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Biomedical subjects

W M Miller

Publications and source records attributed to W M Miller.

At least 73 records · Page 4Linked to original sources
PubMed1980

Epidemiological studies of calf respiratory disease in a large commercial veal unit.

Records of treatments for respiratory disease among 952 calves in a large intensive veal unit were analysed. The frequency of disease was heavily age-dependent in the 34 batches of 28 calves with a peak at five weeks of age and little disease before the fourth or after the eighth week. The effect was evident for all of the three indices of disease examined: the numbers of first treatments, numbers of new courses of treatment and the total number of treatments. Transient synchronisation of outbreaks of disease in separate batches was observed but attempts to correlate the level of disease with climatic events, using data from local meteorological stations, were unsuccessful. Disease was shown to be clustered within crops of calves at one end of the housing or the other, indicating that contact spread may have been important. A variation in the amount of disease on each day of the week may have been attributable to restricted feeding on Sundays.

Age Factors↗
PubMed1977

Metabolic fate of [14C]cefamandole, a parenteral cephalosporin antibiotic, in rats and dogs.

The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion.

Animals↗
PubMed1977

Progressive hypereosinophilia with lung nodules due to thyroid carcinoma.

An elderly woman had dyspnea, a thyroid mass and multiple lung nodules on chest radiographs. She developed hypereosinophilia over a three-month period in which multiple diagnostic procedures were performed, without definition of the disease process. At post-mortem examination, the primary lesion was found to be a poorly differentiated carcinoma of the thyroid, metastatic to lung. This is the second case of hypereosinophilia related to metastatic thyroid carcinoma. The intensity of the hypereosinophilia in this case was increased by the administration of thyroid-stimulating hormone and by the development of necrosis of the lung nodules.

Aged↗
PubMed1976

Reaction pathways of in vivo stereoselective conversion of ethylbenzene to (-)-mandelic acid.

1. Mandelic acid formed in vivo from ethylbenzene as well as from various oxidation intermediates was laevo mandelic acid and was of surprisingly high optical purity. 2. Reaction sequences are proposed for the stepwise oxidation of ethylbenzene to mandelic acid. 3. Although the initial hydroxylation of ethylbenzene to methylphenyl-carbinol is stereoselective, the optical activity of mandelic acid is not established at this point since the optical centre is destroyed in the second step, dehydrogenation to acetopheneone. 4. Acetophenone appears to be a precursor of not only mandelic acid and benzoylformic acid but benzoic acid as well. 5. The route from acetophenone involves conversion to omega-hydroxyacetophenone and subsequent reduction to glycol and/or oxidation to phenylglyoxal. 6. The configuration of mandelic acid is determined either during reduction of hydroxyacetophenone or reduction of phenylglyoxal.

Animals↗
PubMedDate not supplied

The lactate issue revisited: novel feeding protocols to examine inhibition of cell proliferation and glucose metabolism in hematopoietic cell cultures.

It is well established that cell proliferation in batch (unfed) hematopoietic cell cultures is greatly inhibited relative to that in cultures with feeding. What is not known, however, is the nature of this inhibition. On the basis of our observations in hematopoietic cultures that cell proliferation ceases when the lactate concentration ([lactate]) exceeds 20 mM (accompanied by a decrease in culture pH), we investigated the effect of lactate accumulation on cell proliferation, metabolism, and differentiation. We differ in our approach from previous efforts in that we have tried to more accurately recreate the manner in which lactate accumulates in culture by employing a daily feeding protocol in which [lactate] and/or pH in the fresh medium was adjusted to match the conditions prior to feeding. We conclude that the decrease in pH associated with lactate accumulation significantly inhibits both cell proliferation and metabolism. Although inhibition in cultures with high [lactate] and low pH is similar to that in unfed cultures, pH control in unfed cultures does not alleviate the inhibition, indicating that other inhibitory factors are also present. Thus, pH control is necessary, but not sufficient, to eliminate inhibition of cell growth and metabolism in unfed hematopoietic cell cultures. We also conclude that high [lactate] and low pH have little effect on cell differentiation in fed cultures, although there is evidence to suggest that low pH may play a role in monocyte differentiation in unfed cultures.

Bone Marrow Cells↗
PubMedDate not supplied

Effects of abrupt and gradual osmotic stress on antibody production and content in hybridoma cells that differ in production kinetics.

AB2-143.2 cells exhibit non-growth-associated antibody production (constant specific antibody production rate (qAb) throughout batch culture), while IND1 cells exhibit growth-associated production (decrease in qAb during stationary phase). AB2-143.2 cells increase qAb following abrupt batch osmotic stress. Enhanced antibody production in IND1 cells after batch osmotic shock is evidenced as maintenance of the higher exponential phase qAb into the stationary phase. AB2-143.2 cells also increase qAb in response to gradual osmotic stress in continuous culture. In contrast, IND1 cells decrease qAb during gradual osmotic stress. Although the two cell lines differ in antibody production, they have very similar intracellular antibody content profiles. Both show (1) constant antibody content during the exponential phase in control culture with a decrease as cells enter stationary phase; (2) maintenance of exponential-phase antibody content into the stationary phase after batch osmotic shock; and (3) no change in antibody content in response to gradual osmotic stress.

