PubMed Health⌕ Search

Biomedical subjects

Michael D Kennedy

Publications and source records attributed to Michael D Kennedy.

11 recordsLinked to original sources
PubMed2006

Regional muscle oxygenation differences in vastus lateralis during different modes of incremental exercise.

BACKGROUND: Near infrared spectroscopy (NIRS) is used to assess muscle oxygenation (MO) within skeletal muscle at rest and during aerobic exercise. Previous investigations have used a single probe placement to measure MO during various forms of exercise. However, regional MO differences have been shown to exist within the same muscle which suggests that different areas of the same muscle may have divergent MO. Thus, the aim of this study was to examine whether regional differences in MO exist within the same muscle during different types of incremental (rest, 25, 50, 75, 100 % of maximum) exercise (1 leg knee extension (KE), 2 leg KE, or cycling). METHODS: Nineteen healthy active males (Mean +/- SD: Age 27 +/- 4 yrs; VO2max: 55 +/- 11 mL/kg/min) performed incremental exercise to fatigue using each mode of exercise. NIRS probes were placed on the distal and proximal portion of right leg vastus lateralis (VL). Results were analyzed with a 3-way mixed model ANOVA (probe x intensity x mode). RESULTS: Differences in MO exist within the VL for each mode of exercise, however these differences were not consistent for each level of intensity. Comparison of MO revealed that the distal region of VL was significantly lower throughout KE exercise (1 leg KE proximal MO - distal MO = 9.9 %; 2 leg KE proximal MO - distal MO = 13 %). In contrast, the difference in MO between proximal and distal regions of VL was smaller in cycling and was not significantly different at heavy workloads (75 and 100 % of maximum). CONCLUSION: MO is different within the same muscle and the pattern of the difference will change depending on the mode and intensity of exercise. Future investigations should limit conclusions on MO to the area under assessment as well as the type and intensity of exercise employed.

Journal Article↗
PubMed2005

Statistical approach for detection and localization of a fluorescing mouse tumor in Intralipid.

We present a method for detecting and localizing a fluorescing tumor obscured underneath several millimeters of a multiply scattering, homogeneous medium from fluorescence measurements made above the surface. Using a statistical model of the measurement system, we develop approaches for detection by use of a binary hypothesis testing approach and localization by use of maximum-likelihood estimation. We also compute the probability of tumor detection and the Cramér-Rao lower bound for the localization estimate error, which are performance metrics that could potentially be optimized in an experimental design. We validate the methods in an experimental study involving an excised mouse tumor tagged with a new folate-indocyanine dye and obscured under a tissue-simulating lipid suspension.

Algorithms↗
PubMed2005

Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia.

In the pathogenesis of atherosclerosis, macrophages become activated and play a crucial role in plaque formation. Activated synovial macrophages have recently been shown to express receptors for folic acid. We have determined whether activated macrophages also over-express folate receptor (FR) in atherosclerosis. Most normal cells express little or no FR, and, if FR is present on activated macrophages, folate-linked compounds and drugs could be selectively targeted to those cells that do express FR. To evaluate the FR on macrophages of atherosclerotic animals, golden Syrian hamsters were maintained on a hyperlipidemic diet until extensive vascular lesions had developed. Uptake of folic acid conjugated to fluorescent tags was then examined in tissue fragments from lesion-prone areas, and peritoneal activated macrophages were harvested from the same animals. Spectrofluorimetric and fluorescence microscopic analyses showed a significantly greater uptake of folate-conjugates by peritoneal macrophages of hyperlipidemic hamsters compared with those of hamsters fed a normal or folate-deficient diet. Systemically administered folate-fluorescent conjugates were found to accumulate as bright spots in protrusions of atherosclerotic plaques populated by macrophages, whereas a low level of fluorescence was detected uniformly dispersed across the lesion. The uptake of the folate conjugate by U937 macrophage cells grown in a high-lipid culture medium was significantly higher than in controls. Our data thus indicate that hyperlipidemic conditions induce an increased uptake of folate attributable to the over-expression of FRs on activated macrophages. This increase in FR expression can be exploited to deliver folate-linked compounds selectively to atherosclerotic lesions.

Animals↗
PubMed2005

Erythrocyte adhesion is modified by alterations in cellular tonicity and volume.

