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Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 289 records · Page 16Linked to original sources
PubMed1985

The two embryonic U1 RNA genes of Xenopus laevis have both common and gene-specific transcription signals.

We have cloned and sequenced the 1842-bp repeat DNA encoding the two Xenopus laevis embryonic U1 RNAs, xU1a and xU1b. Although these two U1 RNAs are almost identical in sequence and are coordinately expressed during early embryogenesis, the flanking sequences of their genes show very little homology. Both genes contain two short conserved sequences, centered around positions -55 and +19, that probably are essential for 5' and 3' end formation of U1 RNAs, respectively. Efficient transcription of either gene in stage VI oocytes requires gene-specific promoter elements, located upstream of position -220. In the xU1b gene, these required 5'-flanking sequences include an 18-bp palindrome that has potential for Z-DNA formation. When injected separately into stage VI oocytes, the xU1a and xU1b genes are equally well transcribed, but co-injection of the two genes, either as the full length repeat or as two separate subclones, results in preferential accumulation of xU1b RNA. This competitive advantage of the xU1b gene in injected oocytes apparently is the result of preferred binding of one or more transcription factors that are limiting in these oocytes.

Animals↗
PubMed1985

Nuclease S1-sensitive sites in multigene families: human U2 small nuclear RNA genes.

We show here that human U2 small nuclear RNA genes contain a 'strong nuclease S1 cleavage site' (SNS1 site), a sequence that is very sensitive to digestion by nuclease S1. This site is located 0.50-0.65 kb downstream of the U2 RNA coding region. It comprises a 0.15-kb region in which (dC-dT)n:(dA-dG)n co-polymeric stretches represent greater than 90% of the sequence. Nuclease S1 is able to excise unit length repeats of the human U2 RNA genes both from cloned fragments and total human genomic DNA. The precise locations of the cleavage sites are dependent on the superhelicity of the substrate DNA. In negatively supercoiled substrates, cleavages are distributed over the entire 0.15-kb region, but in linearized substrates, they occur within a more limited region, mainly at the boundary of the SNS1 site closest to the human U2 RNA coding region. Nuclease S1 cleavage of negatively supercoiled substrates occurs at pHs as high as 7.0; in contrast, cleavage of linearized substrates requires a pH less than 5.0, indicating that supercoiling contributes to the sensitivity of this site. Mung bean nuclease gives results similar to that observed with nuclease S1.

Base Sequence↗
PubMed1985

Survival in 222 adult patients with acute leukaemia treated with intermittent combination chemotherapy programme.

222 patients aged 15-59 years with acute leukaemia were treated with intermittent combination chemotherapy consisting of six 5-day courses of cytotoxic drugs as induction treatment followed by 3 years of maintenance therapy in patients who obtained complete remission (CR). CR was achieved in 50.3% of 161 patients (early deaths included) with acute myelogenous leukaemia (AML). The observed cumulative 5-yr survival rate (observation time 1-12.25 yr) calculated by the life table method was 12% in AML. Among patients who obtained CR, those aged 40-59 yr appeared to fare better than younger patients (5-yr survival: 24%). The M-3 subtype was an adverse prognostic factor. In acute lymphoblastic leukaemia (ALL) the CR rate was 83.6% and the observed cumulative 5-yr survival rate was 14%. Women fared better than men.

Adolescent↗
PubMed1985

The bovine papillomavirus distal "enhancer" is not cis essential for transformation or for plasmid maintenance.

We constructed a mutant of bovine papillomavirus type 1 (BPV-1) DNA that lacked a transcriptional enhancer located 3' to the polyadenylation site of the early viral RNAs expressed in transformed cells. This mutant DNA, when separated from the procaryotic sequences, transforms mouse cells with an efficiency comparable to that of the full BPV-1 genome, and it exists as a stable multicopy plasmid in transformed cells. The BPV-1 distal enhancer suppresses the effects of a cis-inhibitory element in pML2 sequences but is not essential for the expression of the viral genes involved in cellular transformation or plasmid maintenance.

Animals↗
PubMed1985

Expression of a human U1 RNA gene introduced into mouse cells via bovine papillomavirus DNA vectors.

We introduced a gene for human U1 small nuclear RNA, HU1-1, into mouse C127 cells via bovine papillomavirus (BPV) vectors. After transfection, up to 15% of the total U1 RNA in transformed cells was encoded by the introduced human genes. High levels of expression of the human gene were observed when the recombinant viral DNAs were maintained either as plasmids or after integration into high-molecular-weight DNA. As few as 400 and 35 base pairs of 5' and 3' flanking region sequences, respectively, were sufficient for transcription of human U1 RNA, and no increase in the level of expression was observed with HU1-1 DNA containing several kilobases of flanking region sequences. Several of the transformed cell lines contained the recombinant BPV DNA apparently integrated into the host genome. Integration or rearrangement or both of the U1-BPV DNA was promoted when the HU1-1 gene was positioned at the BamHI site downstream of the BPV transforming region. At least two variants of the U1-BPV DNAs were able to cause morphological transformation of cells despite the fact that these DNAs lacked a BPV transcriptional enhancer element.

