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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 127 records · Page 7Linked to original sources
PubMed1995

Cost analysis of immunomagnetic marrow purging for neuroblastoma: in-house purging versus submission to purging centers.

High-dose chemoradiotherapy in conjunction with autologous bone marrow transplantation has been used in the treatment of advanced stage neuroblastoma. Because of frequent marrow involvement, marrow purging methods, such as the immunomagnetic technique, have been developed. Current cost constraints force institutions to consider in-house purging versus submission of marrow to purging centers. Our analysis demonstrates that 15 procedures per year are needed to justify an up-front investment in equipment and supplies with a break-even period of 5 years. This number is also required to keep technical proficiency current without frequent retraining of personnel. The analysis includes start-up costs for institutions without a bone marrow processing laboratory, as well as for institutions already processing marrow or peripheral blood stem cells. For institutions performing fewer procedures per year, submission of marrow to purging centers is more cost effective than in-housing purging.

Bone Marrow Purging↗
PubMed1995

Effects of energy restriction and exercise on skeletal muscle and adipose tissue in women as measured by magnetic resonance imaging.

The effects of energy restriction alone (diet alone, DO) and energy restriction combined with endurance exercise (diet and exercise, DE) on lean tissue (LT), skeletal muscle (SM), and adipose tissue (AT) were evaluated in 24 obese women (DO, n = 12; DE, n = 12). The prescribed diet created an estimated daily deficit of 4.19 MJ (1000 kcal). LT, SM, and AT were measured by using magnetic resonance imaging (MRI). The weight loss observed for the DO group (-10.0 +/- 4.0 kg) was not significantly different from that of the DE group (-11.7 +/- 3.0 kg). However, the composition of the weight loss was significantly different between groups because the DE group lost significantly greater (P = 0.05) quantities of AT (-11.3 +/- 3.8 L) than the DO group (-8.3 +/- 3.6 L). Furthermore, whereas LT measured by MRI was maintained in the DE group, a modest (approximately 4%) but significant (P < 0.01) reduction in LT was observed in the DO group. Similarly, measurement of SM by MRI in the appendicular region revealed a preservation of SM in the DE group, but a significant (P < 0.01) reduction in the DO group. Maximal oxygen consumption (L) was significantly improved (approximately 9%) in the DE group (P < 0.01). These findings provide evidence that the combination of energy restriction and exercise result in a greater reduction of AT and preservation of LT and SM compared with energy restriction alone.

Adipose Tissue↗
PubMed1995

Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy.

The advanced lesions of atherosclerosis occlude the affected artery by increasing the thickness of the intima. The focal thickening of the intima is due to a large increase in smooth muscle cells, formation of new connective tissue matrix by these smooth muscle cells and, in hyperlipidemic individuals, the accumulation of intracellular and extracellular lipid. Additionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury" may lead to cellular infiltration and proliferation. Localized cellular infiltration of monocytes and T cells may be due to changes in adhesive properties of the endothelial surface, involving the expression of specific adhesion molecules. The directed cell migration and proliferation may represent the cells' response to polypeptide growth factors, acting singly or in concert. These peptide growth factors also modulate matrix synthesis and degradation, angiogenesis, cell-cell adhesion and cellular metabolism, including lipid uptake. In atherosclerosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface receptors are expressed at low or undetectable levels. Their up-regulation in early and developing atherosclerotic lesions suggests a pathogenic role for these molecules. Increased levels of isoflavonoids, in particular genistein, which are associated with consumption of soy-based diets, inhibit cell adhesion, alter growth factor activity and inhibit cell proliferation involved in lesion formation.

Animals↗
PubMed1995

Similar distribution of trans fatty acid isomers in partially hydrogenated vegetable oils and adipose tissue of Canadians.

