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Biomedical subjects

J A O'Neil

Publications and source records attributed to J A O'Neil.

16 recordsLinked to original sources
PubMed1991

Oxidation of LDL: role in atherogenesis.

Oxidation of LDL is proposed to accelerate atherogenesis by the following sequence of events. LDL accumulates in atherosclerotic plaques, presumably due to interaction with intimal proteoglycans. The LDL then undergoes oxidation, and aldehydic products of lipid peroxidation such as HNE or other aldehyde products derived from lipid peroxidation, induce blocking of lysine residues on apo B. This results in its recognition by the scavenger receptor on tissue macrophages at sites in which LDL concentrations are low. At sites in which the LDL concentration is high, modification with such products induces intermolecular cross-linking and particle aggregation. The aggregated, oxidized LDL particles are then phagocytosed by tissue macrophages to induce lipid loading of these cells and the formation of foam cells, a characteristic of the earliest atherosclerotic lesion. By these mechanisms oxidation of LDL accelerates atherogenesis.

Animals↗
PubMed1991

Quantification of apo[a] and apoB in human atherosclerotic lesions.

Lipoprotein[a] or Lp[a] is a cholesterol-rich plasma lipoprotein that is associated with increased risk for cardiovascular disease. To better understand this association we determined the amount of apo[a] and apoB as possible estimates for Lp[a] and low density lipoprotein (LDL) accumulation in atherosclerotic lesions and in plasma, from patients undergoing vascular surgery, using specific radioimmunoassays for apolipoprotein[a] and apolipoprotein B. Apo[a] and apoB were operationally divided into a loosely bound fraction obtained by extracting minced samples of plaque with phosphate-buffered saline (PBS), and a tightly bound fraction obtained by extracting the residual tissue with 6 M guanidine-HCl (GuHCl). We found that 83% of all apo[a] but only 32% of all apoB in lesions was in the tightly bound fraction. When normalized for corresponding plasma levels, apo[a] accumulation in plaques was more than twice that of apoB. All fractions of tissue apo[a], loosely bound, tightly bound, and total, correlated significantly with plasma apo[a]. However, no significant correlations were found between any of the tissue fractions and plasma apoB. If all apo[a] and apoB had been associated with intact Lp[a] or LDL particles, the calculated mass of tightly bound Lp[a] would actually have exceeded that of tightly bound LDL in five cases with plasma Lp[a] levels above 5 mg apo[a] protein/dl. When PBS and GuHCl extracts of lesions were subjected to one-dimensional electrophoresis, the major band stained for lipid and immunoblotted positively for apo[a] and apoB, suggesting the presence of some intact Lp[a] in these extracts. These results suggest that Lp[a] accumulates preferentially to LDL in plaques, and that plaque apo[a] is directly associated with plasma apo[a] levels and is in a form that is less easily removable than most of the apoB. This preferential accumulation of apo[a] as a tightly bound fraction in lesions, could be responsible for the independent association of Lp[a] with cardiovascular disease in humans.

Aged↗
PubMed1986

Mycotic embolism and embolomycotic aneurysms. Neglected lessons of the past.

During the past decade, nine patients with bacterial endocarditis have required management of mycotic emboli and/or aneurysms in this center. In these patients, 25 separate mycotic emboli or aneurysms were identified. Among these were four visceral, 11 lower extremity, one aortic, one hypogastric, and eight cerebral lesions. Multiple sites were involved in seven of the nine patients (78%). Presenting symptoms were secondary to acute expansion of mycotic aneurysms in three patients and secondary to rupture of aneurysms in four patients. Mycotic emboli produced cerebral infarction in two patients and acute ischemia in six patients. Asymptomatic mycotic aneurysms of the middle cerebral, hepatic, hypogastric, and profunda femoris arteries and asymptomatic emboli to the profunda femoris and tibial arteries were found during angiographic study. Management included resection alone (7 aneurysms), resection and graft replacement (2 aneurysms and 2 emboli), embolectomy (2), or observation. There was no mortality or loss of limb in these patients. This experience underscores the frequent multiplicity of mycotic emboli and/or aneurysms and stresses the importance of empiric angiographic survey to exclude silent yet potentially lethal visceral and cerebral mycotic foci in patients with bacterial endocarditis and peripheral emboli or aneurysms.

Adult↗
PubMed1984

Identification of procalcitonin in a rat medullary thyroid carcinoma cell line.

As a first step in studying the biosynthesis of the peptide hormone calcitonin, we have identified procalcitonin species in CA-77 cells, a newly developed rat medullary thyroid carcinoma cell line. mRNA extracted from the cells directed the synthesis of a putative procalcitonin in a reticulocyte lysate translation system containing microsomal membranes. Both this species and a radiolabeled form of immunoreactive calcitonin from intact cells had the same retention time during reverse phase high performance liquid chromatography. The putative cellular procalcitonin was also immunoprecipitated by antiserum to a synthetic peptide whose sequence constitutes the COOH-terminal 16 residues of preprocalcitonin. The polypeptide had a Mr = 13,400, as estimated by gel filtration chromatography under denaturing conditions. Microsequencing of the [35S]methionine-labeled polypeptide indicated that residues 13, 32, and 34 of procalcitonin were methionine. Similar analysis of the peptide labeled with [3H]proline indicated that residues 2 and 11 of the precursor were proline. The positions of methionine and proline could be aligned in a unique manner with the NH2-terminal half of the preprocalcitonin sequence inferred from cDNA analyses. These results indicate that procalcitonin consists of 111 amino acids and suggest that a 25-residue signal sequence is cotranslationally cleaved from preprocalcitonin. From the procalcitonin sequence we can now predict the sequence of likely biosynthetic intermediates and mature secretory products derived from the NH2-terminal as well as COOH-terminal regions of the precursor.