Animals↗
PubMed1984

Human U2 and U1 RNA genes use similar transcription signals.

We have analyzed the requirements for human U2 RNA transcription by injection of cloned U2/6 RNA genes into nuclei of Xenopus laevis oocytes. Two forms of human U2 RNAs accumulate, a major species corresponding to mature-sized U2 RNA and a minor species corresponding to a 3'-extended precursor. This RNA polymerase II transcription requires only 258 and 94 bp of 5'- and 3'-flanking region sequences, respectively. Efficient U2 RNA synthesis depends on a promoter element located between positions -258 and -198. This region contains a 12-bp direct repeat which strongly resembles a comparable upstream promoter element of the human U1 RNA genes. Sequences between -258 and -198 also confer on the U2 RNA template the ability to complete with co-injected U1 RNA templates for a snRNA gene-specific transcription factor(s). Transcription of U2 RNA is reduced off templates containing an active RNA polymerase III transcription unit, presumably because of relaxation or sequestration of the DNA. In vitro transcription of the U2 RNA gene, like that of the U1 RNA gene, is initiated upstream of the point corresponding to the 5' end of in vivo synthesized RNA.

Amanitins↗
PubMed1984

Consequences of assessment and intervention among elderly people: a three year randomised controlled trial.

Over three years 285 randomly selected subjects aged 75 years or more and living in a suburb of Copenhagen were visited every three months in their own homes (the intervention group) to assess whether scheduled medically and socially preventive intervention would influence the number of admissions to hospitals or nursing homes, the number of contacts with general practice, or mortality. A randomly selected group of 287 people of the same age and sex were visited during the final three months of the study (the control group). Two hundred and nineteen admissions to hospitals (4884 bed days) were registered for the intervention group compared with 271 (6442 bed days) for the control group. Especially during the second half of the study, a significant reduction in the number of admissions to hospitals was seen in the intervention group. Twenty people in the intervention group and 29 in the control group moved into nursing homes (p greater than 0.05). The corresponding numbers of deaths were 56 and 75 (p less than 0.05). No difference was seen in the number of contacts with general practice. Significantly fewer emergency medical calls, however, were registered for the intervention group. Subjects in the intervention group benefited from the regular visits and the increased distribution of aids and modifications to their homes to which these led. The regular visits probably also produced an important increase in confidence.

Aged↗
PubMed1984

Synthesis of human U1 RNA. II. Identification of two regions of the promoter essential for transcription initiation at position +1.

We have analyzed the requirements for human U1 RNA transcription catalyzed by RNA polymerase II. In Xenopus laevis oocytes, a human U1 RNA gene with only 231 and 35 nucleotides of the 5' and 3' flanking regions, respectively (Lund, E. and Dahlberg, J. E. (1984) J. Biol. Chem. 259, 2013-2021), is able to support accumulation of human U1 RNA. We show that the point in the template corresponding to the 5' end of U1 RNA is a site of transcription initiation. That result rules out the possibility that the 5' end of U1 RNA is generated by cleavage and capping of a precursor RNA. The accumulation of correctly initiated human U1 RNA transcripts requires at least two essential upstream elements. The region between positions -231 and -203 is indispensable for transcription both in oocytes and in vitro. The other region, between positions -105 and -6, fixes the location of the 5' ends of the U1 RNA transcripts in oocytes while not altering the overall level of transcription. This latter region contains a sequence located around position -50, which we propose serves as the analog of the T-A-T-A sequence in U1 and U2 RNA genes.

Animals↗
PubMed1984

True genes for human U1 small nuclear RNA. Copy number, polymorphism, and methylation.

The nucleotide sequence of a human U1 small nuclear RNA gene (HU1-1) is presented, along with several hundred nucleotides of its 5' and 3' flanking regions. We demonstrate that the immediate 5' flanking region sequences are a highly specific hydridization probe capable of distinguishing U1 RNA true genes from pseudogenes. The copy number of U1 RNA genes was determined to be constant, about 30/haploid genome equivalent in six different individuals. Nevertheless, several restriction enzyme cleavage site polymorphisms exist in these genes. We also show that C-C-G-G sequences in the vicinity of U1 RNA true genes are not methylated, but they are methylated near pseudogenes. Genomic DNAs of mouse, frog, chicken, and fruit fly contain sequences homologous to the human U1 RNA gene coding region but not to the 5' flanking region. This suggests that sequences important for expression of U1 RNA genes constitute only a minor part of the 5' flanking regions. In the HU1-1 locus, sequences similar to the consensus T-A-T-A-A-A box are located about 45 and 210 base pairs upstream of the point corresponding to the 5' end of the mature RNA. Several additional direct repeats which may be regulatory elements are present in the upstream region. A few short inverted repeats which probably constitute a transcription termination signal are in the region corresponding to the 3' end of the U1 RNA.

Bacteriophage lambda↗