The objective of this study was to evaluate the composition of trans fatty acids in the subcutaneous fat of Canadians relative to the composition of dietary sources of trans fatty acids. The fatty acid composition, total trans acid content, and the geometric and positional isomer distribution of unsaturated fatty acids of subcutaneous adipose tissue of Canadians were determined using a combination of capillary gas-liquid chromatography and silver nitrate thin-layer chromatography. The mean total trans fatty acid content was 6.80% at the abdominal site and 5.80% at the lateral thigh site. Total trans isomers of linoleic acid (18:2n-6) were present at 1.17% in abdominal and 1.59% in thigh adipose tissue, with 9c.12t-18:2 being the most prevalent isomer followed by 9c-13t-18:2 and 9t,12c,-18:2. The oleic acid (18:1) trans isomer distribution in adipose tissue differed from that in butter fat, but it was similar to that in partially hydrogenated vegetable oils. The reverse was true for the 18:1 cis isomers. Total 18:1 trans isomers were inversely related to 18:2n-6 content in adipose tissue, suggesting the trans fatty acid intake is inversely related to the intake of linoleic acid. Partially hydrogenated vegetable oils appear to be the major source of trans fatty acids in adipose tissue of Canadians.

Adipose Tissue↗
PubMed1995

Cell biology of atherosclerosis.

The process of atherosclerosis is a life-threatening disease that affects critical organs including the heart and brain. It results from the influence of noxious agents associated with hyperlipidemia, hypertension, diabetes, cigarette smoking, homocysteinemia, and other agents that may, in altering the homeostatic condition of the artery wall, injure the endothelium and smooth muscle. The result is a protective, inflammatory, fibroproliferative response that becomes excessive and in its excess results in the disease process we call atherosclerosis.

Animals↗
PubMed1995

Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. II. Cellular composition and proliferation.

In nonhuman primates (Macaca nemestrina) treated with the antioxidant probucol during diet-induced hypercholesterolemia, intimal lesion area in the thoracic aorta was decreased, with increased resistance of plasma LDL to oxidation. The cellular and molecular changes associated with the decrease in lesion size in the probucol-treated hypercholesterolemic animals are quantitatively evaluated in this study. Lesions from the probucol-treated animals appear less mature and have altered lipid distribution. Abundant lipid-laden smooth muscle cells are found in the intima and media of the probucol-treated animals, with fewer medial lipid-laden macrophages, compared with lesions at similar sites in the control hypercholesterolemic animals. In both the control and probucol-treated animals, macrophages are the predominant cells in most lesions, but the ratio of macrophages to smooth muscle cells is decreased in the lower thoracic and upper abdominal aortic sites in the probucol-treated animals. Lesions at all aortic sites in the probucol-treated animals have a 35% to 80% reduction in the percentage of cells in cell cycle traverse, as indicated by immunostaining for proliferating cell nuclear antigen (% PCNA-positive). In both groups, macrophages and smooth muscle cells are PCNA-positive, but the majority (> 60%) are macrophages. No difference in % PCNA-positive cells is seen in the iliac arteries, where the most advanced lesions were present at the time probucol administration was initiated. Limited Northern analysis of growth-regulatory molecules possibly involved in the cellular changes associated with lesions shows a 30% to 50% decrease in mRNA levels of platelet-derived growth factor (PDGF) B-chain, PDGF beta-receptor, colony-stimulating factor type 1, and monocyte chemotactic protein 1. Thus, a potential role for an antioxidant such as probucol in the treatment of atherosclerosis may be to alter the early inflammatory fibroproliferative processes of the disease. Whether these effects are directly related to the antioxidant properties or some other activity of probucol is not yet known.

Animals↗
PubMed1995

The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro.

