Home About us Contact
|
Home About us Contact | ||
|
|
||
Transcript Expression (transcript + expression)
Selected AbstractsEpidermal transient down-regulation of retinol - binding protein 4 and mirror expression of apolipoprotein Eb and estrogen receptor 2a during zebrafish fin and scale developmentDEVELOPMENTAL DYNAMICS, Issue 11 2006Angèle Tingaud-Sequeira Abstract Very little is known about the molecular control of skin patterning and scale morphogenesis in teleost fish. We have found radially symmetrical epidermal placodes with down-regulation of retinol - binding protein 4 (rbp4) expression during the initial paired fin and scale morphogenesis in zebrafish (Danio rerio). This finding may be related to changes in keratinocyte cytodifferentiation and/or the integument retinoid metabolism. rbp4 transcripts are expressed afterward in the central epidermis of the scale papilla and gradually extend to the epidermis, covering the growing scale, whereas no transcripts were detected in posterior margin epidermis. In contrast, induction of apolipoprotein Eb (apoeb) and up-regulation of estrogen receptor 2a (esr2a) transcripts were observed in the epidermis at initiator sites of zebrafish ectodermal/dermal appendage morphogenesis. This expression was maintained in the posterior margin epidermis of the formed scales. esr2a was also strongly expressed in neuromasts, whereas no rbp4 and apoeb transcripts were detected in these mechanosensory structures. The observed epidermal molecular events suggest that epidermis patterning is due to an activator,inhibitor mechanism operational at epidermal,dermal interaction sites. rbp4 transcript expression was also strongly down-regulated by 1-phenyl-2-thio-urea (PTU). As this inhibitor is commonly used to block obscuring pigmentation during in situ hybridization studies, this finding suggests that PTU should be used with caution, particularly in studying skin development. Developmental Dynamics 235:3071,3079, 2006. © 2006 Wiley-Liss, Inc. [source] Interleukin-5 does not influence differential transcription of transmembrane and soluble isoforms of IL-5R, in vivoEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Jonas Byström Abstract:, Interleukin-5 (IL-5) promotes signal transduction and expansion of eosinophil colonies in bone marrow via interactions with its heterodimeric receptor (IL-5R). Two variants encoding soluble forms of the alpha subunit (sIL-5R,) have been described, although the signals promoting and/or limiting differential transcription remain to be clarified. Objectives:,Our intent was to explore the role of IL-5 in regulating differential transcription of these splice variants in vivo. Methods:,We have designed a quantitative reverse transcriptase-polymerase chain reaction assay to detect transcripts encoding the transmembrane, soluble 1 and 2 forms of IL-5R, in two strains of wild-type (BALB/c and C57BL/6) and corresponding IL-5 gene-deleted mice. Wild-type mice respond to S. mansoni infection with a gradual increase in serum IL-5 and eosinophilia, which is not observed in IL-5 gene-deleted mice. Results and conclusions:,We find that IL-5 is not necessary for differential splicing to occur in vivo, as all three forms of the IL-5R, are detected in both strains of IL-5 gene-deleted mice, with ratios of transcript expression (transmembrane : soluble 1 : soluble 2) that were indistinguishable from their wild-type counterparts. Differential splicing does vary markedly between strains, potentially because of local effects of strain-specific polymorphisms. [source] TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lungEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Amrita D. Joshi Abstract We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3+/+) and TLR3 gene-deficient (TLR3,/,) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni -sensitized TLR3+/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3,/, mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3+/+ mice. Macrophages from TLR3,/, mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4+CD25+ T cells were present in the lungs of TLR3,/, mice compared with TLR3+/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3,/, mice released significantly higher levels of IL-17 levels relative to TLR3+/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology. [source] Changes in alternative brain-derived neurotrophic factor transcript expression in the developing human prefrontal cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009Jenny Wong Abstract In this study, we determined when and through which promoter brain-derived neurotrophic factor (BDNF) transcription is regulated during the protracted period of human frontal cortex development. Using quantitative real-time polymerase chain reaction, we examined the expression of the four most abundant alternative 5, exons of the BDNF gene (exons I, II, IV, and VI) in RNA extracted from the prefrontal cortex. We found that expression of transcripts I,IX and VI,IX was highest during infancy, whereas that of transcript II,IX was lowest just after birth, slowly increasing to reach a peak in toddlers. Transcript IV,IX was significantly upregulated within the first year of life, and was maintained at this level until school age. Quantification of BDNF protein revealed that levels followed a similar developmental pattern as