Biomedical subjects
K D Campbell
Publications and source records attributed to K D Campbell.
CD66 family members are associated with tyrosine kinase activity in human neutrophils.
The granulocyte activation Ags, CD66a, CD66b, CD66c, and CD66d, are expressed at low levels on resting blood granulocytes, but their surface expression is up-regulated following stimulation. CD66a, in contrast to CD66b and CD66c which are anchored to the membrane via a glycosyl-phosphatidylinositol linkage, is a transmembrane protein with a cytoplasmic domain. We have previously reported that CD66a is phosphorylated in human neutrophils, largely on tyrosine, with a lower level of phosphoserine. We have now found that CD66a undergoes a rapid increase in phosphorylation following stimulation with FMLP, platelet-activating factor, and 12-O-tetradecanoyl-phorbol-13-acetate. This increase in phosphorylation was transient, with maximal phosphorylation observed by 1 min and a return to base line by 5 min following stimulation. Protein kinase activity was detected in neutrophils associated with CD66a, CD66b, and CD66c. Most of the protein kinase activity associated with these Ags was tyrosine kinase activity, with a lesser amount of threonine and serine kinase activities. Lyn and Hck accounted for much of the associated tyrosine kinase activity. The data suggest that phosphorylation of CD66a on tyrosine by an associated tyrosine kinase may play a role in the function of CD66a. In addition, associated tyrosine kinase activity may play a role in signal transduction from CD66a, CD66b, and CD66c to regulate other cell functions.
CD50 (ICAM-3) is phosphorylated on tyrosine and is associated with tyrosine kinase activity in human neutrophils.
CD50 (ICAM-3) is expressed at a high level on resting blood granulocytes, monocytes, and lymphocytes. The constitutive high expression of CD50 on resting leukocytes suggests that it is an important LFA-1 ligand in the initiation of the immune/inflammatory response. Using a radiolabeling technique initially designed to detect ecto-protein kinase activity, we found that CD50 mAbs immunoprecipitated a approximately 125- to 170-kDa phosphoprotein from human neutrophils. Phosphorylation was increased after stimulation with the chemotactic agent FMLP, platelet-activating factor, 12-O-tetradecanoyl-phorbol-13-acetate, and the calcium ionophore A23187. This increase in phosphorylation was transient with the maximal phosphorylation, being observed by 1 min. Phosphoamino acid analysis revealed that CD50 contained predominantly phosphotyrosine. Although this assay system was designed initially to detect ecto-protein kinase activity, subsequent studies have shown that membrane proteins can be phosphorylated on the cytoplasmic domain under these conditions. When CD50 was immunoprecipitated from solubilized neutrophils, protein tyrosine kinase activity associated with CD50 was detected in the immunoprecipitate. The data suggest that phosphorylation of CD50 on tyrosine by an associated tyrosine kinase plays a role in the function of CD50.
The nonoperative management of unilateral neonatal hydronephrosis: natural history of poorly functioning kidneys.
During the last 5 years we have followed nonoperatively all neonates with unilateral hydronephrosis and suspected ureteropelvic junction obstruction, regardless of the degree of hydronephrosis, shape of the diuretic renogram washout curve or initial degree of functional impairment. Of 104 patients 7 (7%) ultimately required pyeloplasty for obstruction, which was defined as a greater than 10% reduction in differential glomerular filtration rate and/or progression of hydronephrosis. Pyeloplasty returned renal function to pre-deterioration levels in all kidneys. In 16 patients with profound hydronephrosis and initial differential renal function less than or equal to 40% all traditional diagnostic tests for assessing obstruction, including diuretic renography washout pattern, were inaccurate in diagnosing obstruction and predicting which kidney would deteriorate. In 15 of 16 poorly functioning hydronephrotic kidneys rapid improvement in absolute and per cent differential renal function was observed, and the level of initial differential renal function served as a useful guide for timing of further diagnostic studies. Unilateral neonatal hydronephrosis appears to be a relatively benign condition and the risk of developing renal obstruction appears relatively slight. Because of diagnostic inaccuracy, the low risk of developing obstructive injury and the fact that many newborn kidneys with hydronephrosis rapidly improve function and dilation, it appears safe to follow neonatal unilateral hydronephrosis closely and nonoperatively.
The effect of lower body positive pressure on the exercise capacity of individuals with spinal cord injury.
The purpose of this study was to determine the effect lower body positive pressure (LBPP) has on the cardiovascular/exercise capacities of individuals with spinal cord injury (SCI) during both arm crank exercise (ACE) and wheelchair exercise performed on a treadmill (WCTM). Ten male adults (age = 31.1 +/- 10 yr) with SCI and five male nondisabled (ND) adults (31.2 +/- 10 yr) participated in this study. The ND subjects performed ACE only. For subjects with SCI, significantly higher (P < 0.025) peak VO2 (1042 +/- 212 vs 839 +/- 218 ml.min-1), peak VE (46 +/- 17 vs 35 +/- 9 l.min-1), and work rate (50 +/- 15 vs 40 +/- 13 W) were seen during ACE with LBPP. No significant differences for peak VO2, VE, or work rate were seen for the ND subjects with LBPP during ACE. In addition, significantly higher peak VO2 (960 +/- 322 vs 828 +/- 312 ml.min-1) was recorded with LBPP for the subjects with SCI during WCTM. Cardiac output (Q, l.min-1; CO2 rebreathing method) was measured at 50% peak VO2 for both ND subjects and subjects with SCI during ACE. Subjects with SCI demonstrated significantly higher SV (94 +/- 20 vs 84 +/- 20 ml) with LBPP. No differences were observed in SV at 50% peak VO2 during ACE for the ND subjects with LBPP. The results of this study suggest that for individuals with SCI, LBPP augments exercise capacity by preventing the redistribution of blood to the lower extremities.
