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Biomedical subjects

R G Knowlton

Publications and source records attributed to R G Knowlton.

At least 73 records · Page 4Linked to original sources
PubMed1987

Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation.

We have studied the feasibility of using DNA restriction fragment-length polymorphisms (RFLP) to study marrow engraftment in 27 patients after allogeneic bone marrow transplantation, and have compared these results with those obtained using red blood cell antigens, cytogenetics, and immunoglobulin allotypes. Using highly polymorphic DNA probes, we have documented stable chronic mixed hematopoietic chimerism, have identified transient mixed chimeras, have excluded mixed chimerism with high probability in retrospective studies even when a pretransplant DNA sample was not available, have documented marrow engraftment in the early posttransplant period, and have studied the origin of leukemic cells in patients with recurrent disease. We have evaluated the advantages and disadvantages of several genetic markers and have developed tentative statements concerning the prognosis of patients with mixed chimerism. We conclude that DNA RFLP are powerful and practical genetic markers in bone marrow transplantation studies and that further studies of mixed hematopoietic chimerism are warranted.

Antigens, Surface↗
PubMed1987

Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies.

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

Acute Disease↗
PubMed1987

Plasma volume changes and cardiovascular responses associated with weight lifting.

Ten experienced weight lifters were studied to determine the influence of strenuous, free-weight, squat lift exercise on changes in plasma volume, mean arterial pressure, and the rate pressure product. After a 40-min postural adjustment prior to upright exercise, each subject completed eight sets of eight repetitions of the squat exercise at 55% of the one-repetition maximum. Electrocardiogram heart rate was monitored throughout the test, and blood pressure was determined at the completion of each exercise set. Arterialized capillary blood was drawn during sitting and standing pre-exercise and at the end of the second, fourth, sixth, and eighth sets for the measurement of hemoglobin, hematocrit, and plasma protein concentration, and after the last set for blood lactate. Five additional subjects participated in a postural control comparison. The results of the ANOVA showed a significant loss in plasma volume over the trials which was 2 1/2 times greater than for the control subjects (17.9 vs 7.7% loss) over the same period of time. Exercise rate pressure product increased by 2.85 times resting while only 1.1 times resting for the control subjects. An elevation in mean arterial pressure was found to be correlated to changes in plasma volume, r = -0.98. This study found that plasma volume is reduced while the rate pressure product is increased during the squat lift exercise.

Adult↗
PubMed1986

Metabolic responses of women to exercise attributable to long term use of a manual wheelchair.

The purpose of this study was to determine the effects of long term use of a manual wheelchair by wheelchair-confined women (means = 14.6 years) on physiological responses to wheelchair ergometry. Six experimental subjects were compared to six able bodied women during maximal exercise as well as submaximal wheelchair ergometry at 50 and 80% of peak VO2. The wheelchair dependent women achieved higher power outputs, greater efficiency at the higher submaximal workload, less metabolic acidosis during submaximal exercise as well as less ventilatory stress. There was no significant difference in peak VO2 between the two groups of women. Because these were not athletically trained women, it was concluded that the long term use of a manual wheelchair leads to physiological adaptations favourable to the daily requirements of wheelchair locomotion.

Acid-Base Equilibrium↗
PubMed1986

Relationships of aerobic capacity and percent body fat with plasma free fatty acid following walking.

We investigated relationships of peak VO2 and percent body fat with postexercise plasma free fatty acid (FFA) and glycerol concentrations in 14 men using multiple-regression techniques. During 1 h of walking (36% of peak VO2), no significant differences in plasma-FFA response were attributed to either peak VO2 or percent body fat. However, individuals with higher peak VO2S tended to have greater elevations in plasma-glycerol concentration during exercise (p = 0.074). They also had greater peak FFA concentrations and FFA X glycerol(-1)-molar ratios immediately after exercise and faster subsequent clearing of excess FFA from the blood (p less than 0.05). Percent fat was not related to postexercise plasma glycerol, FFA, FFA X glycerol-1 responses. Differing postexercise FFA responses, as related to peak VO2, were due, not to varying rates of lipolysis but rather to different rates of FFA mobilization and utilization.

Adipose Tissue↗
PubMed1986

Characterization of a spontaneous mutation to a beta-thalassemia allele.

