    2001-01-01

    Mammalian female fertility depends on complex interactions between the ovary and the extraovarian environment (e.g., the hypothalamic-hypophyseal ovarian axis). The role of plasma lipoproteins in fertility was examined using HDL-receptor SR-BI knockout (KO) mice. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes, and are infertile. Fertility was restored when the structure and/or quantity of abnormal HDL was altered by inactivating the apoAI gene or administering the choleste...

  11. Complex radiation diagnosis of associated intracardiac abnormality

    International Nuclear Information System (INIS)

    It is shown that patients with congenital heart diseases having signs of cardiodismorphic complex in form of associated intercardiac abnormalities require special attention after surgical correction of the principal defect. It is connected with the fact that the associated abnormalities may become with time the basic factors influencing the progress and forecast of the disease

  12. An Abnormal Vibrational Mode of Torsion Pendulum

    Institute of Scientific and Technical Information of China (English)

    赵亮; 涂英; 顾邦明; 胡忠坤; 罗俊

    2003-01-01

    In the experiment for the determination of the gravitational constant G, we found an abnormal vibrational mode of the torsion pendulum. The abnormal mode disappeared as a magnetic damper was introduced to the torsion pendulum system. Our experimental results also show that the magnetic damper can be used to suppress the high frequency vibrational noises to torsion pendulums effectively.

  13. Abnormal Raman spectral phenomenon of silicon nanowires

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Raman spectra of two one-dimensional silicon nanowire samples with different excitation wavelengths were measured and an abnormal phenomenon was discovered that the Raman spectral features change with the wavelengths of excitation. Closer analysis of the crystalline structure of samples and the changes in Raman spectral features showed that the abnormal behavior is the result of resonance Raman scattering selection effect.

  14. Abnormal Event Detection Using Local Sparse Representation

    DEFF Research Database (Denmark)

    Ren, Huamin; Moeslund, Thomas B.

    2014-01-01

    measurement based on the difference between the normal space and local space. Specifically, we provide a reasonable normal bases through repeated K spectral clustering. Then for each testing feature we first use temporal neighbors to form a local space. An abnormal event is found if any abnormal feature...

  15. Nail abnormalities in patients with vitiligo*

    Science.gov (United States)

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738

  16. [Abnormality in bone metabolism after burn].

    Science.gov (United States)

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  17. Principles of gene therapy

    Directory of Open Access Journals (Sweden)

    Mammen Biju

    2007-01-01

    Full Text Available Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics and future percepts and the technical and ethical issues of using gene therapy.

  18. Chromosomal abnormalities in patients with sperm disorders

    Directory of Open Access Journals (Sweden)

    L. Y. Pylyp

    2013-02-01

    Full Text Available Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intracytoplasmic sperm injection in particular, enable the transmission of chromosomal abnormalities to the progeny. Therefore, cytogenetic studies are important in patients with male factor infertility before assisted reproduction treatment. The purpose of the current study was to investigate the types and frequencies of chromosomal abnormalities in 724 patients with infertility and to estimate the risk of chromosomal abnormalities detection in subgroups of patients depending on the severity of spermatogenic disruption, aiming at identifying groups of patients in need of cytogenetic studies. Karyotype analysis was performed in 724 blood samples of men attending infertility clinic. Chromosomal preparation was performed by standard techniques. At least 20 GTG-banded metaphase plates with the resolution from 450 to 750 bands per haploid set were analysed in each case. When chromosomal mosaicism was suspected, this number was increased to 50. Abnormal karyotypes were observed in 48 (6.6% patients, including 67% of autosomal abnormalities and 33% of gonosomal abnormalities. Autosomal abnormalities were represented by structural rearrangements. Reciprocal translocations were the most common type of structural chromosomal abnormalities in the studied group, detected with the frequency of 2.6% (n = 19, followed by Robertsonian translocation, observed with the frequency of 1.2% (n = 9. The frequency of inversions was 0.6% (n = 4. Gonosomal abnormalities included 14 cases

  19. Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.

    Directory of Open Access Journals (Sweden)

    Artyom A Alekseyenko

    Full Text Available The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at "entry sites" that contain a consensus sequence motif ("MSL recognition element" or MRE. However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex and female Kc cells (which lack the complex, we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome.

  20. Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum

    Science.gov (United States)

    Yu, Tian; Yaguchi, Yuichiro; Echevarria, Diego; Martinez, Salvador; Basson, M. Albert

    2011-01-01

    Fibroblast growth factors (FGFs) and regulators of the FGF signalling pathway are expressed in several cell types within the cerebellum throughout its development. Although much is known about the function of this pathway during the establishment of the cerebellar territory during early embryogenesis, the role of this pathway during later developmental stages is still poorly understood. Here, we investigated the function of sprouty genes (Spry1, Spry2 and Spry4), which encode feedback antagonists of FGF signalling, during cerebellar development in the mouse. Simultaneous deletion of more than one of these genes resulted in a number of defects, including mediolateral expansion of the cerebellar vermis, reduced thickness of the granule cell layer and abnormal foliation. Analysis of cerebellar development revealed that the anterior cerebellar neuroepithelium in the early embryonic cerebellum was expanded and that granule cell proliferation during late embryogenesis and early postnatal development was reduced. We show that the granule cell proliferation deficit correlated with reduced sonic hedgehog (SHH) expression and signalling. A reduction in Fgfr1 dosage during development rescued these defects, confirming that the abnormalities are due to excess FGF signalling. Our data indicate that sprouty acts both cell autonomously in granule cell precursors and non-cell autonomously to regulate granule cell number. Taken together, our data demonstrate that FGF signalling levels have to be tightly controlled throughout cerebellar development in order to maintain the normal development of multiple cell types. PMID:21693512

  1. Effects of high dosage irradiation on nutrition content in Ginkgo biloba

    International Nuclear Information System (INIS)

    The nutrition content, microelement and sense index of the irradiated ginkgo biloba were studied. The results showed that there were no difference in the content of crud fat and microelement between treatment with high dosage irradiation and contrast. The total soluble sugar and carbohydrate in the ginkgo biloba after high dosage irradiation increased 84% and 6.6%-25.3% respectively, but the vitamin C decreased 27.7%-50.3%. The index of color, hardness and odour decreased as the irradiation dosage increased

  2. Frequency and clinical significance of erythrocyte genetic abnormalities in Omanis.

    OpenAIRE

    White, J. M.; Christie, B S; Nam, D; S. Daar; Higgs, D R

    1993-01-01

    The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of...

  3. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  4. BCL-6、MYC和p53基因异常与弥漫性大B细胞淋巴瘤免疫学亚型及预后的关系%Correlation of BCL-6, MYC and p53 gene abnormalities with immunological subtypes and prognosis of diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    孙冠星; 曹祥山; 李青; 王志林

    2012-01-01

    目的 探讨弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者BCL-6、MYC和p53基因的异常情况,用并分析它们与免疫学亚型及预后的关系.方法 应用间期荧光原位杂交技术分析46例DLBCL患者BCL-6、MYC和p53基因的异常情况,用免疫组织化学技术(Envision法)对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1、BCL-2和Ki-67标记,根据Hans的分类方法将其分为生发中心B细胞型(germinal center B cell,GCB型)和非生发中心B细胞型(non-germinal center B cell,non-GCB型).结果 46例患者中,BCL-6基因重排10例,BCL-6重排与BCL-6蛋白的表达两者之间差异无统计学意义(P=0.245).BCL-6基因重排与DLBCL患者的总生存时间(P=0.138)和无进展生存时间(P=0.095)无统计学相关性.MYC重排4例,全部见于GCB型.p53基因缺失14例,p53基因缺失组与p53基因正常组相比,生存时间差异有统计学意义(总生存时间:P=0.046;无进展生存时间::P=0.043).结论 间期荧光原位杂交技术可以快速、准确、灵敏的检测BCL-6、MYC和p53基因的异常.BCL-6基因重排与BCL-6蛋白的表达之间无统计学相关性.MYC重排多见于GCB亚型组,p53基因缺失的患者预后较差.p53基因可以作为判断DLBCL预后的参考指标.%Objective To investigate BCL-6,MYC and p53 genes abnormalities in diffuse large B-cell lymphoma (DLBCL) and correlate the result with immunosubtypes and prognosis.Methods Interphase fluorescence in situ hybridization (I-FISH) was performed to detect the BCL-6,MYC and p53 genes.Immunohistochemistry (Envision method) was used to measure the expressions of CD3,CD10,CD20,BCL-6,MUM-1,BCL-2 and Ki-67 genes in DLBCL.The patients were classified into germinal center B cell-like (GCB) and non-GCB subtypes according to Hans' algorithm.Results BCL-6 rearrangement was detected in 10 of 46 DLBCL cases.The presence of gene rearrangement had no correlation with BCL-6 protein expression (P=0.245).Overall survival (OS,P=0

  5. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification. PMID:27074556

  6. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  7. Development of agar diffusion method for dosage of gramicidin

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Reis Solano

    2011-09-01

    Full Text Available Gramicidin, an antimicrobial peptide active against Gram positive bacteria, is commonly used in pharmaceutical preparations for topical use. Considering that only the turbidimetric method has been described in the literature, the present study sought to develop and validate an agar diffusion method for the dosage of gramicidin. The method was developed and validated using the Kocuria rhizophila ATCC 9341 as a test microorganism. Two designs were used: a 3x3 parallel-line model, and a 5x1 standard curve. The validation demonstrated that the method follows the linear model (r²= 0.994, presenting a significant regression between the zone diameter of growth inhibition and the logarithm of the concentration within the range of 5 to 25.3 µg/mL. The results obtained for both designs were precise, having a relative standard deviation (R.S.D. for intra-day precision of 0.81 for the 3x3 assay and 1.90 for the 5x1 assay. For the inter-day precision, the R.S.D. was 1.35 for the 3x3 and 2.64 for the 5x1. The accuracy was verified and results confirmed to be accurate, having a tolerance interval of 95%, which lay within permitted limits and appropriate trueness. In addition, the method was considered selective, with limit of detection and upper and lower limits of quantification of 2.00, 5.00 and 25.3 µg/mL, respectively. No difference in precision between the designs used in the agar diffusion method was evident (p>0.05. The method proved to be appropriate for the microbiological dosage of the raw material gramicidin.A gramicidina, um peptídeo antimicrobiano ativo contra bactérias Gram positivo, é utilizada em preparações farmacêuticas de uso tópico. Neste trabalho procurou-se desenvolver e validar outro método para o doseamento de gramicidina tendo em vista que somente o método turbidimétrico é descrito. O método de difusão em ágar foi desenvolvido e validado utilizando como microrganismo teste Kocuria rhizophila ATCC 9341. Foram utilizados

  8. Genetic abnormalities in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Zamboni Giuseppe

    2003-01-01

    Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.

  9. Significance of BCL6, MYC, P53 genes abnormalities for the prognosis of diffuse large B-cell lymphoma%BCL6、MYC、P53基因异常对弥漫大B细胞淋巴瘤预后的影响

    Institute of Scientific and Technical Information of China (English)

    高攀科; 李青; 王志林; 严峰; 鲁常青; 曹祥山

    2014-01-01

    Objective To explore the influence of BCL6,MYC,P53 genes abnormalities can on the prognosis of diffuse large B-cell lymphoma (DLBCL),and to identify independent prognostic factors for DLBCL in order to facilitate clinical prognosis and selection of stratification treatment for the patients.Method Sixty five newly diagnosed DLBCL pathological specimens were collected from 2009 to 2012.Interphase fluorescence in situ hybridization technique (Ⅰ-FISH) was used to detect the status of BCL6,MYC and P53 genes.Clinical factors were combined with immunohistochemical results for multiple-factor survival analysis.Results The rates of BCL6 gene rearrangement,P53 gene deletion and MYC rearrangement were 21.5% (14/65),35.4% (23/65) and 7.7% (5/65),respectively.BCL6 rearrangement group has obviously poorer overall survival (OS) (P < 0.05).COX proportional hazards model analysis showed that gender,BCL6 protein,BCL6 rearrangement,Ki67 index were prognosis factors independent of international prognostic index (IPI).Conclusion BCL6 can influence the prognosis of patients with DLBCL at gene and protein levels and both are independent prognostic factors for DLBCL.%目的 探讨BCL6、MYC、P53基因异常对弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者预后的影响,筛选独立的预后因素,为DLBCL患者临床预后判断及分层治疗的选择提供依据.方法 收集本院2009年1月至2012年12月有完整随访资料的新诊断的DLBCL患者的病理标本65例,应用间期荧光原位杂交技术分别检测患者标本肿瘤细胞BCL6、MYC重排以及P53缺失的情况,并结合临床指标及免疫组化结果进行多因素生存分析.结果 BCL6重排率为21.5%(14/65),P53缺失率为35.4%(23/65),MYC重排率为7.7% (5/65).BCL6重排组预后明显不良(P<0.05).COX多因素生存分析表明,性别、BCL6蛋白、BCL6重排、Ki67是国际预后指数以外的独立预后影响因素.结论 BCL6分别从基因和蛋白水平

  10. PCB1254暴露致幼年斑马鱼视动反应异常及感光细胞发育相关基因表达变化%Exposure to PCB1254 caused abnormal OMR and photoreceptor cells growth-related gene expressions changes in the zebrafish larvae

    Institute of Scientific and Technical Information of China (English)

    张昕; 洪琴; 杨蕾; 张敏; 郭锡熔; 池霞; 童梅玲

    2015-01-01

    Objective:To study the optomotor response( OMR) and retinal photoreceptor cell growth-related gene expressions of zebrafish larvae after exposed to polychlorinated biphenyls ( PCBs ) after fertilization. Methods:Zebrafish were exposed to PCB1254 at concentrations of 0. 125, 0. 25, 0. 5 and 1 mg · L-1 . A blank group and 0. 01% methanol group were set up. After exposed for 7 d, the visual behavior of zebrafish was assessed using OMR tests. The photoreceptor cell growth-related gene ( CRX, RHO, SWS1 and SWS2 ) expressions were also detected. Results:(1) when the grating spatial frequency was 0. 20 LP·mm-1 and the moving speed was 25 cm· s-1, the OMR sensitive ratio decreased significantly in 0. 5 mg·L-1 and 1 mg·L-1 groups(P<0. 05). (2) The SWS2 gene expressions declined significantly in all the experimental groups ( P <0. 05 ) . The CRX, RHO and SWS1 gene expressions all decreased significantly in 0. 5 mg · L-1 and 1 mg · L-1 groups ( P < 0. 05 ) . Conclusion:Exposed to 0. 5 mg · L-1 and 1 mg · L-1 concentrations of PCB1254 can cause abnormal OMR and down-regulations of the photoreceptor cells growth-related gene expressions, indicating that it is necessary to strengthen the monitoring and control of adverse influences of environmental toxin on the children eyes development.%目的::研究受精后暴露PCB1254对斑马鱼幼鱼视动反应及视网膜感光细胞发育相关基因表达的影响。方法:对受精后斑马鱼胚胎进行不同质量浓度的PCB1254(0.125、0.25、0.5、1 mg·L-1)暴露处理,同时设立空白对照和0.01%甲醇对照组。暴露7 d后,观察幼年期斑马鱼视动反应及感光细胞发育相关基因CRX、RHO、SWS1、SWS2表达的变化。结果:(1)当条栅空间频率为0.20线· mm-1,移动速度为25 cm · s-1时,0.5 mg·L-1和1 mg·L-1组的幼鱼视动反应敏感比例明显降低(P<0.05)。(2)各实验浓度组的SWS2基因表达均明显下调( P <0.05),0.5 mg · L-1和1 mg · L-1

  11. Amphibian abnormalities on National Wildlife Refuges

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This fact sheet outlines a study done to 1) find the percentage of abnormal frogs and toads on the nation’s National Wildlife Refuges and 2) determine how the...

