Biomedical subjects

M R Adams

Publications and source records attributed to M R Adams.

At least 37 records · Page 2Linked to original sources

PubMed2000

Pathophysiology of atherosclerosis: development, regression, restenosis.

There is now a very large number of patients with coronary artery disease who have also undergone percutaneous interventions such as coronary angioplasty. Atherosclerosis and restenosis are two distinct pathologic processes with different underlying pathophysiologic mechanisms, different natural histories, different clinical presentations, and treatment strategies. Management strategies to target both processes are currently poorly applied in clinical practice. The development of integrated management strategies to target atherosclerosis, as well as restenosis in the postprocedural period remains a priority.

Arteriosclerosis↗

PubMed2000

Low-dose contraceptive estrogen-progestin and coronary artery atherosclerosis of monkeys.

OBJECTIVE: To determine the separate and combined effects of the estrogen and progestin components of a modern triphasic oral contraceptive (OC) formulation on extent of coronary artery atherosclerosis. METHODS: Female cynomolgus monkeys (n = 81) were fed atherogenic diets for 32 months. After the first 7 months, they were randomized to four groups and treated triphasically for 21 of each 28 days with ethinyl estradiol (E2) (monkey equivalent of 30-40 microg), levonorgestrel (monkey equivalent of 50-125 microg), a combination of the two steroids, or placebo. RESULTS: Treatment with estrogen alone reduced coronary artery atherosclerosis extent 67% compared with untreated controls (P <.05). Treatment with progestin alone had no effect (P >.20). While atherosclerosis extent in monkeys treated with the combined OC was reduced 28%, this did not differ statistically from the other groups (P >.20). CONCLUSION: In doses used for oral contraception, E2, like all other estrogens studied to date, has a marked inhibitory effect on atherosclerosis progression. Levonorgestrel, at doses used in modern OC formulations, antagonizes this effect. When considered with other experimental evidence, these findings support the concept that progestins used in OCs and hormone replacement therapy can antagonize estrogen's atheroinhibitory effects. Whether this occurs seems to depend on a relative balance between estrogen and progestin with respect to dose, potency, route, and pattern of administration. However, when considered with evidence from previous studies, the findings also indicate a modest atheroinhibitory influence of combination (estrogen-progestin) OCs.

Animals↗

PubMed2000

Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect.

OBJECTIVES: To test the hypothesis that antioxidant therapy would improve endothelial function in smokers. BACKGROUND: Several studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known. METHODS: We studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 +/- 6 years, 8 male subjects, 21 +/- 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit. RESULTS: At baseline, plasma ascorbate level was low in the smokers (42 +/- 21 micromol/liter; normal range, 50 to 150 micromol/liter), increased with vitamin C therapy after 2 h to 120 +/- 54 micromol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 +/- 32 micromol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 +/- 2.0% to 6.3 +/- 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 +/- 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout. CONCLUSION: Oral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels.

Administration, Oral↗

PubMed2000

Transient sensitivity to nisin in cold-shocked Gram negatives.

Rapid chilling in the presence of nisin caused a dose-dependent reduction in the populations of several Gram-negative bacteria, despite the fact that appreciable structural injury to the outer membrane was not detected. Pseudomonas aeruginosa was most affected, followed by Pseudomonas fragi, Salmonella enteritidis PT4, PT7 and Escherichia coli, respectively. Addition of nisin after the chilling treatment had no effect. The results are ascribed to a transient susceptibility caused by phase changes in the lipids associated with the outer membrane, which are rapidly reversed when the cells return to higher temperatures. Combinations of chilling shock, nisin and EDTA gave much lower reductions of Salmonella and Pseudomonas on chicken skin in comparison with broths. This is attributed to a buffering of the temperature shock experienced by adherent bacteria and binding of the nisin by food particles.

Animals↗

PubMed2000

Detecting failed WBC-reduction processes: computer simulations of intermittent and continuous process failure.

BACKGROUND: By regulation, ongoing process control of WBC-reduced processes is performed on 1 percent of WBC-reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer-generated "residual WBC" distributions, sample size sensitivity to continuous or intermittent WBC-reduction failure was examined. STUDY DESIGN AND METHODS: Populations of log-normally distributed values (mean +/- SD, 4.5+/-0.5; n = 10(5)) were generated. Continuous failure (log-normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admixing increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria. RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90-percent confidence, and only if individual WBC values were compared to cutoff. CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low-variance normal distribution, the detection of a high-variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC-reduction process failure, as well as clinically relevant quality limits.