Amino Acid Sequence↗
PubMed1983

Profile of trimazosin: an effective and safe antihypertensive agent.

Trimazosin, a selective alpha-1-adrenoceptor-blocking agent, has been extensively evaluated in over 1000 patients. In hypertensive patients, reduction in elevated blood pressure in both supine and standing positions, consequent to a reduction in systemic vascular resistance, persisted in long-term therapy. Progression of hypertension target organ damage did not occur. Improvement in blood lipids with decreased total serum cholesterol was noted in long-term therapy. In long-term studies, 74% of patients responded at a trimazosin dose of 300 mg/day or less; the maximum dose was 300 mg/day or less in 52% of patients and 200 mg/day or less in 36%. Most patients received twice a day therapy. The side effect profile of trimazosin was comparable to placebo and significantly better than that of either methyldopa or propranolol. Concomitant disease or therapy did not adversely affect the trimazosin safety profile. Hematology, clinical chemistry, and urinary parameters did not indicate deleterious effects. Because of its excellent safety and toleration profile, trimazosin may be particularly suitable in first-line therapy of patients with mild or moderate hypertension.

Antihypertensive Agents↗
PubMed1982

Calcitonin COOH-terminal cleavage peptide as a model for identification of novel neuropeptides predicted by recombinant DNA analysis.

A strategy is presented for identification of putative neurohormones that were predicted by sequence analysis of recombinant cDNa molecules. The nucleotide sequence of a cloned calcitonin cDNA insert predicts that the proteolytic excision of calcitonin from a 136-amino acid precursor should generate two additional peptides derived from regions flanking the calcitonin sequence on the NH2 and carboxyl termini. The predicted 16-amino acid COOH-terminal cleavage peptide (NH2-Asp-Met-Ala-Lys-Asp-Leu-Glu-Thr-Asn-His-His-Pro-Thr-Phe-Gly-Asn-COOH) was chemically synthesized using solid phase procedures. Antibodies against this synthetic hexadecapeptide detect immunologically cross-reactive material in tissue extracts from normal thyroid glands and calcitonin-producing medullary thyroid carcinomas. Each of the four calcitonin mRNA-directed cell-free translation products contain the immunological determinants for both calcitonin and the COOH-terminal cleavage peptide.

Amino Acid Sequence↗
PubMed1981

A carbohydrate-containing form of immunoreactive calcitonin in transplantable rat medullary thyroid carcinomas.

Extracts of transplantable rat medullary thyroid carcinomas were fractionated by concanavalin A-agarose chromatography and SDS-polyacrylamide gel electrophoresis. While tumor extracts contained mostly (greater than 90%) native calcitonin, 4 distinct larger calcitonin species (Mr = 27,000, 17,000, 13,700, and 9,600) were also observed. Glycoprotein fractions from lectin-affinity chromatography of the tumor extracts contained 0.3-1.5% of the total immunoreactive calcitonin. Gel electrophoresis of the pooled glycoprotein fractions demonstrated that the predominant forms of immunoreactive calcitonin were larger than calcitonin monomer. One high molecular weight species (Mr = 9,600), isolated in sufficient quantity from the polyacrylamide gels for reapplication to concanavalin A-agarose, was specifically eluted from the lectin, indicating that it was a glycoprotein. These results are the first evidence that intact C-cells contain at lest one high molecular weight glycoprotein form of immunoreactive calcitonin and suggest that addition and removal of carbohydrate side chains occur during processing of calcitonin precursors to the native hormone.

Animals↗
PubMed1974

Some biochemical properties of Chinese hamster cells sensitive and resistant to actinomycin D.

A graded series of drug-resistant Chinese hamster sublines has been examined for biochemical changes accompanying resistance to actinomycin D. The most highly resistant subline, DC-3F/AD X, is maintained at 10 microg/ml of the antibiotic. It was shown that over 250 times more actinomycin D is required to inhibit RNA synthesis in this subline than in the parental DC-3F line. The DC-3F/AD X subline was also shown to have a somewhat reduced capacity to transport uridine as compared to parental cells. Sensitive cells took up over 50 times more tritiated antibiotic than the most resistant cells, as determined in a 1-h assay. Uptake of actinomycin D was shown to be temperature-dependent in both resistant and sensitive cells and was not influenced by various metabolic inhibitors. Resistance could not be explained by a rapid uptake and release of the antibiotic, as demonstrated in efflux experiments, or by its metabolism. In addition, highly resistant cells which are cross-resistant to puromycin were shown to have a reduced capacity to take up labeled puromycin. These studies provide further evidence indicating that the mechanism of resistance to actinomycin D is reduced permeability to drug and suggesting that cell membrane alteration accounts for resistance to both actinomycin D and puromycin.

Animals↗
PubMedDate not supplied

Teaching basic ethical concepts and decision-making: a staff development application.

Academic nursing programs are increasing the amount of ethical instruction presented to undergraduate and graduate students. However, nurses who graduated several years ago may find themselves without the background and skills needed to discuss the complex bioethical dilemmas they now face. This article presents the development of a continuing education program to acquaint nurses with basic ethical concepts and bioethical decision-making processes. Presentations were piloted with a small group of nurses from the outpatient department of a pediatric tertiary care hospital.

Decision Making↗