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Biomedical subjects

C W Miller

Publications and source records attributed to C W Miller.

At least 127 records · Page 7Linked to original sources

1,25-Dihydroxyvitamin D3 modulates the expression of a lymphokine (granulocyte-macrophage colony-stimulating factor) posttranscriptionally.

We recently showed that 1,25(OH)2D3 sensitively inhibited the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in normal human mitogen-activated peripheral blood lymphocytes and in the human T lymphotropic virus I immortalized T cell line known as S-LB1 at the levels of both mRNA and protein. Using S-LB1 cells as a model system the present paper identifies at least in part the mechanisms by which 1,25(OH)2D3 regulates the expression of GM-CSF. Time-course studies demonstrated that by 6 and 48 h of exposure of S-LB1 cells to 1,25(OH)2D3 (10(-8) M) the GM-CSF mRNA levels were reduced by 50 and 90%, respectively. Studies using cycloheximide as a protein synthesis inhibitor showed that the inhibitory action of 1,25(OH)2D3 on GM-CSF expression was dependent on new protein synthesis. In vitro nuclear run-on assays demonstrated that 1,25(OH)2D3 (10(-8) M) did not change the rate of transcription of the GM-CSF gene. The t1/2 of GM-CSF mRNA, however, was profoundly reduced by 1,25(OH)2D3 when transcription was blocked by actinomycin D compared with the half-life of GM-CSF in the presence of actinomycin D alone (t1/2, less than 0.5 and 4 h, respectively). Taken together, these results demonstrate that 1,25(OH)2D3 regulates expression of the lymphokine GM-CSF posttranscriptionally by influencing the stability of GM-CSF mRNA.

Calcitriol↗

Angioid streaks associated with pseudoxanthoma elasticum in a 13-year-old patient.

This report describes a 13-year-old girl who presented with angioid streaks associated with pseudoxanthoma elasticum (PXE). Extensive retinal pigment epithelial (RPE) mottling, known as peau d'orange, characteristic of PXE, was also noted. The potential complication of choroidal neovascularization is described. Physicians should be aware that angioid streaks and their potentially sight-threatening complications can occur in this age group.

Adolescent↗

Influence of endogenous albumin binding on blood-material interactions.

A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses.

Animals↗

Chronic antithrombogenic biomaterials screen.

The widespread usage of chronic implantable sensors in cardiac device systems has been hampered by both sensor technology issues and the lack of surface passivations with chronic antithrombogenic capabilities. In this study, dummy pacing leads with six types of passivations were implanted for 17 weeks in 36 dogs to assess thrombogenic character, degree of tissue growth and encapulation, and general performance in providing optically clear windows into the blood or body tissues. Asceptic surgical procedures were used and complete blood work-up was performed every two weeks postop. Two dogs served as surgical shams to monitor system artifacts. At explant the devices fairly clearly divided themselves into two groups based on the percent of exposed surface area covered by gross macroscopic tissue accumulations. There were three passivated types in each group. Scanning electron microscopy (SEM) and energy dispersive analysis of x-rays (EDAX) techniques were used to investigate further the samples from the three passivation types that performed "better" based on percent surface area analysis. Issues that became prominent were substrate surface finish and topography, and some mineralization phenomena. Some of the evidence raises the possibility that processes that provide chronic antithrombogenic performance might also enhance mineralization or propensity toward natural breakdown processes. These questions are now being more closely addressed in follow-up studies now in progress.

Animals↗

Cutaneous lesions of lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a rare multisystem disease involving the lungs, skin, and nervous system. The cutaneous disease may be the presenting complaint. A case with nodular and annular infiltrated lesions is reported to encourage the inclusion of lymphomatoid granulomatosis in the differential diagnosis of similar lesions. Prompt diagnosis and early long-term treatment with cyclophosphamide and prednisone can lead to prolonged remissions of this disease. If relapse occurs, prompt treatment with the same regimen may again induce a remission.

Adult↗

Microsurgical management of tetralogy of Fallot in a cat.

A modified Blalock-Taussig shunt was performed on a cat with tetralogy of Fallot. Previous attempts at such palliative surgery in the cat have failed, due to small vessel size. The use of microvascular instrumentation and technique resulted in a patent shunt in this case.

Animals↗

Aerosol delivery in intubated, mechanically ventilated patients.

To study the effects of respiratory failure and mechanical ventilation on aerosol delivery to the lungs, we performed nuclear scans after aerosolization of 5 to 9 mCi of Tc-99m diethylenetriamine pentaacetic acid in seven stable, intubated, and mechanically ventilated patients. The radioactivity reaching the lungs was 2.9 +/- .7% (mean +/- SD) of the administered dose, an amount significantly less than that in three healthy nonintubated subjects and also less than what would be expected in nonintubated subjects from other published reports. We then performed a subsequent study in 15 additional mechanically ventilated patients who were receiving aerosolized bronchodilators through their endotracheal tube. In these patients, heart rate and lung mechanical function values before and after treatment were not significantly different. We conclude from these studies that aerosol delivery in mechanically ventilated patients is significantly reduced and that this is probably due to a combination of suboptimal breathing pattern, intrinsic airway disease, and the endotracheal tube functioning as both a site for aerosol deposition through impaction as well as a barrier to gastrointestinal absorption.

