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C R Sharpe

Publications and source records attributed to C R Sharpe.

At least 37 records · Page 2Linked to original sources
PubMed1992

Two isoforms of retinoic acid receptor alpha expressed during Xenopus development respond to retinoic acid.

Retinoic acid regulates gene expression by binding to receptors that are ligand-dependent transcription factors. The different types of RARs may mediate the diverse effects of RA on different tissues at different stages of development. This implies RAR expression will be spatially and temporally regulated during normal development. To examine this point, cDNA clones encoding RARs have been isolated from Xenopus embryos. Two different classes of RAR alpha have been characterised, they both show most similarity to the RAR alpha 2 isoform. In response to exogenous RA, XRAR alpha 2 transcripts accumulate whilst the level of XRAR gamma decreases. In addition, transcripts from the two XRAR alpha 2 genes are differentially distributed in the neurectoderm of RA treated embryos. Modulation of RAR transcript levels by RA may provide one level of control of RAR gene expression during development.

Amino Acid Sequence↗
PubMed1992

Retinoic acid and the late phase of neural induction.

Regional neural gene expression in Xenopus is the result of a number of processes that continue well beyond the end of gastrulation. By considering two of the basic features of neural induction, the duration of contact between mesoderm and ectoderm and the timing of neural competence, it has been possible to distinguish two phases in neural tissue formation. The late phase includes the period following gastrulation. A factor in determining regional neural gene expression is the difference in inducing ability of the mesoderm that develops during gastrulation along the anterior-posterior axis. The resulting ability to express regional neural genes is subsequently refined during the late phase by a signal that progresses from the posterior part of the embryo. Using a dorsal explant system, it is shown that this progressive signal can be mimicked by the addition of retinoic acid (RA). However, the observation that regions along the anterior-posterior axis respond in different ways to the addition of RA suggests that additional factors are also important in defining regional neural gene expression. One possibility is that the expression of retinoic acid receptors along the axis may demarcate regions that respond to RA in particular ways.

Animals↗
PubMed1991

Retinoic acid can mimic endogenous signals involved in transformation of the Xenopus nervous system.

In the frog Xenopus laevis, signals from the mesoderm divert part of the ectoderm from an epidermal to a neural fate. In the course of neural induction, the neurectoderm also acquires anterior-posterior polarity. In this report, the early expression of two genes, XlHbox6 and the neurofilament gene XIF6, is examined. The pattern of expression of the two genes seen in the tailbud embryo develops progressively over a 4 hr period following gastrulation. Physiological concentrations of retinoic acid can mimic this effect in isolated embryonic explants, consistent with the involvement of retinoic acid, or a closely related molecule, in localizing gene expression along the anterior-posterior axis of the neural tube.

Animals↗
PubMed1990

Regional neural induction in Xenopus laevis.

During development of the Xenopus embryo, the formation of the nervous system depends on an inductive interaction between mesoderm and ectoderm. The result is a neural tube that is regionally differentiated along the anterior-posterior axis from forebrain to spinal cord. The discovery of genes whose transcripts can be used as molecular markers for different regions of the nervous system has permitted reassessment of the existing theories of neural tissue formation. Although the neural inducing molecules remain elusive, the mechanism by which cells interact to form a regionally differentiated nervous system is becoming clearer.

Animals↗
PubMed1990

The induction of anterior and posterior neural genes in Xenopus laevis.

We have investigated the interactions between mesoderm and ectoderm that result in the formation of a regionally differentiated nervous system in Xenopus embryos. We have used genes expressed at different positions along the neural tube as regional markers of neural induction in both whole, and in experimentally manipulated embryos. By comparing transcription from the anterior marker, XIF3, with that from the posterior marker, X1Hbox6, and the general neural marker XIF6, we have shown that the normal induction process requires interactions between ectoderm and mesoderm that persist through gastrulation into the late neurula stages. We have found that competence of the ectoderm to respond to induction is lost at the same early neurula stage for all three marker genes. Using rhodamine dextran-labelled mesoderm, we have established that the duration of contact between ectoderm and mesoderm required for gene activation in conjugates is the same for each of the markers. We have, however, identified regions of the mesoderm that can induce different combinations of neural marker gene expression. The anterior mesoderm induces expression of the anterior marker, XIF3, and the later migrating posterior mesoderm induces the ectoderm overlying it to express the posterior marker X1Hbox6. It has been proposed that neural inducing signals reach the ectoderm by two different routes: from mesoderm lying directly beneath the ectoderm or along the plane of the ectoderm. We have assessed the contribution of each route in respect of our three neural markers and find that a signal passing directly from mesoderm to ectoderm fully accounts for neural gene expression. We were unable to detect an inducing signal that passes along the plane of the ectoderm.