  12. Low-set ears and pinna abnormalities

    Science.gov (United States)

    ... because they do not affect hearing. However, sometimes cosmetic surgery is recommended. Skin tags may be tied off, ... 5 years old. More severe abnormalities may require surgery for cosmetic reasons as well as for function. Surgery to ...

  13. The glycometabolism abnormality among schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    吴小立

    2013-01-01

    Objective To explore the potential glycometabolism abnormality and the related factors of schizophrenia patients in China. Methods This cross-sectional study included 44 healthy controls(group 1) and 178 inpatient

  14. FLOATING GASTRO-RETENTIVE DOSAGE FORMS - A NOVEL APPROACH FOR TARGETED AND CONTROLLED DRUG DELIVERY

    Directory of Open Access Journals (Sweden)

    Aleksandar Aleksovski

    2012-04-01

    Full Text Available Controlled (modified release dosage forms are one of the key concepts in drug delivery, leading to enhanced drug bioavailability and increased patient’s compliance. However conventional modified release dosage forms encounter one big disadvantage- lack of site-specific drug delivery. Scientists developed different kinds of targeted oral controlled release forms. One of these are gastro-retentive systems- systems which can remain in the stomach region for prolonged period of time and thereby release the active compound in controlled fashion. Floating dosage forms are the most promising approach of all gastro-retentive systems. They are capable to float over the gastric content in longer time intervals. This article makes a review on floating dosage forms in general, different approaches for achieving flotation, advantages and disadvantages of this drug delivery concept. For better understanding the topic,an emphasis is made also on the anatomical and physiological features of the stomach and on the factors affecting gastric retention.

  15. A comparative study of two dosage levels of ibuprofen syrup in children with pyrexia.

    Science.gov (United States)

    Kotob, A

    1985-01-01

    In a study of the antipyretic effect of two dosage levels of ibuprofen syrup in children with fever due to a variety of causes, forty-four out of the fifty children admitted completed the 24-hour trial period, twenty-three receiving 20 mg ibuprofen/kg body-weight, twenty-one receiving 30 mg/kg ibuprofen. Both dosage levels gave highly significant (p less than 0.001) reductions in rectal temperatures, with a statistically significant reduction, at the 5% level, in favour of the higher dose at 12 and 20 hours. No side-effects were reported at either dosage level, and the taste was acceptable to all the children. It is concluded that ibuprofen was a useful and effective antipyretic drug in the population studied, and that the higher dosage is preferable to the lower, being more effective, equally palatable, and giving rise to no side-effects in this study. PMID:3888726

  16. A study on the effects of ozone dosage on dissolved-ozone flotation (DOF) process performance.

    Science.gov (United States)

    Jin, Xin; Jin, Pengkang; Wang, Xiaochang

    2015-01-01

    Dissolved-ozone flotation (DOF) is a tertiary wastewater treatment process, which combines ozonation and flotation. In this paper, a pilot-scale DOF system fed by secondary effluent from a wastewater treatment plant (WWTP) in China was used to study the effect of ozone dosage on the DOF process performance. The results show that an ozone dosage could affect the DOF performance to a large extent in terms of color and organic matter removal as well as disinfection performance. The optimal color and organic matter removal was achieved at an ozone dosage of 0.8 mg/l. For disinfection, significant improvement in performance could be achieved only when the organic matter removal was optimal. The optimal ozone dosage of at least 1.6 mg/l was put forward, in this case, in order to achieve the optimal color, turbidity, organic matter and disinfection performance.

  17. Echocardiographic abnormalities in type IV mucopolysaccharidosis.

    OpenAIRE

    John, R. M.; Hunter, D; Swanton, R. H.

    1990-01-01

    Cardiac involvement is well recognised in most forms of the mucopolysaccharidoses but there is poor documentation of abnormalities specific to Morquio's syndrome (type IV mucopolysaccharidosis). Ten patients with the classic form or type A Morquio's syndrome with a median age of 12.5 years underwent echocardiographic assessment. Abnormalities were detected in six (60%) cases with mitral valve involvement in five patients and aortic valve disease in four. One patient had severe mitral leaflet ...

  18. Prevalence of asymptomatic urinary abnormalities among adolescents

    Directory of Open Access Journals (Sweden)

    Mohamed Fouad

    2016-01-01

    Full Text Available To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1% individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8% at the second screening, (P <0.001. Hematuria was the most common urinary abnormalities detected in 245 (9.8% adolescents who had persistent urine abnormalities; 228 (9.1% individuals had non glomerular hematuria. The hematuria was isolated in 150 (6% individuals, combined with leukocyturia in 83 (3.3% individuals, and combined with proteinuria in 12 (0.5% individuals. Leukocyturia was detected in 150 (6% of all studied adolescents; it was isolated in 39 (1.6% individuals and combined with proteinuria in 28 (1.1% of them. Asymp- tomatic bacteriuria was detected in 23 (0.9% of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6% of all the studied adolescents; 45 (1.8% indivi- duals had <0.5 g/day and twenty (0.8% individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01 and (P <0.001, respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

  19. Abnormal uterine bleeding: a clinicohistopathological analysis

    OpenAIRE

    Anupamasuresh Y; Suresh YV; Prachi Jain*,

    2014-01-01

    Background: Abnormal uterine bleeding (AUB) is one of the most common problem for the patients and the gynecologists. It adversely effects on the quality of life and psychology of women. It is of special concern in developing country as it adds to the causes of anemia. Management of Abnormal Uterine Bleeding (AUB) is not complete without tissue diagnosis especially in perimenopausal and post-menopausal women. Histological characteristics of endometrial biopsy material as assessed by light mic...

  20. Medical Costs of Abnormal Serum Sodium Levels

    OpenAIRE

    Shea, Alisa M.; Hammill, Bradley G.; Curtis, Lesley H.; Szczech, Lynda A.; Schulman, Kevin A

    2008-01-01

    An abnormal serum sodium level is the most common electrolyte disorder in the United States and can have a significant impact on morbidity and mortality. The direct medical costs of abnormal serum sodium levels are not well understood. The impact of hyponatremia and hypernatremia on 6-mo and 1-yr direct medical costs was examined by analyzing data from the Integrated HealthCare Information Services National Managed Care Benchmark Database. During the period analyzed, there were 1274 patients ...

  1. Heterotaxy syndromes and abnormal bowel rotation

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Beverley [Stanford University, Lucile Packard Children' s Hospital, Department of Radiology, Stanford, CA (United States); Koppolu, Raji; Sylvester, Karl [Lucile Packard Children' s Hospital at Stanford, Department of Surgery, Stanford, CA (United States); Murphy, Daniel [Lucile Packard Children' s Hospital at Stanford, Department of Cardiology, Stanford, CA (United States)

    2014-05-15

    Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

  2. Abnormalities of gut vessels in Turner's syndrome.

    OpenAIRE

    Reinhart, W H; Mordasini, C.; Stäubli, M.; Scheurer, U.

    1983-01-01

    We describe a 57-year-old patient with Turner's syndrome, iron deficiency anaemia and intestinal vascular abnormalities. Colonoscopy revealed 2 widely dilated, tortuous veins in the terminal ileum and several smaller ectatic veins and haemangioma-like malformations throughout the colon. Laparotomy for herniotomy showed only minimal vascular abnormalities of the serosal surface. Patients with Turner's syndrome and anaemia should be checked for these lesions by endoscopy, and conversely, in pat...

  3. Carbamazepine for acute psychosis with eeg abnormalities

    OpenAIRE

    Ivković Maja; Damjanović Aleksandar; Marinković Dragan; Paunović Vladimir R.

    2004-01-01

    Aim. To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment. Methods. Eleven medication-naive patients diagnosed with acute paranoid psychosis with associated EEG abnormalities were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6), and carbamazepine group (n=5) with the addition of carbamazepine (600 mg/day) to fluphenazine...

  4. Abnormal Chromosome Segregation May Trigger Tumors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Cancer is a primary threat to human health as it kills millions of people each year.Scientists have shown that 75% of human cancers have an abnormal number of chromosomes in cells,and the proportion of the cells with an abnormal chromosome number is tightly and positively related to malignance progression and metastasis of cancers. But the pathological mechanism behind the anomaly still remains unknown.

  5. Evidence of portuguese stock market abnormal returns

    OpenAIRE

    Duarte, Elisabete Mendes; Oliveira, Lisete Trindade

    2011-01-01

    According to the stock market efficiency theory, it is not possible to consistently beat the market. However, technical analysis is more and more spread as an efficient way to achieve abnormal returns. In fact there is evidence that momentum investing strategies provide abnormal returns in different stock markets, Jegadeesh, N. and Titman, S. (1993), George, T. and Hwang, C. (2004) and Du, D. (2009). In this work we study if like other markets, the Portuguese stock market also allows to obtai...

  6. The effects of treatment satisfaction and therapeutic dosage on adolescent drinking outcomes

    OpenAIRE

    Schulte, Marya T.

    2009-01-01

    The current study examined the impact of non-specific treatment factors, therapeutic dosage and treatment satisfaction, on drinking behaviors and consequences among adolescents participating in a voluntary, high school- based alcohol intervention (N = 94). Path analysis served to test the primary model in which satisfaction and dosage were predicted to influence severity of alcohol use (i.e., number of binge drinking episodes and alcohol-related problems within the past 30 days) three months ...

  7. Spectrophotometric Method for Simultaneous Estimation of Escitalopram Oxalate and Clonazepam in Tablet Dosage Form

    OpenAIRE

    Kakde R; Satone D

    2009-01-01

    A simple, accurate and precise spectrophotometric method has been developed for simultaneous estimation of escitalopram oxalate and clonazepam in combined dosage form. Simultaneous equation method is employed for simultaneous determination of escitalopram oxalate and clonazepam from combined dosage forms. In this method, the absorbance was measured at 238 nm for escitalopram oxalate and 273 nm for clonazepam. Linearity was observed in range of 5-100 μg/ml and 5-50 μg/ml for escitalo...

  8. Pharmacist, general practitioner, and nurse perceptions, experiences, and knowledge of medication dosage form modification

    OpenAIRE

    Nissen, Lisa

    2013-01-01

    Thi-My-Uyen Nguyen,1 Esther TL Lau,1,3 Kathryn J Steadman,1 Julie AY Cichero,1 Kaeleen Dingle,2 Lisa M Nissen1,3 1School of Pharmacy, University of Queensland, Brisbane, QLD, Australia; 2School of Public Health, Queensland University of Technology, Brisbane, QLD, Australia; 3School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia Background: People often modify oral solid dosage forms when they experience difficulty swallowing them. Modifying dosage forms m...

  9. How to determine the dosage of oral progesterone among patients with menstrual disorders?

    Institute of Scientific and Technical Information of China (English)

    ZHENG Ting-ping; SUN Ai-jun; WANG Ya-ping; XUE Wei; JIANG Ying; ZHANG Ying; CHEN Rong; JIN Li-na; LANG Jing-he

    2012-01-01

    Background Few studies have given suggestions on appropriate individual progesterone dosage in patients with progesterone deficiency.This study was designed to provide a reference for the clinical use of oral progesterone by exploring the relationship among Body Mass Index (BMI),dosage of progesterone,and serum progesterone concentration.Many gynecology and obstetrics doctors are unfamiliar with progesterone Ireatment.Our study is intended to help determine the dosage of oral progesterone.Methods This was a block randomized,open-label,prospective clinical trial.Eighty women undergoing cessation of menses were recruited,given oral progesterone therapy for 10 consecutive days.They were randomly assigned to four groups (four different doses of progesterone,n=20):group A 100 mg/d,group B 200 mg/d,group C 300 mg/d,and group O 400 mg/d.Results Seventy-four patients (92.5%,74/80) completed the study.It was observed that administration of progesterone significantly increased serum progesterone concentration in the four groups (all P <0.001).And there is a positive correlation between the increase and dosage (rp=0.613,P <0.001).A further linear regression analysis found the major regression equation:when 18.5 kg/m2 ≤BMI <24 kg/m2,Y=8.4820×10~003x (R2=0.425,P <0.001); Y was the increase of serum progesterone concentration in nmol/L,and X was the dosage of oral progesterone in mg/d.Conclusions Serum progesterone levels went up linearly as the dosage increased.The higher the patient's BMI,the higher dosage would be needed to achieve the same serum progesterone concentration.The appropriate dosage of oral progesterone for different patients can be roughly calculated in light of the results of this study.

  10. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Damien Marechal

    Full Text Available Down syndrome (DS results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

  11. Efficiency of individual dosage of digoxin with calculated concentration

    Directory of Open Access Journals (Sweden)

    Zhao L

    2014-07-01

    digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function.Conclusion: The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model. Keywords: serum digoxin concentration, predicted concentration, renal insufficiency

  12. Regulatory RNAs and chromatin modification in dosage compensation: A continuous path from flies to humans?

    Directory of Open Access Journals (Sweden)

    Lavranos Giagkos

    2008-03-01

    Full Text Available Abstract Chromosomal sex determination is a widely distributed strategy in nature. In the most classic scenario, one sex is characterized by a homologue pair of sex chromosomes, while the other includes two morphologically and functionally distinct gonosomes. In mammalian diploid cells, the female is characterized by the presence of two identical X chromosomes, while the male features an XY pair, with the Y bearing the major genetic determinant of sex, i.e. the SRY gene. In other species, such as the fruitfly, sex is determined by the ratio of autosomes to X chromosomes. Regardless of the exact mechanism, however, all these animals would exhibit a sex-specific gene expression inequality, due to the different number of X chromosomes, a phenomenon inhibited by a series of genetic and epigenetic regulatory events described as "dosage compensation". Since adequate available data is currently restricted to worms, flies and mammals, while for other groups of animals, such as reptiles, fish and birds it is very limited, it is not yet clear whether this is an evolutionary conserved mechanism. However certain striking similarities have already been observed among evolutionary distant species, such as Drosophila melanogaster and Mus musculus. These mainly refer to a the need for a counting mechanism, to determine the chromosomal content of the cell, i.e. the ratio of autosomes to gonosomes (a process well understood in flies, but still hypothesized in mammals, b the implication of non-translated, sex-specific, regulatory RNAs (roX and Xist, respectively as key elements in this process and the location of similar mediators in the Z chromosome of chicken c the inclusion of a chromatin modification epigenetic final step, which ensures that gene expression remains stably regulated throughout the affected area of the gonosome. This review summarizes these points and proposes a possible role for comparative genetics, as they seem to constitute proof of

  13. Radiation dosage reduction in general dental practice using digital intraoral radiographic systems

    International Nuclear Information System (INIS)

    This report describes the radiation dosage reduction possible in the general dental practice with two CCD (charge-coupled device)-based intraoral radiographic systems; the RVG-S (Trophy Radiologie, Vincennes, France) and the Sens-A-Ray (Regam Medical Systems, Sundsvall, Sweden). Radiation dosages (air-kerma; Gy) necessary for obtaining clinically acceptable images were measured at the cone tip using an ionization chamber type 660-1 (Nuclear Associates, Victoreen, Inc., Carle Place, New York, USA). When the RVG-S was used with an Oramatic 70 (Trophy Radiologie) X-ray generator, dosages at the cone tip ranged from 322 to 612 μGy. These corresponded to 40-60% of the dosages necessary when using Ektaspeed dental X-ray film (Eastman Kodak, Rochester, New York, USA) with a Heliodent 70 (Siemens, Erlangen, Germany) X-ray generator. At 60 kVp, the Sens-A-Ray reduced the dosage in the order of 30% compared with Ektaspeed dental X-ray film. Reduction in radiation dosage is one of the benefits of digital intraoral radiographic systems in general dental clinics. The RVG-S provides greater dose savings than does the Sens-A-Ray. (author)

  14. Radiation dosage reduction in general dental practice using digital intraoral radiographic systems.

    Science.gov (United States)

    Hayakawa, Y; Shibuya, H; Ota, Y; Kuroyanagi, K

    1997-02-01

    This report describes the radiation dosage reduction possible in the general dental practice with two CCD (charge-coupled device)-based intraoral radiographic systems: the RVG-S (Trophy Radiologie, Vincennes, France) and the Sens-A-Ray (Regam Medical Systems, Sundsvall, Sweden). Radiation dosages (air-kerma; Gy) necessary for obtaining clinically acceptable images were measured at the cone tip using an ionization chamber type 660-1 (Nuclear Associates, Victoreen, Inc., Carle Place, New York, USA). When the RVG-S was used with an Oramatic 70 (Trophy Radiologie) X-ray generator, dosages at the cone tip ranged from 322 to 612 microGy. These corresponded to 40-60% of the dosages necessary when using Ektaspeed dental X-ray film (Eastman Kodak, Rochester, New York, USA) with a Heliodent 70 (Siemens, Erlangen, Germany) X-ray generator. At 60 kVp, the Sens-A-Ray reduced the dosage in the order of 30% compared with Ektaspeed dental X-ray film. Reduction in radiation dosage is one of the benefits of digital intraoral radiographic systems in general dental clinics. The RVG-S provides greater dose savings than does the Sens-A-Ray.