Blood Component Removal↗

PubMed2000

Detecting failed WBC-reduction processes: a quality assurance program introduced in a blood center.

BACKGROUND: Pragmatic yet statistically valid quality assurance (QA) programs are necessary so that blood centers can select, validate, and monitor their WBC-reduction processes. A QA system for WBC-reduction processes based on the practical application of statistical theory within a large blood center was developed. The system identifies parameters for procedure and component evaluation and provides sample size and formatting suggestions. STUDY DESIGN AND METHODS: Analyses of both procedure and component performance were undertaken during the purchase, validation, and control of filtration and apheresis WBC-reduction processes at Blood Centers of the Pacific from 1997 through 1999. QA analysis was categorized on the basis of whether the process was new to the organization or was a modification of a previously validated system. The numbers of samples necessary to consistently detect failure in platelet yield, unit volume, pH, and WBC count was statistically determined by parametric and nonparametric techniques. RESULTS: Parametric analysis (power analysis) of the mean +/- SD of smaller numbers of samples was highly sensitive to shifted distributions, but only if the shift was normally distributed. Nonparametric analysis, necessary when the nature of the underlying distribution is unknown, suggested a minimal sample of 40 was required to achieve high confidence that significant bimodal failure (a secondary population with WBCs 5% above the cutoff) would be detected. CONCLUSION: A QA system, developed for the evaluation of new or revised WBC-reduction processes, was based on statistical analysis of normally and non-normally distributed process failure. The number of samples was determined that allowed the achievement of confidence and tolerance levels considered appropriate within the blood center. Suggestions for outlier evaluation and a format for performance documentation have also been developed. To better define blood center quality goals, further research is necessary on donor and component biologic variability and the most significant modes of WBC-reduction process failure.

Blood Banks↗

PubMed2000

Complex transcriptional regulatory mechanisms control expression of the E2F3 locus.

E2F transcription activity has been shown to play a critical role in cell growth control, regulating the expression of a variety of genes that encode proteins important for the initiation of DNA replication and cell cycle regulation. We have shown that the E2F3 locus encodes two protein products: the E2F3a product, which is tightly regulated by cell growth, and the E2F3b product, which is constitutively expressed throughout the cell cycle. To further explore the mechanism controlling the expression of the two E2F3 gene products, we analyzed the genomic sequences flanking the 5' region of E2F3a and E2F3b. We find that a series of E2F binding sites confer negative control on the E2F3a promoter in quiescent cells, similar to the control of the E2F1 and E2F2 promoters. In addition, a group of E-box elements, which are Myc binding sites, confer responsiveness to Myc and are necessary for full activation of the E2F3a promoter in response to growth stimulation. Based on these results and past experiments, it appears that the E2F1, E2F2, and E2F3a genes are similarly regulated by growth stimulation, involving a combination of E2F-dependent negative control and Myc-mediated positive control. In contrast, the constitutive expression of the E2F3b gene more closely reflects the control of expression of the E2F4 and E2F5 genes.

Base Sequence↗

PubMed2000

Atherogenic lipids and endothelial dysfunction: mechanisms in the genesis of ischemic syndromes.

Atherogenic lipids, particularly oxidized low-density lipoprotein, are responsible for a wide range of cellular dysfunctions within the vessel wall. The effects on endothelial cells disrupt normal control of vasomotion, with a reduction of effective nitric oxide activity, the development of a procoagulant surface, chronic low-grade inflammation, and abnormal cell growth. These changes are central not only in the development of atherosclerosis but also in the evolution of both stable and unstable ischemic syndromes. There is growing evidence that these abnormal changes in cell function respond rapidly to changes in the atherogenic lipids. Certain cell functions can improve within hours or days of cholesterol lowering.

Arteriosclerosis↗

PubMed1999

Effect of chelators and nisin produced in situ on inhibition and inactivation of gram negatives.

