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Biomedical subjects

T M Miller

Publications and source records attributed to T M Miller.

29 records · Page 2Linked to original sources

Human alpha- and gamma-thrombin specificity with tripeptide p-nitroanalide substrates under physiologically relevant conditions.

Kinetic parameters [the Michaelis-Menten (Km), catalytic (kcat), and specificity (kcat/Km) constants] were determined for human alpha- and gamma-thrombins with the chromogenic substrate S-2238 (H-D-Phe-Pip-Arg-p-nitroanilide), Chromozym-TH (Tos-Gly-Pro-Arg-p-nitroanilide), and Spectrozyme-TH (H-D-HHT-Ala-Arg-p-nitroanilide) under physiologically relevant conditions (0.15 M NaCl buffered with 10 mM HEPES and 10 mM Tris-HCL, pH 7.4 at 37 degrees C). No major differences were found between alpha-thrombin with high fibrinogen clotting activities (greater than 3,500 killo clotting units/g) and gamma-thrombin with essentially no clotting activities (less than 10 kCU/g), although the Km values and in most cases kcat values for alpha-thrombin were slightly lower than for the gamma-thrombin. At 37 degrees C, relative to 23 degrees C, Km values increased 2-fold for S-2238, approximately 1.5-fold for Chromozym-TH, and remained essentially the same for Spectrozyme-TH (e.g., reciprocal substrate binding), whereas the kcat values increased for all 3 substrates (e.g., enzyme turnover). This caused kcat/Km values to decrease slightly for S-2238, remain the same for Chromozym-TH, and increase for Spectrozyme-TH (e.g., enzyme efficiency). Since spontaneous hydrolysis was not limiting at 37 degrees C, assays employing these substrates may be satisfactorily performed under physiologically relevant conditions. Under these conditions, kcat/Km ratios for the 3 substrates are similar to that for the A alpha cleavage in fibrinogen by alpha-thrombin.

Chromogenic Compounds↗

The effect of pulse-modulated thermal radiation on the time-intensity relationship for dermal pain.

A simple experimental model was used to examine the relationship between modulation and hazard for thermal bioelectromagnetic effects. The inner forearms of 11 human volunteers were exposed to continuous and pulse-modulated thermal radiation from an incandescent light source. The time of irradiation required to produce threshold pain sensation was measured as a function of the average power density (450-2500 m W cm-2), pulse repetition frequency (continuous, 0.4 Hz, 8.0 Hz) and duty cycle (continuous, 0.33, 0.50). The resulting 32 sets of data could be described by a single power function expression which relates time and power density through a regression slope. The slope was found to depend on the modulation of the radiation, but not on the age of the subject or wet bulb globe temperature (WBGT). The minimum average power density which could elicit pain within 200 sec (an effective threshold intensity) was determined to be independent of modulation, regression slope, subject age and WBGT.

Adult↗

Evidence for two physiologically distinct gap junctions expressed by the chick lens epithelial cell.

Lens epithelial cells communicate with two different cell types. They communicate with other epithelial cells via gap junctions on their lateral membranes, and with fiber cells via junctions on their apices. We tested independently these two routes of cell-cell communication to determine if treatment with a 90% CO2-equilibrated medium caused a decrease in junctional permeability; the transfer of fluorescent dye was used as the assay. We found that the high-CO2 treatment blocked intraepithelial dye transfer but not fiber-to-epithelium dye transfer. The lens epithelial cell thus forms at least two physiologically distinct classes of gap junctions.

Animals↗

Gap junction structures after experimental alteration of junctional channel conductance.

Gap junctions are known to present a variety of different morphologies in electron micrographs and x-ray diffraction patterns. This variation in structure is not only seen between gap junctions in different tissues and organisms, but also within a given tissue. In an attempt to understand the physiological meaning of some aspects of this variability, gap junction structure was studied following experimental manipulation of junctional channel conductance. Both physiological and morphological experiments were performed on gap junctions joining stage 20-23 chick embryo lens epithelial cells. Channel conductance was experimentally altered by using five different experimental manipulations, and assayed for conductance changes by observing the intercellular diffusion of Lucifer Yellow CH. All structural measurements were made on electron micrographs of freeze-fracture replicas after quick-freezing of specimens from the living state; for comparison, aldehyde-fixed specimens were measured as well. Analysis of the data generated as a result of this study revealed no common statistically significant changes in the intrajunctional packing of connexons in the membrane plane as a result of experimental alteration of junctional channel conductance, although some of the experimental manipulations used to alter junctional conductance did produce significant structural changes. Aldehyde fixation caused a dramatic condensation of connexon packing, a result not observed with any of the five experimental uncoupling conditions over the 40-min time course of the experiments.

Animals↗

Oxygen deficiency hazards associated with liquefied gas systems: derivation of a program of controls.