transcript IV,IX. In situ hybridization of mRNA in cortical sections showed the highest expression in layers V and VI for all four BDNF transcripts, whereas moderate expression was observed in layers II and III. Interestingly, although low expression of BDNF was observed in cortical layer IV, this BDNF mRNA low-zone decreased in prominence with age and showed an increase in neuronal mRNA localization. In summary, our findings show that dynamic regulation of BDNF expression occurs through differential use of alternative promoters during the development of the human prefrontal cortex, particularly in the younger age groups, when the prefrontal cortex is more plastic. [source] Molecular analyses and identification of promising candidate genes for loci on mouse chromosome 1 affecting alcohol physical dependence and associated withdrawalGENES, BRAIN AND BEHAVIOR, Issue 5 2008D. L. Denmark We recently mapped quantitative trait loci (QTLs) with large effects on predisposition to physical dependence and associated withdrawal severity following chronic and acute alcohol exposure (Alcdp1/Alcw1) to a 1.1-Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3. Here, we provide a detailed analysis of the genes within this interval and show that it contains 40 coding genes, 17 of which show validated genotype-dependent transcript expression and/or non-synonymous coding sequence variation that may underlie the influence of Alcdp1/Alcw1 on ethanol dependence and associated withdrawal. These high priority candidates are involved in diverse cellular functions including intracellular trafficking, oxidative homeostasis, mitochondrial respiration, and extracellular matrix dynamics, and indicate both established and novel aspects of the neurobiological response to ethanol. This work represents a substantial advancement toward identification of the gene(s) that underlies the phenotypic effects of Alcdp1/Alcw1. Additionally, a multitude of QTLs for a variety of complex traits, including diverse behavioral responses to ethanol, have been mapped in the vicinity of Alcdp1/Alcw1, and as many as four QTLs on human chromosome 1q have been implicated in human mapping studies for alcoholism and associated endophenotypes. Thus, our results will be primary to further efforts to identify genes involved in a wide variety of behavioral responses to alcohol and may directly facilitate progress in human alcoholism genetics. [source] Expression profiles and clinical relationships of ID2, CDKN1B, and CDKN2A in primary neuroblastomaGENES, CHROMOSOMES AND CANCER, Issue 4 2004Sigrun Gebauer Despite considerable research into the etiology of neuroblastoma, the molecular basis of this disease has remained elusive. In contrast to the absence of expression of the known tumor suppressor CDKN2A (also known as p16 and INK4A) in a wide variety of tumor types we have found in previous studies that CDKN2A protein is paradoxically highly expressed in many advanced stage neuroblastomas and unrelated to RB1 status. In the present study, we sought to identify the mechanistic relationships that might influence CDKN2A expression and negate its influence on tumor cell proliferation. In this regard, we examined the role of the tumor-suppressor gene CDKN1B (also known as p27 and Kip1) and the oncogene ID2 in relationship to CDKN2A expression, MYCN amplification, and neuroblastoma pathogenesis in 17 neuroblastoma cell lines and 129 samples of primary tumors of all stages. All neuroblastoma cell lines expressed the ID2 transcript and protein. However, although the majority of primary neuroblastomas also expressed the ID2 transcript, expression of the ID2 protein was undetectable or only barely detectable, regardless of transcript expression. In both cell lines and primary tumors, ID2 expression was independent of both CDKN2A and MYCN expression. In primary neuroblastomas, CDKN1B protein was expressed in significantly fewer advanced-stage neuroblastomas than early-stage neuroblastomas, but its expression had no relationship with CDKN2A expression or MYCN amplification. We concluded that the paradoxical expression of CDKN2A in neuroblastoma cannot be explained by inactivation of the tumor-suppressor gene CDKN1B or overexpression of the oncogene ID2. We further concluded that ID2 is not a target of MYCN regulation nor is it a prognostic factor for neuroblastoma. Finally, the loss of CDKN1B in advanced-stage neuroblastoma suggests this protein may play a role in the neuroblastoma disease process. © 2004 Wiley-Liss, Inc. [source] Calcium Channel TRPV6 Expression in Human Duodenum: Different Relationships to the Vitamin D System and Aging in Men and Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2006FRCP, Julian RF Walters MA Abstract Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women. Introduction: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system. Materials and Methods: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)2D]. Results: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)2D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)2D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)2D, but there was a significant decrease with age (r = ,0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively). Conclusions: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women. [source] Expression of p16INK4a in peripheral