  15. Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of β-methyl-amino-L-alanine (BMAA).

    Science.gov (United States)

    Frøyset, Ann Kristin; Khan, Essa Ahsan; Fladmark, Kari Espolin

    2016-01-01

    The non-protein amino acid β-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up-regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression. PMID:27404450

  16. Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of β-methyl-amino-L-alanine (BMAA)

    Science.gov (United States)

    Frøyset, Ann Kristin; Khan, Essa Ahsan; Fladmark, Kari Espolin

    2016-01-01

    The non-protein amino acid β-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up-regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression. PMID:27404450

  17. A time stamp comparative analysis of frequent chromosomal abnormalities in Romanian patients.

    Science.gov (United States)

    Suciu, Nicolae; Plaiasu, Vasilica

    2014-01-01

    Chromosome abnormalities represent the leading cause in many human genetic disorders. Gain or loss of genetic material can disrupt the normal expression of genes important in fetal development and result in abnormal phenotypes. Approximately 60% of first-trimester spontaneous abortions exhibit karyotype abnormalities. The majority of these abnormalities consist of numerical chromosomal changes, such as autosomal trisomy, monosomy X and polyploidy. In our current study, 411 cases were analyzed over a period of 5 years, which reflected the incidence of cytogenetic abnormalities in Romania. Down syndrome showed the highest frequency at 79%. At 2.6% structural chromosome abnormality syndromes and Turner syndrome followed suit. Next were the Edwards and Patau syndromes with an incidence of 1.2%. Klinefelter, Cri du chat and Wolf-Hirschhorn syndromes all had an incidence of 0.7%. Finally, the lowest frequencies were shown by Williams at 0.4% and only one case of Beckwith-Wiedemann syndrome with abnormal karyotype. The average maternal age at childbirth was 31.15 years (SD = 6.96) and the average paternal age was 33.41 years (SD = 7.17). PMID:23570267

  18. Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice

    Science.gov (United States)

    Fukuda, Atsushi; Mitani, Atsushi; Miyashita, Toshiyuki; Sado, Takashi; Umezawa, Akihiro; Akutsu, Hidenori

    2016-01-01

    In female mammals, activation of Xist (X-inactive specific transcript) is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist) is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist. PMID:27788132

  19. Comparative sex chromosome genomics in snakes: differentiation, evolutionary strata, and lack of global dosage compensation.

    Directory of Open Access Journals (Sweden)

    Beatriz Vicoso

    Full Text Available Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females. Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae, but completely heteromorphic sex chromosomes in both garter snakes (Colubridae and pygmy rattlesnake (Viperidae. Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases. This demonstrates that mutation rates are male-biased in snakes (male-driven evolution, but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex

  20. Haploinsufficiency after successive loss of signaling reveals a role for ERECTA-family genes in Arabidopsis ovule development.

    Science.gov (United States)

    Pillitteri, Lynn Jo; Bemis, Shannon M; Shpak, Elena D; Torii, Keiko U

    2007-09-01

    The Arabidopsis genome contains three ERECTA-family genes, ERECTA (ER), ERECTA-LIKE 1 (ERL1) and ERL2 that encode leucine-rich repeat receptor-like kinases. This gene family acts synergistically to coordinate cell proliferation and growth during above-ground organogenesis with the major player, ER, masking the loss-of-function phenotypes of the other two members. To uncover the specific developmental consequence and minimum threshold requirement for signaling, ER-family gene function was successively eliminated. We report here that ERL2 is haploinsufficient for maintaining female fertility in the absence of ER and ERL1. Ovules of the haploinsufficient er-105 erl1-2 erl2-1/+ mutant exhibit abnormal development with reduced cell proliferation in the integuments and gametophyte abortion. Our analysis indicates that progression of integument growth requires ER-family signaling in a dosage-dependent manner and that transcriptional compensation among ER-family members occurs to maintain the required signaling threshold. The specific misregulation of cyclin A genes in the er-105 erl1-2 erl2-1/+ mutant suggests that downstream targets of the ER-signaling pathway might include these core cell-cycle regulators. Finally, genetic interaction of the ER family and the WOX-family gene, PFS2, reveals their contribution to integument development through interrelated mechanisms. PMID:17652352

  1. Fetal calcifications are associated with chromosomal abnormalities.

    Directory of Open Access Journals (Sweden)

    Ellika Sahlin

    Full Text Available The biological importance of calcifications occasionally noted in fetal tissues (mainly liver at autopsy or ultrasound is largely unexplored. Previous reports hint at an association to infection, circulatory compromise, malformations or chromosomal abnormalities. To identify factors associated with calcifications, we have performed a case-control study on the largest cohort of fetuses with calcifications described thus far.One-hundred and fifty-one fetuses with calcifications and 302 matched controls were selected from the archives of the Department of Pathology, Karolinska University Hospital. Chromosome analysis by karyotyping or quantitative fluorescence-polymerase chain reaction was performed. Autopsy and placenta reports were scrutinized for presence of malformations and signs of infection.Calcifications were mainly located in the liver, but also in heart, bowel, and other tissues. Fetuses with calcifications showed a significantly higher proportion of chromosomal abnormalities than controls; 50% vs. 20% (p<0.001. The most frequent aberrations among cases included trisomy 21 (33%, trisomy 18 (22%, and monosomy X (18%. A similar distribution was seen among controls. When comparing cases and controls with chromosomal abnormalities, the cases had a significantly higher prevalence of malformations (95% vs. 77%, p=0.004. Analyzed the other way around, cases with malformations had a significantly higher proportion of chromosomal abnormalities compared with controls, (66% vs. 31%, p<0.001.The presence of fetal calcifications is associated with high risk of chromosomal abnormality in combination with malformations. Identification of a calcification together with a malformation at autopsy more than doubles the probability of detecting a chromosomal abnormality, compared with identification of a malformation only. We propose that identification of a fetal tissue calcification at autopsy, and potentially also at ultrasound examination, should infer

  2. Droplet digital PCR-aided screening and characterization of Pichia pastoris multiple gene copy strains.

    Science.gov (United States)

    Cámara, Elena; Albiol, Joan; Ferrer, Pau

    2016-07-01

    Pichia (syn. Komagataella) pastoris is a widely used yeast platform for heterologous protein production. Expression cassettes are usually stably integrated into the genome of this host via homologous recombination. Although increasing gene dosage is a powerful strategy to improve recombinant protein production, an excess in the number of gene copies often leads to decreased product yields and increased metabolic burden, particularly for secreted proteins. We have constructed a series of strains harboring different copy numbers of a Rhizopus oryzae lipase gene (ROL), aiming to find the optimum gene dosage for secreted Rol production. In order to accurately determine ROL gene dosage, we implemented a novel protocol based on droplet digital PCR (ddPCR), and cross validated it with conventional real-time PCR. Gene copy number determination based on ddPCR allowed for an accurate ranking of transformants according to their ROL gene dosage. Results indicated that ddPCR was particularly superior at lower gene dosages (one to five copies) over quantitative real-time PCR (qPCR). This facilitated the determination of the optimal ROL gene dosage as low as two copies. The ranking of ROL gene dosage versus Rol yield was consistent at both small scale and bioreactor chemostat cultures, thereby easing clone characterization in terms of gene dosage dependent physiological effects, which could be discriminated even among strains differing by only one ROL copy. A selected two-copy strain showed twofold increase in Rol specific production in a chemostat culture over the single copy strain. Conversely, strains harboring more than two copies of the ROL gene showed decreased product and biomass yields, as well as altered substrate consumption specific rates, compared to the reference (one-copy) strain. Biotechnol. Bioeng. 2016;113: 1542-1551. © 2015 Wiley Periodicals, Inc. PMID:26704939

  3. Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, N.; Toth, B.B.; Hoar, R.E.; Ried, H.L.; Sullivan, M.P.; McNeese, M.D.

    1984-06-01

    Sixty-eight long-term survivors of childhood cancer were evaluated for dental and maxillofacial abnormalities. Forty-five patients had received maxillofacial radiation for lymphoma, leukemia, rhabdomyosarcoma, and miscellaneous tumors. Forty-three of the 45 patients and the remaining 23 who had not received maxillofacial radiation also received chemotherapy. Dental and maxillofacial abnormalities were detected in 37 of the 45 (82%) radiated patients. Dental abnormalities comprised foreshortening and blunting of roots, incomplete calcification, premature closure of apices, delayed or arrested tooth development, and caries. Maxillofacial abnormalities comprised trismus, abnormal occlusal relationships, and facial deformities. The abnormalities were more severe in those patients who received radiation at an earlier age and at higher dosages. Possible chemotherapeutic effects in five of 23 patients who received treatment for tumors located outside the head and neck region comprised acquired amelogenesis imperfecta, microdontia of bicuspid teeth, and a tendency toward thinning of roots with an enlarged pulp chamber. Dental and maxillofacial abnormalities should be recognized as a major consequence of maxillofacial radiation in long-term survivors of childhood cancer, and attempts to minimize or eliminate such sequelae should involve an effective interaction between radiation therapists, and medical and dental oncologists.

  4. Carbamazepine for acute psychosis with eeg abnormalities

    Directory of Open Access Journals (Sweden)

    Ivković Maja

    2004-01-01

    Full Text Available Aim. To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment. Methods. Eleven medication-naive patients diagnosed with acute paranoid psychosis with associated EEG abnormalities were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6, and carbamazepine group (n=5 with the addition of carbamazepine (600 mg/day to fluphenazine treatment. Clinical Global Impression (CGI, Brief Psychiatric Rating Scale (BPRS, Scale for the Assessment of Negative Symptoms (SANS, and EEG were assessed on the baseline and after 6 weeks of treatment. Paired and two-tailed t-tests were used for statistical significance. Results. All the patients showed significant improvement of mental state after 6 weeks of treatment with no significant differences in CGI, BPRS, and total SANS scores in relation to the therapy with carbamazepine. Nevertheless, after 6 weeks of the treatment, EEG findings were significantly better in carbamazepine group, in relation to the findings from the onset of the treatment, as well as in comparison to sole fluphenazine group. Conclusion. Although carbamazepine stabilized abnormal brain electrical activities it seemed that the associated EEG abnormalities were not significant for acute psychosis observed. These preliminary results suggested that there was no convincing evidence that carbamazepine was efficient as the augmentation of antipsychotic treatment for patients with both acute paranoid psychosis and EEG abnormalities.

  5. OPHTHALMOLOGIC ABNORMALITIES IN CHILDREN WITH IMPAIRED HEARING

    Directory of Open Access Journals (Sweden)

    Inderjit

    2014-02-01

    Full Text Available AIM: To determine the nature of ophthalmologic abnormalities in severe and profound grades of hearing impaired children and to treat visual impairment if any at the earliest . MATERIAL AND METHODS: Study was conducted on100 children in the age group of 5 - 14 years with severe and profound hearing loss visiting outpatient department of Ram Lal Eye and ENT hospital Govt. Medical College Amritsar and subjected to detailed ophthalmological examination. RESULTS: 100 children in the age group 5 - 14 years with hearing impairment were enrolled for t he study , 68 had profound and 32 had severe hearing loss . Visual disorders were found to be as high as 71%. Highest percentage was seen in children aged 7 years. Majority of them (50% had refractive error. Out of these 50 children , 28(56% had myopia , 10 (20% hypermetropia and 12(24% had astigmatism . The other ophthalmic abnormalities in our study were conjunctivitis 14(19.71% , fundus abnormalities and squint 11(15.49% , blepharitis 5 (7.04% , vitamin A deficiency 6 (8.04% , amblyopia 8 (11.26% , pupil disorder 3 (4.22% , cataract 3 (4.22% and heterochromia iridis 7 (9.85%. CONCLUSION : The high prevalence of ophthalmic abnormalities in deaf children mandate screening them for possible ophthalmic abnormalities. Early diagnosis and correction of visual d isturbances would go a long way in social and professional performance of these children.

  6. Dysmorphometrics: the modelling of morphological abnormalities

    Directory of Open Access Journals (Sweden)

    Claes Peter

    2012-02-01

    Full Text Available Abstract Background The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. Methods A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. Results We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. Conclusion The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.

  7. Prevalence of asymptomatic urinary abnormalities among adolescents.

    Science.gov (United States)

    Fouad, Mohamed; Boraie, Maher

    2016-05-01

    To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1%) individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8%) at the second screening, (P adolescents who had persistent urine abnormalities; 228 (9.1%) individuals had non glomerular hematuria. The hematuria was isolated in 150 (6%) individuals, combined with leukocyturia in 83 (3.3%) individuals, and combined with proteinuria in 12 (0.5%) individuals. Leukocyturia was detected in 150 (6%) of all studied adolescents; it was isolated in 39 (1.6%) individuals and combined with proteinuria in 28 (1.1%) of them. Asymptomatic bacteriuria was detected in 23 (0.9%) of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6%) of all the studied adolescents; 45 (1.8%) individuals had adolescents from rural than urban areas (P adolescents in our population.

  8. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. PMID:27178343

  9. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties.

  10. Enhanced monitoring of abnormal emergency department demands

    KAUST Repository

    Harrou, Fouzi

    2016-06-13

    This paper presents a statistical technique for detecting signs of abnormal situation generated by the influx of patients at emergency department (ED). The monitoring strategy developed was able to provide early alert mechanisms in the event of abnormal situations caused by abnormal patient arrivals to the ED. More specifically, This work proposed the application of autoregressive moving average (ARMA) models combined with the generalized likelihood ratio (GLR) test for anomaly-detection. ARMA was used as the modelling framework of the ARMA-based GLR anomaly-detection methodology. The GLR test was applied to the uncorrelated residuals obtained from the ARMA model to detect anomalies when the data did not fit the reference ARMA model. The ARMA-based GLR hypothesis testing scheme was successfully applied to the practical data collected from the database of the pediatric emergency department (PED) at Lille regional hospital center, France. © 2015 IEEE.