Animals↗
PubMedDate not supplied

Glycosylation of CHO-derived recombinant tPA produced under elevated pCO2.

Carbon dioxide is a metabolic byproduct of mammalian cell metabolism that can accumulate in poorly ventilated cultures. A buildup of CO2 at constant pH will be accompanied by an increase in medium osmolality. We have examined the glycosylation of tissue plasminogen activator (tPA) produced under serum-free conditions by recombinant Chinese hamster ovary (CHO) cells (MT2-1-8 cell line) in response to elevated pCO2 at constant or elevated osmolality. The proportion of sialic acids comprising N-glycolylneuraminic acid decreased from 2.3-4.0% under 36 mmHg pCO2 to 1.5-2.2% under 250 mmHg pCO2. No changes were observed in the total sialic acid content, the content of other monosaccharides, the relative amounts of type I and type II tPAs, the distribution of surface charges, or the proportion of high-mannose oligosaccharides-even though these conditions have previously been shown to inhibit the specific growth rate of MT2-1-8 cells by 30-40% and the specific tPA production rate by as much as 40%. These results suggest robust glycosylation of tPA by CHO cells.

Animals↗
PubMedDate not supplied

Characterization of hematopoietic cell expansion, oxygen uptake, and glycolysis in a controlled, stirred-tank bioreactor system.

Cultures of umbilical cord blood and mobilized peripheral blood mononuclear cells were carried out in a stirred bioreactor with pH and dissolved oxygen control. Expansion of total cells and colony-forming units granulocyte-macrophage was greatly enhanced by the use of a cell-dilution feeding protocol (as compared to a cell-retention feeding protocol). The specific oxygen consumption rate (qO2) for these cultures ranged from 1.7 x 10(-8) to 1.2 x 10(-7) micromol/(cell.h). The maximum in qO2 for each culture closely corresponded with the maximum percentage of progenitor or colony-forming cells (CFCs) present in the culture. The maximum qO2 values are slightly less than those reported for hybridomas, while the lowest qO2 values are somewhat greater than those reported for mature granulocytes. Examination of the ratio of lactate production to oxygen consumption in these cultures suggests that post-progenitor cells of the granulomonocytic lineage obtain a greater portion of their energy from glycolysis than do CFCs. The different metabolic profiles of CFCs and more mature cells suggest that monitoring the uptake or production of oxygen, lactate, and other metabolites will allow estimation of the content of several cell types in culture.

Bioreactors↗
PubMedDate not supplied

Transport in a grooved perfusion flat-bed bioreactor for cell therapy applications.

This study considers the transport of oxygen (a growth-associated solute) and lactate (a metabolic byproduct) in a flat-bed perfusion chamber modified to retain cells through the addition of grooves, perpendicular to the direction of flow, at the chamber bottom. The chamber has been successfully applied to hematopoietic cell culture and may be useful for other basic and applied biomedical applications. The objective of this study is to characterize the culture environment in terms of solute transport under various operational conditions. This will allow one to improve the design and operating strategy of the perfusion system for maximizing cell numbers. The system is numerically simulated using the finite element package FIDAP. The reaction kinetics describing oxygen uptake by cells are simplified to zero order to give an upper bound for the oxygen consumption. A flat-bed chamber without grooves is considered here as a benchmark. We show that the growth environment is not oxygen limited (local oxygen concentration above 10 microM) for a variety of flow rates and culture conditions (qO2 = 0.1 micromol/(10(6) cells h)). With a medium flow rate of 2.5 mL/min through the reactor, the model predicts that the 29-cm2 reactor can support at least 33.4 x 10(6) total cells when the inlet medium is in equilibrium with high (20%) oxygen concentration. The culture becomes oxygen limited however for the same flow rate for low (5%) oxygen concentration and can only support 7.2 x 10(6) total cells. Comparison of grooved vs nongrooved chambers reveals that the presence of grooves only affects solute transport on a local scale. This result is attributed to the small size (200 microgram) of the cavities relative to the chamber dimensions. The comparison also yields an empirical relation that allows for rapid estimation of oxygen and lactate concentrations in the grooves using only the numerical simulation of the simpler nongrooved chamber. Finally, our investigation shows that, while decreasing the spacing between cavities decreases the total number of cells the reactor can support, the efficiency of the reactor is increased by 25% (on an area basis) without growth restriction.

Bioreactors↗