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Biomedical subjects

J O'Neil

Publications and source records attributed to J O'Neil.

At least 73 records · Page 4Linked to original sources
PubMed1991

Macrophage degradation of LDL extracted from human aortic plaques: effect of isolation conditions.

Several laboratories have recently reported on the structural and functional characteristics of an LDL fraction isolated from atherosclerotic lesions, designated A-LDL. Given the wide variety of tissue sources and isolation conditions that have been employed, we have addressed whether several procedures currently used affect the interaction of A-LDL with macrophages, and, if so, by what mechanisms. We isolated A-LDL from human aortic plaques by ultracentrifugation and gel filtration chromatography. Although some differences in the chromatographic elution profiles on gel filtration were apparent between homogenized and nonhomogenized extracts, A-LDL isolated from the same pool of plaque minces with or without homogenization showed no differences in macrophage degradation or inhibition of this degradation by excess acetyl-LDL. A-LDL isolated from plaques obtained at surgery or at autopsy less than 12 hr after death also showed no major differences in macrophage recognition, suggesting that post-mortem changes were probably not affecting cell recognition. However, A-LDL particles underwent aggregation when subjected to concentration, when stored for periods of 2 weeks or more, or when subjected to vortexing. The aggregated A-LDL was degraded more readily by macrophages than unaggregated A-LDL, and inhibition of degradation of aggregated A-LDL by excess acetyl-LDL was less than for unaggregated A-LDL. Collectively, these studies show that although post-mortem changes and tissue homogenization do not appreciably affect the interaction of A-LDL with macrophages in culture, other isolation and preparation conditions have dramatic effects which could explain some of the diversity of A-LDL metabolism reported in the literature.

Animals↗
PubMed1991

The effectiveness of an intervention to promote successful performance on NCLEX-RN for baccalaureate students at risk for failure.

This study evaluated the effectiveness of an intervention designed to enhance the performance of high-risk baccalaureate students on the National Council Licensure Examination for Registered Nurses (NCLEX-RN). Thirty senior nursing students met risk criteria drawn from the NCLEX-RN prediction literature: a nursing grade point average (GPA) of 2.40 or below, a ranking on the Mosby Assesstest at or below the 20th percentile, and/or a diagnosed learning disability. Fourteen students in this nonrandomized, posttest-only study received the intervention. Sixteen students served as a control group. The groups were equivalent on 12 academic variables prior to treatment. Concepts of test-wiseness and test-coaching served as the basis for the intervention. The NCLEX-RN passing rate for the group participating in the intervention was 92.9% compared to 50% for the control group. The findings of this study provide preliminary evidence that a long-term intervention can assist high-risk students in passing the NCLEX-RN.

Adult↗
PubMed1990

Macrophage uptake of cholesterol-containing particles derived from LDL and isolated from atherosclerotic lesions.

A variety of different cholesterol-rich particles with different physical and chemical structures can be isolated from human atherosclerotic lesions. Many of these particles are internalized in an unregulated fashion by macrophages in culture, leading to lipid loading of these cells. However, the in vivo relevance of this uptake is still uncertain. In this overview, we have summarized data obtained primarily in our laboratory on low density lipoprotein (LDL)-like particles (A-LDL) and large cholesterol-rich droplets isolated from human atherosclerotic lesions. Based on our studies, we propose a variety of different mechanisms of uptake. A-LDL can be internalized by the LDL receptor or the scavenger receptor on macrophages in culture; the latter uptake mechanism can lead to lipid loading. In addition, at high concentrations A-LDL can undergo aggregation, possibly due to intermolecular cross-bridging by aldehydes released during oxidation of these particles. The aggregates are subsequently internalized by macrophages by phagocytosis, a process which appears to be independent of the LDL or scavenger receptor. By contrast, arterial smooth muscle cells do not take up these aggregates. Large cholesteryl ester-rich particles isolated from human lesions, and derived from LDL that had been degraded by hydrolytic enzymes in the extracellular space of the arterial wall, or from inclusions released from lysed foam cells, are also internalized via phagocytosis by macrophages in culture. Since some of these particles contain apoliproteins and/or proteins that are ligands for receptors on macrophages, initial receptor-mediated binding may precede and facilitate subsequent phagocytosis in some cases. Uptake of the diverse group of cholesteryl ester-rich particles in plaques can induce lipid loading of macrophages and therefore may lead to further growth of the atherosclerotic plaque.

Arteriosclerosis↗
PubMed1989

Effects of hypoglycemia and prolonged fasting on insulin and glucagon gene expression. Studies with in situ hybridization.