We have studied a nuclear family containing a single child with severe beta-thalassemia intermedia, a Greek-Cypriot mother with hematological findings of beta-thalassemia trait, and a Polish father who is hematologically normal. Since both the child and her father were heterozygous for a DNA polymorphism within the beta-globin gene, it was possible to clone and sequence the beta-globin gene identical by descent from both the child and her father. A nonsense mutation in codon 121 (GAA----TAA) was found in the beta-globin gene of the child, while the same gene from her father lacked this mutation and was normal. This mutation has not been previously observed among over 200 beta-thalassemia genes characterized in Caucasians. Since the mutation eliminates an EcoRI site in the beta-globin gene, we could show that the mutation is not present in genomic DNA of the father. To rule out germinal mosaicism, sperm DNA of the father was also digested with EcoRI, and the mutant EcoRI fragment was not observed under conditions that would detect the mutation if it were present in at least 2% of sperm cells. Routine HLA and blood group testing supported stated paternity. In addition, studies with 17 DNA probes that detect multiple allele polymorphisms increased the probability of stated paternity to at least 10(8):1. These data provide evidence that the G----T change in codon 121 of the beta-globin gene in the child is the result of a spontaneous mutation that occurred during spermatogenesis in a paternal germ cell.

Alleles↗
PubMed1986

Use of highly polymorphic DNA probes for genotypic analysis following bone marrow transplantation.

The use of DNA markers known as restriction fragment length polymorphisms is a sensitive and informative method of distinguishing patient and allogeneic donor cells after bone marrow transplantation. To apply the test, it is necessary in each case to find DNA probes that display patient-specific and donor-specific bands in Southern transfer hybridization. We have isolated a set of 12 cloned DNAs from highly polymorphic loci by which siblings can usually be distinguished. With just four of these probes, we can expect to distinguish the genotypes of the recipient and a sibling donor in more than 99% of cases (except between identical twins). The availability of many highly polymorphic probes also allows selection of an optimal probe for each case, one that can detect both the patient and donor-specific bands in a single hybridization with maximum resolution and sensitivity. We have applied these probes to the analysis of cells from peripheral blood and bone marrow after transplantation and demonstrated their usefulness in confirming engraftment of donor cells or graft rejection, and in detecting mixed lympho-hematopoietic chimerism.

Base Sequence↗
PubMed1985

Plasma FFA responses to prolonged walking in untrained men and women.

Gender differences in plasma FFA responses to 90 min of treadmill walking at 35% VO2max were investigated in six men and six women following an overnight fast. The subjects represented average values for maximal oxygen uptake and body fat percentage for age and gender. Mean plasma FFA concentration at 45 and 90 min of exercise were significantly (P less than 0.05) higher for women (0.82 mmol X 1(-1), 0.88 mmol X 1(-1)) than men (0.42 mmol X 1(-1), 0.59 mmol X 1(-1)). Lower R values for women throughout the exercise period indicated a greater percentage fat in total metabolism than for men while the FFA/glycerol results supported greater lipolytic activity for women. The uniformity of percent fat in metabolism for women from rest to exercise showed that FFA release from adipose tissue increased rapidly with the onset of exercise which was not the case for men. Comparison of metabolic data as well as a statistical analysis (ANCOVA) controlling for the influence of VO2max and percentage body fat on FFA plasma concentration suggested that gender differences in FFA responses to prolonged submaximal exercise can be expected to occur in untrained subjects.

Adult↗
PubMed1983

Simple method to determine sincerity of effort during a maximal isometric test of grip strength.

The purpose of this study was to establish a simple method to determine the legitimacy of a maximal voluntary grip contraction (MVGC). To achieve this, 36 subjects were randomly assigned to either a sincere (S) or faker group (F) and asked without investigator knowledge to execute either a MVGC or 75% MVGC on a specially designed grip dynamometer. The dynamometer was attached to a load cell with analog output obtained from a strip chart recorder at 50 mm X sec.-1. The force curves were evaluated empirically and also analyzed according to the following components: rate of force application (SLP), peak force (PK), average force divided by peak force (DEV) and peak force divided by body weight (WTRATIO). Average values for S and F subjects respectively were; SLP 2217 vs 1642 n X s-1, PK 499 vs 387 n, and DEV 0.91 vs 0.72. When all variable were transformed to z-scores, summed for each subject and categorized by sum into upper and lower 50% groups by gender, 87.5% of the females (N = 16) and 80% of the males (N = 20) were correctly classified as S or F subjects. Based upon a discriminant analysis performed by gender, DEV was found to be the only significant predictor for females with DEV, SLP and WTRATIO being significant predictors for the males. It was concluded that S and F subjects can be determined from the results of a maximal isometric grip strength test based upon a simple configuration analysis of an isometric force curve.

Adult↗
PubMed1981

The mechanical efficiency of wheelchair dependent women during wheelchair ergometry.