  11. Abnormal Head Position in Infantile Nystagmus Syndrome

    Science.gov (United States)

    Noval, Susana; González-Manrique, Mar; Rodríguez-Del Valle, José María; Rodríguez-Sánchez, José María

    2011-01-01

    Infantile nystagmus is an involuntary, bilateral, conjugate, and rhythmic oscillation of the eyes which is present at birth or develops within the first 6 months of life. It may be pendular or jerk-like and, its intensity usually increases in lateral gaze, decreasing with convergence. Up to 64% of all patients with nystagmus also present strabismus, and even more patients have an abnormal head position. The abnormal head positions are more often horizontal, but they may also be vertical or take the form of a tilt, even though the nystagmus itself is horizontal. The aim of this article is to review available information about the origin and treatment of the abnormal head position associated to nystagmus, and to describe our treatment strategies. PMID:24533187

  12. Advances in understanding paternally transmitted Chromosomal Abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  13. Parsing abnormal grain growth in specialty aluminas

    Science.gov (United States)

    Lawrence, Abigail Kremer

    Grain growth in alumina is strongly affected by the impurities present in the material. Certain impurity elements are known to have characteristic effects on abnormal grain growth in alumina. Specialty alumina powders contain multiple impurity species including MgO, CaO, SiO2, and Na 2O. In this work, sintered samples made from alumina powders containing various amounts of the impurities in question were characterized by their grain size and aspect ratio distributions. Multiple quantitative methods were used to characterize and classify samples with varying microstructures. The grain size distributions were used to partition the grain size population into subpopulations depending on the observed deviation from normal behavior. Using both grain size and aspect ratio a new visual representation for a microstructure was introduced called a morphology frequency map that gives a fingerprint for the material. The number of subpopulations within a sample and the shape of the distribution on the morphology map provided the basis for a classification scheme for different types of microstructures. Also using the two parameters a series of five metrics were calculated that describe the character of the abnormal grains in the sample, these were called abnormal character values. The abnormal character values describe the fraction of grains that are considered abnormal, the average magnitude of abnormality (including both grain size and aspect ratio), the average size, and variance in size. The final metric is the correlation between grain size and aspect ratio for the entire population of grains. The abnormal character values give a sense of how different from "normal" the sample is, given the assumption that a normal sample has a lognormal distribution of grain size and a Gaussian distribution of aspect ratios. In the second part of the work the quantified measures of abnormality were correlated with processing parameters such as composition and heat treatment conditions. A

  14. Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism

    NARCIS (Netherlands)

    Vorstman, JAS; Staal, WG; van Daalen, E; van Engeland, H; Hochstenbach, PFR; Franke, L

    2006-01-01

    The identification of the candidate genes for autism through linkage and association studies has proven to be a difficult enterprise. An alternative approach is the analysis of cytogenetic abnormalities associated with autism. We present a review of all studies to date that relate patients with cyto

  15. Congenital abnormalities (a bibliography with abstracts). Report for 1964-November 1979

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, E.A.

    1979-12-01

    Radiation hazards, food additives, gene mutations, musculoskeletal diseases, neoplasms, leukemia, rubella and chromosomes as related to congenital abnormalities are topics covered by the citations of research reports in the bibliography. (This updated bibliography contains 184 abstracts, 18 of which are new entries to the previous edition.)

  16. Congenital abnormalities (a bibliography with abstracts). Report for 1964-Nov 77

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, E.A.

    1977-11-01

    Radiation hazards, food additives, gene mutations, musculoskeletal diseases, neoplasms, leukemia, rubella and chromosomes as related to congenital abnormalities are topics covered by the citations of research reports in the bibliography. (This updated bibliography contains 141 abstracts, 30 of which are new entries to the previous edition.)

  17. Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

    DEFF Research Database (Denmark)

    Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian;

    2012-01-01

    Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model f...

  18. Nonpathologizing trauma interventions in abnormal psychology courses.

    Science.gov (United States)

    Hoover, Stephanie M; Luchner, Andrew F; Pickett, Rachel F

    2016-01-01

    Because abnormal psychology courses presuppose a focus on pathological human functioning, nonpathologizing interventions within these classes are particularly powerful and can reach survivors, bystanders, and perpetrators. Interventions are needed to improve the social response to trauma on college campuses. By applying psychodynamic and feminist multicultural theory, instructors can deliver nonpathologizing interventions about trauma and trauma response within these classes. We recommend class-based interventions with the following aims: (a) intentionally using nonpathologizing language, (b) normalizing trauma responses, (c) subjectively defining trauma, (d) challenging secondary victimization, and (e) questioning the delineation of abnormal and normal. The recommendations promote implications for instructor self-reflection, therapy interventions, and future research.

  19. Anaesthesia in operations of congenital craniofacial abnormalities

    Directory of Open Access Journals (Sweden)

    Jahangirie B

    1996-07-01

    Full Text Available Some syndromes that are characterized by abnormalities of the skull, facial bones, and mandibule, most of these patients are from the pediatric population. For the anaesthetic management of patients with various craniofacial dysostosis are as follows: 1 The necessary for careful evaluation of the airway by simply observing the patient. 2 Evaluation of the patient for abnormalities of the heart and lungs. 3 Patients may also have increased intracranial pressure. 4 Anaesthetic drugs and techniques: no particular drugs is recommended. Techniques controlled ventilation. 5 All patients should be cared in the intensive care unit after operation between 24-48 hours

  20. Hemorheological abnormalities in human arterial hypertension

    Science.gov (United States)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  1. [Some problems for dosage form based on questionnaire surveying compliance in patients taking tamsulosin hydrochloride].

    Science.gov (United States)

    Ogata, Ikuko; Yamasaki, Keishi; Tsuruda, Atsuko; Tsuzaki, Shoichiro; Ishimatsu, Takashi; Hirayama, Hideo; Seo, Hakaru

    2008-02-01

    After the dosage form of tamsulosin hydrochloride was changed from a capsule to on orally disintegrating tablet (ODT, Harnal D), we often received patient complaints and noted an increase in noncompliance with medication regimens. The change in dosage form appeared to cause poor compliance by patients who had become accustomed to the light pink/white capsule over many years. Therefore, we carried out a questionnaire survey of patients taking the ODT form to determine the effects of changing the dosage form and the usefulness of the ODT. Most (92%) of respondents took the ODT with water. In addition, 16% missed taking the medicine after the change in dosage form. ODT is a dosage form that is easy to take for patient with dysphagia, or those on restricted water intake. However, it appears that elderly men and patients with visual disorders cannot distinguish the ODT from other medicines and this affects patient compliance. In conclusion, all pharmaceutical companies should consider the design of medications in terms of coloration, indications, or shape in anticipation of the aging society in future, so that patients can distinguish them. Furthermore, sufficient pharmaceutical care is needed to improve both compliance and safety management for the elderly. PMID:18239377

  2. Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

    2015-11-15

    The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

  3. Effects of pH value and coagulant dosage on contact filtration of humic substances

    Institute of Scientific and Technical Information of China (English)

    蒋绍阶; 刘宗源; 梁建军

    2009-01-01

    Humic substances (especially fulvic acid (FA)) are the major components of natural organic matter (NOM) that widely exist in drinking water source. Due to their potential effects on public health,the removal of FA was one of the main concerns during the water treatment. Therefore,the contact filtration of FA by using aluminum sulfate as coagulant on the basis of jar tests was carried out. The effects of pH and coagulant dosage on the FA removal and the development of head loss were investigated. The results show that the range of pH value during the FA contact filtration can be effectively influenced by the dosage of aluminum sulfate,and the high aluminum sulfate dosage is an important factor that can result in early filter breakthrough. The FA filtration by deep-bed filtration or by membrane filtration is sometimes disparate under the same coagulation conditions. The choice of aluminum sulfate dosage by the method of membrane filtration,i.e. the "true color measurement",may result in inappropriate filter run,whereas it can be determined with simple jar tests by observing the formation of micro flocs. Considering the effects of pH on aluminum sulfate dosage and FA removal,the optimal pH range of 5.5?6.0 is suggested.

  4. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing's Syndrome.

    Science.gov (United States)

    Fujii, Kentaro; Miyashita, Kazutoshi; Kurihara, Isao; Hiratsuka, Ken; Sato, Seiji; Yokota, Kenichi; Kobayashi, Sakiko; Shibata, Hirotaka; Itoh, Hiroshi

    2016-01-01

    Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing's syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing's syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol). However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing's syndrome.

  5. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing's Syndrome.

    Science.gov (United States)

    Fujii, Kentaro; Miyashita, Kazutoshi; Kurihara, Isao; Hiratsuka, Ken; Sato, Seiji; Yokota, Kenichi; Kobayashi, Sakiko; Shibata, Hirotaka; Itoh, Hiroshi

    2016-01-01

    Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing's syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing's syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol). However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing's syndrome. PMID:27375907

  6. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing’s Syndrome

    Directory of Open Access Journals (Sweden)

    Kentaro Fujii

    2016-01-01

    Full Text Available Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing’s syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing’s syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol. However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing’s syndrome.

  7. NMR-based Metabonomic Study on Rat's Urinary Metabolic Response to Dosage of Triptolide

    Institute of Scientific and Technical Information of China (English)

    XIA,Shengan; LIU,Huilang; ZHU,Hang; ZHOU,Zhiming; ZHANG,xu; LIU,Maili

    2009-01-01

    An NMR-based metabonomic approach was used to examine rat's urinary response to dosage of triptolide (TP),a major component responsible for the immunosuppressive and anti-inflammatory effects of Tripterygium wilfordii Hook F (TWHF).The urine samples of Wistar rats were collected at various time intervals before and after dosage of TP (i.p.) and measured using conventional 1 H NMR spectroscopy.The data were statistically analyzed using a principle component analysis (PCA).The results showed that biochemical variation induced by TP was time-related,and the maximal alteration in the metabolites appeared at 16 h,and partially recovered 56 h later after dosage,Increment in relative concentrations of taurine,creatine,trimethylamine N-oxide and decrement in citrate,succinate,2-oxoglutarate and hippurate were observed in the urine after dosage of TP.In addition,2'-deoxycytidine appeared 0-16 h later after the dosage,which may be considered as another biomarker for the acute hepatotoxicity.It suggested that TP may disturb the metabolism of energy and gut microflora,and may cause acute liver lesion and a slight renal impair.These results were also supported by the conventional analysis of clinical plasma chemistry and histopathology.The information observed in this article may be useful for giving insight into mechanism of liver injury induced by TP.

  8. Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Jin Sun; Jie-Ming Shi; Tian-Hong Zhang; Kun Gao; Jing-Jing Mao; Bing Li; Ying-Hua Sun; Zhong-Gui He

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo formulation was achieved by mixing slow- and rapid-of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs9.83±0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn preparations were statistically bioequivalent. Furthermore,percentage absorption in vivo and the cumulative percentage release in vitro.CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.

  9. Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

    CERN Document Server

    Song, J H; Choi, W K

    2002-01-01

    The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

  10. Reversible splenial abnormality in hypoglycemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun; Choi, Jeong Yoon; Koh, Seong-Beom [Korea University School of Medicine, Department of Neurology, Guro Hospital, Seoul (Korea); Lee, Younghen [Korea University School of Medicine, Department of Radiology, Ansan Hospital, Ansan City (Korea)

    2007-03-15

    Lesions involving the splenium of the corpus callosum (SCC) have been rarely reported in cases of hypoglycemic brain injury. We identified signal abnormalities in the SCC in three adult patients with hypoglycemic encephalopathy by using diffusion-weighted imaging (DWI) on a 1.5-T MR scanner. Repeat DWI was performed in all patients following a marked clinical improvement, and MR angiography and routine MRI were also performed. We examined each patient's detailed medical history and blood laboratory tests in order to exclude other conditions causing similar SCC abnormalities. Initial DWI was performed during which each patient showed altered mental status that was attributed to profound hypoglycemia. We observed an identical pattern of DWI abnormality characterized by high signals in the SCC with apparent diffusion coefficient reductions that were reversed completely within several days following appropriate correction of hypoglycemia. T2-weighted or FLAIR images also showed no residual lesion in the SCC and MR angiography was normal in all patients. These case reports suggest that the SCC should be added to the list of selective vulnerability to hypoglycemia and that hypoglycemia, in turn, be included in the differential diagnosis of reversible SCC abnormalities. (orig.)

  11. Reversible splenial abnormality in hypoglycemic encephalopathy

    International Nuclear Information System (INIS)

    Lesions involving the splenium of the corpus callosum (SCC) have been rarely reported in cases of hypoglycemic brain injury. We identified signal abnormalities in the SCC in three adult patients with hypoglycemic encephalopathy by using diffusion-weighted imaging (DWI) on a 1.5-T MR scanner. Repeat DWI was performed in all patients following a marked clinical improvement, and MR angiography and routine MRI were also performed. We examined each patient's detailed medical history and blood laboratory tests in order to exclude other conditions causing similar SCC abnormalities. Initial DWI was performed during which each patient showed altered mental status that was attributed to profound hypoglycemia. We observed an identical pattern of DWI abnormality characterized by high signals in the SCC with apparent diffusion coefficient reductions that were reversed completely within several days following appropriate correction of hypoglycemia. T2-weighted or FLAIR images also showed no residual lesion in the SCC and MR angiography was normal in all patients. These case reports suggest that the SCC should be added to the list of selective vulnerability to hypoglycemia and that hypoglycemia, in turn, be included in the differential diagnosis of reversible SCC abnormalities. (orig.)

  12. Abnormal Events for Emergency Trip in HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Guk Hun; Choi, M. J.; Park, S. I.; Kim, H. W.; Kim, S. J.; Park, J. H.; Kwon, I. C

    2006-12-15

    This report gathers abnormal events related to emergency trip of HANARO that happened during its operation over 10 years since the first criticality on February 1995. The collected examples will be utilized to the HANARO's operators as a useful guide.

  13. Psychology Faculty Perceptions of Abnormal Psychology Textbooks

    Science.gov (United States)

    Rapport, Zachary

    2011-01-01

    The problem. The purpose of the current study was to investigate the perceptions and opinions of psychology professors regarding the accuracy and inclusiveness of abnormal psychology textbooks. It sought answers from psychology professors to the following questions: (1) What are the expectations of the psychology faculty at a private university of…

  14. Dynamic Abnormal Grain Growth in Refractory Metals

    Science.gov (United States)

    Noell, Philip J.; Taleff, Eric M.

    2015-11-01

    High-temperature plastic deformation of the body-centered cubic (BCC) refractory metals Mo and Ta can initiate and propagate abnormal grains at significantly lower temperatures and faster rates than is possible by static annealing alone. This discovery reveals a new and potentially important aspect of abnormal grain growth (AGG) phenomena. The process of AGG during plastic deformation at elevated temperatures, termed dynamic abnormal grain growth (DAGG), was observed at homologous temperatures between 0.52 and 0.72 in both Mo and Ta sheet materials; these temperatures are much lower than those for previous observations of AGG in these materials during static annealing. DAGG was used to repeatedly grow single crystals several centimeters in length. Investigations to date have produced a basic understanding of the conditions that lead to DAGG and how DAGG is affected by microstructure in BCC refractory metals. The current state of understanding for DAGG is reviewed in this paper. Attention is given to the roles of temperature, plastic strain, boundary mobility and preexisting microstructure. DAGG is considered for its potential useful applications in solid-state crystal growth and its possibly detrimental role in creating undesired abnormal grains during thermomechanical processing.

  15. Esophageal motility abnormalities in gastroesophageal reflux disease

    Institute of Scientific and Technical Information of China (English)

    Irene; Martinucci; Nicola; de; Bortoli; Maria; Giacchino; Giorgia; Bodini; Elisa; Marabotto; Santino; Marchi; Vincenzo; Savarino; Edoardo; Savarino

    2014-01-01

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

  16. Craniofacial abnormalities among patients with Edwards Syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2013-09-01

    Full Text Available OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES. METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%. Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%, abnormalities of the ear helix/dysplastic ears (70%, prominent occiput (52%, posteriorly rotated (46% and low set ears (44%, and short palpebral fissures/blepharophimosis (46%. Other uncommon - but relevant - abnormalities included: microtia (18%, orofacial clefts (12%, preauricular tags (10%, facial palsy (4%, encephalocele (4%, absence of external auditory canal (2% and asymmetric face (2%. One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES, craniofacial alterations may be variable among these patients. The OAVS findings in this sample are noteworthy. The association of ES with OAVS has been reported once in the literature.

