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Biomedical subjects

C L McDowell

Publications and source records attributed to C L McDowell.

At least 19 recordsLinked to original sources
PubMed1998

Effects of methocel A15LV, polyethylene glycol, and polyvinyl alcohol on CD13 and CD33 receptor surface content and metabolism of HL60 cells cultured in stirred tank bioreactors.

Flow cytometry was used to examine the effect of hydrodynamic forces in a stirred tank bioreactor on the CD13 and CD33 receptor surface content of HL60 (human promyelocytic leukemia) cells. A step increase in agitation rate from 80 to 400 rpm reduced the HL60 cell apparent growth rate and increased the CD13 receptor surface content per cell, on average, by 95%. In contrast, this step increase in agitation rate to 400 rpm decreased the CD33 receptor surface content per cell, on average, by 10%. The protective effects of 0.1% Methocel A15LV, polyethylene glycol (PEG), and polyvinyl alcohol (PVA) on CD13 and CD33 receptor surface content were examined under agitation at 300 rpm in parallel 2 L bioreactor runs. The average CD33 receptor surface content was unaffected by the presence of Methocel A15LV or PEG, while PVA had a slight protective effect. In contrast, in terms of CD13 receptor content, HL60 cells agitated at 300 rpm with Methocel A15LV, PEG, or PVA behaved like cells agitated at 80 rpm with no media additives (McDowell and Papoutsakis, 1998). That is, Methocel A15LV, PEG, and PVA prevented the transduction of mechanical forces which affect CD13 cell content. HL60 cells cultured with 0.1% A15LV, PEG or PVA under conditions of mild agitation (60 rpm) in spinner flasks exhibited glucose consumption and lactate production rates that were approximately 20% lower than values of cultures containing no additive. Under conditions of agitation at 300 rpm in the 2 L bioreactor, the presence of A15LV, PEG, and PVA reduced the HL60 glucose consumption and lactate production rates by approximately 50%. Thus, media additives can dramatically reduce lactate accumulation in agitated bioreactors due to cell growth, in addition to providing protection from cellular injury.

Antigens, CD↗
PubMed1998

Serum increases the CD13 receptor expression, reduces the transduction of fluid-mechanical forces, and alters the metabolism of HL60 cells cultured in agitated bioreactors.

The effects of serum medium concentration on the CD13 receptor surface content and mRNA levels of HL60 (human promyelocytic leukemia) cells were examined using flow cytometry and Northern blotting. Increasing the serum concentration from 2.5% to 10% and from 5% to 10% increased the CD13 receptor surface content of HL60 cells by 100% and 25%, respectively, in spinner flasks agitated at 60 rpm. In bioreactors at 80 rpm, increasing the serum concentration from 2.5% to 10% and from 5% to 10% increased the CD13 receptor surface content by 60% and 35%, respectively. This increase in CD13 receptor surface content was correlated with a 30% and a 20% increase in CD13 mRNA levels. Increasing serum concentrations also increased the average HL60 cell size under non-damaging conditions (60 rpm in spinner flasks, 80 rpm in bioreactors). Under conditions of agitation at 300 rpm in 2 L bioreactors, increasing serum concentrations (2.5% vs. 10%, 5% vs. 10%) allowed for higher HL60 apparent growth rates, but decreased the CD13 receptor surface content and mRNA levels. In view of our earlier findings on the effects of agitation on the CD13 antigen, these data suggest that serum reduces the transduction of mechanical forces that affect CD13 expression. At 300 rpm, HL60 cells cultured in 10% serum exhibited glucose consumption and lactate production rates that were approximately 50% and 60% lower than the values of cells cultured in 5% and 2.5% serum, respectively.

Bioreactors↗
PubMed1998

Increased agitation intensity increases CD13 receptor surface content and mRNA levels, and alters the metabolism of HL60 cells cultured in stirred tank bioreactors.

Flow cytometry and Northern blotting were used to examine the effects of hydrodynamic forces in stirred tank bioreactors on CD13 receptor surface content and mRNA levels of HL60 (human promyelocytic leukemia) cells. A step increase in agitation rate from 80 to 300 or 400 rpm reduced the apparent HL60 growth rate in a dose-dependent manner. This step increase in agitation rate (to 300 or 400 rpm) also increased the CD13 receptor surface content on averge by 30% and 100%, respectively. This increase in CD13 receptor surface content was correlated with a 10% and a 60% increase in CD13 mRNA levels. We also observed a significant and very reproducible drop in CD13 expression over the course of a batch bioreactor run (80 rpm). Although we have no explanation for this, we show that the decrease in CD13 receptor surface content can be (at least partially, if not fully) explained by the corresponding decrease in CD13 mRNA. HL60 cell cultures agitated at 300 and 400 rpm exhibited glucose consumption and lactate production rates that were approximately 40% and 90% greater than values of the cultures agitated at 80 rpm. The physiological and practical implications of these results are discussed.

