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At least 163 records · Page 9Linked to original sources

Left ventriculometry: the Minnesota experience with a bioengineering approach.

Left ventriculography is used by cardiologists, surgeons, and pharmacologists. Cardiologists use it to assess ventricular function and to scan the results of longitudinal studies to follow the course of the patient. Surgeons employ the results to appreciate changes following surgery, as improvement postbypass, and to compare the effectiveness of alternative procedures or maneuvers. Pharmacologists examine the results to assess the consequences of drug administration. In patients with ischemic heart disease, left ventriculography is an indispensable adjunct to selective coronary arteriography, and it provides anatomic and functional information important for diagnosis and for predicting the outcome of the patient. Using the results from cine left ventriculography, it is possible to calculate the EDV, ESV, SV, and EF and thus to evaluate the pump function of the left ventricle objectively, quantitatively, and reproducibly. However, these measures indicate total left ventricular function. A more detailed analysis of the cine left ventriculogram can provide specific information about the impaired segments. Methods for measuring and calculating the volume changes of the entire left ventricle were described and illustrated with their clinical implementation. Five methods of determining regional myocardial wall motion were applied to a population of subjects with normal wall motion and to patients with abnormal wall motion. The method was chosen which agreed best with the visual assessment of the cine by experienced cardiovascular radiologists. Clinical applications of regional wall motion assessment were described. A computer-compatible data base was created for roentgen images of a normally and of an abnormally contracting left ventricle, and this data base was contributed to a national repository for computer-compatible data bases. An automatic pattern recognition method was used to determine whether regional wall motion was normal or abnormal, and it was able to distinguish between these two groups satisfactorily. Current trends in ventriculography were described. A bioengineering approach has been used to solve the problem of measuring and describing the wall motion of the left ventricle of the human heart. The approach has been applied to the analysis of the contraction of the whole ventricle, regional wall motion, and the temporal pattern of wall motion. The mathematical equations underlying the analysis have been given, explained, and illustrated with examples. The implementation of the analyses using computers was discussed. The assumptions and sources of error have received particular attention.

Angiocardiography↗

Bioengineering and the skin: from standard error to standard operating procedure.

Bioengineering techniques for examination of the skin, measuring principles and sources of error relative to technique, study design, measuring conditions and variability related to test subjects and preconditioning are reviewed. Principles of validation and standard operating procedures (SOP) are discussed, including guidelines for measurement of transepidermal water loss (TEWL) and laser Doppler cutaneous blood flow. Today typical errors are not related to a measuring device but to the way it is used.

Biomedical Engineering↗

Professions, professional ethics, and bioengineering.

The distinguishing features of professions, professionalization, and the institutionalization of expertise are discussed. Drawing on this discussion, a composite picture of a profession is developed. Using that composite picture, the question whether bioengineering is a profession is raised and answered affirmatively; the implications of that answer are explored. The institutional aspects and problems of contemporary professional practice receive special attention. It is argued that undertaking the task of constructing ethical structures of practice is itself an obligation of professional ethics. An approach that can be employed in that undertaking and, then, with one difference that is explained, used in making individual ethical decisions in one's capacity as a professional is suggested and defended. A key element in that defense is the fact that the approach squarely faces and successfully deals with what one writer calls the problems of knowledge and interest.

Biomedical Engineering↗

Computational biology instruction at the University of Washington Center for Bioengineering.

Computational tools are rapidly becoming an essential component of molecular biology research. However, there is as yet relatively little attention paid to computational biology in the standard curricula of most biology programs. We describe here some of the graduate computational biology courses we have developed in the Center for Bioengineering at the University of Washington, with special emphasis on instructional methods and approaches that appear to work well.

Computational Biology↗

Kinetics of product inhibition in alcohol fermentation. Reprinted from Biotechnology and Bioengineering, Vol. X, Issue 6, Pages 845-864 (1968).

The inhibitory effect of ethanol concentration p in a medium on the specific rates of growth mu and ethanol production nu of a specific strain of baker's yeast was studied in a chemostat, where except for ethanol as the product, only the concentration of glucose S was controlled to limit the metabolic activity of the yeast. This was designed to supplement the previous findings from the batch experiment, in which ethanol was added artificially and no substrate components were limiting the metabolism of the same yeast, that mu = mu(0)e(-k(1)p) and nu = nu(0)e(-k(1)p), where k(1) and k(2) are empirical constants and subscript the 0 denotes respective values at p = 0. The effects of p on the values of mu and nu were confirmed by the Line-weaver-Burk plot to belong to noncompetitive inhibition. The formulas here for mu and nu as affected by p, if extrapolated to the case of no limiting substrates, were in good agreement in respective forms with those derived previously from the batch experiment, though the values of corresponding coefficients in these formulas were different. The differential equations for mu and nu as functions of both p and S and, in addition for the rate of glucose consumption as correlated by the yield factors either with the cell growth rate or the rate of ethanol production, were solved properly with a digital computer. A kinetic pattern calculated so far was discussed with reference to the data obtained in the batch experiment and those relevant to actual "sake" brewing.