  17. Vitamin D and Risk of Neuroimaging Abnormalities.

    Science.gov (United States)

    Littlejohns, Thomas J; Kos, Katarina; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Llewellyn, David J

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants. PMID:27166613

  18. Histomorphological study of submandibulary glands of rats submitted to low dosage of X-radiation

    International Nuclear Information System (INIS)

    The minimal dosage of X-ray that is likely to induce cellular alterations is unknown and there are just a few reports with low dosage in odontologic literature. The authors developed a histomorphological analysis of the submandibulary glands of rat that received low dosage of X radiation. The body of the animals was covered with a lead lamin leaving the cervical area uncovered. The submandibular glands were exposed to 1,80 Gy of X-radiation in a single dose. After 24, 48, 72 hours, 7, 14 and 21 days the glands were excised, fixed and prepared for analysis in light microscopy. Mild degenerative changes and nuclear pleomorfism, mainly on the first three experimental periods were observed. (author)

  19. Real life Dosages and Costs of TNFα inhibitor therapy for RA patients in Denmark

    DEFF Research Database (Denmark)

    Hostenkamp, Gisela; Sørensen, Jan; Hetland, Merete Lund

    2009-01-01

    an average dosage per kg body weight ratio was calculated from non-missing observations for reduced, standard and increased treatment regimes respectively and applied to patients with missing data on dosage. The annual dosage, duration and treatment costs were analysed at the end of each treatment line using...... of treatment. Cost estimates based on short term observational data or on instruction leaflets from manufacturers may provide wrong cost assessments of TNF-alpha therapy. It is important to take the long term cost structure into account to arrive at unbiased treatment cost estimates.......Background: When estimating the cost of biological treatment many analyses rely on cross sectional data or standard consumption patterns indicated in the manufacturers' instruction leaflet. Unless such consumption patterns truly reflect routine clinical practice they may result in wrong assumptions...

  20. Application methods and dosages of thiamethoxam in thrips control on tomato plants

    Directory of Open Access Journals (Sweden)

    Raetano Carlos Gilberto

    2003-01-01

    Full Text Available Thrips is one of the most important vector species of the tomato spotted wilt tospovirus (TSWV in Brazil. Two different pesticide application methods, drench x spray, using thiamethoxam were compared with commonly used insecticides for thrips control in tomato plants, Debora Plus. The experimental design consisted of a complete randomized block design with seven treatments and four replicates. Dosages of 150 and 200 g of a.i. per ha were used in just one drench application and 50 g of a.i. ha-1 sprayed, at weekly intervals, 48 days after sowing. The control efficacy of thiamethoxam was compared to diafenthiuron (400 g of a.i. ha-1, profenofos + cypermethrin (320+32 g of a.i. ha-1, respectively and methamidophos (60 g of a.i. per hectolitre of water in spray application. Cumulative number of plants with tospoviruses and the F. schultzei population from ten flowers per plot were registered. The mean cumulative number of plants with tospoviruses among treatments was not significantly different. No significant difference between thiamethoxam application methods and dosages on F. schultzei control, 24 days after application, were observed for thrips population. One drench application of higher dosages of thiamethoxam proved to be more environmentally advantageous than the pesticide applied at dosages of 50 g of a.i. ha-1 at weekly intervals. The vector control efficacy of thiamethoxam varied from 93 to 95%, independently of the application method and dosages. Diafenthiuron and profenofos + cypermethrin showed less efficacy (78 and 88%, respectively but greater than those with methamidophos (71%. The products and dosages tested did not cause phytotoxicity in tomato leaves.

  1. Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunction, and autistic mannerisms

    OpenAIRE

    Huijbregts, Stephan CJ; Loitfelder, Marisa; Rombouts, Serge A.; Swaab, Hanna; Verbist, Berit M; Arkink, Enrico B; van Buchem, Mark A; Veer, Ilya M.

    2015-01-01

    Background Neurofibromatosis type 1 (NF1) is a single-gene neurodevelopmental disorder, in which social and cognitive problems are highly prevalent. Several commonly observed central nervous system (CNS) abnormalities in NF1 might underlie these social and cognitive problems. Cerebral volumetric abnormalities are among the most consistently observed CNS abnormalities in NF1. This study investigated whether differences were present between NF1 patients and healthy controls (HC) in volumetric m...

  2. c-myc、p53和p16的表达及GNAS1基因突变在骨的纤维结构不良中的意义%Abnormal expression of c-myc,p53,p16 protein and GNAS1 gene mutation in fibrous dysplasia

    Institute of Scientific and Technical Information of China (English)

    唐娟; 赵红叶; 郑莉; 张惠箴; 蒋智铭

    2009-01-01

    Objective To study the significance of c-myc,p53 and p16 protein expression in fibrous dysplasia,to detect the GNAS1 gene mutation in fibrous dysplasia,and to explore the property of fibrous dysplasia.Methods The expression of c-myc,p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy,1 Mazabraud syndrome and 20 control cases (10 cases of bony callus,10 cases of osteosarcoma). Genomic DNA extraction,PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.Results C-myc protein immunoreactivity was detected in 91 percentage of FD(P=0.001).Compared with the negative control group,the difference was significant.P16 positive waa detected in 34 FD cases(P=0.001).The difference was significant as compared with the positive control group.Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation.PCR amplification was successful in 12 of 35 FD cases.Two of the 12 FD cases were detected to have GNAS1 gene mutation,in which 1 case waa FD of Mazabraud syndrome,1 case was a monostotic lesion.Concimiom C-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease.P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD.The abnormal expression of the gene p16 might play an important role in the formation of FD.The GNAS1 mutation exist in FD.All of the results indicate that FD could be a neoplasia disease.caused by multiple factors leading to a dysfunction of bone development.%目的 检测c-myc、p53和p16蛋白在骨的纤维结构不良(FD)中的表达及其意义,检测FD中GNAS1基因第8外显子突变,探讨FD的病变性质.方法 采用免疫组织化学SP法检测35例FD(包括1例FD恶变,1例Mazabraud综合征)及20例对照组(10例骨痂、10例骨肉瘤)中c-myc、p53和p16蛋白表达.

  3. Miniaturized approach for excipient selection during the development of oral solid dosage form

    DEFF Research Database (Denmark)

    Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus;

    2014-01-01

    The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... approach can be used for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

  4. Predictors of ovarian response in intrauterine insemination patients and development of a dosage nomogram

    DEFF Research Database (Denmark)

    Freiesleben, N L C; Lossl, K; Bogstad, J;

    2008-01-01

    The objective of this prospective study was to identify predictors of ovarian response in ovulatory patients treated with low-dose recombinant FSH (rFSH), gonadotrophin-releasing hormone antagonist and intrauterine insemination (IUI), and to develop an rFSH dosage nomogram based on the findings.......004) were the strongest independent predictive factors of the number of mature follicles. In conclusion, body weight and antral follicle count may be used to achieve appropriate ovarian response for IUI in ovulatory patients. Based on this, a simple rFSH dosage nomogram was developed for individual ovarian...

  5. Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

    DEFF Research Database (Denmark)

    Nielsen, R E; Lolk, A; Valentin, J B;

    2016-01-01

    mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P ... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

  6. Development and validation of HPTLC method for the estimation of almotriptan malate in tablet dosage form

    Directory of Open Access Journals (Sweden)

    Suneetha A

    2010-01-01

    Full Text Available A new, simple, precise and accurate high performance thin layer chromatographic method has been proposed for the determination of almotriptan malate in a tablet dosage form. The drug was separated on aluminum plates precoated with silica gel 60 GF 254 with butanol:acetic acid:water (3:1:1 was used as mobilephase. Quantitative analysis was performed by densitometric scanning at 300 nm. The method was validated for linearity, accuracy, precision and robustness. The calibration plot was linear over the range of 100-700 ng/band for almotriptan malate. The method was successfully applied to the analysis of drug in a pharmaceutical dosage form.

  7. Effect of low dosages of powdered activated carbon on membrane bioreactor performance.

    Science.gov (United States)

    Remy, Maxime; Temmink, Hardy; Rulkens, Wim

    2012-01-01

    Previous research has demonstrated that powdered activated carbon (PAC), when applied at very low dosages and long SRTs, reduces membrane fouling in membrane bioreactors (MBRs). This effect was related to the formation of stronger sludge flocs, which are less sensitive to shear. In this contribution the long-term effect of PAC addition was studied by running two parallel MBRs on sewage. To one of these, PAC was dosed and a lower fouling tendency of the sludge was verified, with a 70% longer sustainable filtration time. Low PAC dosages showed additional advantages with regard to oxygen transfer and dewaterability, which may provide savings on operational costs. PMID:22339033

  8. Predictors of ovarian response in intrauterine insemination patients and development of a dosage nomogram

    DEFF Research Database (Denmark)

    Freiesleben, Nina La Cour; Lossl, K.; Bogstad, Jeanette Wulff;

    2008-01-01

    The objective of this prospective study was to identify predictors of ovarian response in ovulatory patients treated with low-dose recombinant FSH (rFSH), gonadotrophin-releasing hormone antagonist and intrauterine insemination (IUI), and to develop an rFSH dosage nomogram based on the findings.......004) were the strongest independent predictive factors of the number of mature follicles. In conclusion, body weight and antral follicle count may be used to achieve appropriate ovarian response for IUI in ovulatory patients. Based on this, a simple rFSH dosage nomogram was developed for individual ovarian...... stimulation prior to IUI....

  9. Inborn errors of metabolism: a cause of abnormal brain development.

    Science.gov (United States)

    Nissenkorn, A; Michelson, M; Ben-Zeev, B; Lerman-Sagie, T

    2001-05-22

    Brain malformations are caused by a disruption in the sequence of normal development by various environmental or genetic factors. By modifying the intrauterine milieu, inborn errors of metabolism may cause brain dysgenesis. However, this association is typically described in single case reports. The authors review the relationship between brain dysgenesis and specific inborn errors of metabolism. Peroxisomal disorders and fatty acid oxidation defects can produce migration defects. Pyruvate dehydrogenase deficiency, nonketotic hyperglycinemia, and maternal phenylketonuria preferentially cause a dysgenetic corpus callosum. Abnormal metabolism of folic acid causes neural tube defects, whereas defects in cholesterol metabolism may produce holoprosencephaly. Various mechanisms have been proposed to explain abnormal brain development in inborn errors of metabolism: production of a toxic or energy-deficient intrauterine milieu, modification of the content and function of membranes, or disturbance of the normal expression of intrauterine genes responsible for morphogenesis. The recognition of a metabolic disorder as the cause of the brain malformation has implications for both the care of the patient and for genetic counseling to prevent recurrence in subsequent pregnancies. PMID:11383558

  10. Approach to Investigating Congenital Skeletal Abnormalities in Livestock.

    Science.gov (United States)

    Dittmer, K E; Thompson, K G

    2015-09-01

    Congenital skeletal abnormalities may be genetic, teratogenic, or nutritional in origin; distinguishing among these different causes is essential in the management of the disease but may be challenging. In some cases, teratogenic or nutritional causes of skeletal abnormalities may appear very similar to genetic causes. For example, chondrodysplasia associated with intrauterine zinc or manganese deficiency and mild forms of hereditary chondrodysplasia have very similar clinical features and histologic lesions. Therefore, historical data are essential in any attempt to distinguish genetic and acquired causes of skeletal lesions; as many animals as possible should be examined; and samples should be collected for future analysis, such as genetic testing. Acquired causes of defects often show substantial variation in presentation and may improve with time, while genetic causes frequently have a consistent presentation. If a disease is determined to be of genetic origin, a number of approaches may be used to detect mutations, each with advantages and disadvantages. These approaches include sequencing candidate genes, single-nucleotide polymorphism array with genomewide association studies, and exome or whole genome sequencing. Despite advances in technology and increased cost-effectiveness of these techniques, a good clinical history and description of the pathology and a reliable diagnosis are still key components of any investigation. PMID:25910781

  11. Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis.

    Science.gov (United States)

    Harumoto, Toshiyuki; Anbutsu, Hisashi; Lemaitre, Bruno; Fukatsu, Takema

    2016-01-01

    Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner. PMID:27650264

  12. Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities

    DEFF Research Database (Denmark)

    Hasle, H; Olsen, J H; Hansen, J;

    1998-01-01

    Cytogenetic abnormalities in human malignancies frequently involve chromosome 7. The existence of several tumor suppressor genes on the long arm of chromosome 7 has been suggested in both epithelial and hematologic malignancies. From the Danish Cytogenetic Register, we identified 183 persons...... with constitutional abnormalities involving chromosome 7, including 16 patients with Williams syndrome. By linkage to the Danish Cancer Registry, we found five persons with cancer, including one thyroid carcinoma, three carcinomas of the digestive tract, and one malignant melanoma. There were no cases of leukemia...

  13. Gross morphological head and throat abnormalities of the tufted Araucana embryo.

    Science.gov (United States)

    Pabilonia, M S; Somes, R G

    1981-09-01

    Structural abnormalities of the head and throat of ear-tufted embryos of the Araucana fowl are described. These abnormalities involved the opening to the external auditory meatus and such bones as the mandible, quadrate, columella auris, squamosal, and hyoid apparatus. Structural irregularities are believed to be due to the presence of the Et gene and its influence on the early embryonic closure of the hyomandibular cleft. The diversity of phenotypic expression probably is due to the varied closure of the cleft. PMID:7322992

  14. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

    Directory of Open Access Journals (Sweden)

    Coze Carole

    2006-01-01

    Full Text Available Abstract Background Pleuropulmonary blastoma (PPB is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. Cases presentation We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. Conclusion The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB.

  15. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

    International Nuclear Information System (INIS)

    Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB

  16. 组织CDH1基因异常甲基化和血清HE4检测对卵巢癌和卵巢内异症囊肿的鉴别价值%Value of abnormal methylation of CDH1 gene and the detection of serum HE4 in the identification of ovarian cancer and ovarian endometriosis cyst

    Institute of Scientific and Technical Information of China (English)

    孙蓓; 张熊

    2015-01-01

    Objective To investigate the abnormal methylation of CDH1 gene and the detection of serum hu-man epididymis protein 4 (HE4) in the identification of ovarian cancer and ovarian endometriosis cyst. Methods Thir-ty-eight patients with ovarian cancer (group A), 41 patients with ovarian ectopic cyst (group B) and 42 patients with be-nign uterine or ovarian lesion (the control group) were enrolled in the study. The methylation status of CDH1 gene pro-moter region was detected by methylation-specific polymerase chain reaction, and the levels of serum HE4 were de-tected with enzyme-linked immunosorbent assay. The changes of the above indicators were compared. Results The expression rates of CDH1 DNA methylation in group B, group A, control group were 4.8% (2/41), 39.4% (15/38), 2.3%(1/42), respectively, with no statistically significant difference between group B and the control group (χ2=0.37, P=0.542), but statistically significant difference between group A and the control group (χ2=11.24, P=0.001), as well as between group A and group B (χ2=13.79, P=0.000). The levels of serum HE4 in group B, group A and control group were 52.7 pmol/L, 537.2 pmol/L, 50.3 pmol/L, respectively, with no statistically significant difference between group B and the control group (t=0.63, P=0.532), but statistically significant difference between group A and the control group (t=54.27, P=0.000), as well as between group A and group B (t=55.33, P=0.000). In group A, the DNA expres-sion quantity of CDH1 gene methylation and levels of serum HE4 are correlated (r=0.527, P0.05). Conclusion Joint detection of CDH1 gene methylation and serum HE4 levels can be applied to the differential diagnosis between ovarian endometriosis cyst and ovarian cancer, which improves the diagnosis rate of the two kinds of diseases.%目的 探讨组织上皮-钙粘连素(CDH1)基因异常甲基化和血清人附睾分泌蛋白4 (HE4)检测对卵巢癌和卵巢内异症囊肿的鉴别价值.方法 选

  17. Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunction, and autistic mannerisms

    NARCIS (Netherlands)

    Huijbregts, S.C.; Loitfelder, M.; Rombouts, S.A.R.B.; Swaab, H.; Verbist, B.M.; Arkink, E.B.; Buchem, M.A. van; Veer, I.M.

