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Biomedical subjects

A J Lopez

Publications and source records attributed to A J Lopez.

17 recordsLinked to original sources
PubMed2004

Fast-track management of malignant superior vena cava syndrome.

We report our experience with a combined approach of endovascular biopsy followed by immediate stenting in the management of superior vena cava (SVC) syndrome secondary to obstructing mediastinal masses. A diagnosis of malignancy was obtained in six of eight (75%) biopsies and symptomatic relief was accomplished in all patients. We have found this to be a rapid, safe and effective management strategy that we now consider for all patients presenting with de novo SVC syndrome.

Adult↗
PubMed1999

The endovascular management of blue finger syndrome.

OBJECTIVES: To review our experience of the endovascular management of upper limb embolisation secondary to an ipsilateral proximal arterial lesion. DESIGN: A retrospective study. MATERIALS AND METHODS: Over 3 years, 17 patients presented with blue fingers secondary to an ipsilateral proximal vascular lesion. These have been managed using transluminal angioplasty (14) and arterial stenting (five), combined with embolectomy (two) and anticoagulation (three)/anti-platelet therapy (14). RESULTS: All the patients were treated successfully. There have been no further symptomatic embolic episodes originating from any of the treated lesions, and no surgical amputations. Complications were associated with the use of brachial arteriotomy for vascular access. CONCLUSIONS: Endovascular techniques are safe and effective in the management of upper limb embolic phenomena associated with an ipsilateral proximal focal vascular lesion.

Adult↗
PubMed1999

Trans-acting factors required for inclusion of regulated exons in the Ultrabithorax mRNAs of Drosophila melanogaster.

Alternatively spliced Ultrabithorax mRNAs differ by the presence of internal exons mI and mII. Two approaches were used to identify trans-acting factors required for inclusion of these cassette exons. First, mutations in a set of genes implicated in the control of other alternative splicing decisions were tested for dominant effects on the Ubx alternative splicing pattern. To identify additional genes involved in regulation of Ubx splicing, a large collection of deficiencies was tested first for dominant enhancement of the haploinsufficient Ubx haltere phenotype and second for effects on the splicing pattern. Inclusion of the cassette exons in Ubx mRNAs was reduced strongly in heterozygotes for hypomorphic alleles of hrp48, which encodes a member of the hnRNP A/B family and is implicated in control of P-element splicing. Significant reductions of mI and mII inclusion were also observed in heterozygotes for loss-of-function alleles of virilizer, fl(2)d, and crooked neck. The products of virilizer and fl(2)d are also required for Sxl autoregulation at the level of splicing; crooked neck encodes a protein with structural similarities to yeast-splicing factors Prp39p and Prp42p. Deletion of at least five other loci caused significant reductions in the inclusion of mI and/or mII. Possible roles of identified factors are discussed in the context of the resplicing strategy for generation of alternative Ubx mRNAs.

Alternative Splicing↗
PubMed1999

A review of alternative approaches in the management of iatrogenic femoral pseudoaneurysms.

The management of iatrogenic pseudoaneurysms (IPAs) demands close co-operation between radiologist, vascular surgeon and plastic surgeon. Ideally, each patient should be reviewed employing a team approach. Many IPAs require only observation; those with a volume greater than 6 cm3 will require treatment as spontaneous thrombosis is uncommon. Radiological treatment options include ultrasound guided compression repair (UGCR), embolisation, and covered stenting. Occasionally, these are unsuccessful or contra-indicated, and the vascular surgical approach is discussed in detail. Finally, the role of the plastic surgeon in dealing with skin ischaemia is detailed.

Aneurysm, False↗
PubMed1998

Generation of alternative Ultrabithorax isoforms and stepwise removal of a large intron by resplicing at exon-exon junctions.

Little is known about mechanisms that regulate and ensure accurate processing of complex transcription units with long introns. We investigate this in the Ultrabithorax gene of Drosophila. A consensus 5' splice site is regenerated at the junction between the first exon and a small internal exon (mI); this splice site is used in a developmentally regulated manner to remove mI during subsequent processing of the downstream intron. Conserved elements within mI and an interaction with exon mII modulate use of the regenerated splice site. Structural similarities predict the same process for mII. This resplicing mechanism avoids competition between distant splice sites for control of exon inclusion and allows removal of a 74 kb intron as a series of smaller fragments.

Alleles↗
PubMed1998

Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation.

Alternative splicing of pre-mRNAs is a powerful and versatile regulatory mechanism that can effect quantitative control of gene expression and functional diversification of proteins. It contributes to major developmental decisions and also to fine tuning of gene function. Genetic and biochemical approaches have identified cis-acting regulatory elements and trans-acting factors that control alternative splicing of specific pre-mRNAs. Both approaches are contributing to an understanding of their mode of action. Some alternative splicing decisions are controlled by specific factors whose expression is highly restricted during development, but others may be controlled by more modest variations in the levels of general factors acting cooperatively or antagonistically. Certain factors play active roles in both constitutive splicing and regulation of alternative splicing. Cooperative and antagonistic effects integrated at regulatory elements are likely to be important for specificity and for finely tuned differences in cell-type-specific alternative splicing patterns.

Alternative Splicing↗
PubMed1996

CD-tagging: a new approach to gene and protein discovery and analysis.