blood T-cells is a biomarker of human agingAGING CELL, Issue 4 2009Yan Liu Summary Expression of the p16INK4a tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16INK4a expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16INK4a expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16INK4a, but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16INK4a expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16INK4a expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16INK4a expression in PBTL is an easily measured, peripheral blood biomarker of molecular age. [source] Selective induction of human beta-defensin mRNAs by Actinobacillus actinomycetemcomitans in primary and immortalized oral epithelial cellsMOLECULAR ORAL MICROBIOLOGY, Issue 6 2003E. C. Feucht Human beta-defensin-2, and -3 (hBD-2, -3) are small inducible antimicrobial peptides involved in host defense. Actinobacillus actinomycetemcomitans, a gram-negative facultative anaerobe, is frequently associated with oral disease in humans. A. actinomycetemcomitans, strain JP2, was examined for its ability to modulate hBD-2 and -3 gene expression in normal human oral epithelial cells (NHOECs) and in OKF6/Tert cells, an immortalized cell line derived from human oral epithelial cells. Stimulation of both cell types by live bacteria, at a minimal bacteria/cell ratio of 500 : 1, resulted in increased hBD-3 gene expression. This was not evinced for hBD-2 in either cell type with live bacteria, even at bacteria/cell ratios exceeding 500 : 1. The increased hBD-3 gene expression was dependent upon viable bacteria, and not their lipopolysaccharides (LPS), since heat-killed A. actinomycetemcomitans did not induce hBD-3 transcript expression. The overall similarity between results obtained in OKF6/Tert cells and NHOECs suggest that the OKF6/Tert cell line may be a useful tool in the study of beta-defensin expression in oral epithelium. [source] Multi-factor regulation of pectate lyase secretion by Colletotrichum gloeosporioides pathogenic on avocado fruitsMOLECULAR PLANT PATHOLOGY, Issue 3 2008I. MIYARA SUMMARY Tissue alkalinization during Colletotrichum gloeosporioides attack enhances the expression of PELB, which encodes pectate lyase (PL), and PL secretion, which is considered essential for full virulence. We studied the regulation of PL secretion by manipulation of C. gloeosporioides PELB. PELB was down-regulated by knocking out PAC1, which encodes the PacC transcription factor that regulates gene products with pH-sensitive activities. We functionally characterized a PACC gene homologue, PAC1, from C. gloeosporioides wild-type (WT) Cg-14 and two independent deletion strains, ,pac1372and ,pac1761. Loss-of-function PAC1 mutants showed 85% reduction of PELB transcript expression, delayed PL secretion and dramatically reduced virulence, as detected in infection assays with avocado fruits. In contrast, PELB was up-regulated in the presence of carbon sources such as glucose. When glucose was used as a carbon source in the medium for the WT strain and the ,pac1 mutant at pH 6.0, PELB transcript expression and PL secretion were activated. Other sugars, such as sucrose and fructose (but not galactose), also activated PELB expression. These results suggest that the pH-regulated response is only part of a multi-factor regulation of PELB, and that sugars are also needed to promote the transition from quiescent to active necrotrophic development by the pathogen. [source] The homeobox HOXB13 is expressed in human minor salivary glandORAL DISEASES, Issue 4 2006C Cazal Background:, Homeobox are a family of developmental genes involved in morphogenesis and cellular differentiation. Participation of homeobox within normal and malignant tissue has been recently discussed in the literature. Objective:, To analyze the presence of HOXB13 transcript expression in human minor salivary gland. Material and methods:, Ten-micrometer sections from frozen samples were evaluated employing non-radioactive in situ hybridization technique and HOXB13 mRNA probes. Results:, HOXB13 was found to be expressed in ducts and mucous acini but not in serous acini. Conclusions:, Results suggest that HOXB13 transcripts are differently expressed in normal mucous and serous acini, and it may possibly reflect a different role in salivary gland carcinogenesis. [source] Transcriptional profiling of hexaploid wheat (Triticum aestivum L.) roots identifies novel, dehydration-responsive genesPLANT CELL & ENVIRONMENT, Issue 5 2007MOHSEN MOHAMMADI ABSTRACT We used a long-oligonucleotide microarray to identify transcripts that increased or decreased in abundance in roots of dehydration-tolerant hexaploid bread wheat, in response to withholding of water. We observed that the major classes of dehydration-responsive genes (e.g. osmoprotectants, compatible solutes, proteases, glycosyltransferases/hydrolases, signal transducers components, ion transporters) were generally similar to those observed previously in other species and osmotic stresses. More specifically, we highlighted increases in transcript expression for specific genes including those putatively related to the synthesis of asparagine, trehalose, oligopeptide transporters, metal-binding proteins, the gamma-aminobutyric acid (GABA) shunt and transcription factors. Conversely, we noted a decrease in transcript abundance for diverse