Osteopontin is an arginine-glycine-aspartate containing acidic glycoprotein postulated to mediate adhesion, migration, and biomineralization in diverse tissues. The mechanisms explaining this multifunctionality are not well understood, although it is known that one osteopontin receptor is the alpha v beta 3 integrin. In this work, we studied human smooth muscle cells varying in alpha v beta 3 levels to identify additional osteopontin receptors. We report that, in addition to alpha v beta 3, both alpha v beta 5 and alpha v beta 1 are osteopontin receptors. Moreover, the presence or absence of alpha v beta 3 on the cell surface altered the adhesive and migratory responses of smooth muscle cells to osteopontin. Adhesion of alpha v beta 3-deficient cell populations to osteopontin was only half that of cells containing alpha v beta 3, and migration toward an osteopontin gradient in the Boyden chamber was dependent on cell surface alpha v beta 3. Although alpha v beta 3-deficient smooth muscle cells were unable to migrate to osteopontin, they did migrate significantly in response to vitronectin and fibronectin. These findings represent the first description of alpha v beta 5 and alpha v beta 1 as osteopontin receptors and suggest that, while adhesion to osteopontin is supported by integrins containing beta 1, beta 3, and beta 5, migration in response to osteopontin appears to depend on alpha v beta 3. Thus, interaction with distinct receptors is one mechanism by which osteopontin may initiate multiple functions.

Adult↗
PubMed1995

Development and testing of nursing home quality indicators.

In this article, the authors report on the development and testing of a set of indicators of quality of care in nursing homes, using resident-level assessment data. These quality indicators (QIs) have been developed to provide a foundation for both external and internal quality-assurance (QA) and quality-improvement activities. The authors describe the development of the QIs, discuss their nature and characteristics, address the development of a QI-based quality-monitoring system (QMS), report on a pilot test of the QIs and the system, comment on methodological and current QI validation efforts, and conclude by raising further research and development issues.

Accidental Falls↗
PubMed1995

Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease.

The liver is the major source of circulating insulinlike growth factor-I (IGF-I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability. We aimed to assess the direct effects of liver dysfunction on serum levels of IGF-1 and its major binding proteins by measuring fasting levels of growth hormone, IGF-1, IGFBP-1, IGFBP-3, insulin, C peptide, and glucose in 35 patients with cirrhosis and during an oral glucose tolerance test in 16 of those patients. Serum levels of growth hormone (GH) were high in the patients: median, 12.0 mU/L (range, 1 to 87) compared with normals, 0.95 mU/L (0.1 to 20) (P < .0005) and serum IGF-1 levels were low: 81 ng/mL (38 to 153) versus 193 ng/mL (151 to 235) (P < .0001). Serum IGFBP-3 levels were low in the patients: 1.59 mg/L (0.46 to 4.43) compared with normals, 5.41 (4.34 to 6.11) (P < .0001), and there was a significant negative correlation between IGFBP-3 levels and Childs Pugh score (r = .63 P < .0001). Fasting IGFBP-1 levels were significantly higher in the patients 31 ng/mL (11 to 92) than normals, 14 (7 to 20) (P < .0001). There was no correlation between fasting insulin and IGFBP-1 levels despite high fasting insulin levels. A decrease in IGFBP-1 levels was seen during the glucose tolerance test (GTT) in all patients. In conclusion, there are significant changes in the levels of two of the major IGF-1 binding proteins that may further limit the bioavailability of already low circulating IGF-1 levels. Substrate availability appears to be a stronger influence on fasting IGFBP-1 levels than does insulin, and the close correlation of IGFBP-3 with liver function indicates a dominant regulatory role of the hepatocyte.

Adult↗
PubMed1995

Restriction fragment length polymorphism of the apolipoprotein B gene and response to dietary fat and cholesterol.