We tested the hypothesis that dehydration-induced alterations in red blood cell (RBC) membrane organisation or composition contribute to sickle cell adhesion in sickle cell disease (SCD). To examine the role of RBC hydration in adhesion to the subendothelial matrix protein thrombospondin-1 (TSP), normal and sickle RBCs were incubated in buffers of varying tonicity and tested for adhesion to immobilised TSP under flow conditions. Sickle RBCs exhibited a decrease in TSP binding with increasing cell hydration (P<0.005), suggesting that cellular dehydration may contribute to TSP adhesion. Consistent with this hypothesis, normal RBCs showed an increase in TSP adhesion with increasing dehydration (P<0.01). Furthermore, increased TSP adhesion of normal RBCs could also be induced by isotonic dehydration using nystatin-sucrose buffers. Finally, TSP adhesion of both sickle RBCs and dehydrated normal RBCs was inhibited by the anionic polysaccharides, chondroitin sulphate A and high molecular weight dextran sulphate, but not by competitors of CD47-, band 3-, or RBC phosphatidylserine-mediated adhesion. More importantly, we found increased adhesion of nystatin-sucrose dehydrated normal mouse RBCs to kidney capillaries following re-infusion in vivo. In summary, these findings demonstrate that changes in hydration can significantly impact adhesion, causing normal erythrocytes to display adhesive properties similar to those of sickle cells and vice versa.

Adolescent↗
PubMed2004

Uptake and trafficking of fluorescent conjugates of folic acid in intact kidney determined using intravital two-photon microscopy.

Intravital two-photon microscopy was used to follow the uptake and trafficking of fluorescent conjugates of folic acid in the rat kidney. Intravenously administered folate-linked dye molecules quickly filled the plasma volume but not cellular components of the blood. Glomerular filtration occurred immediately and binding to proximal tubule cells was seen within seconds. Fluorescence from a pH-insensitive conjugate of folic acid, folate Texas red (FTR), was readily observed on the apical surface of the proximal tubules and in multiple cellular compartments, but little binding or uptake could be detected in any other kidney cells. Fluorescence from a pH-sensitive conjugate of folic acid, folate fluorescein, was seen only on the apical surface of proximal tubule cells, suggesting that internalized folate conjugates are localized to acidic compartments. The majority of the FTR conjugate internalized by proximal tubules accumulated within a lysosomal pool, as determined by colocalization studies. However, portions of FTR were also shown by electron microscopy to undergo transcytosis from apical to basal domains. Additional studies with colchicine, which is known to depolymerize microtubules and interrupt transcytosis, produced a marked reduction in endocytosis of FTR, with accumulation limited to the subapical region of the cell. No evidence of cytosolic release of either folate conjugate was observed, which may represent a key difference from the cytosolic deposition seen in neoplastic cells. Together, these data support the argument that folate conjugates (and, by extrapolation, physiological folate) bind to the apical surface of proximal tubule cells and are transported into and across the cells in endocytic compartments.

Animals↗
PubMed2003

Effects of a comprehensive cardiac rehabilitation program on quality of life and exercise tolerance in women: A retrospective analysis.

BACKGROUND: Currently, there are a lack of investigations that have examined the effect of participating in a comprehensive cardiac rehabilitation program on quality of life and physiological measures in women of different ages. The purpose of this investigation was to examine the effect of participating in a comprehensive cardiac rehabilitation program on quality of life, exercise tolerance, blood pressure and lipids in women between 33 and 82 years of age. METHODS: The 126 women participated in a 14-week cardiac rehabilitation program that consisted of 7 weeks of formal supervised exercise training and 7 weeks of unsupervised exercise and lifestyle modification. Physiologic and quality of life outcome measures obtained at the outset and after 14 weeks included: 1) exercise treadmill time; 2) resting and peak systolic and diastolic blood pressure; 3) total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and Triglycerides; 4) Cardiac Quality of Life Index questionnaire. RESULTS: Significant improvements were found in the following quality of life measures after participating in the cardiac rehabilitation program: physical well being, psychosocial, worry, nutrition and symptoms. No significant differences were seen for any QOL variable between the different age groups. Significant improvements were seen in exercise tolerance (+21%) and high density lipoprotein (+5%). CONCLUSION: Cardiac rehabilitation may play an important role in improving quality of life, exercise tolerance and high density lipoprotein cholesterol levels in younger and older women with underlying cardiovascular disease.

Journal Article↗
PubMed2003

Evaluation of folate conjugate uptake and transport by the choroid plexus of mice.