Aerosols↗

Hypoxic moderation of renal hypertension in the miniature swine.

Eleven male Yucatan miniature swine were subjected to unilateral renal artery constriction (RAC) with an intact contralateral kidney. Five pigs remained at laboratory altitude of 1524 m and served as normoxic, hypertensive controls (NH) while the other six (HH) were subjected to a simulated altitude of 4267 m for 9 weeks to determine the effect of hypoxia on the development of renal hypertension. Systemic blood pressure was increased less in HH as compared with NH. Data from three sib-pairs represented in each treatment group suggested a diverse, apparently familial response to RAC. The hypertensive process, irrespective of treatment groups, included a diminution of free circulating serum thyroxin and an increase in serum sodium. Hypoxia moderates renal hypertension in the miniature pig primarily via a decrement in stroke volume and cardiac output.

Animals↗

Specific globin mRNAs in human erythroleukemia (K562) cells.

Specific globin mRNA accumulation was quantitated in several lines of K562 cells in the absence and the presence of hemin. Using specific cloned DNA probes, the amounts of zeta, alpha, epsilon and gamma mRNAs were shown to be increased 2-3-fold in the presence of 20 microM hemin. No delta- or beta-globin mRNAs were detectable in any of the lines. In one line, Bos, there was a marked decrease in epsilon-globin mRNA, which increased with hemin, although still to much lower levels than in the other lines. The decreased epsilon-globin mRNA accumulation in Bos is shown to be due to decreased epsilon-globin gene transcription.

Cell Line↗

Echocardiographic assessment of congenital aortic stenosis in dogs.

Eleven dogs with congenital aortic stenosis were studied with M-mode echocardiography. In these dogs, the aorta was increased in dimension during diastole (P less than 0.02) and systole (P less than 0.05). The left ventricular outflow tract was decreased in dimension (P less than 0.01). There was premature, early systolic closure of the aortic valve in 45% of the dogs. Concentric hypertrophy of the left ventricle was confirmed via echocardiography, as evidenced by increased dimension of the left ventricular wall (P less than 0.01) and interventricular septum (P less than 0.01).

Animals↗

An examination of the environmental half-time for radionuclides deposited on vegetation.

After radionuclides are deposited on vegetation, environmental removal processes combine with radioactive decay to reduce the quantity of initial contamination. The time in which one-half of the radioactivity is removed from vegetation by environmental processes alone is referred to as the environmental half-time, Tw. For long-lived radionuclides, the dose to man via ingestion of contaminated terrestrial foods may be directly influenced by values of Tw, provided that environmental removal processes dominate root uptake and time is sufficiently long between initial exposure of vegetation and harvest. Values of Tw reported in the literature for various radionuclides and methods of deposition are examined. Factors affecting the variability of Tw are related in part to the physicochemical form of the depositing substance, vegetation type and growth form, climate, season, and experimental procedure. For growing vegetation, values of Tw are generally lower than those reported for dormant vegetation. Values of Tw for iodine vapor and iodine particulate are less than values of Tw reported for particulates of other elements. Values of Tw determined on a per unit vegetation mass basis are also less than values of Tw determined on a per unit ground area basis, the differences being attributable to the effects of growth dilution. Although an assessor has a range from which to select a value of Tw for the purpose of estimating contamination by long-lived radionuclides, the variability in Tw is small in comparison to many other parameters used in environmental radiological assessments.

Half-Life↗

Echocardiographic assessment of mitral valve motion, cardiac structures, and ventricular function in dogs with atrial fibrillation.

Eleven dogs with atrial fibrillation were examined echocardiographically. During atrial fibrillation, there was no evidence of atrial contraction in the left ventricle or aorta, or on the mitral valve leaflets. Measurement of cardiac structures in echocardiograms showed decreased sizes for the aorta (P less than 0.01), interventricular septum (P less than 0.01), and posterior left ventricular wall (P less than 0.02). Evidence of decreased contractility of the left ventricle was noticed with the decreased amplitude of motion of the posterior left ventricular wall (P less than 0.001) and decreased fractional shortening (P less than 0.01). Not every QRS resulted in systolic or diastolic motion in the mitral and aortic valve leaflets, thus helping to account for the pulse deficits normally seen during atrial fibrillation.

Animals↗

Comparison of observed and predicted air concentrations for 18.6 micron fluorescein particles.

From 1967 to 1973, numerous atmospheric dispersion experiments were conducted at Hanford, Washington, by the staff of Battelle Pacific Northwest Laboratories. We compared published data from those experiments to predictions made by the Gaussian plume atmospheric dispersion model for conditions similar to the field releases. The express purpose of the study was to consider the effects of non-zero dry deposition parameters on the accuracy of the model predictions of ground-level normalized air concentrations by comparing these predictions to the published Hanford field observations. Predictions were made consistent with existing dose assessment practices. We conclude that for the conditions tested, the predictive capability of the model was most improved when the deposition velocity parameters (vd) and the gravitational fall velocity (vg) were both set equal to 1.8 cm/s.

Air Pollution, Radioactive↗