    2015-01-01

    Neurofibromatosis type 1 (NF1) is a single-gene neurodevelopmental disorder, in which social and cognitive problems are highly prevalent. Several commonly observed central nervous system (CNS) abnormalities in NF1 might underlie these social and cognitive problems. Cerebral volumetric abnormalities

  18. Embalse NGS: Abnormal event procedures development lifecycle

    International Nuclear Information System (INIS)

    Based on the present used philosophy in Canada and in Atucha Nuclear Generating Station (Argentina) it was decided to develop the Abnormal Event Procedures (EOP's) in a logical diagram format. The EOP's have in general two parts: the diagnosis and the operative action to mitigate the event. Some serious incidents can be resolved by the EOP's, but the philosophy is first, to satisfy the EOP's requirements. Taking into account the operating experience, the Final Safety Report and the results of simulations done by appropriate codes, it was possible to obtain the corresponding sequence for each abnormal event. With the information available in the Control Room (windows, alarms, trends, etc) for each part of the EOP's was associated the instrumentation that the operator must observe. 3 figs

  19. Abnormal fetal head shape: aetiology and management

    DEFF Research Database (Denmark)

    Petersen, Olav Bjørn; David, Anna; Thomasson, Louise;

    2007-01-01

    Background: Abnormal head shape is an uncommon finding on prenatal ultrasound, often associated with breech presentation, spinabifida, aneuploidy or secondary to oligohydramnios or fetal position. Other aetiologies are rarer and may be more difficult to define. Objective: To determine the aetiology...... (lemon-shaped), 18.4% with aneuploidy (mostly strawberry-shaped). 19.5% were dolicocephalic, most secondary to fetal position or oligohydramnios (see table). 13 had confirmed craniosynostosis, including thanatophoric dysplasia, Craniofrontonasal dysplasia, Aperts syndrome, Baller-Gerold syndrome, I......-cell disease, Muenke craniosynostosis and two with an as yet undefined craniosynostosis syndrome. Overall, 16.5 % had an underlying genetic syndrome. Conclusions: Abnormal fetal head shape may be a normal variant, but is commonly associated with a wide variety of underlying pathologies. In view of the high...

  20. Chromosomal abnormalities in a psychiatric population

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

    1995-02-27

    Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

  1. Spinal cord injury without radiographic abnormality

    Directory of Open Access Journals (Sweden)

    Singh Anil

    2006-01-01

    Full Text Available Spinal cord injury without radiological abnormality is rare in adults. Below we present a case report of 20 yrs old male with isolated cervical cord injury, without accompanying vertebral dislocation or fracture involving the spinal canal rim. He fell down on plain and smooth ground while carrying 40 kg weight overhead and developed quadriparesis with difficulty in respiration. Plain radiographs of the neck revealed no fractures or dislocations. MRI showed bulky spinal cord and an abnormal hyper intense signal on the T2W image from C2 vertebral body level to C3/4 intervertebral disc level predominantly in the anterior aspect of the cord The patient was managed conservatively with head halter traction and invasive ventilatory support for the initial 7 days period in the ICU. In our patient recovery was good and most of the neurological deficit improved over 4 weeks with conservative management.

  2. [Psychiatric manifestations due to abnormal glucocorticoid levels].

    Science.gov (United States)

    Lommerse, K M; Dijkstra, F N; Boeke, A J P; Eekhoff, E M W; Jacobs, G E

    2016-01-01

    This clinical case presentation describes the disease trajectory in two patients who presented with psychiatric symptoms as a result of abnormal serum glucocorticoid levels. One case involves a 58-year-old man with hypercortisolism, the other case concerns a 55-year-old woman with hypocortisolism. In both cases there was a considerable diagnostic delay in recognizing the underlying adrenal gland pathology. Abnormal glucocorticoid levels, caused by endocrine disorders, often results in psychiatric symptoms. Delay in diagnosis may have adverse consequences. Hyper- or hypocortisolism should be considered in patients who present with an atypical presentation of psychiatric symptoms. Moreover, the absence of specific physical signs or symptoms at first presentation in such patients does not exclude an underlying endocrinological cause. Therefore, physical and psychiatric reassessment of such patients should be considered at regular intervals. PMID:27507414

  3. Abnormal cervical cytology and health care use

    DEFF Research Database (Denmark)

    Frederiksen, Maria Eiholm; Baillet, Miguel Vázquez-Prada; Dugué, Pierre-Antoine;

    2015-01-01

    OBJECTIVE: This study aimed to assess the long-term use of health care services in women with abnormal cytology results compared to women with normal cytology results. METHODS: We did a nationwide population-based study, using women aged 23 to 59years participating in the national organized......" the cytology result and for the 5-year period "after" the result. RESULTS: During the "before" period exposed women had more contacts to GPs, more contacts to psychologists/psychiatrist, and more hospital admissions than non-exposed women. In both exposed and non-exposed women, health care use increased from...... the "before" to the "after" period. This increase was significantly higher for exposed than non-exposed women regarding contacts to GP, admissions to hospitals, and drug use. CONCLUSION: Women with abnormal cytology results constitute a selected group with a higher health care use than other women even before...

  4. Migraine and structural abnormalities in the brain

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal Mohammad; Ashina, Messoud

    2014-01-01

    PURPOSE OF REVIEW: The aim is to provide an overview of recent studies of structural brain abnormalities in migraine and to discuss the potential clinical significance of their findings. RECENT FINDINGS: Brain structure continues to be a topic of extensive research in migraine. Despite advances...... in neuroimaging techniques, it is not yet clear if migraine is associated with grey matter changes. Recent large population-based studies sustain the notion of increased prevalence of white matter abnormalities in migraine, and possibly of silent infarct-like lesions. The clinical relevance of this association...... is not clear. Structural changes are not related to cognitive decline, but a link to an increased risk of stroke, especially in patients with aura, cannot be ruled out. SUMMARY: Migraine may be a risk factor for structural changes in the brain. It is not yet clear how factors such as migraine sub-type, attack...

  5. Predicting gas in place in abnormal reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Stelly, O.V. II; Farshad, F.F.

    1981-06-01

    Application of the conventional gas material balance equation to abnormally pressured volumetric reservoirs results in erroneous estimates of ultimate recovery. In view of the increasing number and importance of this type of reservoir, the program presented results in more realistic predictions. In abnormally pressured reservoirs, the formation is not supporting as great a portion of the overburden stress. Thus, when pressure is depleted, the sand grains and connate water of the formation expand. These factors tend to reduce the available hydrocarbon pore space acting as a drive mechanism. Thus, production is due to a combination of factors that cause subsequent changes in effective compressibility of the formation rather than just gas compressibility. Hammelindl proposed a correction factor equivalent to the ratio of effective compressibility to gas compressibility. This is applied to the results obtained for normally pressured reservoirs.

  6. 76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

    Science.gov (United States)

    2011-07-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of... Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug... informed FDA that it has transferred ownership of, and all rights and interest in, NADA 092-150 for...

  7. Meta-analysis : High-dosage vitamin E supplementation may increase all-cause mortality

    NARCIS (Netherlands)

    Miller, ER; Pastor-Barriuso, R; Dalal, D; Riemersma, RA; Appel, LJ; Guallar, E

    2005-01-01

    Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a me

  8. Reduction transport of corrosion products through the secondary circuit by increasing the dosage of ammonia

    International Nuclear Information System (INIS)

    Reduce transport of corrosion products through the Secondary Circuit, mainly magnetite, by increasing the dosage of ammonia in order to reduce oxides accumulation in the Steam Generators top of tube sheet where become hard sludge, as one of the TTS denting mitigation actions. (Author)

  9. Effect of low dosages of powdered activated carbon on membrane bioreactor performance

    NARCIS (Netherlands)

    Remy, M.J.J.; Temmink, H.; Rulkens, W.H.

    2012-01-01

    Previous research has demonstrated that powdered activated carbon (PAC), when applied at very low dosages and long SRTs, reduces membrane fouling in membrane bioreactors (MBRs). This effect was related to the formation of stronger sludge flocs, which are less sensitive to shear. In this contribution

  10. The Effects of Methylphenidate in the Classroom: What Dosage, for Which Children, for What Problems?

    Science.gov (United States)

    Northup, John; Gulley, Veronica; Edwards, Stephanie; Fountain, Laura

    2001-01-01

    In this study we conducted single-case analyses of the dosage and time-course effects of methylphenidate (MPH; Ritalin) on disruptive classroom behavior, math and reading performance, and social engagement. Clear individual differences were demonstrated (a) across children; (b) across academic, behavioral, and social domains of functioning; (c)…

  11. A practical thrice weekly ertapenem dosage regime for chronic hemodialysis patients

    NARCIS (Netherlands)

    Bosma, M.; De Man, P.; Rietveld, A.; Touw, D.; Geerlings, C.

    2013-01-01

    Background: Ertapenem is a parenteral carbapenem. In patients undergoing hemodialysis a dosage reduction of 50%, as a dose of 0.5 gram once daily, is advised. Hospital admission or specialised home care is needed to administer ertapenem. As these patients are already visiting the hospital 3 times a

  12. LABORATORY PROTECTION RATE OF TORN BEDNETS TREATED WITH THREE DOSAGES OF PYRETHROIDE AGAINST ANOPHELES CULICIFACIES

    Directory of Open Access Journals (Sweden)

    G. Babaee

    2007-05-01

    Full Text Available Evaluated under laboratory condition. The objective of the present study was to observe the effect of impregnated torn bednets on the number of bites by An. culicifacies A glass made tunnel test was designed to The effect of torn bednets treated with three dosages of cyfluthrin 5% EW, were induce hungry female mosquitoes to pass through holes cut in the pyrethroid treated nets. A guinea pig used as bait to attract mosquitoes through circular holes in the netting. With untreated netting, 72-87% of laboratory-reared females passed through the holes overnight, 64-92% blood-fed successfully and 0.3/9-4/3% died. When the netting was treated with cyfluthrin at doses of 25, 50 and 100 mg a.i./m2, the entry Index (the proportions that passed through the holes overnight were 43.37%, 42.82% and 24.72%; mortality rates were 66.31%, 81.45% and 95.99%; and the feeding rate were 45%, 27% and 3%. In conclusion it should be stressed that efficacy of pyrethroid impregnated bednets using “Tunnel Tests” showing acceptable protection rate both in lower and higher dosages as well as cause dead in the blood-fed mosquitoes. In addition, the higher dosages of these three dosages pyrethroid provided good levels of protection against An. culicifacies.

  13. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    Science.gov (United States)

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8.

  14. 75 FR 26646 - Oral Dosage Form New Animal Drugs; Orbifloxacin Suspension

    Science.gov (United States)

    2010-05-12

    ... redelegated to the Center for Veterinary Medicine, 21 CFR part 520 is amended as follows: PART 520--ORAL... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs... of an oral suspension containing orbifloxacin for the treatment of various bacterial infections...

  15. Response of Microbial Community to Petroleum Stress and Phosphate Dosage in Sediments of Jiaozhou Bay, China

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yangguo; CHEN Min; BAI Jie; LI Xinwei; Farhana Zulfiqar; WANG Qianli

    2014-01-01

    The dynamic microcosms were used to evaluate the effect of oil spills on microbial ecological system in marine sedi-ment and the enhancement of nutrient on the oil removal. The function and structure of microbial community caused by the oil pollu-tion and phosphate dosage were simultaneously monitored by dehydrogenase activity assay and PCR-denaturing gradient gel elec-trophoresis (DGGE) techniques. The results indicated that the amount of total bacteria in all dynamic microcosms declined rapidly with incubation time. The number of petroleum-degrading bacteria and the activity of sediment dehydrogenase were gradually en-hanced by petroleum in the oil-treated microcosms, while they both showed no obvious response to phosphate dosage. In comparison, phosphate spiked heterotrophic bacteria and they showed a significant increase in amount. DGGE profiles indicated that petroleum dosage greatly changed community structure, and the bacteria belonged to class Deltaproteobacteria, and phyla Bacteroidetes and Chlorobi were enriched. This study demonstrated that petroleum input greatly impacted the microbial community structure and con-sequently the marine sediment petroleum-degrading activity was enhanced. Phosphate dosage would multiply heterotrophic bacteria but not significantly enhance the petroleum degradation.

  16. Treatment of Meniere's Disease with A Heavy Dosage of Gu Sui Bu (Rhizoma Drynariae)

    Institute of Scientific and Technical Information of China (English)

    Peng Tun

    2006-01-01

    @@ In treating Meniere's disease, author has found that the compatible use of heavy dosage of Gu Sui Bu (骨碎补 Rhizoma Drynariae) can produce very good effect for relieving dizziness, vertigo and tinnitus. Some of the sample cases are cited in the following.

  17. Prevention and Treatment of Shivering after Intracranial Surgery Using Different Dosages of Tramadol

    Institute of Scientific and Technical Information of China (English)

    Yu-hua Qi; Guo-nian Wang; Shu-yan Wang

    2005-01-01

    @@ During the anesthesia recovery period, shivering is a common uncomfortable complaint of patients increasing oxygen consumption, carbon dioxide production, intraocular and intracranial pressures, all disadvantage for intracranial tumor surgery. The aim of our study is to observe the effect of different dosages of tramadol in the prevention and treatment of shivering after intracranial surgery.

  18. A comparison of test methods for determining in vitro drug release from transdermal delivery dosage forms.

    Science.gov (United States)

    Mazzo, D J; Fong, E K; Biffar, S E

    1986-01-01

    Three test methods for determining in vitro drug release rate from transdermal delivery dosage forms were tested for equivalency of results, ease of implementation and precision. The 'paddle-over-disk' (POD) method is under consideration by the USP as a standarized method for release-rate testing of all transdermal delivery dosage forms. The 'reciprocating disk' (RD) and 'diffusion cell' (DC) methods are both commonly employed throughout the pharmaceutical industry. The three methods were demonstrated to be equivalent in terms of release rate profile (curve shape) and total drug released over the lifetime of the dosage form tested (Transderm-Scop). The precision for the RD method as measured by the mean relative standard deviation over all time points was 4.6%; the precision of the POD method was 5.4% and that for the DC method was 6.7%. Steady-state flux values derived from the POD and RD methods were equivalent ( approximately 4 microg cm(-2) h(-1)) but were approximately 25% greater than the steady-state flux value derived from the DC method ( approximately 3 microg cm(-2) h(-1)). All three methods gave results which were within the specifications of the manufacturer (CIBA-GEIGY). The POD method was the easiest to use on a routine basis, required the least amount of specialized equipment and most resembled the current test methodology for dissolution testing of other dosage forms such as tablets or capsules.

  19. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    van der Elst, K. C. M.; Bruggemann, R. J. M.; Rodgers, M. G. G.; Alffenaar, J. W. C.