Animals↗
PubMed1989

Case-control study of hydrocarbon exposures in patients with renal cell carcinoma.

A retrospective case-control study tested the hypothesis that exposure to hydrocarbon combustion products is associated with the development of renal cell carcinoma. One control per case, matched for sex, date of birth (within 5 years) and urologist, was chosen. Controls were patients who presented with hematuria and were shown not to have a urinary tract tumour. A total of 164 cases and 161 controls responded to mailed questionnaires and telephone interviews. Smoking more than 20 cigarettes per day was associated with the presence of metastatic renal cell carcinoma (p less than 0.001). Exposure to burning coal was associated with an increased relative risk of the disease but only when the exposure occurred between the ages of 10 and 24 years (p less than 0.05). Dose-response relations were demonstrated for intensity of exposure (p less than 0.025) and duration of occupational exposure (p less than 0.05). The distribution of latent periods from first exposure to diagnosis was bimodal, with one mode at 21 to 30 years and another at 41 to 50 years. Occupational exposure to tar or pitch or both was also associated with an increased relative risk of renal cell carcinoma (p less than 0.05).

Adolescent↗
PubMed1989

Embryonic induction and muscle gene activation.

Embryonic induction, a process in which the differentiation of a cell is determined by its proximity to other kinds of cells, is of major importance in animal development. We review here what is known of the steps by which a muscle-specific actin gene is first activated by embryonic induction in early amphibian embryos.

Actins↗
PubMed1989

XIF3, a Xenopus peripherin gene, requires an inductive signal for enhanced expression in anterior neural tissue.

A full-length cDNA clone for the Xenopus intermediate filament gene XIF3 has been isolated. It is very similar in sequence to the rat intermediate filament cDNA clone 73 that is thought to encode the neuronal intermediate filament protein 'peripherin'. By analysing dissected embryos, we show that XIF3 is expressed predominantly in anterior and dorsal structures and most strongly in the brain of the tailbud (stage 26) embryo. In situ hybridization shows XIF3 transcripts to be localized in neural tissue and especially in regions that most probably correspond to the motor neurones of the neural tube and to some cranial nerve ganglia. New XIF3 transcripts are first found at the start of gastrulation at a low level throughout the ectoderm and are not localized to the presumptive neurectoderm. Expression subsequently increases by about 10-fold in neural tissue, and requires an interaction of the mesoderm with overlying ectoderm. Because new transcripts are found predominantly in neural tissue of the head, this response can be used as a marker of anterior neural induction.

Amino Acid Sequence↗
PubMed1988

Developmental expression of a neurofilament-M and two vimentin-like genes in Xenopus laevis.

A hamster vimentin cDNA probe has been used to isolate and characterize three Xenopus laevis intermediate filament genes, named XIF1, XIF3 and XIF6. Of these, XIF6 shows 89% homology at the amino acid level to a portion of porcine neurofilament-M. XIF6 is transcribed solely in nervous tissue of embryos, commencing at the late neural tube stage. Expression is totally dependent on an interaction between mesoderm and ectoderm during gastrulation and can be used as a marker of neural induction. XIF1 shows 94% homology and XIF3 83% homology to hamster vimentin at the amino acid level over a region of the protein. Although XIF1 and XIF3 show more homology to vimentin than to any other intermediate filament gene, they have distinct temporal and spatial patterns of expression. XIF1 expression most resembles that of vimentin in higher vertebrates, being expressed in embryonic myotome and nerve cord, whilst XIF3 is unusual in that its expression is restricted predominantly to the head in tailbud embryos.

Amino Acid Sequence↗
PubMed1988

Vimentin expression in oocytes, eggs and early embryos of Xenopus laevis.

Immunocytochemical studies using a monoclonal anti-porcine vimentin antibody reveal a well-organized pattern of staining in Xenopus laevis oocytes, eggs and early embryos. The positions of Xenopus vimentin and desmin in two-dimensional (2D) polyacrylamide gels were first established by immunoblotting of muscle Triton extracts with anti-intermediate filament antibodies (anti-IFA), which cross-react with all intermediate filament proteins (IFPs). The anti-porcine vimentin reacts with vimentin and desmin in muscle 2D immunoblots, but only reacts with one polypeptide in oocyte blots in the position predicted for vimentin (Mr 55 x 10(3), pI 5.6). Using an anti-sense probe derived from a Xenopus vimentin genomic clone in RNase protection assays, we show that expression of vimentin begins in previtellogenic oocytes. The level of expression remains constant throughout oogenesis and in unfertilized eggs. These data suggest that vimentin is expressed in oocytes and eggs. Most interestingly, the immunocytochemical results also show that vimentin is present in the germ plasma of oocytes, eggs and early embryos. It is therefore possible that vimentin has an important role in the formation or behaviour of early germ line cells.

