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Biomedical subjects

A Bird

Publications and source records attributed to A Bird.

At least 91 records · Page 5Linked to original sources
PubMed1995

Studies of DNA methylation in animals.

We have been studying the evolution and function of DNA methylation in vertebrate animals using three related approaches. The first is to further characterise proteins that bind to methylated DNA. Such proteins can be viewed as 'receptors' of the methyl-CpG 'ligand' that mediate downstream consequences of DNA modification. The second approach involves CpG islands. These patches of non-methylated DNA coincide with most gene promoters, but their origin and functional significance have only recently become the subject of intensive study. The third approach is to trace the evolution of DNA methylation. Genomic methylation patterns of vertebrates are strikingly different from those of invertebrates. By studying methylation in animals that diverged from common ancestors near to the invertebrate/vertebrate boundary, we will assess the possibility that changes in DNA methylation contributed causally to the evolution of the complex vertebrate lineage.

Animals↗
PubMed1994

Ivermectin and onchocercal optic neuritis: short-term effects.

In 1982 the macrocyclic lactone, ivermectin, was first tested in human patients with onchocerciasis. It has since undergone phase I to IV trials and is now being widely distributed in onchocercal areas. The previous microfilaricide, diethylcarbamazine citrate (DEC), is known to precipitate or exacerbate active optic neuritis in some onchocercal patients, as part of a wider inflammatory response (the Mazzotti reaction). Ivermectin may also cause a mild reaction, especially in people with high microfilarial loads. Few data are available concerning the effect of ivermectin on active optic neuritis. A large, randomised, double-masked, phase IV trial is reported. Individuals were screened for evidence of optic nerve disease (OND), and those identified as possible cases of OND underwent detailed ophthalmic examination, including fluorescein angiography, before being dosed with ivermectin or placebo. A total of 6831 persons were screened of whom 856 (13%) underwent angiography prior to dosing. At 7-14 days after dosing an attempt was made to re-examine 50% of adults over the age of 20 years, including all those with OND. Six hundred and eighty-eight repeat or new angiograms were performed. During this period, 5 new cases of active optic neuritis and one case of exacerbation of existing optic neuritis were identified. Five of these individuals had received placebo and one ivermectin. Two individuals with optic neuritis before dosing had improved after 7-14 days. One had received placebo, the other ivermectin. Ivermectin does not appear to precipitate or exacerbate optic neuritis at a period of 7-14 days.

Adolescent↗
PubMed1994

Step down heating and melphalan: cytotoxic interactions and clinical implications.

Step down heating from 41.8 degrees C (10, 15 and 20 min) to 40.5 degrees C (55, 50 and 45 min respectively) was studied in vitro in L929 sarcoma cells in the presence and absence of increasing doses of melphalan. Results for heat killing alone demonstrated that step down heating for 20 min (but not 10 or 15 min) at 41.8 degrees C was equivalent to 41.8 degrees C x 65 min. Heat enhancement of melphalan, however, was observed at 10, 15 and 20 min with thermal enhancement ratios of 8.3, 10.3 and 8.5 respectively (p < or = 0.01), consistent with the enhancement of 41.8 degrees C x 65 min. The relevance of these data to hyperthermic limb perfusions for the treatment of malignant melanoma and sarcoma are discussed.

Animals↗
PubMed1994

Structure and expression of the chicken retinoblastoma gene.

The molecular cloning and initial characterization of the complementary DNA encoding the chicken homologue of the human retinoblastoma susceptibility gene product Rb are described. Chicken Rb (chRb) was found to be highly homologous to human, mouse, and Xenopus Rb in primary amino acid sequence, underlining its conserved function in cell cycle control in higher eukaryotes. The highest level of homology was found within the Rb "pocket domains" and at the Rb COOH terminus, whereas the extreme NH2 terminus of chRb is divergent. We also show that transcription of chRb initiates at multiple start sites within a DNA segment which represents a CpG island. ChRb is transcribed as a 4.7-kilobase (kb) mRNA species in a variety of normal chicken tissues and oncogene-transformed hematopoietic cells. However, in v-rel-transformed cell lines, a variant 3.1-kb Rb-specific mRNA was detected in addition to the 4.7-kb transcript. ChRb is expressed as a 104 kilodalton protein and is therefore slightly smaller than the mammalian Rb proteins.

Amino Acid Sequence↗
PubMed1993

Number of CpG islands and genes in human and mouse.

Estimation of gene number in mammals is difficult due to the high proportion of noncoding DNA within the nucleus. In this study, we provide a direct measurement of the number of genes in human and mouse. We have taken advantage of the fact that many mammalian genes are associated with CpG islands whose distinctive properties allow their physical separation from bulk DNA. Our results suggest that there are approximately 45,000 CpG islands per haploid genome in humans and 37,000 in the mouse. Sequence comparison confirms that about 20% of the human CpG islands are absent from the homologous mouse genes. Analysis of a selection of genes suggests that both human and mouse are losing CpG islands over evolutionary time due to de novo methylation in the germ line followed by CpG loss through mutation. This process appears to be more rapid in rodents. Combining the number of CpG islands with the proportion of island-associated genes, we estimate that the total number of genes per haploid genome is approximately 80,000 in both organisms.

Animals↗
PubMed1993

Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2.

MeCP2 is a chromosomal protein which binds to DNA that is methylated at CpG. In situ immunofluorescence in mouse cells has shown that the protein is most concentrated in pericentromeric heterochromatin, suggesting that MeCP2 may play a role in the formation of inert chromatin. Here we have isolated a minimal methyl-CpG binding domain (MBD) from MeCP2. MBD is 85 amino acids in length, and binds exclusively to DNA that contains one or more symmetrically methylated CpGs. MBD has negligable non-specific affinity for DNA, confirming that non-specific and methyl-CpG specific binding domains of MeCP2 are distinct. In vitro footprinting indicates that MBD binding can protect a 12 nucleotide region surrounding a methyl-CpG pair, with an approximate dissociation constant of 10(-9) M.