Antigens, Surface↗
PubMed1994

Residence time distributions of various tracers in tumors: implications for drug delivery and blood flow measurement.

BACKGROUND: The evaluation of rates of tumor blood flow with small, rapidly diffusing tracers requires an accurate model for mass transport within the tissue and tracer biodistribution. It is generally assumed that the whole tumor or several tumor regions act as well-mixed compartments, an assumption that has never been evaluated in tumors. PURPOSE: The purpose of this study was to assess the accuracy of compartmental flow models in tissue-isolated tumors. METHODS: We measured the residence time distributions of various tracers with the use of ex vivo perfusion of tissue-isolated rat R3230AC mammary tumors. This approach permits simultaneous, independent measurements of total blood flow and tracer concentrations in afferent and efferent vessels. The isolated tumors were perfused with Krebs-Henseleit solution, to which could be added D2O saline and either 3% by volume F44-E (a perfluorocarbon emulsion) or 1% by weight fluorescein isothiocyanate (FITC)-albumin. A pulse of D2O and one of the other tracers was added to the perfusing liquid, and the relative concentrations of both D2O and perfluorocarbon or FITC-albumin were measured in the tumor effluent. D2O and the perfluorocarbon were measured with an imaging spectrometer tuned to either 2H or 19F. FITC-albumin concentrations were measured by luminescence spectrometry. The results were analyzed using various compartmental models. RESULTS: The tracer residence time distribution deviated from that expected for a single well-mixed compartment. Only half of the D2O left the tumor with a time constant consistent with the known perfusate flow. The remainder exited the tumor more rapidly than expected, and neither vascular shunting nor macroscopic flow heterogeneity accounts for this component of the D2O flow. However, two-compartment models provide an improved fit to the data. CONCLUSIONS: Our experiments demonstrate that the simple compartmental model used to estimate blood flow with diffusible tracers is not accurate. IMPLICATIONS: The nonideal blood flow found in our experiments reflects phenomena that may have important effects in the development of pharmacokinetic models of drug delivery to tumors. The accuracy of blood flow measurements, made with such techniques as nuclear magnetic resonance, positron-emission tomography, and computed tomography, may also be affected when they rely on the assumption that the tumor is a collection of well-mixed compartments.

Adenocarcinoma↗
PubMed1994

Is right hemisphere decline in the perception of emotion a function of aging?

The hypothesis that the right cerebral hemisphere declines more quickly than the left cerebral hemisphere in the normal aging process was tested using accuracy and intensity measures in a facial recognition test and using response time and response bias measures in a tachistoscopic paradigm. Elderly and younger men and women (N = 60) participated in both experiments. Experiment 1 required facial affect identification and intensity ratings of 50 standardized photographs of 5 affective categories: Happy, Neutral, Sad, Angry, and Fearful. The elderly were significantly less accurate in identifying facial affective valence. This effect was found using negative and neutral expressions. Results for happy expressions, however, were consistent with the younger group. In Experiment 2, age differences in hemispheric asymmetry were evaluated using presentation of affective faces in each visual field. Following prolonged experience with the affective stimuli during Experiment 1, the elderly showed heightened cerebral asymmetry for facial affect processing compared to the younger group. Both groups showed a positive affective bias to neutral stimuli presented to the left hemisphere. Elderly and younger subjects scored significantly higher on Vocabulary and Block Design subtests of the WAIS-R, respectively. Overall, the findings suggest that the elderly have more difficulty processing negative affect, while their ability to process positive affect remains intact. The results lend only partial support to the right hemi-aging hypothesis.

Adolescent↗
PubMed1989

Tetraplegia.

A group of tetraplegic patients was asked to choose the function which they would prefer above all others if they could have one restored. The list of choices included sexual function, bowel and bladder function, walking, and hand function. Hand function was the most popular choice. Fortunately, the means to respond to their choice is available. Those tetraplegics who have been cared for in the past decades by interested reconstructive surgeons have had their wished-for hand function improved in a useful fashion.

Electric Stimulation Therapy↗
PubMed1977

Tendon healing: an experimental model in the dog.

Based upon the studies of the healing process in dogs in which profundus tendons were severed partially by a method in which the cut surfaces remained in contact and the area of division was in an undamaged area of the sheath, it was shown that healing of the tendon took place without evidence of vascular contribution from the sheath. Vascular loop patterns, similar to those seen in synovial lining of joints or on either side of the growth plate of growing bone, were found on the surface of the tendons in the area of mesotenon reflection, the osseotendinous junctions, where the vinculum joined the tendon, and in various areas of the tendon sheath. No other vessels were found. A theory for nutrition of the tendon is proposed analagous to that postulated for maintenance of cartilage, first with the formation of synovial fluid by the vascular loop system and then a diffusion phase dependent upon the repetitive loading and unloading of the tissue to force the fluid into the system of canaliculi in the tendon.

Animals↗