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Biomedical subjects

R G Knowlton

Publications and source records attributed to R G Knowlton.

At least 55 records · Page 3Linked to original sources

Physiological and biomechanical differences between wheelchair-dependent and able-bodied subjects during wheelchair ergometry.

The purpose of this study was to compare the physiological and biomechanical responses of wheelchair-dependent persons (WCD) to able-bodied persons (AB) during manual wheelchair ergometry. Five WCD and five AB performed a discontinuous wheelchair ergometer test starting at 12.8 W at 30 rev.min-1 (57 m.min-1) with increments of 7.0 W at 6-min intervals. Biomechanical data were collected 3.5 min into each stage followed by the collection of physiological data. After the fifth stage, peak oxygen consumption was determined by having the subject work against a resistance of 14.7-19.6 N at 30 rev.min-1. The WCD had significantly higher net mechanical efficiency at 26.7, 33.6 and 40.6 W in comparison to the AB. The WCD had significantly greater shoulder extension at the point of initial wheel contact as measured by the shoulder angle, while the AB had significantly greater shoulder range of motion at all work rates in comparison to the WCD. The results demonstrate that a significant physiological difference exists in the manner by which WCD and AB accomplish wheelchair ergometry. The biomechanical differences between AB and WCD were found to be a prominent factor contributing to the higher mechanical efficiency of WCD over AB. It was concluded that basic physiological and biomechanical differences exist between WCD and AB in manual wheelchair locomotion and that these differences are important considerations to the interpretation of data in wheelchair ergometry studies.

Adult↗

Partial deletions of a sequence family ("DXS278") and its physical linkage to steroid sulfatase as detected by pulsed-field gel electrophoresis.

pCRI-S232 (DXS278) is a 7-kb genomic sequence that hybridizes to multiple polymorphic X-linked restriction fragments on standard Southern analysis. Physical mapping of pCRI-S232 by pulsed-field gel electrophoresis (PFGE) suggests that a sequence in S232 is repeated in multiple X-chromosomal regions in normal individuals. Steroid sulfatase (STS) and DXS237 each hybridize to two of six X-linked SfiI fragments detected by S232. Two independent familial STS deletions, one of which is associated with a phenotype of ichthyosis plus ocular albinism (XI/OA1) and the other with nystagmus plus Rud syndrome, lack some but not all of the normal S232 PFGE fragments. We isolated a DNA fragment, E25B1.8, from a cosmid that contains S232. E25B1.8 detects a subset of the S232 polymorphic fragments on standard Southern blots plus new constant fragments; some, but not all, of the E25B1.8-hybridizing fragments are deleted in the XI/OA1 and Rud syndrome/nystagmus males. The simpler, but highly informative, polymorphism detected by E25B1.8 (DXS452) also eliminates an "intralocus" recombination seen with S232. We conclude that (1) males with STS deletions and complex phenotypes are partially deleted for DXS278, (2) DXS237 and part of DXS278 lie within 800 kb of STS, and (3) a repeat sequence within or around pCRI-S232 is probably located in multiple X-chromosomal locations spanning at least 2-3 Mb.

Arylsulfatases↗

Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans.

Because it has previously been shown that it takes much more caffeine to cause fat mobilization in vitro than in vivo, it has been suggested that there may be an active metabolite working with caffeine causing an increase in lipolysis in vivo. To determine the relationship between the appearance of paraxanthine (caffeine's major dimethylxanthine metabolite) and free fatty acid (FFA) mobilization after intravenous caffeine administration, 10 men were studied at rest after receiving a dose of 4 mg/kg lean body mass. Venous blood samples were obtained before dosing and at minutes 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180. Serum levels of FFA, glycerol, caffeine, and paraxanthine were determined in duplicate. Concentrations of FFA and glycerol were corrected for plasma volume changes. A high negative correlation was seen between decreases in caffeine and increases in FFA (r = -0.90) and a high positive correlation was seen between the appearance of paraxanthine and FFA (r = 0.93). It was concluded that paraxanthine may play a role in increased lipolysis after caffeine administration in humans.

Adult↗

Circulatory and thermal adjustments to prolonged exercise in paraplegic women.