The ability of chelators and nisin generated in situ to inhibit and inactivate E. coli and other gram negatives in a model substrate was investigated. The effect of various chelators and different concentrations of exogenous nisin on inhibition of E. coli in broth medium showed that only EDTA and pyrophosphates were able to cause appreciable inhibition of E. coli by nisin. In a broth where L. lactis NCFB 497 produced nisin in a concentration of 250-300 IU/ml, pyrophosphates were unable to inactivate E. coli. Under the same conditions, addition of EDTA led to inactivation of E. coli at neutral and slightly acidic pH only. A cocktail of strains of E. coli was less sensitive than E. coli ATCC 25922 alone. Pseudomonas aeruginosa was more sensitive and salmonellae more resistant. EDTA also caused a slight reduction in the L. lactis population and its biochemical activity as regards pH drop and acid production. Some of the inhibition of E. coli could be ascribed to the physical presence of Lactococcus cells rather than their metabolites excreted into the medium. Failure to observe any inhibition in fermented broths at their natural pH (4.0) was ascribed to the poor chelating power of EDTA under acid conditions.

Anti-Bacterial Agents↗

PubMed1999

Arterial endothelial dysfunction related to passive smoking is potentially reversible in healthy young adults.

BACKGROUND: Passive smoking is associated with early arterial damage, but the potential for reversibility of this damage is unknown. OBJECTIVE: To assess the reversibility of arterial endothelial dysfunction, a key marker of early atherosclerosis. DESIGN: Cross-sectional study. SETTING: Academic medical center. PARTICIPANTS: 60 healthy persons 15 to 39 years of age: 20 with no exposure to active or passive smoking, 20 nonsmoking passive smokers (exposure to environmental tobacco smoke for > or = 1 hour per day for > or = 2 years), and 20 former passive smokers. MEASUREMENTS: Arterial endothelial function measured by noninvasive ultrasonography. RESULTS: Endothelium-dependent dilatation was significantly better in former passive smokers (5.1% +/- 4.1% [range, -1.2% to 15.6%]) than in current passive smokers (2.3% +/- 2.1% [range, -0.2% to 6.7%]) (P = 0.01), although both groups were significantly impaired compared with nonsmoking controls (8.9% +/- 3.2% [range, 2.1% to 16.7%]) (P < or = 0.01 for both comparisons). CONCLUSIONS: In healthy young adults, arterial endothelial dysfunction related to passive smoking seems to be partially reversible.

Adolescent↗

PubMed1999

Safety of industrial lactic acid bacteria.

Lactic acid bacteria (LAB) are ubiquitous in fermented and non-fermented foods and are common components of the human commensal microflora. This long history of human exposure and consumption has led to the reasonable conclusion that they are generally safe. Recent attention has also focused on their possible role as probiotic bacteria, promoting beneficial health effects. There have, however, been a number of reports of human infections caused by LAB and these are reviewed. In most cases, the source of the infection was the commensal LAB flora rather than ingested bacteria and the patient had some underlying disease or predisposing condition. Even as opportunistic pathogens, the LAB, with the notable exception of the enterococci, are much less successful than a number of other members of the commensal microflora. The use of new strains for probiotic use is likely to require more detailed evidence for their safety, particularly if the strains have been genetically modified or have been derived from animals. Procedures that have been proposed for assessing the safety of new strains are described.

Endocarditis, Bacterial↗

PubMed1999

Lack of antioxidant activity of the antiatherogenic compound L-arginine.