PURPOSE: Because the choroid plexus (CP) is enriched in cell surface folate receptors, an investigation was initiated to evaluate whether folate receptor-mediated transcytosis might be exploited to deliver folate conjugates into the brain. METHODS: Balb/c mice were injected with radioactive and fluorescent conjugates of folate to measure and image their uptake by the CP. RESULTS: Retention of a radioactive folate conjugate, folate-diethylenetriaminepentaacetic acid (DTPA)-111In, into the brain of balb/c mice was observed, although repeated injections or prolonged release via an osmotic pump of the compound did not result in increased brain uptake. Uptake of an 125I-labeled anti-folate receptor antibody into the brain was very low, and no competition was observed with unlabeled antibody. Imaging of brain thin-sections and whole brain tissue from a mouse injected with folate-fluorescein revealed strong fluorescence in the CP, but virtually no where else in the brain. CONCLUSIONS: Both fluorescence and radioimaging results demonstrate specific uptake of small molecular weight folate conjugates into CP cells of the murine brain, but no significant transport of the molecules across the CSF. Furthermore, no uptake of larger folate-linked proteins by choroid plexus cells is observed, suggesting folate conjugate size may strongly influence access to CP folate receptors.

Animals↗
PubMed2003

Optical imaging of metastatic tumors using a folate-targeted fluorescent probe.

We describe the use of a tumor targeting ligand, the vitamin folic acid, to deliver an attached fluorescent probe to both primary and metastatic tumors overexpressing the folate receptor. Upon laser excitation, derived images of normal tissues generally show little or no fluorescence, whereas images of folate receptor-expressing tumors display bright fluorescence that can be easily distinguished from adjacent normal tissue. Furthermore, metastatic tumor loci of submillimeter size can also be visualized without the aid of image processing or enhancement. The sharp distinction between tumor and normal tissues provided by this technique could find application in the localization and resection of tumor tissue during surgery or in the enhanced endoscopic detection and staging of cancers.

Animals↗
PubMed2003

Development of race profiles for the performance of a simulated 2000-m rowing race.

The purpose of this study was to determine the race profile for a 2000-m simulated rowing race as well as the effect of training and gender on the race profile. Nineteen men and 19 women undertook a 2000-m simulated rowing race before and after 10 weeks of a typical off-season training program for rowing. Velocity was calculated every 200 m and the deviation in velocities from the mean race velocity (MRV) was plotted every 200 m to produce race profiles for each gender before and after training. The three fastest male rowers varied approximately 0.02 m.s from the MRV after training and displayed a constant-pace model. The fastest female rowers displayed an all-out strategy after training, producing large deviations from MRV. Average squared deviations from the mean (SDM) determined that all groups except the fastest females had a reduction in MRV deviation after training. These results suggest that the optimal race profile for a simulated 2000-m rowing race may be different between genders. Training reduces SDM and influences both male and female pacing patterns such that both exhibit a pacing strategy that is more similar to that of elite athletes in other events of similar and shorter duration.

Adult↗
PubMed2003

Modeling the relationship between velocity and time to fatigue in rowing.

INTRODUCTION: Several mathematical models describe the relationship between velocity and time to fatigue. PURPOSE: The purposes of this study were to evaluate different critical velocity (V(critical)) models applied to rowing ergometry and to investigate prediction of performance time in a 2000-m race based on results from shorter trials. METHODS: Sixteen men performed seven rowing ergometer tests. Velocity and time to fatigue data from the 200-m (approximately 0.5 min) to 1200-m (approximately 3 min) trials and from the 200-m to 2000-m (approximately 6.5 min) trials were fit to a two-parameter hyperbolic model, a three-parameter hyperbolic model, and a three-parameter exponential model. RESULTS: Including data from the 2000-m trial generally resulted in higher R2 and smaller SEE. V(critical) from the three versions of the two-parameter model were 4.71 +/- 0.28 m x s(-1), 4.80 +/- 0.27 m x s(-1), and 5.04 +/- 0.24 m x s(-1) (P < 0.001). The two three-parameter models had high R2 (0.991 and 0.990, respectively) and generated parameter estimates that appeared reasonable. Time for a 2000-m race was predicted better using the two-parameter model (r > 0.974) than using the three-parameter models (r = 0.820-0.870). CONCLUSION: It is necessary to include the relatively long 2000-m predicting trial to describe accurately the velocity-time relationship in rowing. The two-parameter model may be useful in predicting time for a 2000-m race but is not otherwise appropriate for modeling when predicting trials of <1 min duration are included. Choice of model and duration of trials must be considered when using mathematical modeling to derive V(critical) and other parameters in rowing.

Adult↗