OBJECTIVE: The relationship between response to dietary fat and cholesterol, and the EcoRI restriction fragment length polymorphism (RFLP) of the apolipoprotein B(apoB) gene was examined. DESIGN: Forty-nine free-living subjects took part in a prospective double-blind crossover dietary intervention study. The apoB EcoRI cutting site was present in five women and 18 men (E+) and absent in 15 women and 11 men (E-). INTERVENTION: Subjects consumed a low fat (25% energy), low cholesterol (less than 200 mg/day) diet. After two weeks on this background diet (baseline) subjects were randomly assigned to consume a liquid supplement for three weeks which was either fat and cholesterol free or which contained fat (30 to 36 g) and cholesterol (650 to 780 mg). After the first three-week period subjects switched to the other supplement. Blood samples were collected for plasma lipid analysis after an overnight fast on two consecutive days at the end of baseline and on three consecutive days after each three-week supplement period. RESULTS: There was no significant difference in response to diet between the RFLP groups. Changes in plasma total, low density lipoprotein (LDL), high density lipoprotein(HDL), HDL2 and HDL3 cholesterol or plasma triglyceride were not different between the two RFLP groups. There was a significant difference between RFLP groups for baseline HDL2-cholesterol (0.31 +/- 0.04 and 0.16 +/- 0.02 mmol/L for E- and E+ subjects, respectively) which was independent of sex and apoE genotype (P = 0.032). CONCLUSIONS: These results indicate that the EcoRI RFLP of the apoB gene is not associated with response to dietary fat and cholesterol.

Apolipoproteins B↗
PubMed1995

Response of total and regional lean tissue and skeletal muscle to a program of energy restriction and resistance exercise.

We evaluated the effects of energy restriction and resistance exercise on lean tissue (LT), skeletal muscle (SM) and adipose tissue (AT) in fourteen obese women. The prescribed diet created a daily 1000 kilocalorie (4.18 MJ) deficit. LT, SM and AT were measured using a magnetic resonance imaging (MRI) model whereby 41 transverse images were acquired over the entire body. Although significant (P < 0.01) losses were observed for bodyweight (-10.4 +/- 2.7 kg), and total AT volume (-9.8 +/- 2.5 l), no significant changes were observed for whole body LT (P > 0.05). For MRI-LT this observation remained true for upper and lower body regions. Measurement of MRI-SM in the appendicular region revealed that SM was preserved in both the arm and leg regions (P > 0.05). These findings provide evidence that lean tissues, in particular skeletal muscle, are preserved and adiposity is substantially reduced in response to weight loss induced by the combination of resistance exercise and moderate energy restriction.

Adipose Tissue↗
PubMed1994

Platelet-derived growth factor (PDGF) receptor alpha-subunit mutant and reconstituted cell lines demonstrate that transforming growth factor-beta can be mitogenic through PDGF A-chain-dependent and -independent pathways.

Mitogenic stimulation of connective tissue cells by transforming growth factor-beta (TGF-beta) has two unusual properties; entry into S-phase is delayed compared with that induced by other mitogens, and the dose response is biphasic, with low concentrations stimulating and high concentrations inhibiting or having no effect. A hypothesis that provides an explanation for both of these properties is that TGF-beta stimulates proliferation indirectly by inducing synthesis of platelet-derived growth factor (PDGF) A-chain, which in turn stimulates proliferation via autocrine activation of the PDGF receptor alpha-subunit (PDGFR alpha). High concentrations of TGF-beta reduce PDGFR alpha expression and break the autocrine loop. We tested this hypothesis by determining whether TGF-beta and interleukin-1 alpha can induce DNA synthesis in connective tissue (3T3) cells derived from the Patch mouse line in which the PDGFR alpha gene is deleted. We found that these cells do respond mitogenically to TGF-beta and interleukin-1 alpha, indicating that PDGF A-chain induction is not the sole mechanism of mitogenic stimulation. Reestablishing PDGFR alpha expression via transfection with a human PDGFR alpha construct enhanced the response to TGF-beta. Neutralizing anti-PDGF antiserum reduced TGF-beta stimulation of PDGFR alpha-expressing 3T3 cells by about 35%. We conclude that induction of PDGF A-chain/PDGFR alpha autocrine stimulation does contribute to the ability of TGF-beta to stimulate connective tissue cells, but that there is, in addition, a PDGF-independent pathway.