L-Arginine, the physiologic substrate of nitric oxide synthase, has antiatherogenic properties in animal models of atherosclerosis, and improves endothelial function in hypercholesterolemic humans. Some of these effects may be mediated by increased production of nitric oxide; however, some investigators have postulated a direct antioxidant action related to its aminoguanidine moiety. We aimed therefore, to assess the antioxidant properties of L-arginine. The antioxidant properties of 200 microM L-arginine. 200 microM D-arginine and 200 microM L-glutamate were compared with the powerful antioxidant ascorbate and a control (phosphate-buffered saline). Compounds were tested using four in vitro methods: (1) the Esterbauer technique (which tests the ability of the compounds to scavenge free radicals or chelate transition metals); (2) the effect on the autoxidation of ascorbate; (3) anti-tocopherol mediated peroxidation (which tests the compound's ability to synergize with alpha-tocopherol to prevent mild chemically induced LDL oxidation); and (4) the ability of the compounds to attenuate alpha-tocopherol radical in micellular emulsions (TRAA). The above methods were repeated using the metabolites of the test compounds after incubation with human endothelial cells. Ex vivo studies were then carried out by measuring levels of lipid peroxide production (using HPLC with UV and chemiluminescence detection) in three healthy volunteers before and 2 h after a single 7-g oral dose of L-arginine. By the Esterbauer technique, L-arginine increased lag time by 45% compared to control, as did D-arginine by 50%; L-glutamate had no effect and ascorbate increased lag time by 325%. Neither L-arginine, D-arginine or L-glutamate had significant effects on the autoxidation of ascorbate or anti-tocopherol mediated peroxidation. By the TRAA method, L-arginine had a small effect on preventing the decay of tocopherol. The results were similar for the studies of the compound's metabolites. In ex vivo studies, no changes were seen in lipid peroxide levels following acute dosage with L-arginine. L-Arginine has only weak and non-specific antioxidant effects, suggesting that its major cardioprotective benefits occur through other mechanisms, such as via the nitric oxide pathway.

Adult↗

PubMed1999

An investigation of the presence of ultramicrocells in natural mineral water.

The presence of 'ultramicrocells' in natural mineral water, capable of passing through a 0.2 micron filter, has been demonstrated. Filters allowing the greatest proportion of viable (culturable) cells to pass ranked in the order, 0.4 micron polycarbonate (5.02%) > 0.2 micron polycarbonate (0.02%) > or = 0.45 micron cellulose nitrate (0.02%) > 0.2 micron cellulose acetate (< 0.002%). Following incubation for 4 d at 22 degrees C, viable counts in filtered mineral water increased from < 2-8.7 x 10(2) cfu ml-1(-2).8 x 10(4)-1.9 x 10(6) cfu ml-1. Successive filtration/incubation cycles of mineral water increased the proportion of cells passing through a 0.2 micron cellulose acetate filter from < 0.003% to 0.11% and 0.69%, suggesting selection for 'ultramicrocells'. Cells isolated from this process and grown on liquid R2A medium were thin, Gram-negative rods, of 0.15-0.40 micron wide and 0.50-6.20 microns long. Membrane filtration techniques used for pathogen detection in mineral waters will not retain all the cells present. If pathogens are able to form ultramicrocells, these may go undetected.

Cellulose↗

PubMed1999

The role of surface physicochemical properties in determining the distribution of the autochthonous microflora in mineral water bottles.

Investigation of the distribution of the viable autochthonous microflora in three brands of 1-2-month-old bottled mineral water showed that 1.8 x 10(4) (S.E.M. 8.9 x 10(3), n = 5) to 1.2 x 10(5) (S.E.M. 1.3 x 10(4), n = 5) cfu ml-1 were planktonic cells while 11 (S.E.M. 4, n = 5)-632 (S.E.M. 176, n = 5) cfu cm-2 were found in the biofilm. The biofilm represented between 0.03 and 1.79% of the total viable microbial population in the 1.5 litre bottles studied. Scanning electron microscopy studies showed that the cells adhering to the polyethylene terephthalate (PET) bottles were predominantly rod-shaped, sparsely distributed over the surface. In contrast, the cells adhering to the high density polyethylene (HDPE) caps were found to be mainly clumps of coccoid cells, suggesting that the bottle may provide different microhabitats for different microfloras. Large-scale roughness, such as that observed as lettering inside the cap (average height (z) = 93 microns) was associated with a 46-fold increase in cell numbers. Increased small-scale roughness, as measured by atomic force microscopy on PET and HDPE surfaces (average roughness (Ra) = 5-551 (nm), showed no correlation with adhesion. Investigations of surface hydrophobicity by the sessile drop technique showed that contact angles (theta) were greater on the HDPE caps (theta = 89-96 degrees) than on the PET surfaces (theta = 69-80 degrees). However, no correlation was found between contact angle and attached cell numbers. Measurements of surface electrostatic charge by streaming potential showed that the PET carried an overall negative charge, measuring -15.9 to -16.6 mV in mineral water. No significant change in charge occurred when the monomer composition of the PET was altered. It was concluded that surface roughness, in particular the scale of surface topographical features, is the most important physicochemical surface characteristic determining the distribution of the autochthonous microflora in mineral water bottles.