Animals↗
PubMed1987

A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction.

A homeobox sequence has been used to isolate a new Xenopus cDNA, named XIHbox6. A short probe from this gene serves as an early marker of posterior neural differentiation in the Xenopus nervous system. The gene recognized by this cDNA sequence is first transcribed at the late gastrula stage and solely in the posterior neural cells. The gene is expressed when ectodermal and mesodermal tissues of an early gastrula are placed in contact, but not by either tissue cultured on its own. However, gene expression is most easily inducible in ectoderm from the dorsal region, i.e., in ectoderm normally destined to form neural structures. This establishes the principle, in contrast to previous belief, that the induction of the embryonic nervous system involves a predisposition of the ectoderm and does not depend entirely on an interaction with inducing mesoderm.

Animals↗
PubMed1986

Organ distribution of apolipoprotein gene transcripts in 6-12 week postfertilization human embryos.

In the liver and the yolk sack of 6-12 week postfertilization human embryos, we have detected RNA transcripts from the following apolipoprotein genes: AI, AII, B, CII, CIII and E. The mRNA from the apolipoprotein CIII gene was relatively more abundant in the total RNA from the yolk sack than in that from the liver. The gut and adrenals contained transcripts of all these apolipoprotein genes apart from apolipoprotein AII. The kidneys and heart contained some apolipoprotein transcripts. In conjunction with previous studies, these results suggest that in the human embryo apolipoprotein genes are transcribed in a much larger range of organs than is the case in the adult. Many of these organs lack endoderm tissues.

Apolipoprotein A-I↗
PubMed1985

Comparison of the human apolipoprotein genes. Apo AII presents a unique functional intron-exon junction.

The structure and function of the apolipoproteins are of interest because of their central role in lipid metabolism. We report the complete primary structure of the human apo AII and CIII genes. These, like apo AI, contain three introns located at conserved positions. This may reflect their evolutionary and functional relationship. Indeed, computer-aided analysis shows that these apolipoproteins and apo AIV (rat), CI, CII and E contain homologous amino acid sequences. In the case of apo AI, AII and CIII, such sequences are encoded by equivalent exons. Finally, the apo AII gene presents a unique intron-exon junction sequence 5' (G-T)16G-G-G-C-A-G 3' that, although departing considerably from the accepted consensus (Py)15X-Py-A-G, appears to function efficiently both in vivo and in a transient expression system.

Apolipoprotein A-I↗
PubMed1985

Deoxyribonucleic acid polymorphism in the apolipoprotein A-1-C-III gene cluster. Association with hypertriglyceridemia.

A DNA sequence polymorphism, revealed by digestion of human DNA with the restriction endonuclease Sst-1 and hybridization with an apolipoprotein A-I complementary DNA clone, has been shown to be located in or close to the 3' noncoding region of the apolipoprotein C-III gene. This polymorphism is found in significantly increased prevalence (P less than 0.001) in Caucasian hypertriglyceridemic subjects compared with race-matched controls, and its distribution in normal individuals of differing racial origins is reported. Furthermore, no alteration of high density lipoprotein or apolipoprotein A-I and apolipoprotein C-III phenotypes was observed in individuals with or without the polymorphism.

Adolescent↗
PubMed1984

A case-control study of alcohol consumption and drinking behaviour in patients with acute gout.

The alcohol intake and drinking behaviour of 24 patients who presented with acute gout in a family practice over a 5-year period were compared with these features of a control population matched for sex, age, weight and use of hyperuricemia-inducing diuretics. The average weekly alcohol intake of the group with gout was twice that of the control group (p less than 0.02), and a statistically significant relation was found between alcohol abuse and acute gout (p less than 0.05). About half of the patients with gout drank excessively. Acute gout should be considered a possible clinical sign of alcohol abuse.

Acute Disease↗
PubMed1984

Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance.

The structure and function of the genes encoding the polypeptide components of plasma lipoproteins are of interest because of the central role they play in the regulation of lipid metabolism. We have now completed our previous studies on the human apoAI gene and furthermore isolated and sequenced cDNA clones for apoAII , CII and CIII. The nucleotide sequences show the signal peptides of apoAII , CII and CIII to be 18, 22 and 20 amino acids in length, respectively, and in addition that prepro apoAII bears a classical propeptide structure of 5 amino acids. The amino acid homology detected between apoCII and pro- apoAI is discussed, as is the gene arrangement of the 5' non-coding region of apoAI mRNA. The relative liver mRNA levels of the 4 apolipoproteins analysed in this study have been estimated and compared with their corresponding plasma products. The data reported here provide an essential basis for further studies of structural and functional alleles of apo AI, AII, CII and CIII genes.

Amino Acid Sequence↗