We describe a new method for gene discovery and analysis, CD-tagging, that puts specific molecular tags on a gene, its transcript and its protein product. The method has been successfully tested in two organisms, the haploid unicellular alga Chlamydomonas reinhardtii and the metazoan Drosophila melanogaster. The method utilizes a specially designed DNA molecule, the CD-cassette, that contains splice acceptor and donor sites surrounding a short open reading frame. Insertion of the CD-cassette into an intron in a target gene introduces a new exon, represented by the open reading frame of the CD-cassette, surrounded by two functional hybrid introns. As a result (i) the gene is tagged by a specific nucleotide sequence, (ii) the mRNA is tagged by a specific nucleotide sequence and (iii) the protein is tagged by a specific peptide sequence. Because these tags are unique, specific nucleotide or antibody probes can be used to obtain and/or analyze the gene, transcript or protein. As a gene discovery technology, CD-tagging has two unique advantages: 1) Genes can be identified through a primary screen at the protein level, and so the very process by which a gene is identified provides specific empirical information about its biological function. 2) The cassette arms, which are spliced out of the transcript of the target gene, are available to carry a wide variety of DNA sequences, such as genes encoding drug resistance that can be used to select for the presence of the CD-cassette in the genome.

Animals↗
PubMed1994

Technical note: radiological insertion of an implantable drug delivery system.

A fully implantable drug delivery system has been shown to overcome many of the problems of long-term venous access. Traditionally these have required surgical implantation but we describe a simple, cost-effective and successful technique for the percutaneous insertion of an implantable vascular device (Vascuport, Ohmeda) in the angiography suite under local anaesthesia. It was successful in all 19 patients in whom it was attempted, with only one minor complication. We recommend that the procedure should be performed in X-ray departments using screening and conventional guidewire techniques.

Anesthesia, Local↗
PubMed1992

Case report: therapeutic bronchial artery embolization in a case of Takayasu's arteritis.

The pulmonary arteries are frequently involved in Takayasu's arteritis with a reported incidence of 41-100% in affected individuals. Patients are usually asymptomatic, however, often despite extensive pulmonary involvement. We describe a patient with Takayasu's arteritis who presented with haemoptysis caused by bronchial artery hypertrophy secondary to occlusive pulmonary arterial disease, who was treated by bronchial artery embolization. This is, to our knowledge, the first reported case of haemoptysis secondary to Takayasu's arteritis successfully treated by embolization.

Adult↗
PubMed1991

Immunochemical dissection of the Ultrabithorax homeoprotein family in Drosophila melanogaster.

The homeotic gene Ultrabithorax (Ubx) specifies metameric identities in multiple tissues of the thorax and abdomen in Drosophila melanogaster. Alternatively spliced Ultrabithorax mRNAs encode five protein isoforms that differ in internal sequences immediately adjacent to a homeodomain DNA-binding motif. Each of these proteins is phosphorylated in vivo at multiple serine and threonine residues. An extensive panel of monoclonal antibodies was raised against the Ultrabithorax proteins, including antibodies specific for individual isoforms and antibodies that discriminated between different phosphorylation states. Characterization of these antibodies provided insights into shared and isoform-specific features of Ultrabithorax protein structure that may be functionally important. Immunohistochemical staining experiments demonstrated that each isoform is expressed in a different stage- and tissue-specific pattern and suggested that Ultrabithorax protein phosphorylation is also developmentally regulated. These results support the hypothesis that alternative splicing and phosphorylation modulate developmentally specific functions of the Ubx gene.

Amino Acid Sequence↗
PubMed1988

Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule.

Trimetrexate (TMQ; NSC 352122) is a potent inhibitor of dihydrofolate reductase with good activity against murine i.p.-implanted B16 melanoma and colon 26 tumors. Preclinical antineoplastic activity, demonstrated schedule dependency, and data suggesting effectiveness against methotrexate-resistant cells prompted a Phase I clinical and pharmacokinetic study of trimetrexate using an i.v. daily x5 schedule. Forty-three good performance status patients were treated with 12 dose levels using daily doses varying from 0.5 to 15 mg/m2/d. Plasma and urine samples were obtained for pharmacokinetic analysis using a high-performance liquid chromatographic method. Myelosuppression was dose limiting and 15 mg/m2/d x5 was the maximum tolerated dose. White blood cell (WBC) and platelet toxicity were noted at doses of 1.6 mg/m2 and above. Median WBC and platelet nadirs occurred on approximately Days 11-12 with recovery by Days 15-18. Nonhematological toxicity included mucositis, nausea and vomiting, stomatitis, diarrhea, and rash. Evidence for antitumor activity was seen in seven patients. Trimetrexate elimination from plasma could be represented as either a bi- or triexponential process. Terminal elimination half-lives were in the range of 5-14 h in patients represented by a triexponential model. Approximately 10-20% of the dose administered was excreted in urine over a 24-h period. The recommended starting dose for patients in Phase II trials using the d x5 i.v. schedule is 8.0 mg/m2/d repeated every 21 days. Dose escalations may be possible depending on the extent of prior therapy and individual tolerance of the drug.

Adolescent↗
PubMed1988

Studies on the mechanism of the acute and carcinogenic effects of N-nitrosodimethylamine on mink liver.

Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. We have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared them with those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N7-methylguanine and O6-methylguanine adducts. Biotransformation of NDMA by liver slices to CO2 was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also to a higher intrinsic susceptibility of their liver cells to a given chemical insult.

Animals↗