In situ hybridization of proinsulin and proglucagon mRNA was performed in rat pancreas to assess prohormone gene expression during various glucopenic conditions. During a 4-d fast mean blood glucose declined by 48 mg/dl; proinsulin mRNA signal density remained normal while proglucagon mRNA signal density more than doubled. At the end of a continuous 12-d insulin infusion blood glucose averaged 53 +/- 12 mg/dl; proinsulin mRNA signal density declined to 30% of controls while proglucagon mRNA signal density more than doubled. In insulinoma-bearing NEDH rats blood glucose averaged 34 +/- 3.5 mg/dl; the proinsulin mRNA signal was virtually undetectable and proglucagon mRNA signal density was more than twice the controls. There was no detectable change in either beta-cell area or islet number in rats subjected to fasting or insulin infusion, but in insulinoma-bearing rats beta cell area was markedly reduced. Thus compensation during 4 d of starvation involves an increase in glucagon gene expression without change in insulin gene expression or beta cell mass. In moderate insulin-induced hypoglycemia glucagon gene expression is increased and insulin gene expression decreased. In more profound insulinoma-induced hypoglycemia, in addition to the foregoing changes in hormone gene expression, there is a profound reduction in the number of insulin-expressing cells.

Animals↗
PubMed1989

Excessive burden of end-state renal disease among Canadian Indians: a national survey.

Analysis of data from the Canadian National Renal Failure Register indicates that Canadian Natives are at much higher risk for end-stage renal disease (ESRD) than the Canadian population in general. Using two population estimates for the total Native population, the age-standardized incidence rate of newly registered ESRD cases between 1981 and 1986 among Natives was at least 2.5 times (and may be as high as four times) the national rate. Natives were particularly at higher risk for ESRD to diabetes, glomerulonephritis, and pyelonephritis, whereas for the other causes the risk was no different from that of other Canadians. As technologically sophisticated treatment facilities are only available in major urban centers, Native ESRD patients and their families living in remote areas of Canada are faced with major psychosocial disruptions of relocation.

Canada↗
PubMed1988

Extracts of human atherosclerotic lesions can modify low density lipoproteins leading to enhanced uptake by macrophages.

Plasma low density lipoproteins (LDL) and/or other lipoproteins containing apo B that accumulate in atherosclerotic lesions of human aortas exhibit structural changes that are associated with enhanced uptake in an unregulated fashion by macrophages in culture, resulting in the formation of foam cells in vitro. In an attempt to better characterize the structure-function modifications, we have incubated plasma LDL with extracts of human atherosclerotic plaques obtained at surgery, and determined whether such plaque-modified LDL also demonstrates enhanced uptake by cultured mouse peritoneal macrophages (MPM). Enhanced uptake was found which was linear over a concentration range of 100 micrograms lipoprotein protein/ml, as assessed by enhanced degradation of [125I]LDL and by stimulation of cholesterol esterification. Extracts of non-arterial human tissue were unable to induce this modification, suggesting tissue specificity. When delipidated apo B from tissue-treated [125I]LDL was subjected to SDS-PAGE, autoradiograms demonstrated, in addition to the B-100 band of apo B, a doublet of higher molecular weight than B-100 and a band just entering the gel, both at the expense of the B-100 band. No lower molecular weight bands suggestive of apo B degradation were seen. Modest increases in LDL electrophoretic mobility and thiobarbituric acid reactive substances were found following the incubation of LDL with plaque extracts. These changes could be inhibited by butylated hydroxytoluene (BHT), suggesting that free radical-induced lipid peroxidation was responsible for these modifications. However, since BHT did not inhibit the uptake of the tissue-incubated LDL by macrophages, the actual modification responsible for enhanced macrophage recognition did not appear to be free radical-induced. Uptake of plaque-modified [125I]LDL was inhibited by only 22% by a 20-fold excess of acetyl LDL or plaque-modified LDL. If the latter did not represent a mixture of modified and unmodified particles, this result would suggest that uptake was not mediated by the scavenger receptor. It is possible that foam cells are formed in vivo when LDL particles, which have been modified by interacting with components of the arterial wall, are taken up by tissue macrophages.

Animals↗
PubMed1988

Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients.

Although the serum lipoprotein fraction Lp(a) has been associated with coronary artery atherosclerosis, its relationship to narrowing of saphenous vein grafts has not previously been elucidated. We therefore measured serum Lp(a) levels in 167 symptomatic patients undergoing cardiac catheterization who had had coronary artery bypass surgery 0.7 to 14.3 years earlier. Lp(a), total cholesterol, and total triglyceride levels were compared with the degree of saphenous vein graft stenosis to test for any association. Serum Lp(a) levels were significantly associated with the degree of stenosis of saphenous vein grafts (r = .24, p = .002). Mean Lp(a) levels (mg/dl) in the 135 patients with stenosis were almost double (32.0 +/- 32.7, mean +/- SD) those in the 32 patients with no graft stenosis (16.7 +/- 22.6; p = .002). Graft stenosis was not associated with previous myocardial infarction, hypertension, obesity, diabetes, or smoking. Serum cholesterol levels (mg/dl) were slightly higher in the stenosis group (251.3 +/- 69) than in the no-stenosis group (231.8 +/- 48.8), but the difference was of borderline significance (p = .06). A stepwise increase in mean Lp(a) was found in groups of patients with increasing vein graft stenosis. At a serum Lp(a) level of 31.6 mg/dl or above, 92% of the patients demonstrated vein graft stenosis. Thus, patients with elevated Lp(a) levels have an increased risk of developing saphenous vein graft stenosis after coronary bypass surgery.

Cardiac Catheterization↗
PubMed1988

Treatment of tumors of the thoracic and lumbar spinal column.