The circulatory and thermal responses to 90 min of wheelchair ergometer exercise were examined in five wheelchair dependent (WD) women with low level spinal dysfunction and five able-bodied (AB) women who served as a comparison group. Metabolic rate during exercise was 221 W for WD and 255 W for AB (P greater than 0.05). Oral temperature (Tor), mean skin temperature (Tsk), oxygen uptake (VO2), heart rate (HR), and cardiac output (Qc) were assessed periodically throughout the exercise period. Ambient conditions were 24-25 degrees C and 38-52% relative humidity. A significant group X time interaction was found for Tor (P less than 0.001) and Tsk (P less than 0.001). Tor of the WD group steadily increased during the exercise, whereas the AB group showed a stable Tor. Tsk of WD increased rapidly during the first 5-10 min of exercise and continued to rise at a slower rate throughout the exercise. In contrast, Tsk of AB rose to a peak during the first 10 min and then showed a decreasing trend. VO2 and HR remained stable in both groups throughout the exercise period. Following an initial increase in Qc from minute 10 to minute 20 in both groups, values for WD continually decreased until Qc at 80 min was 14% lower than at 10 min. The findings suggest that the WD women had greater thermoregulatory strain than the AB women as indicated by a higher Tor and Tsk and by an inability to maintain Qc due to paralysis of the lower limbs and perhaps an increase in cutaneous blood volume.

Body Temperature↗

Venous and fingertip blood to calculate plasma volume shift following exercise.

This study determined whether fingertip blood samples used to calculate percentage change in calculated plasma volume following exercise were in agreement with values obtained from venous blood samples. Twenty-five subjects engaged in two cycle ergometer exercises at 100 and 200 W, with percentage plasma volume shift (% PVS) determined after each from venous (VB) and fingertip (FT) blood. Values for % PVS were FT -6.25% compared with VB -8.04% (P less than 0.05), with the correlation between the two methods at r = 0.88. The following equation was established: corrected FT % PVS = (0.8662 * FT) - 2.625; SEE = 2.60%. In order to cross-validate this equation, fifteen additional subjects submitted to VB and FT. Corrected FT % PVS using the established equation resulted in a mean value of 9.53 compared with 10.53% for actual VB % PVS. Although these means were not significantly different, there was approximately a 25% chance that the corrected FT % PVS would be more than one standard error of estimate from the regression line. It was concluded that FT underestimates VB % PVS. However, when limited to group data, FT can be corrected to favorably represent VB % PVS following moderate to heavy cycle ergometer exercise.

Adult↗

Krabbe disease locus mapped to chromosome 14 by genetic linkage.

Using genetic linkage we have localized the gene coding for galactocerebrosidase (GALC) to human chromosome 14. Patients with Krabbe disease and their family members were assayed for GALC activity in leukocytes or fibroblasts and were classified as affected, carrier, noncarrier, or unknown. Polymorphic DNA markers from chromosome 14 demonstrated a multipoint LOD score of 3.40 with GALC located 13 cM centromere distal to CRI-C70 (D14S24). This finding is consistent with the location of the mouse twitcher mutation (a model of human GALC deficiency) on chromosome 12, which has substantial homology to human chromosome 14. Our data do not support a previous report's localization of GALC to chromosome 17.

Chromosomes, Human, Pair 14↗

Circulatory and metabolic responses of women to arm crank and wheelchair ergometry.

This study compared the circulatory and metabolic responses of arm crank ergometer (ACE) exercise to those of wheelchair ergometer (WCE) exercise during maximal and submaximal intensities. Maximal intensity exercise was defined as the highest power output (PO) achieved on each ergometer. The submaximal responses were compared at an equivalent absolute (PO = 25W) and relative (66% peak oxygen uptake [VO2]) intensity. On separate days and in random sequence, nine untrained able-bodied women performed a discontinuous incremental test for peak VO2 using either ACE or WCE. Each exercise bout was approximately six minutes, interspersed with four-minute rest periods. VO2 and heart rate (HR) were measured during each stage of the test and blood lactate concentrations were measured five minutes postexercise. Peak PO, ventilation (VE), and HR were significantly higher (p less than 0.05) on the ACE, with no significant difference in peak VO2 or postexercise blood lactate concentration. When compared at equivalent submaximal PO levels (25W), VO2, VE, and HR were significantly higher (p less than 0.05) on the WCE than on the ACE. In contrast, ACE exercise elicited a higher PO (p less than 0.05) at an equivalent relative metabolic load (66% peak VO2). These results suggest that in women wheelchair ergometry is less metabolically efficient than arm crank ergometry at submaximal exercise intensities. However, at maximal intensity exercise, ACE exercise imposes greater central circulatory stress. The finding that a higher peak HR was elicited by the ACE than the WCE suggests that exercise testing needs to be ergometer-specific when the results are to be used for exercise prescription.

Adult↗

An extremely polymorphic locus on the short arm of the human X chromosome with homology to the long arm of the Y chromosome.