Culture Media↗

Measurement of heat evolution and correlation with oxygen consumption during microbial growth. Reprinted from Biotechnology and Bioengineering, Vol. XI, Issue 3, Pages 269-281 (1968).

A procedure for measuring the rate of heat production from a fermentation has been developed. The method is based on measuring the rate of temperature rise of the fermentation broth resulting from metabolism, when the temperature controller is turned off. The heat accumulation measured in this manner is then corrected for heat losses and gains. A sensitive thermistor is used to follow the temperature rise with time. This procedure is shown to be as accurate as previous methods but much simpler in execution. Using this technique, the rate of heat production during metabolism was found to correlate with the rate of oxygen consumption. Experiments were performed using bacteria (E. coli and B. subtilis), a yeast (C. intermedia), and a mold (A. niger). The substrates investigated included glucose, molasses, and soy bean meal. The proportionality constant for the correlation is independent of the growth rate, slightly dependent on the substrate, and possibly dependent on the type of organism growth. This correlation has considerable potential for predicting heat evolution from the metabolism of microorganisms on simple or complex substrates and providing quantitative parameters necessary for heat removal calculations.

Aspergillus niger↗

Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Reprinted from Biotechnology and Bioengineering, Vol. XI, Issue 6, Pages 1101-1110 (1969).

Streptomyces peucetius var. caesius, obtained from S. peucetius, the daunomycin producing microorganism, by mutagenic treatment, differs from the parent culture by the color of the vegetative and aerial mycelia and by its antibiotic producing ability. S. peucetius var. caesius accumulates adriamycin in submerged and aerated culture on a medium containing glucose, brewer's yeast, and inorganic salts both in shake flasks and in stirred fermenters. Isolation of the product is performed by solvent extraction, chromatography on buffered cellulose columns, and crystallization as the hydrochloride. The new antitumor agent, adriamycin, is the 14-hydroxy derivative of daunomycin.

Antibiotics, Antineoplastic↗

The immobilization of microbial cells, subcellular organelles, and enzymes in calcium alginate gels. Reprinted from Biotechnology and Bioengineering, Vol. XIX, No. 3, Pages 387-397 (1977).

Saccharomyces cerevisiae cells, Kluyveromyces marxianus cells, inulase, glucose oxidase, chloroplasts, and mitochondria were immobilized in calcium alginate gels. Ethanol production from glucose solutions by an immobilized preparation of S. cerevisiae was demonstrated over a total of twenty-three days, and the half-life of such a preparation was shown to be about ten days. Immobilized K. marxianus, inulase, and glucose oxidase preparations were used to demonstrate the porosity and retraining properties of calcium alginate gels. Calcium alginate-immobilized chloroplasts were shown to perform the Hill reaction. Some experiments with immobilized mitochondria are reported.

Alginates↗

Continuous enzymatic transformation in an enzyme membrane reactor with simultaneous NAD(H) regeneration. Reprinted from Biotechnology and Bioengineering, Vol. XXIII, No. 12, Pages 2789-2802 (1981).

Multienzyme reaction systems with simultaneous coenzyme regeneration have been investigated in a continuously operated membrane reactor at bench scale. NAD(H) covalently bound to polyethylene glycol with a molecular weight of 10(4) [PEG-10,000-NAD(H)] was used as coenzyme. It could be retained in the membrane reactor together with the enzymes. L-leucine dehydrogenase (LEUDH) was used as catalyst for the reductive amination of alpha-ketoisocaproate (2-oxo-4-methylpentanoic acid) to L-leucine. Formate dehydrogenase (FDH) was used for the regeneration of NADH. Kinetic experiments were carried out to obtain data which could be used in a kinetic model in order to predict the performance of an enzyme membrane reactor for the continuous production of L-leucine. The kinetic constants V(max) and k(m) of the enzymes are all in the same range regardless of whether native NAD(H) or PEG-10,000-NAD(H) is used as coenzyme. L-leucine was produced continuously out of alpha-ketoisocaproate for 48 days; a maximal conversion of 99.7% was reached. The space-time yield was 324 mmol/L day (or 42.5 g/L day).

Bioreactors↗

Analysis of growth rate effects on productivity of recombinant Escherichia coli populations using molecular mechanism models. Reprinted from Biotechnology and Bioengineering, Vol. 26, Issue 1, Pages 66-73 (1984).

The influence of growth rate on Escherichia coli plasmid content and expression of a cloned-gene product has been described by a mathematical model based upon the molecular mechanism of lambdadv plasmid replication and known relationships between growth rate and transcription and translation activities of the host cell. The model simulates correctly decreases in plasmid content with increasing growth rate as observed experimentally for pBR322, NR1, R1, and Col E1 plasmids. A maximum with respect to growth rate in intracellular product accumulation is indicated by the model, as is a transient overshoot in product concentration following a shift from smaller to larger growth rate. Available data, although very limited, show the same trends. These results, obtained without parameter or kinetic form adjustments or manipulation, clearly illustrate the advantages of kinetic descriptions of recombinant systems based upon the pertinent molecular mechanisms.

Escherichia coli↗