    2012-01-01

    The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

  20. Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy

    NARCIS (Netherlands)

    E.C. van Dalen; H.J.H. van der Pal; H.N. Caron; L.C.M. Kremer

    2006-01-01

    Background The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline dosage schedules (i.e. peak doses and infusion durations) have been studied. Objectives The primary objective was to determine the occ

  1. 75 FR 54492 - Ophthalmic and Topical Dosage Form New Animal Drugs; Gentamicin and Betamethasone Ophthalmic...

    Science.gov (United States)

    2010-09-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New Animal Drugs; Gentamicin and Betamethasone Ophthalmic Solution AGENCY: Food and Drug Administration, HHS...) for gentamicin sulfate and betamethasone acetate ophthalmic solution. This action is being taken...

  2. Models of Neurodevelopmental Abnormalities in Schizophrenia

    OpenAIRE

    POWELL, Susan B

    2010-01-01

    The neurodevelopmental hypothesis of schizophrenia asserts that the underlying pathology of schizophrenia has its roots in brain development and that these brain abnormalities do not manifest themselves until adolescence or early adulthood. Animal models based on developmental manipulations have provided insight into the vulnerability of the developing fetus and the importance of the early environment for normal maturation. These models have provided a wide range of validated approaches to an...

  3. Computed tomography in abnormalities of the hip

    Energy Technology Data Exchange (ETDEWEB)

    Visser, J.D.; Jonkers, A.; Klasen, H.J. (Rijksuniversiteit Groningen (Netherlands). Academisch Ziekenhuis); Hillen, B. (Rijksuniversiteit Groningen (Netherlands). Lab. voor Anatomie en Embryologie)

    1982-06-26

    The value of computed tomography in the assessment of abnormalities of the hip is demonstrated with the aid of an anatomical preparation and in patients with, respectively, congenital dislocation of a hip, dislocation of the hip in spina bifida, an acetabular fracture and a Ewing tumour. The anteversion of the acetabulum and femur and the instability index of the hip joint can be measured by means of computed tomography.

  4. Neurostructural Abnormalities in Pediatric Anxiety Disorders

    OpenAIRE

    Strawn, Jeffrey R.; Hamm, Lisa; Fitzgerald, Daniel A.; Fitzgerald, Kate D.; Monk, Christopher S.; Phan, K. Luan

    2015-01-01

    Functional neuroimaging studies have consistently demonstrated abnormalities in fear and threat processing systems in youth with anxiety disorders; however, the structural neuroanatomy of these systems in children and adolescents remains largely unknown. Using voxel-based morphometry (VBM), gray matter volumes were compared between 38 medication-free patients with anxiety disorders (generalized anxiety disorder; social phobia; separation anxiety disorder, mean age: 14.4 ± 3 years) and 27 comp...

  5. Computed tomography in abnormalities of the hip

    International Nuclear Information System (INIS)

    The value of computed tomography in the assessment of abnormalities of the hip is demonstrated with the aid of an anatomical preparation and in patients with, respectively, congenital dislocation of a hip, dislocation of the hip in spina bifida, an acetabular fracture and a Ewing tumour. The anteversion of the acetabulum and femur and the instability index of the hip join can be measured by means of computed tomography. (Auth.)

  6. OPHTHALMOLOGIC ABNORMALITIES IN CHILDREN WITH IMPAIRED HEARING

    OpenAIRE

    Inderjit; Jagdeepak; Prempal; Anup Narayanrao

    2014-01-01

    AIM: To determine the nature of ophthalmologic abnormalities in severe and profound grades of hearing impaired children and to treat visual impairment if any at the earliest . MATERIAL AND METHODS: Study was conducted on100 children in the age group of 5 - 14 years with severe and profound hearing loss visiting outpatient department of Ram Lal Eye and ENT hospital Govt. Medical College Amritsar and subjected to detailed ophthalmological examination. R...

  7. ABNORMALITIES OF ERG IN CONGENITAL ANIRIDIA

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    Congenital aniridia is generally associated with nystagmus, corneal pannus, cataract, ectopia lentis, glaucoma, macular hypoplasia, optic nerve hypoplasia and compromised visual function. Many theories have been proposed, including a failure in the development of the neural ectoderm and/or an aberrant development of mesoderm. We observed the ERG from 19 patients with congenital aniridia. Fourteen patients had abnormal ERG, including the reduced a wave trough under dark adapted red stimuli with dark adap...

  8. Congenital anorectal abnormalities in six dogs.

    Science.gov (United States)

    Prassinos, N N; Papazoglou, L G; Adamama-Moraitou, K K; Galatos, A D; Gouletsou, P; Rallis, T S

    2003-07-19

    Congenital anorectal abnormalities were diagnosed in three male and three female dogs. One dog had anal stenosis, three had a persistent anal membrane, and the other two had an imperforate anus associated with a rectovaginal fistula. Five of the dogs were treated surgically, and four of them which were followed up for periods ranging from one to five years continued to pass faeces normally. PMID:12892267

  9. Chromagen lenses and abnormal colour perception

    OpenAIRE

    O. Matthew Oriowo; Abdullah Z. Alotaibi

    2011-01-01

    Background: The Chromagen lens system comprises of tinted spectacle or contact lenses, each with a specific colour wavelength filter which controls the spectra of the light entering the eye. This study investigated whether spectacle-mounted Chromagen lenses would enhance colour perception in individuals with abnormal colour vision.Methods: The Ishihara colour test was used to test for colour vision deficiency (CVD) and also to evaluate the effect of the Chromagen spectacle lens on colour perc...

  10. Chronic daily headache: biochemical and neurotransmitter abnormalities

    OpenAIRE

    Gallai, Virgilio; Sarchielli, Paola; Genco, Sergio; Alberti, Andrea; D'Andrea, Giovanni

    2000-01-01

    Although chronic daily headache (CDH) represents one of the most relevant complaints of patients in headache centers, the mechanisms underlying the chronicization of head pain are poorly understood. Experimental animal models of chronic pain suggest the involvement of a functional disturbance of several neuronal pathways. The disturbances include an abnormal excitability of nociceptive fibers supplying pain-sensitive structures in the brain responsible for peripheral sensitization (chronic ne...

  11. Abnormal Activity Detection Using Pyroelectric Infrared Sensors

    Directory of Open Access Journals (Sweden)

    Xiaomu Luo

    2016-06-01

    Full Text Available Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process.

  12. Autism and chromosome abnormalities-A review.

    Science.gov (United States)

    Bergbaum, Anne; Ogilvie, Caroline Mackie

    2016-07-01

    The neuro-behavioral disorder of autism was first described in the 1940s and was predicted to have a biological basis. Since that time, with the growth of genetic investigations particularly in the area of pediatric development, an increasing number of children with autism and related disorders (autistic spectrum disorders, ASD) have been the subject of genetic studies both in the clinical setting and in the wider research environment. However, a full understanding of the biological basis of ASDs has yet to be achieved. Early observations of children with chromosomal abnormalities detected by G-banded chromosome analysis (karyotyping) and in situ hybridization revealed, in some cases, ASD associated with other features arising from such an abnormality. The introduction of higher resolution techniques for whole genome screening, such as array comparative genome hybridization (aCGH), allowed smaller imbalances to be detected, some of which are now considered to represent autism susceptibility loci. In this review, we describe some of the work underpinning the conclusion that ASDs have a genetic basis; a brief history of the developments in genetic analysis tools over the last 50 years; and the most common chromosome abnormalities found in association with ASDs. Introduction of next generation sequencing (NGS) into the clinical diagnostic setting is likely to provide further insights into this complex field but will not be covered in this review. Clin. Anat. 29:620-627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012322

  13. Schizophrenia, abnormal connection, and brain evolution.

    Science.gov (United States)

    Randall, P L

    1983-03-01

    Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslexia and the syndromes of Kanner and Gilles de la Tourette. As new and unique extensions of specialized function emerge within the evolving brain, biological trial and error of connection both within and between them may produce individuals possessing phylogenetically advanced abilities, or equally, others possessing a wide range of abnormalities including those which comprise the schizophrenia syndrome. A dormant phenotypic potential for schizophrenia may exist in individuals who never develop symptoms during the course of a lifetime though some of these may become clinically apparent under the influence of various precipitating factors. It is concluded that abnormal functional connection and its normal and "supernormal" counterparts may be natural, essential, and inevitable consequences of brain evolution, and that this may have been so throughout the history of vertebrate brain evolution.

  14. Postoperative pituitary hormonal disturbances and hormone replacement therapy time and dosage in children with craniopharyngiomas

    Institute of Scientific and Technical Information of China (English)

    LI Gui-mei; SUN Xiao-jun; SHAO Peng

    2008-01-01

    BackgroundThe proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas (CP) often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency (MPHD). This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy (HRT) time and dosage in children with CP.Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of (10.63 3.18) years (Group A) and 10 male patients of group A aged >10 years (Group B) were entailed. Thirty age-, sex- and Tanner stage-matched normal children (control Group A), and 44 male older children >10 years (control Group B) served as controls. The serum concentrations of insulin-like growth factor-1 (IGF-1), growth hormone (GH), free thyroxine (FT4), thyroid-stimulating hormone (TSH), adrenocorticortropic hormone (ACTH), cortisol (COR), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine (L-T4) dosage and primary FT4 in CP patients after resection. Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased (P <0.001); however, E2 and PRL were significantly increased (P <0.001) in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus (Dl) by water deprivation test and MRI. There was a significant negative linear regression (r= -0.8, P <0.001) between L-T4 and primary FT4 in Group A patients with CP

  15. Abnormalities Occurring during Female Gametophyte Development Result in the Diversity of Abnormal Embryo Sacs and Leads to Abnormal Fertilization in indicaljaponica Hybrids in Rice

    Institute of Scientific and Technical Information of China (English)

    Yu-Xiang Zeng; Chao-Yue Hu; Yong-Gen Lu; Jin-Quan Li; Xiang-Dong Liu

    2009-01-01

    Embryo sac abortion is one of the major masons for sterility in indicaljaponica hybrids In rice. To clarify the causal mechanism of embryo sac abortion, we studied the female gametophyte development in two indicaljaponica hybrids via an eosin B staining procedure for embryo sac scanning using confocal laser scanning microscope. Different types of abnormalities occurred during megasporogenesis and megagamatogenesis were demonstrated. The earliest abnormality was observed in the megasporocyte. A lot of the chalazal-most megaspores were degenerated before the mono-nucleate embryo sac stage. Disordered positioning of nucleus and abnormal nucallus tissue were characteristics of the abnormal female gametes from the mono-nucleate to four-nucleate embryo sac stages. The abnormalities that occurred from the early stage of the eight-nucleate embryo sac development to the mature embryo sac stage were characterized by smaller sizes and wrinkled antipodals. Asynchronous nuclear migration, abnormal positioning of nucleus, and degeneration of egg apparatus were also found at the eight-nucleate embryo sac stage. The abnormalities that occurred during female gametophyte development resulted in five major types of abnormal embryo sacs. These abnormal embryo sacs led to abnormal fertilization. Hand pollination using normal pollens on the spikelets during anthesis showed that normal pollens could not exclude the effect of abnormal embryo sac on seed setting.

  16. Pharmacokinetic estimation for therapeutic dosage regimens (PETDR)--a software program designed to determine intravenous drug dosage regimens for veterinary applications.

    Science.gov (United States)

    Riviere, J E; Frazier, D L; Tippitt, W L

    1988-12-01

    Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3210265

  17. Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time.

    LENUS (Irish Health Repository)

    Semkovska, Maria

    2010-11-23

    To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT.

  18. Perceived functional impact of abnormal facial appearance.

    Science.gov (United States)

    Rankin, Marlene; Borah, Gregory L

    2003-06-01

    Functional facial deformities are usually described as those that impair respiration, eating, hearing, or speech. Yet facial scars and cutaneous deformities have a significant negative effect on social functionality that has been poorly documented in the scientific literature. Insurance companies are declining payments for reconstructive surgical procedures for facial deformities caused by congenital disabilities and after cancer or trauma operations that do not affect mechanical facial activity. The purpose of this study was to establish a large, sample-based evaluation of the perceived social functioning, interpersonal characteristics, and employability indices for a range of facial appearances (normal and abnormal). Adult volunteer evaluators (n = 210) provided their subjective perceptions based on facial physical appearance, and an analysis of the consequences of facial deformity on parameters of preferential treatment was performed. A two-group comparative research design rated the differences among 10 examples of digitally altered facial photographs of actual patients among various age and ethnic groups with "normal" and "abnormal" congenital deformities or posttrauma scars. Photographs of adult patients with observable congenital and posttraumatic deformities (abnormal) were digitally retouched to eliminate the stigmatic defects (normal). The normal and abnormal photographs of identical patients were evaluated by the large sample study group on nine parameters of social functioning, such as honesty, employability, attractiveness, and effectiveness, using a visual analogue rating scale. Patients with abnormal facial characteristics were rated as significantly less honest (p = 0.007), less employable (p = 0.001), less trustworthy (p = 0.01), less optimistic (p = 0.001), less effective (p = 0.02), less capable (p = 0.002), less intelligent (p = 0.03), less popular (p = 0.001), and less attractive (p = 0.001) than were the same patients with normal facial

  19. Immunogenicity of two different dosages (10 and 5 μg) of recombinant DNA hepatitis B vaccine in healthy neonates

    NARCIS (Netherlands)

    R. Del Cancho (R.); P.M. Grosheie (P.); M. Voogd-Schotanus (M.); W. Huisman (Willem); R.A. Heijtink; S.W. Schalm (Solko)

    1994-01-01

    textabstractThe immunogenicity of a half (5 μg) and a full (10 μg) dosage of recombinant DNA yeast-derived hepatitis B vaccine (HB-Vax-DNA) in healthy neonates was assessed in order to compare two candidate dosages of vaccine. After randomization 174 newborns of HBsAg-negative mothers entered the st

  20. The use of a novel combination of diagnostic molecular and cytogenetic approaches in horses with sexual karyotype abnormalities: a rare case with an abnormal cellular chimerism.

    Science.gov (United States)

    Demyda-Peyrás, S; Anaya, G; Bugno-Poniewierska, M; Pawlina, K; Membrillo, A; Valera, M; Moreno-Millán, M

    2014-05-01

    Sex chromosome aberrations are known to cause congenital abnormalities and unexplained infertility in horses. Most of these anomalies remain undiagnosed because of the complexity of the horse karyotype and the lack of specialized laboratories that can perform such diagnoses. On the other hand, the utilization of microsatellite markers is a technique widely spread in horse breeding, mostly because of their usage in parentage tests. We studied the usage of a novel combination of diagnostic approaches in the evaluation of a very uncommon case of chromosomal abnormalities in a Spanish purebred colt, primarily detected using a commercial panel of short tandem repeat (STR) makers. Based on these results, we performed a full cytogenetic analysis using conventional and fluorescent in situ hybridization techniques with individual Equus caballus chromosome X and Equus caballus chromosome Y painting probes. We also tested the presence of two genes associated with the sexual development in horses and an extra novel panel of eight microsatellite markers specifically located in the sex chromosome pair. This is the first case report of a leukocyte chimerism between chromosomally normal (64,XY) and abnormal (63,X0) cell lines in horses. Our results indicate that the use of the short tandem repeat markers as a screening technique and as a confirmation utilizing cytogenetic techniques can be used as a very interesting, easy, and nonexpensive diagnostic approach to detect chromosomal abnormalities in the domestic horse.