The use of liquefied gases in industry and research has become commonplace. Release into the atmosphere of these gases will result in a displacement of air and a reduction in the oxygen concentration. Exposure to reduced levels of oxygen may cause reduced abilities, unconsciousness or death. This paper describes the derivation of a novel program of controls for oxygen deficiency hazards. The key to this approach is a quantitative assessment of risk for each planned operation and the application of control measures to reduce that risk to an acceptable level. Five risk levels evolve which are based on the probability of fatality. Controls such as training, oxygen monitoring equipment, self-rescue respirators and medical surveillance are required when the probability of fatality exceeds 10(-7) per hour. The quantitative nature of this program ensures an appropriate level of control without undue burden or expense.

Accidents, Occupational↗

Endocytosis of synaptic vesicle membrane at the frog neuromuscular junction.

Frog nerve-muscle preparations were quick-frozen at various times after a single electrical stimulus in the presence of 4-aminopyridine (4-AP), after which motor nerve terminals were visualized by freeze-fracture. Previous studies have shown that such stimulation causes prompt discharge of 3,000-6,000 synaptic vesicles from each nerve terminal and, as a result, adds a large amount of synaptic vesicle membrane to its plasmalemma. In the current experiments, we sought to visualize the endocytic retrieval of this vesicle membrane back into the terminal, during the interval between 1 s and 2 min after stimulation. Two distinct types of endocytosis were observed. The first appeared to be rapid and nonselective. Within the first few seconds after stimulation, relatively large vacuoles (approximately 0.1 micron) pinched off from the plasma membrane, both near to and far away from the active zones. Previous thin-section studies have shown that such vacuoles are not coated with clathrin at any stage during their formation. The second endocytic process was slower and appeared to be selective, because it internalized large intramembrane particles. This process was manifest first by the formation of relatively small (approximately 0.05 micron) indentations in the plasma membrane, which occurred everywhere except at the active zones. These indentations first appeared at 1 s, reached a peak abundance of 5.5/micron2 by 30 s after the stimulus, and disappeared almost completely by 90 s. Previous thin-section studies indicate that these indentations correspond to clathrin-coated pits. Their total abundance is comparable with the number of vesicles that were discharged initially. These endocytic structures could be classified into four intermediate forms, whose relative abundance over time suggests that, at this type of nerve terminal, endocytosis of coated vesicles has the following characteristics: (a) the single endocytotic event is short lived relative to the time scale of two minutes; (b) earlier forms last longer than later forms; and (c) a single event spends a smaller portion of its lifetime in the flat configuration soon after the stimulus than it does later on.

Animals↗

An empirical time-intensity relationship for thermal bioelectromagnetic effects.

Published experimental data for three thermal/harmful bioelectromagnetic effects (lethality, cataractogenesis, and threshold pain sensation) are examined in an effort to develop a generally consistent empirical expression relating the time of irradiation necessary to induce an effect to the intensity of the radiation. A critical organ is assigned to each effect and the SAR's in these organs are estimated, when necessary, from the incident power density. It is found that all the data can be satisfactorily described by a single power function expression which gives the exposure duration as a function of the SAR in the critical organ and an experiment-specific constant.

Animals↗

Survey on body image, weight, and diet of college students.

In this study, college students visiting a university health service were categorized according to various anthropometric measurements and completed a questionnaire. Fifty-five per cent of the men were realistic in their self-perception of body size, but 63 per cent of the women perceived themselves to be one category of weight higher than they actually were. Fifty-six per cent of the students sampled (but only 60 per cent of those who were dissatisfied with their body images) said they were modifying their eating practices. The majority of students were realistic in their goals for weight loss, but 46 per cent of the women wanted to be underweight or slightly underweight.

Adolescent↗

Collaborative needs assessment and systems development in Alabama: Process and products.

This article describes the implementation of a collaborative project and its results, involving a department of maternal and child health (DMCH) in a school of public health and a state department of public health. The state received a federal grant to enhance systems development for women and children. Adequate information regarding the existing system of health care was lacking. The state contracted with the DMCH for assistance in designing and conducting a needs assessment, whose purpose was to (1) identify strengths and weaknesses in the state system of care, (2) provide baseline information for targeting resources and measuring change, and (3) initiate an on-going process of assessment and evaluation of need. The DMCH collected data about financial and nonfinancial barriers to care from state-level health agency and organization experts, county-level service personnel, and consumers. The contributions to understanding the needs of the state offered by the information garnered in the three surveys helped the state in setting immediate and long-range objectives. The presence of the school of public health and the focus of its particular DMCH on assisting state agencies provided an atmosphere in which the state could ask for assistance and the university could respond in a way that was useful and relevant to the state's needs. Medical Subject Headings (MeSH): assessment, health planning, health priorities, interprofessional relations, program planning, public health.

Alabama↗