Base Sequence↗
PubMed1993

CpG islands.

Explore the source record for details and available documents.

Animals↗
PubMed1992

Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA.

Methylation of mammalian DNA can lead to repression of transcription and alteration of chromatin structure. Recent evidence suggests that both effects are the result of an interaction between the methylated sites and methyl-CpG-binding proteins (MeCPs). MeCP1 has previously been detected in crude nuclear extracts. Here we report the identification, purification, and cDNA cloning of a novel MeCP called MeCP2. Unlike MeCP1, the new protein is able to bind to DNA that contains a single methyl-CpG pair. By staining with an antibody, we show that the distribution of MeCP2 along the chromosomes parallels that of methyl-CpG. In mouse, for example, MeCP2 is concentrated in pericentromeric heterochromatin, which contains a large fraction (about 40%) of all genomic 5-methylcytosine.

Amino Acid Sequence↗
PubMed1992

Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein.

Repression of transcription from densely methylated genes can be mediated by the methyl-CpG binding protein MeCP-1 (Boyes and Bird, 1991). Here we have investigated the effect of methylation on genes with a low density of methyl-CpG. We found that sparse methylation could repress transfected genes completely, but the inhibition was fully overcome by the presence in cis of an SV40 enhancer. Densely methylated genes, however, could not be reactivated by the enhancer. In vitro studies showed that the sparsely methylated genes bound weakly to MeCP-1 and that binding interfered with transcription. In the absence of available MeCP-1, methylation had minimal effects on transcription. From these and other results we propose that sparsely methylated genes form an unstable complex with MeCP-1 which prevents transcription when the promoter is weak. This complex can be disrupted by a strong promoter, thereby allowing the methylated gene to be transcribed.

Animals↗
PubMed1992

Localization of two genes for Usher syndrome type I to chromosome 11.

The Usher syndromes (USH) are autosomal recessive diseases characterized by congenital sensorineural hearing loss and progressive pigmentary retinopathy. While relatively rare in the general population, collectively they account for approximately 6% of the congenitally deaf population. Usher syndrome type II (USH2) has been mapped to chromosome 1q (W. J. Kimberling, M. D. Weston, C. Möller, et al., 1990, Genomics 7: 245-249; R. A. Lewis, B. Otterud, D. Stauffer, et al., 1990, Genomics 7: 250-256), and one form of Usher syndrome type I (USH1) has been mapped to chromosome 14q (J. Kaplan, S. Gerber, D. Bonneau, J. Rozet, M. Briord, J. Dufier, A. Munnich, and J. Frezal, 1990. Cytogenet. Cell Genet. 58: 1988). These loci have been excluded as regions of USH genes in our data set, which is composed of 8 French-Acadian USH1 families and 11 British USH1 families. Both of these sets of families show linkage to loci on chromosome 11. Linkage analysis demonstrates locus heterogeneity between these sets of families, with the French-Acadian families showing linkage to D11S419 (Z = 4.20, theta = 0) and the British families showing linkage to D11S527 (Z = 6.03, theta = 0). Genetic heterogeneity of the data set was confirmed using HOMOG and the M test (log likelihood ratio > 10(5)). These results confirm the presence of two distinct USH1 loci on chromosome 11.

Chromosome Mapping↗
PubMed1992

Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep.

Pregnant ewes and their fetuses were chronically catheterized using aseptic procedures under general anaesthesia, and the ewes were then fed either lucerne chaff alone, or lucerne mixed with dried plant material obtained from one of three forb species, Tribulus terrestris (caltrop), Abelmoschus ficulneus (native rosella) or Ipomoea lonchophylla (cowvine), from 103-112 days gestation until term. Ingestion of the forb material was not associated with changes in maternal blood gases, plasma glucose concentrations, or the length of gestation. However, ingestion of rosella seed was associated with a significantly greater fall of fetal arterial pO2 with advancing gestation, and ingestion of either rosella or cowvine was associated with significantly lower fetal mean arterial pressure at 127-131 days, compared with the Tribulus and lucerne groups. Also, the incidence of fetal breathing movements was significantly lower, and did not show a normal day-night variation, in each of the forb-fed groups compared with the lucerne-fed group. The results indicate that these forb plants may contain substances that affect the functional development of the fetal brain. Although ingestion of these plants did not appear to affect the outcome of pregnancy in this study, the possibility that these forbs have a greater impact in sheep populations with poor nutrition and in more extreme environmental conditions is discussed.

Animal Feed↗
PubMed1992

Immortalization of conditionally transformed chicken cells: loss of normal p53 expression is an early step that is independent of cell transformation.

Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype. The expressions of two tumor suppressor genes, the retinoblastoma (Rb) gene and the p53 gene, were investigated during senescence, crisis, and cell line establishment. In temperature-sensitive (ts)-v-erb B erythroblasts and ts-v-src fibroblasts (as well as in v-myc macrophages), loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization. In contrast, expression of the Rb gene was unchanged at all stages of immortalization. Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts, even in lines that were immortal and lacked p53. The results demonstrate that the process of immortalization is distinct from cell transformation, probably requiring different mutational events.

Animals↗
PubMed1992

Transcriptional repression by methylation of CpG.

Methylated DNA in mammals is associated with transcriptional repression and nuclease resistant chromatin. In this review we discuss how these effects may be mediated by proteins that bind to methylated DNA.

Animals↗