classes of glutathione and sulphur-related enzymes, specific amino acids, as well as MATE-efflux carrier proteins. From these data, we identified a novel, dehydration-induced putative AP2/ERF transcription factor, which we predict to function as a transcriptional repressor. We also identified a dehydration-induced ,little protein' (LitP; predicted mass: 8 kDa) that is highly conserved across spermatophytes. Using qRT-PCR, we compared the expression patterns of selected genes between two related wheat genotypes that differed in their susceptibility to dehydration, and confirmed that these novel genes were highly inducible by water limitation in both genotypes, although the magnitude of induction differed. [source] Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007K Sahadevan Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1,4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1,3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Effects of female steroid hormones on A-type K+ currents in murine colonTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006Elizabeth A. H. Beckett Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause. [source] Endothelial Gene Expression in Kidney Transplants with Alloantibody Indicates Antibody-Mediated Damage Despite Lack of C4d StainingAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009Banu Sis Anti-HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody-mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial-associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T-cell-mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody-mediated allograft damage and poor graft outcome. [source] The Causal Element for the Lactase Persistence/ non-persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in EuropeansANNALS OF HUMAN GENETICS, Issue 4 2003M. Poulter Summary Expression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis -acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11-site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at ,14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA ,22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the ,14 kb T allele and the ,22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non-persistent individuals who were mainly of non-UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the ,14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the ,14 kb SNP and LCT. The combined data shows that although the ,14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity. [source] Growth failure in a child showing characteristics of Seckel syndrome: possible effects of IGF-I and endogenous IGFBP-3CLINICAL ENDOCRINOLOGY, Issue 2 2002A. Schmidt Summary Seckel syndrome is an autosomal-recessive disorder with a frequency of less than 1/10 000 births in which there are multiple malformations including severe short stature. We report on a patient with Seckel syndrome with a current body height of ,7·5 SDS. Laboratory investigations at the age of 19 months revealed high levels of IGF-I, IGF-II and IGFBP-3. These data suggested the existence of IGF-I resistance possibly caused by impairment of the IGF-I receptor (IGF-IR) or altered IGFBPs. The purpose of this investigation was to examine whether the growth retardation in a Seckel syndrome patient is related to an alteration in the IGF system. Analysis of IGF-IR mRNA of patient's and control fibroblasts by solution hybridization/RNase protection assay did not show differences of IGF-IR transcript expression or size. Affinity crosslinking studies using [125I]-IGF-I showed normal-sized IGF-IR,ligand complexes. Mutation analysis of the complete coding regions of the IGF-I and IGF-IR genes showed no evidence of genetic alterations. Ligand blot analysis of IGFBPs secreted by the patient's fibroblasts showed stronger signals than control cells. Quantitative measurement of IGFBP-3 in cell-conditioned media was performed by radioimmunoassay (RIA) and revealed a sixfold increase when compared to control fibroblasts. We conclude that in this patient with Seckel syndrome and severe growth impairment IGF-I resistance is possibly related to altered production of IGFBP-3. [source] Hepatopancreatic multi-transcript expression patterns in the crayfish Cherax quadricarinatus during the moult cycleINSECT MOLECULAR BIOLOGY, Issue 6 2007Y. Yudkovski Abstract Alterations of hepatopancreatic multi-transcript expression patterns, related to induced moult cycle, were identified in male Cherax quadricarinatus through cDNA microarray hybridizations of hepatopancreatic transcript populations. Moult was induced by X,organ sinus gland extirpation or by repeated injections of 20-hydroxyecdysone. Manipulated males were sacrificed at premoult or early postmoult, and a reference population was sacrificed at intermoult. Differentially expressed genes among the four combinations of two induction methods and two moult stages were identified. Biologically interesting clusters revealing concurrently changing transcript expressions across treatments were selected, characterized by a general shift of expression throughout premoult and early postmoult vs. intermoult, or by different premoult vs. postmoult expressions. A number of genes were differentially expressed in 20-hydroxyecdysone-injected crayfish vs. X,organ sinus gland extirpated males. [source] | |||||||||||||