Bacterial Adhesion↗

PubMed1999

Effect of milk proteins on adhesion of bacteria to stainless steel surfaces.

Stainless steel coupons were treated with skim milk and subsequently challenged with individual bacterial suspensions of Staphylococcus aureus, Pseudomonas fragi, Escherichia coli, Listeria monocytogenes, and Serratia marcescens. The numbers of attached bacteria were determined by direct epifluorescence microscopy and compared with the attachment levels on clean stainless steel with two different surface finishes. Skim milk was found to reduce adhesion of S. aureus, L. monocytogenes, and S. marcescens. P. fragi and E. coli attached in very small numbers to the clear surfaces, making the effect of any adsorbed protein layer difficult to assess. Individual milk proteins alpha-casein, beta-casein, kappa-casein, and alpha-lactalbumin were also found to reduce the adhesion of S. aureus and L. monocytogenes. The adhesion of bacteria to samples treated with milk dilutions up to 0.001% was investigated. X-ray photoelectron spectroscopy was used to determine the proportion of nitrogen in the adsorbed films. Attached bacterial numbers were inversely related to the relative atomic percentage of nitrogen on the surface. A comparison of two types of stainless steel surface, a 2B and a no. 8 mirror finish, indicated that the difference in these levels of surface roughness did not greatly affect bacterial attachment, and reduction in adhesion to a milk-treated surface was still observed. Cross-linking of adsorbed proteins partially reversed the inhibition of bacterial attachment, indicating that protein chain mobility and steric exclusion may be important in this phenomenon.

Animals↗

PubMed1999

Effect of Lp(a) on the early functional and structural changes of atherosclerosis.

Epidemiologic studies have shown a significant relationship between elevated plasma levels of Lp(a) and increased risk of cardiovascular events; however, the mechanisms by which elevated Lp(a) levels produce this increased risk are not known. To test the hypothesis that high Lp(a) levels might contribute to the development of subclinical atherosclerosis, we examined the influence of Lp(a) levels on early functional and structural atherosclerotic vascular changes. Flow-mediated (endothelium-dependent) and nitrate-mediated (smooth muscle-dependent) arterial dilations were measured by high-resolution ultrasound in 241 normal healthy subjects (aged 15 to 69 years; 116 men). In addition, carotid artery intima-media thickness was measured by ultrasound in 71 subjects. Plasma Lp(a) was measured using a 2-sided immunoradiometric assay (cohort median, 10 mg/dL; interquartile range, 3.9 to 24.4 mg/dL). In these subjects, there were no significant relationships between Lp(a) and arterial endothelial function, smooth muscle responses, or carotid wall thickness (P>0.25). By contrast, other lipid risk factors, such as LDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratio, were significantly correlated with abnormal arterial function and structure (P</=0.01). These data suggest that elevated Lp(a) levels do not confer cardiovascular risk by contributing to the early functional or structural changes of atherosclerosis.

Adolescent↗

PubMed1999

Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats.

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.

Animals↗

PubMed1999

Detection of presymptomatic atherosclerosis: a current perspective.

Atherosclerosis, the pathological process underlying myocardial infarction, stroke and other occlusive vascular disease, is the major cause of death in the Western world. The development of techniques to accurately and reproducibly detect and measure the early changes of atherosclerosis and/or to identify subjects at highest cardiovascular risk may aid in the development of prevention strategies and facilitate a decrease in morbidity and mortality from atherosclerosis. Increasing understanding of the pathophysiology of early atherosclerosis has allowed the development of a number of potential methods for the assessment of the early stages of atherosclerosis in humans. These include techniques for assessing early structural changes in the coronary arteries with electron-beam computed tomography and magnetic resonance imaging. External vascular ultrasound has also been used to image other circulations as a surrogate marker for coronary atherosclerosis, e.g. the measurement of carotid artery intima-media thickness. Early functional changes of atherosclerosis have also been described many years before the development of structural changes. A number of techniques have been developed to measure endothelial dysfunction, one of the earliest changes of atherosclerosis, including non-invasive measurement of endothelial function using external vascular ultrasound. A variety of serum markers have also been described, and may be useful markers of atherosclerosis. We discuss some of the more promising techniques for the detection of early, presymptomatic atherosclerosis.

Arteriosclerosis↗