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P Avila

Publications and source records attributed to P Avila.

13 recordsLinked to original sources
PubMed1991

[Cough caused by angiotensin-converting enzyme inhibitors. A series of cases collected by spontaneous notification of adverse reactions].

Cough is one of the possible untoward adverse drug effects of angiotensin converting enzyme inhibitors. We describe the available information on 50 cough episodes attributable to captopril and 18 episodes attributable to enalapril reported to the Spanish Drug Surveillance System. Cough represented 37% and 39% of the reports of side effects of captopril and enalapril, respectively. There was a remarkable female predominance among the patients with cough. Cough developed at very low doses (15 mg of captopril and 5 mg of enalapril daily), although the patients on captopril who developed cough were receiving higher doses than those who presented other side effects. A high proportion of patients (29%) continued with the drug for more than six months after cough had developed, suggesting the need for a wider knowledge of this side effect.

Aged↗
PubMed1990

Site-specific recombination by mutants of Tn21 resolvase with DNA recognition functions from Tn3 resolvase.

The resolvases from the transposons Tn3 and Tn21 are homologous proteins but they possess distinct specificities for the DNA sequence at their respective res sites. The DNA binding domain of resolvase contains an amino acid sequence that can be aligned with the helix-turn-helix motif of other DNA binding proteins. Mutations in the gene for Tn21 resolvase were made by replacing the section of DNA that codes for the helix-turn-helix with synthetic oligonucleotides. Each mutation substituted one amino acid in Tn21 resolvase with either the corresponding residue from Tn3 resolvase or a residue that lacks hydrogen bonding functions. The ability of these proteins to mediate recombination between res sites from either Tn21 or Tn3 was measured in vivo and in vitro. With one exception, where a glutamate residue had been replaced by leucine, the activity of these mutants was similar to that of wild-type Tn21 resolvase. A further mutation was made in which the complete recognition helix of Tn21 resolvase was replaced with that from Tn3 resolvase. This protein retained activity in recombining Tn21 res sites, though at a reduced level relative to wild-type; the reduction can be assigned entirely to weakened binding to this DNA. Neither this mutant nor any other derivative of Tn21 resolvase had any detectable activity for recombination between res sites from Tn3. The exchange of this section of amino acid sequence between the two resolvases is therefore insufficient to alter the DNA sequence specificity for recombination.

Amino Acid Sequence↗
PubMed1990

DNA binding by mutants of Tn21 resolvase with DNA recognition functions from Tn3 resolvase.

Substitution of amino acids within the section of Tn21 resolvase that corresponds to a helix-turn-helix structure, with the equivalent residues from Tn3 resolvase, yields proteins that retain the ability to mediate recombination between res sites from Tn21. These proteins had no recombinational activity on res sites from Tn3, even when the complete recognition helix had been exchanged. In this study, the binding of these mutants of Tn21 resolvase to DNA fragments containing res from either Tn21 or Tn3 was analysed by DNase I footprinting and by gel retardation. With DNA containing res from Tn21, the mutants bound to all three of the binding sites for resolvase (I, II, and III) but with a lower affinity than wild-type Tn21 resolvase. No complexes were detected between Tn3 resolvase and Tn21 DNA. With DNA containing res from Tn3, both the mutants and wild-type Tn21 resolvase bound to sites II and III, forming similar complexes to those with Tn3 resolvase: some of the mutants had higher affinities for these two sites on Tn3 DNA than on Tn21 DNA. In contrast, at site I in res from Tn3 (the location of the recombinational cross-over), the derivatives of Tn21 resolvase formed aberrant complexes whose structures differed radically from that with Tn3 resolvase. Alterations in the amino acid sequence of resolvase, within the helix-turn-helix region, therefore modulate the affinity of the protein for its target sequence in the DNA, but the specificity of resolvase for recombination at its cognate res sites is determined by the resultant organization of the DNA-protein complex.

Base Sequence↗
PubMed1990

General organization of the conjugal transfer genes of the IncW plasmid R388 and interactions between R388 and IncN and IncP plasmids.

The complete conjugal transfer gene region of the IncW plasmid R388 has been cloned in multicopy vector plasmids and mapped to a contiguous 14.9-kilobase segment by insertion mutagenesis. The fertility of the cloned region could still be inhibited by a coresident IncP plasmid. The transfer region has been dissected into two regions, one involved in pilus synthesis and assembly (PILW), and the other involved in conjugal DNA metabolism (MOBW). They have been separately cloned. PILW also contains the genes involved in entry exclusion. MOBW contains oriT and the gene products required for efficient mobilization by PILW. MOBW plasmids could also be mobilized efficiently by PILN, the specific pilus of the IncN plasmid pCU1, but not by PILP, the specific pilus of the IncP plasmid RP1.

Cloning, Molecular↗
PubMed1988

Analysis of the variable endpoints generated by one-ended transposition of Tn21.

One-ended transposition of Tn21 generates recombinants usually containing a whole copy of the donor replicon plus a short duplication of it (S. Mötsch, R. Schmitt, P. Avila, F. de la Crue, E. Ward, and J. Grinsted, Nucleic Acids Res. 13:3335-3342, 1985). This work shows that recombinants containing less than a whole copy of the donor replicon (hereafter called short recombinants) could also be detected when plasmid donors which contained two selectable genetic markers were used. Short recombinants were produced at the same frequency from TnpR+ donor molecules as from TnpR- donor molecules in a RecA- background. Therefore, they were not resolution products of larger recombinants. This result invalidates a previous hypothesis to explain one-ended transposition, that is, that one-ended transposition arises from the use of secondary ends by the transposition apparatus. On the other hand, it suggests that one-ended transposition of Tn21 occurs via a simple insertion mechanism.

Base Sequence↗
PubMed1985

Junction sequences generated by 'one-ended transposition'.

In the presence of the cognate transposase, plasmids containing a single inverted repeat (IR) sequence of Tn21 or of Tn1721 can fuse efficiently with other plasmids ('one-ended transposition'). The junctions across the sequences of donor and recipient DNA in recombinants generated by this process have been determined. These show that the segment of donor DNA starts precisely at the IR sequence (it is variable at the other end), and is flanked by a direct repeat of host DNA (usually 5bp) that was present only once in the original host sequence. These are characteristics of recombinants generated by transposition of Tn21 and Tn1721 themselves, suggesting that the mechanism of one-ended transposition is very similar to that of the corresponding entire elements.

Base Sequence↗
PubMed1984

Plasmids containing one inverted repeat of Tn21 can fuse with other plasmids in the presence of Tn21 transposase.

In the presence of the Tn21 transposase, plasmids that contain a single Tn21 inverted repeat sequence fuse efficiently with other plasmids. This reaction occurs in recA strains, is independent of the transposon-encoded resolution system, and results in insertions into different sites in the recipient plasmid. All fusion products studied contained at least one complete copy of the donor plasmid; most also contained some duplication of it as well. The data are consistent with processive models of transposition.

Base Sequence↗
PubMedDate not supplied

Site-specific recombination and shuffling of resistance genes in transposon Tn21.

Many multidrug-resistant transposons found in natural isolates of Gram-negative bacteria are close relatives of Tn21. Thus, the Tn21 subgroup of the Tn3 family of transposable elements is the most successful homogeneous group in acquiring resistance to newly introduced antibiotics. This paper summarizes the mode of acquisition of resistance genes by these elements.

Amino Acid Sequence↗