A genomic DNA clone named CRI-S232 reveals an array of highly polymorphic restriction fragments on the X chromosome as well as a set of non-polymorphic fragments on the Y chromosome. Every individual has multiple bands, highly variable in length, in every restriction enzyme digest tested. One set of bands is found in all males, and co-segregates with the Y chromosome in families. These sequences have been regionally localized by deletion mapping to the long arm of the Y chromosome. Segregation analysis in families shows that all of the remaining fragments co-segregate as a single locus on the X chromosome, each haplotype consisting of three or more polymorphic fragments. This locus (designated DXS278) is linked to several markers on Xp, the closest being dic56 (DXS143) at a distance of 2 cM. Although it is outside the pseudoautosomal region, the S232 X chromosome locus shows linkage to pseudoautosomal markers in female meiosis. In determining the X chromosome S232 haplotypes of 138 offspring among 19 families, we observed three non-parental haplotypes. Two were recombinant haplotypes, consistent with a cross-over among the S232-hybridizing fragments in maternal meiosis. The third was a mutant haplotype arising on a paternal X chromosome. The locus identified by CRI-S232 may therefore be a recombination and mutation hotspot.

Cell Line↗

The effect of voluntary ventilation on acid-base responses to a Moo Duk Tkow form.

Voluntary control of breathing is taught in Moo Duk Tkow in order to maximize force during striking, kicking, and blocking. Form, a formalized practice routine which incorporates these techniques, is a short predetermined sequence of arm and leg movements performed at high intensity which includes a number of pauses. The purpose of this study was to investigate the acid-base and lactate responses to a beginning level form, Ki Cho I. Nine subjects, five black belts and four brown belts, were asked to perform Ki Cho I at competitive intensity. Arterialized finger capillary blood was drawn prior to and immediately after the form for the determination of pH, bicarbonate, base excess, and PCO2 by use of the Siggaard-Anderson Nomogram. Heart rate was obtained by ECG, and lactate was measured by enzymatic assay. Statistically significant differences (p less than .05) were found for all variables. Mean pre and post values (+/- standard deviations) were: pH 7.39 +/- .04 to 7.34 +/- .03; base excess -.3 +/- 1.2 to -2.8 +/- 1.7 mEq/L; bicarbonate 23.7 +/- 1.0 to 21.8 +/- 1.4 mEq/L; PCO2 39.9 +/- 3.9 to 45.1 +/- 5.4 mmHg; lactate 1.51 +/- .71 to 3.23 +/- 1.56 mM; and heart rate 74.9 +/- 12.6 to 132.1 +/- 17.0 bpm. The mean form time was 17.2 +/- 1.8 s. It was concluded that respiratory compensation does not occur and that respiratory acidosis may contribute to the metabolic acidosis.

Acid-Base Equilibrium↗

Cardiovascular and ventilatory responses during formalized T'ai Chi Chuan exercise.

T'ai Chi Chuan (TCC) is a widely practiced Chinese martial art said to physically develop balance and coordination as well as enhance emotional and mental health. TCC consists of a series of postures combined into a sequential movement providing a smooth, continuous, low-intensity activity. The purpose of this study was to examine the ventilatory and cardiovascular responses to the Long Form of Yang's style TCC. In addition, the subjects' TCC responses were compared to their ventilatory and cardiovascular responses during cycle ergometry at an oxygen consumption (VO2) equivalent to the mean TCC VO2. Six experienced (M = 8.3 yrs) male TCC practitioners served as subjects with data collected during the Cloud H and movement of the TCC exercise. Significantly (p less than .05) lower responses for ventilatory frequency (Vf) (11.3 and 15.7 breaths.min-1), ventilatory equivalent (VE/VO2) (23.47 and 27.41), and the ratio of dead space ventilation to tidal volume (VD/VT) (20 and 27%) were found in TCC in comparison to cycle ergometry. The percentage of minute ventilation used for alveolar ventilation was significantly higher during TCC (p less than .03) than cycle ergometry, with mean values of 81.1% and 73.1%, respectively. Cardiac output, stroke volume, and heart rate were not significantly different between TCC exercise and cycle ergometry at the same oxygen consumption. We concluded that, during TCC, expert practitioners show significantly different ventilatory responses leading to more efficient use of the ventilatory volume than would be expected from comparable levels of exertion on a cycle ergometer.

Adult↗

Chromosomal assignment of 14 genomic probes for highly polymorphic loci.

Over 500 probes revealing restriction fragment length polymorphisms (RFLPs) have been isolated by Schumm et al. (1988). We describe here the chromosomal assignment of 14 of the most highly polymorphic markers in that set of probes, with polymorphism information content values of up to 0.98. The probes were mapped using a panel of human x rodent somatic cell hybrids and were found to be distributed among nine different autosomes. Chromosome localization of such highly polymorphic markers has been an important step in the construction of the human genetic map, as a large number of RFLP probes has now been localized by genetic linkage studies to these loci.