  1. Synergistic action on hypnosia: Yinao capsules with pentobarbital sodium of threshold and sub-threshold dosages

    Institute of Scientific and Technical Information of China (English)

    Guilan Zhang; Mingsan Miao; Jingjing Shi; Yalei Yang

    2007-01-01

    BACKGROUND: Sedative and hypnotic drugs could cure insomnia in a dependent manner, and traditional Chinese medicine has some superiority in treating insomnia.OBJECTIVE: To observe the synergistic action of Yinao capsules with pentobarbital sodium in threshold and sub-threshold dosages in hypnosia and sedation.DESIGN: A completely randomized grouping design and control experiment.SETTING: Pharmacological laboratory, College of Pharmacy, Henan College of Traditional Chinese Medicine.MATERIALS: Totally 200 grade Ⅱ Kunming mice of 18 - 21 g, either male or female, were used. Yinao capsules, main ingredients of which were turtleback glue, thinleaf milkwort root, Chinese magnoliavine fruit,mythic fungus, tangshen, ginseng and grassleaf sweetflag rhizome, were offered by Chinese-American Huayi Pharmacy, Co.,Ltd. (ratified number: 040901); Kangnaoshuai capsules, main ingredients of which were prepared rehmannia root, tuber fleeceflower root, ginseng, membranous milkvetch root, thinleaf milkwort root, Fushen, grassleaf sweetflag rhizome, spine date seed, lecithin, barbary wolfberry fruit, pueraria root,vitamin E, etc., were produced by Shijiazhuang Siyao, Co.,Ltd. (ratified number: 040964); Pentobarbital sodium was produced by China Medicine (Group) Shanghai Chemical Reagent, Co,.Ltd. (Ratified number:030816). ZZ-6 mice spontaneous activity apparatus was produced by Chengdu Taimeng Science and Technology, Co.,Ltd.METHODS: The experiment was carried out in the Animal Experimental Center, Henan College of spontaneous activity of mice: Fifty mice were randomly divided into five groups with 10 mice in each group:Mice in the large, middle and small dosages of Yinao capsules groups were intragastrically infused with Yinao capsules suspension (1.36, 0.68, 0.34 g/kg); Those in the Kangnaoshuai capsules group were infused with Kangnaoshuai suspension (1.12 g/kg); Those in the control group were given physiologic saline of the same volume. The mice were administrated once a day for

  2. Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes

    Science.gov (United States)

    Abáigar, María; Robledo, Cristina; Benito, Rocío; Ramos, Fernando; Díez-Campelo, María; Hermosín, Lourdes; Sánchez-del-Real, Javier; Alonso, Jose M.; Cuello, Rebeca; Megido, Marta; Rodríguez, Juan N.; Martín-Núñez, Guillermo; Aguilar, Carlos; Vargas, Manuel; Martín, Ana A.; García, Juan L.; Kohlmann, Alexander; del Cañizo, M. Consuelo; Hernández-Rivas, Jesús M.

    2016-01-01

    To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases. 285 abnormalities were identified in 71 patients (23.6%). Three high-risk MDS cases (1.2%) displayed chromothripsis involving exclusively chromosome 13 and affecting some cancer genes: FLT3, BRCA2 and RB1. All three cases carried TP53 mutations as revealed by NGS. Moreover, in the whole series, the integrative analysis of aCGH and NGS enabled the identification of cryptic recurrent deletions in 2p23.3 (DNMT3A; n = 2.8%), 4q24 (TET2; n = 10%) 17p13 (TP53; n = 8.5%), 21q22 (RUNX1; n = 7%), and Xp11.4 (BCOR; n = 2.8%), while mutations in the non-deleted allele where found only in DNMT3A (n = 1), TET2 (n = 3), and TP53 (n = 4). These cryptic abnormalities were detected mainly in patients with normal (45%) or non-informative (15%) karyotype by conventional cytogenetics, except for those with TP53 deletion and mutation (15%), which had a complex karyotype. In addition to well-known copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed the presence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located. PMID:27741277

  3. Heterotaxia syndrome: the role of screening for intestinal rotation abnormalities

    OpenAIRE

    Choi, M.; Borenstein, S.; Hornberger, L; Langer, J.

    2005-01-01

    Background: Heterotaxia syndrome involves multiple anomalies, including cardiac malformations and intestinal rotation abnormalities. Most authors recommend routine radiological evaluation, with laparotomy and Ladd procedure if a rotation abnormality is found.

  4. Persistent Mosaicism for 12p Duplication/Triplication Chromosome Structural Abnormality in Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Amy L. Shackelford

    2013-01-01

    Full Text Available We present a rare case of mosaicism for a structural abnormality of chromosome 12 in a patient with phenotypic features of Pallister-Killian syndrome. A six-month-old child with dysmorphic features, exotropia, hypotonia, and developmental delay was mosaic for both a normal karyotype and a cell line with 12p duplication/triplication in 25 percent of metaphase cells. Utilization of fluorescence in situ hybridization (FISH identified three copies of probes from the end of the short arm of chromosome 12 (TEL(12p13 locus and the subtelomere (12p terminal on the structurally abnormal chromosome 12. Genome-wide SNP array analysis revealed that the regions of duplication and triplication were of maternal origin. The abnormal cell line in our patient was present at 25 percent at six months and 19 months of age in both metaphase and interphase cells from peripheral blood, where typically the isochromosome 12p is absent in the newborn. This may suggest that the gene(s resulting in a growth disadvantage of abnormal cells in peripheral blood of patients with tetrasomy 12p may not have the same influence when present in only three copies.

  5. Abnormalities of chromosome No. 1: significance in malignant transformation

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1978-01-01

    Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.

  6. Transcriptional changes in response to X chromosome dosage in the mouse: implications for X inactivation and the molecular basis of Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Sargent Carole A

    2010-02-01

    Full Text Available Abstract Background X monosomic mice (39,XO have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO. The generally accepted hypothesis to explain this discrepancy is that the number of genes on the mouse X chromosome which escape X inactivation, and thus are expressed at higher levels in females, is very small. However this hypothesis has never been tested and only a small number of genes have been assayed for their X-inactivation status in the mouse. We performed a global expression analysis in four somatic tissues (brain, liver, kidney and muscle of adult 40,XX and 39,XO mice using the Illumina Mouse WG-6 v1_1 Expression BeadChip and an extensive validation by quantitative real time PCR, in order to identify which genes are expressed from both X chromosomes. Results We identified several genes on the X chromosome which are overexpressed in XX females, including those previously reported as escaping X inactivation, as well as new candidates. However, the results obtained by microarray and qPCR were not fully concordant, illustrating the difficulty in ascertaining modest fold changes, such as those expected for genes escaping X inactivation. Remarkably, considerable variation was observed between tissues, suggesting that inactivation patterns may be tissue-dependent. Our analysis also exposed several autosomal genes involved in mitochondrial metabolism and in protein translation which are differentially expressed between XX and XO mice, revealing secondary transcriptional changes to the alteration in X chromosome dosage. Conclusions Our results support the prediction that the mouse inactive X chromosome is largely silent, while providing a list of the genes potentially escaping X inactivation in rodents. Although the lower expression of X-linked genes in XO mice may not be relevant in the particular tissues/systems which are affected in human X chromosome monosomy, genes deregulated in XO mice are good candidates for

  7. Fetal MR Imaging of Gastrointestinal Abnormalities.

    Science.gov (United States)

    Furey, Elizabeth A; Bailey, April A; Twickler, Diane M

    2016-01-01

    Fetal magnetic resonance (MR) imaging plays an increasing and valuable role in antenatal diagnosis and perinatal management of fetal gastrointestinal (GI) abnormalities. Advances in MR imaging data acquisition and use of motion-insensitive techniques have established MR imaging as an important adjunct to obstetric ultrasonography (US) for fetal diagnosis. In this regard, MR imaging provides high diagnostic accuracy for antenatal diagnosis of common and uncommon GI pathologic conditions. In the setting of fetal GI disease, T1-weighted images demonstrate the amount and distribution of meconium, which is crucial to the diagnostic capability of fetal MR imaging. Specifically, knowledge of the T1 signal intensity characteristics of fetal meconium, the normal pattern of meconium with advancing gestational age, and the expected caliber of small and large bowel in the fetus is key to diagnosis of abnormalities of the GI tract. Use of ultrafast T2-weighted sequences for evaluation of the expected location and morphology of fluid-containing structures, including the stomach and small bowel, in the fetal abdomen further aids in diagnostic confidence. Uncommonly encountered fetal GI pathologic conditions, especially cloacal dysmorphology, may demonstrate characteristic MR imaging patterns, which may add additional information to that from fetal US, allowing improved fetal and neonatal management. This article discusses common indications for fetal MR imaging of the GI tract, imaging protocols for fetal GI MR imaging, the normal appearance of the fetal GI tract with advancing gestational age, and the imaging appearances of common fetal GI abnormalities, as well as uncommon fetal GI conditions with characteristic appearances. (©)RSNA, 2016. PMID:27163598

  8. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-01-01

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

  9. Study of the relationship between dosage of oral progesterone and concentration of serum progesterone

    Institute of Scientific and Technical Information of China (English)

    Zheng Ting-ping; Sun Ai-jun; Wang Ya-ping; Jiang Ying; Zhang Ying; Chen Rong; Jin Li-na; Lang Jing-he

    2012-01-01

    Objective: To explore the relationship among body mass index (BMI),dosage of progesterone (P) and serum progesterone concentration,and provide reference for the clinical use of oral progesterone.Methods: This was a random,open-label,prospective clinical trial.Eighty women meeting the criteria for enrollment were recruited from July 2010 to March 2011 in outpatient clinic of Peking Union Medical College Hospital and given oral progesterone therapy for consecutive 10 days.They were randomly assigned into four groups according to the different doses of progesterone: group A 100 mg/day,group B 200 mg/day,group C 300 mg/day and group D 400 mg/day.Results: Seventy four patients (92.5%,74/80) accomplished the study.It can be observed that administration of different dosage of P could significantly increase serum P concentration (all P<0.001).And there was a positive correlation between the increase of P concentration and dosage (rp =0.613,P<0.001).Furthermore,the medians of the increase of serum P concentration in 4 groups were 14.71 nmol/L in group A,28.47 nmol/L in group B,58.89 nmol/L in group C,72.69 nmol/L in group D.When BMI<24 kg/m2 (42 cases),the median of the increase of P levels was 13.90 nmol/L,37.22 nmol/L,62.55 nmol/L,and 119.02 nmol/L in group A,B,C and D,respectively,while BMI ≥24 kg/m2 (32 cases),the median of increase was 8.93 nmol/L,24.82 nmol/L,24.87 nmol/L,and 63.48 nmol/L,respectively.In addition,significant difference was found only in group D between women with BMI<24 kg/m2 and with BMI≥24 kg/m2 (P=0.010).Conclusions: Serum progesterone levels go up linearly with the dosage increasing.The greater BMI the patient have,the larger dosage may be needed to achieve the same serum progesterone concentration.The individual dosage of oral progesterone needed can be roughly calculated in the light of the result of this study.

  10. Radiological and orthopedic abnormalities in Satoyoshi syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Haymon, M.L. [Children`s Hospital, New Orleans, LA (United States). Dept. of Radiology; Willis, R.B. [Children`s Hospital, New Orleans, LA (United States). Dept. of Orthopedics; Ehlayel, M.S. [Div. of Genetics, Dept. of Pediatrics, Louisiana State Univ. Medical Center, Orleans, LA (United States)]|[Louisiana State Medical Center, New Orleans, LA (United States). Center for Molecular and Human Genetics; Lacassie, Y. [Div. of Genetics, Dept. of Pediatrics, Louisiana State Univ. Medical Center, Orleans, LA (United States)]|[Louisiana State Medical Center, New Orleans, LA (United States). Center for Molecular and Human Genetics]|[Children`s Hospital, New Orleans, LA (United States). Dept. of Pediatrics

    1997-05-01

    Satoyoshi syndrome is a are disorder on unknown etiology characterized by progressive, painful intermittent muscle spasms, serve skeletal abnormalities mimicking a skeletal dyplasia, malabsorption, alopecia, and amenorrhea. We further report on a 20{sup 1}/{sub 2}-year-old Caucasian woman whith characteristic manifestation of the syndrome. Since the establishment of the diagnostic 1 year ago, she has been treated with prednisone with good response. However, treatment of the multiple deformities and fractures has been difficult and challenging. The early recognition and treatment of this disorder is of utmost importance, as the skeletal deformities and fractures seem to be secondary to the muscular spasms, as suggested by Satoyoshi.

  11. Vitamin D and Risk of Neuroimaging Abnormalities.

    Directory of Open Access Journals (Sweden)

    Thomas J Littlejohns

    Full Text Available Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OHD concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OHD status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval for worsening white matter grade in participants who were severely 25(OHD deficient (<25 nmol/L and deficient (≥25-50 nmol/L were 0.76 (0.35-1.66 and 1.09 (0.76-1.55 compared to participants with sufficient concentrations (≥50 nmol/L. The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OHD deficient and deficient were 0.49 (0.20-1.19 and 1.12 (0.79-1.59 compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OHD deficient and deficient were 1.95 (0.84-4.54 and 0.73 (0.47-1.95 compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of

  12. TRANSIENT ABNORMAL MYELOPOIESIS IN A NEONATE

    Directory of Open Access Journals (Sweden)

    Ketan P

    2013-01-01

    Full Text Available ABSTRACT: Transient abnormal myelopoiesis (TAM is a unique di sorder of newborns associated intimately with Down’s syndrome, present ing with clinical and morphological features indistinguishable from acute myeloid leuka emia (AML. We report a case in a neonate, presenting with severe perinatal asphyxia and cyanosis ; complicated by metabolic acidosis. The hemogram revealed leucocytosis and thrombocytopenia. The peripheral smear showed marked left shift and 55% circulating myeloblasts. Additio nal findings included a hepatomegaly and mild dysmorphic features. The child eventually succu mbed to pulmonary hemorrhage on day one itself. TAM has to be differentiated from conge nital leukemia which portends a poor prognosis

  13. The Spacing Principle for Unlearning Abnormal Neuronal Synchrony

    OpenAIRE

    Popovych, Oleksandr V.; Markos N Xenakis; Peter A. Tass

    2015-01-01

    Desynchronizing stimulation techniques were developed to specifically counteract abnormal neuronal synchronization relevant to several neurological and psychiatric disorders. The goal of our approach is to achieve an anti-kindling, where the affected neural networks unlearn abnormal synaptic connectivity and, hence, abnormal neuronal synchrony, by means of desynchronizing stimulation, in particular, Coordinated Reset (CR) stimulation. As known from neuroscience, psychology and education, lear...

  14. Abnormal immune parameters in HIV-seronegative haemophilic patients

    NARCIS (Netherlands)

    Allersma, DP; Smid, WM; Briet, E

    1996-01-01

    In HIV-seronegative haemophiliac patients abnormal immune parameters have been demonstrated. In this review data on these abnormalities, their aetiology and clinical consequences are summarized and discussed. The data reviewed show abnormalities at different levels of the adaptive immune system. Mos

  15. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    Science.gov (United States)

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  16. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Trak-Smayra, Viviane [Pathology Department, Saint-Joseph University, Beirut (Lebanon); Martinais, Sophie [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Porceddu, Mathieu [Mitologics SAS, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, 35000 Rennes (France)

    2014-04-01

    Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace

  17. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

    International Nuclear Information System (INIS)

    Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 106 ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 106 ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 102–103 ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace pharmaceuticals could

  18. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    Science.gov (United States)

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  19. Abnormal mandibular growth and the condylar cartilage.

    Science.gov (United States)

    Pirttiniemi, Pertti; Peltomäki, Timo; Müller, Lukas; Luder, Hans U

    2009-02-01

    Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their often disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritis (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage. PMID:19164410

  20. Small Airway Dysfunction and Abnormal Exercise Responses

    Science.gov (United States)

    Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

    2016-01-01

    Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987