From December 1981 to February 1986, 33 patients with tumorous conditions of the spine were treated with anterior, posterior, or combined anterior and posterior surgical techniques. Breast metastases were by far the most common condition, accounting for more than 51% of patients with metastatic spinal disease. The surgeon treating tumorous conditions of the spine must be aware that, to date, the treatment is palliative only. The goals of the surgery and treatment are to reduce pain, preserve or improve neurologic function, and allow early mobilization. Survival overall averaged 9.1 months. Of the 14 patients who had anterior decompression alone, average survival time was 9.9 months. The 14 patients who had posterior procedures had an average survival time of 11.9 months. Five patients treated with combined anterior and posterior procedures survived 9.6 months. Fifteen patients with multiple-level spinal involvement survived 7.9 months, compared with 12.9 months for the 18 patients with single-level spinal involvement. Aggressive surgical treatment definitely improves the quality of life of patients with cord compression or unstable spinal segments secondary to bony destruction. An aggressive approach is indicated because it permits most patients to spend the remainder of their lives relatively pain-free and with intact spinal cord function.

Adult↗
PubMed1988

Thoracolumbar fractures in ankylosing spondylitis. High-risk injuries.

Ankylosing spondylitis may affect the spine segmentally or diffusely. Because all the ligaments become ossified in the involved areas, fractures that occur through this involved segment traverse both bone and ligaments, producing an extremely unstable situation similar to a shearing type of fracture. With a pre-existing severe kyphosis, it may be dangerous to turn the patient to a supine position, because this opens up the fracture and can cause neurologic complications. The radiologic assessment of the spine in ankylosing spondylitis is difficult because the bone is frequently osteoporotic and the disc spaces are poorly outlined. Minor displacements should be looked for, as well as discontinuity of ossified ligaments (especially the interspinous ligaments). Of the seven patients reported in this series, six had fractures undiagnosed at the time of the preliminary examination. Therefore, patients known to have ankylosing spondylitis should be counseled regarding the possibility of a fracture, and if pain persists after an injury, they should be thoroughly investigated radiologically to rule out a potentially serious problem. Reduction of the displacement and stabilization is best achieved with a Luque rectangular rod system, and laminectomy is not indicated.

Accidental Falls↗
PubMed1988

A contoured anterior spinal fixation plate.

There is a need for a specifically designed plate for anterior fixation of the vertebral bodies, contoured to fit closely around the lateral aspect of the spine and wide enough to allow multiple options for placement of at least three screws in each vertebra. The large-diameter cancellous screws should penetrate the opposite cortex. Existing bone plates are inadequate, because they are too narrow and do not allow positioning of more than two screws in each vertebra. The Biomedical Engineering Department of the National Research Council of Canada designed and tested the plate described in this article, with particular attention to providing smooth surfaces to prevent vascular complications. Three lengths of plates have been developed and are used in the area from T11 to L5, with a specific tapered plate for the L5 area to prevent contact with the overlying iliac vessels. This device should be used for stabilization following corpectomy for tumor, decompression of burst fractures, severe disc degeneration, pseudarthrosis, and the multiply operated back.

Adult↗
PubMed1987

Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation of the MAK16 gene and analysis of an adjacent gene essential for growth at low temperatures.

MAK16 is an essential gene on chromosome I defined by the thermosensitive lethal mak16-1 mutation. MAK16 is also necessary for M double-stranded RNA replication at the permissive temperature for cell growth. As part of an effort to clone all the DNA from chromosome I, plasmids that complemented both the temperature-sensitive growth defect, and the M1 replication defects of mak16-1 strains were isolated from a plasmid YCp50: Saccharomyces cerevisiae recombinant DNA library. The two plasmids analysed contained overlapping inserts that hybridized proportionally to strains carrying different dosages of chromosome I. Furthermore, integration of a fragment of one of these clones occurred at a site linked to ade 1, confirming that this clone was derived from the appropriate region of chromosome I. An open reading frame adjacent to MAK16 potentially coding for a 468 amino acid protein was defined by sequence analysis. 185 amino acids of this open reading frame were replaced with a 1.2 kb fragment carrying the S. cerevisiae URA3 gene by a one-step gene disruption. The resulting strains grew at a rate indistinguishable from the wild type at 20 degrees C, 30 degrees C, or 37 degrees C, but could not grow at 8 degrees C. The deleted region is thus essential only at 8 degrees C, and we name this gene LTE1 (low temperature essential).

Base Sequence↗
PubMed1986

Inhibition of vasoactive substances in experimental endotoxin shock.

Using the endotoxin shock model in mongrel dogs, the effects of a cyclooxygenase antagonist (diclofenac sodium) and an antihistamine (chlorpheniramine) were evaluated. Both drugs significantly raised the mean arterial pressure and systemic vascular resistance. The vasomotor activity of histamine appeared to be independent from the one mediated by prostaglandins (cyclooxygenase pathway) since the effect was additive during the first 60 minutes. Yet at 120 minutes only diclofenac sodium continued to be effective, suggesting a sustained role of prostaglandins in the pathophysiology of endotoxin shock.

Animals↗