Few previous studies have attempted to study the response of disabled women to work in a wheelchair. The purpose of this study was to investigate the mechanical efficiency of wheelchair dependent women (WCD) during progressively loaded wheelchair ergometry. Five WCD subjects with an average confinement of 17.8 years were compared to five able bodied women (AB). Neither maximal oxygen uptake, 1.121 WCD and 1.485 AB (L X min-1) or maximal power outputs, 41.6 WCD and 44.1 AB (watts) were significantly different for the groups. The WCD group, however, demonstrated significantly higher mechanical efficiencies at comparable power outputs, p greater than 0.05. This difference remained when comparisons at about 60, 80, and 90% of VO2 max were made. The average efficiencies over these metabolic levels were 14% WCD and 10.6% AB. Stroke length consistently reduced as power outputs increased with the values lower for the WCD subjects. Average values for the submaximal workloads were 3.17 WCD and 3.76 AB (m x stroke-1) which meant a difference that was 18.6% greater in length for the AB group. The possible influence of this upon the efficiency of wheelchair locomotion was discussed.

Adult↗
PubMed1980

Alactic capacity and power: reliability and interpretation.

The purpose of this investigation was to determine test-retest reliability for measuring maximal values of alactic capacity (ALCmax) and alactic power (ALPmax). For this, 31 men and 13 women each completed two ALCmax and ALPmax tests. Test-retest correlation coefficients for ALCmax and ALPmax values were 0.78 and 0.90, respectively. In addition, for both variables no significant differences were found between test no. 1 and test no. 2. Mean ALCmax values of 429 and 317 J . kg-1, as well as mean ALPmax values of 3.79 and 3.08 W . kg-1 were found for the men and women, respectively. Both ALCmax and ALPmax values were lower (p less than 0.05) for women than men. However, for the capacity power ratio (ALCmax . ALPmax-1) no difference was found between men and women. A correlation coefficient of r = 0.61 was found between mean values for ALCmax and ALPmax . ALCmax values were discussed as being related to skeletal muscle phosphagen concentrations, and ALPmax values were discussed as being related to phosphagen splitting rate. The observed sex differences were suggested to reflect a greater percent body fat in women than men.

Adenosine Triphosphate↗
PubMed1980

Effects of toeclip use on metabolic and cardiopulmonary responses to bicycle ergometer exercise.

Toeclips secure the feet to bicycle pedals and are thought to enable greater anticipation of leg musculature in the pedaling motion. To determine the effects of toeclip use on metabolic and cardiopulmonary responses to BERG exercise, 13 female subjects, who had no prior experience with the devices, performed maximal and submaximal work with and without the use of toeclips. Similar oxygen uptake (V02), physical work capacity, pulmonary ventilation (VE), respiratory exchange ratio (R), heart rate (HR), and blood lactate concentration (LA) were found for maximal effort exercise under both conditions. For submaximal exercise (at 30, 60, and 80% maximal V02) performed with and without toeclips, no differences were found for V02, VE, R, HR, LA, cardiac output, stroke volume, and arteriovenous oxygen difference. These data suggest that toeclip use during BERG exercise may not alter metabolic and cardiopulmonary responses of individuals who have no prior experience with the devices.

Adult↗
PubMed1980

Cardiovascular, metabolic, and ventilatory responses of women to equivalent cycle ergometer and treadmill exercise.

The relationships between age and cardiorespiratory and metabolic adjustments during cycle ergometer exercise and treadmill walking were investigated at 30%, 60%, 80%, and maximal aerobic power (VO2max). The subjects were 18 females between the ages of 17-40. Tr-admill walking resulted in an 8 percent greater maximal aerobic power than that observed during cycle ergometer exercise. Higher lactate concentrations, respiratory exchange ratios and lower heart rates during the cycle ergometer test supported the possibility of localized fatigue from anaerobic metabolism as a limitation to aerobic power potential. Contrary to previous observations in males, female subjects die not demonstrate a lower stroke volume or higher heart rate during submaximal cycling compared to treadmill walking. At exercise intensities above 30% Vi2max, plasma bicarbonate and pH were consistently lower following exercise on the cycle ergometer. Respiratory compensation as calculated from "excess ventilation," delta VE/delta HCO3-, was approximately 4 1 min-1/mEq 1-1. Compensation was found to be independent of the type of exercise but linearly related (r=0.99) to the resultant metabolic acidosis. It was concluded that cardiovascular responses to equivalent cycle ergometer and treadmill exercise are similar; however, occurrence of a greater metabolic acidosis during cycle ergometer exercise suggests that a smaller muscle mass is used.

Adolescent↗