Animals↗

Genetic linkage analysis of hereditary arthro-ophthalmopathy (Stickler syndrome) and the type II procollagen gene.

Hereditary arthro-ophthalmopathy (AO), or Stickler syndrome, is a dominantly inherited disorder characterized by vitreo-retinal degeneration and frequently accompanied by epiphyseal dysplasia and premature degenerative joint disease. Three large families with AO were analyzed for clinical manifestations of the disease and for coinheritance of the genetic defect with RFLPs in the type II procollagen gene (COL2A1). Genetic linkage between AO and COL2A1 was demonstrated in the largest family, with a maximum LOD score of 3.52 at a recombination distance of zero. Data from a second family also supported linkage of AO and COL2A1, with a LOD score of 1.20 at a recombination distance of zero. These results are consistent with the conclusion that mutations in the COL2A1 gene are responsible for AO in these two families. In a third AO family, however, recombination between AO and COL2A1 occurred in at least one meiosis, and the data were inconclusive with respect to linkage.

Chromosomes, Human, Pair 12↗

The effects of arm crank training on the physiological responses to submaximal wheelchair ergometry.

The purpose of this investigation was to examine the cardiovascular and metabolic effects of a 5 wk arm crank (AC) training program on submaximal wheelchair (WC) ergometry in able-bodied women. The 6 subjects in the training group (TG) and 4 in the control group (CG) performed a 10 min WC exercise prior to and following the training period at a power output (PO) that elicited 70% of the pre-training peak oxygen uptake (VO2). Steady state VO2, heart rate (HR), cardiac output (Qc) and stroke volume (Vs) were measured. Resting and post-exercise blood lactate concentrations (LA) were measured, the difference was recorded as net LA. The TG exercised on the AC 3 d.wk-1 at a PO that elicited 85% of each subject's recorded peak HR. Each session consisted of four 4 min exercise bouts preceded by a 2 min warm-up and interspersed with 2 min rest periods. After training, the TG had a significantly (p less than 0.05) lower HR, larger Vs and lower LA in response to the WC exercise. Qc and VO2 were not significantly altered. The results demonstrate that the AC exercise program used in this study produced a physiological training effect which was observed during submaximal WC exercise of an intensity frequently encountered during daily WC ambulation. It appears that short-term, moderate intensity AC training offers an adequate stimulus to reduce the stress imposed by wheelchair locomotion.

Adult↗

Identification of more than 500 RFLPs by screening random genomic clones.

As part of our genome-mapping effort, we undertook a large-scale screening study to identify RFLPs useful as genetic markers. Some 1,664 single-copy or repeat-containing phage clones from a Charon 4A genomic library were tested for polymorphism against a panel of DNAs, from five unrelated individuals, digested with eight restriction enzymes. Approximately 30% (515) of the clones revealed polymorphism by Southern hybridization; 67 loci detected had PIC values greater than .5. Restriction enzymes MspI, TaqI, and RsaI were most efficient in detecting polymorphism within the 1-20-kb-fragment size range resolved. With only one exception each of the clones detected polymorphism originating from a single locus.

Cloning, Molecular↗

The effects of obesity and exercise on the pharmacokinetics of caffeine in lean and obese volunteers.

The effects of obesity, exercise, and the interaction of obesity and exercise were examined in 6 caffeine naive, untrained, nonsmoking, college males (3 lean (LV), 3 obese (OV]. Each subject received caffeine (oral, 5.83 mg X kg-1 lean body weight) or placebo (50 mg citrate) prior to 3 h of seated rest and prior to 90 min of treadmill walking (40% of their maximal aerobic power) followed by 90 min of seated recovery. Serum samples were collected at various times and analyzed for caffeine by HPLC. Pharmacokinetic analysis indicated that at rest, OV had a significantly higher absorption rate constant (Ka 0.0757 vs. 0.0397 min-1), lower elimination rate constant (Ke 0.0027 vs. 0.0045 min-1), and longer serum half-life (t1/2 4.37 vs. 2.59 h) in comparison to LV. In exercise, as well as at rest LV and OV had a large difference in the volume of distribution (43.2 vs. 101.1) (rest, 54.1 vs. 103.1). Exercise consistently resulted in a decrease in the maximal serum concentration of caffeine and the area under the curve in OV while having no consistent effect on LV. The interactive effects of obesity and exercise could not be dissociated. However, these results demonstrate that both obesity and exercise have modified the pharmacokinetics of caffeine.

Adult↗