3T3 Cells↗
PubMed1994

Comparison of clinical outcomes for women and men after acute myocardial infarction. The Thrombolysis in Myocardial Infarction Investigators.

OBJECTIVES: To assess differences in morbidity and mortality between men and women with acute myocardial infarction treated with thrombolytic therapy and the relation of differences to baseline patient characteristics and clinical features. DESIGN: Secondary analysis of observational findings among women and men enrolled in a clinical trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction Phase II trial. MEASUREMENTS: Recurrent infarctions and deaths were assessed. MAIN RESULTS: The 6-week mortality rate was greater for women than for men (9% compared with 4%; adjusted relative risk, 1.54; P = 0.01). Death or reinfarction occurred in 15.9% of women and 9.5% of men (adjusted relative risk, 1.33; P = 0.02). Among patients enrolled for treatment with 100 mg of recombinant tissue plasminogen activator and assigned to a conservative strategy of watchful waiting with appropriate backup, the 6-week incidence of death was 7.5% for women and 3.8% for men (P = 0.01). The 6-week incidences of death or reinfarction were 14.2% and 8.9% (P = 0.01) among women and men, respectively. CONCLUSIONS: Among patients in the Thrombolysis in Myocardial Infarction Phase II Trial, who all were diagnosed with myocardial infarction and were eligible to receive thrombolytic therapy, women had higher rates of mortality and morbidity than did men. Older age at the time of myocardial infarction and a history of diabetes accounted for much but probably not all of this difference.

Age Factors↗
PubMed1994

Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes.

Lysophosphatidylcholine is increased in the plasma of hypercholesterolemic patients, is a component of oxidatively modified low-density lipoprotein, and, as such, may play an important role in atherosclerosis. Here we demonstrate that in human monocytes, lysophosphatidylcholine increases the level of mRNA encoding the heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle mitogen. Lysophosphatidylcholine treatment also enhances the release of heparin-binding mitogenic activity by these cells in culture. The anti-inflammatory glucocorticoid dexamethasone inhibits the upregulation of HB-EGF mRNA induced by either lysophosphatidylcholine or bacterial lipopolysaccharide in cultured monocytes. However, the responses induced by lysophosphatidylcholine and by lipopolysaccharide differ in their kinetics. In addition, the response to lysophosphatidylcholine is resistant to the action of cycloheximide, whereas the response to lipopolysaccharide is not, suggesting that the activation mechanisms induced by these two stimuli are different. Since a nuclear run-on assay showed no effect of lysophosphatidylcholine on the transcription of the HB-EGF gene, we speculate that lysophosphatidylcholine may increase the level of HB-EGF mRNA by altering the processing or degradation of primary or mature transcripts. Lysophosphatidylcholine enhancement of monocyte production of HB-EGF may represent an important result of the interactions among oxidized low-density lipoprotein and monocyte-derived macrophages and may play a role in initiation of smooth muscle proliferation in atherogenesis.

Arteriosclerosis↗
PubMed1994

Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines.

Platelet-derived growth factors (PDGF) are potent regulators of cell proliferation. The three isoforms of PDGF AA, AB, and BB are encoded by two genes: PDGF A and PDGF B. The v-sis oncogene is homologous to the PDGF-B gene. v-sis can transform cells that express the appropriate PDGF receptors. Two different types of receptors, PDGF-alpha and PDGF-beta, also encoded by two genes, have been identified. We show that two cell lines. SMS-SB and NALM-6, both derived from pre-B-cell acute lymphocytic leukemias, express the PDGF-A chain gene, and one of them, SMS-SB, releases PDGF-A chains into the media. The SMS-SB cells also express the PDGF-beta receptor, whereas NALM-6 cells express the PDGF-alpha receptor and bind PDGF. This extends the possible targets for PDGF to the B-cell lineage lymphocytes.

Humans↗
PubMed1994

Structural equation modeling and nested ANOVA: effects of lead exposure on maternal and fetal growth in rats.

This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth.

Analysis of Variance↗