The accuracy of predicting treadmill VO2max for adults with mental retardation, with and without Down's syndrome, using ACSM gender- and activity-specific regression equations.
The purpose of this study was to examine the validity of the American College of Sports Medicine's (ACSM) prediction equations for calculating peak oxygen consumption (VO2max) in young adults with mental retardation. A total of 32 subjects with mental retardation participated in this study: 15 young adults with Down's syndrome (DS) and 17 non-DS young adults (NDS). Subjects were matched for age, gender and intelligence quotient (IQ). Subjects were given a standard treadmill-graded exercise test to determine peak heart rate (HR) and peak oxygen consumption (VO2max). Subjects were connected to a metabolic cart during the test. Peak VO2 was predicted using ACSM's prediction equations where predicted VO2max is: men, 57.8-0.445 (age); and women, 42.3-0.356 (age). Statistical significance between groups was determined using a two-tail t-test, with alpha set a priori at 0.05. The DS group had a significantly (P = 0.0003) lower peak HR (DS 155.90 +/- 12.12 vs NDS 175.38 +/- 9.87) and per cent HR achieved (P = 0.0007) (DS 80.26 +/- 6.76 vs NDS 89.39 +/- 4.46) as compared to the NDS group. Differences were also found between groups with respect to peak oxygen consumption. The DS had a significantly (P = 0.006) lower peak oxygen uptake (ml kg-1 min-1) as compared to the NDS group (23.68 +/- 4.01 vs 31.00 +/- 7.11, respectively). Significant differences (P = 0.007) were accordingly observed with respect to per cent predicted oxygen uptake achieved (DS 55.22 +/- 10.61 vs NDS 73.27 +/- 19.15). A nearly two-fold difference (P = 0.01) was observed with respect to the functional aerobic impairment between the DS (44.79 +/- 10.61) and NDS (28.29 +/- 18.63) groups, further illustrating the impaired peak cardiovascular capacities of both groups. The results of this study indicated that use of the ACSM gender and activity specific prediction equations in young adults with mental retardation (DS and NDS), peak VO2 is significantly over-predicted (83.9 and 39.2%, respectively). Therefore, peak oxygen consumption and derived exercise prescriptions must be based on actual measurements, rather than via ACSM prediction equations. Otherwise, training intensities may be over-predicted and impose possible health risks.
The cardiovascular capacities of adults with Down syndrome: a comparative study.
The purpose of this study was to compare the cardiovascular capacities of individuals with Down syndrome (DS) to individuals without Down syndrome who are mentally retarded. Sixteen young adults with DS and 16 individuals without DS (12 males and 4 females, respectively), all with mild/moderate mental retardation, participated in this study. Peak VO2 (absolute and relative), VE (1.min-1), heart rate (HR, b.min-1), and RER (VCO2/VO2) were determined by exercise tests utilizing a treadmill (TM) and Schwinn Air-Dyne ergometer (SAE). The best test result was chosen from the TM and SAE tests and used for statistical comparisons. Cardiac output (Q, 1.min-1) was measured while standing quietly and while walking at 3 mph, 0% grade, using the CO2 rebreathing method for 11 (9 males and 2 females) subjects from each group. Arteriovenous oxygen differences (a-v O2), cardiac index (QI), and stroke volume (SV) were calculated from VO2, Q, HR, and body surface area. Peripheral vascular resistance (PVR), left ventricular work index (LVWI), and left ventricular stroke work index (LVSWI) were calculated from mean arterial pressure, Q, QI, and stroke volume index. Results showed that individuals without DS had statistically significant (P less than 0.01) higher mean peak VO2 (35.6 vs 24.6 ml.kg-1.min-1; 2567 vs 1683 ml.min-1), VE (89.3 vs 59.2 1/min-1), and HR (179 vs 159 b.min-1) than individuals with DS, respectively. No differences in RER were seen between the groups. No differences were seen in cardiovascular parameters measured while quietly standing.(ABSTRACT TRUNCATED AT 250 WORDS)
Mentally retarded individuals--a population at risk?
When comparing the aging process of mentally retarded (MR) persons with the nondisabled population, researchers have established an earlier lower limit for the onset of old age for MR persons and a higher mortality rate. The reason for early senescence has not been successfully resolved, but the finding that cardiovascular disorders are the most prevalent form of disease among elderly MR persons suggests a relationship between lifestyles and higher mortality rate. Indeed, studies that evaluated the cardiovascular fitness (CVF) of MR individuals demonstrated substandard levels of fitness. The results of these studies, however, are not conclusive due to variation in test methodologies, motivational factors, and issues of test validity and reliability. Training studies which have purported to determine trainability of this population have also shown confusing results, perhaps attributed to the same protocol inconsistencies. Therefore, the purposes of this article are 1) to review previous methods of evaluating CVF of MR adults and determine whether testing methodologies invalidate the results of these studies, 2) to review training studies involving adult MR individuals and determine whether this population is capable of improving their CVF, and 3) to identify areas where further research is needed to fully describe the functional cardiovascular characteristics of MR adults.
Fluid shifts with successive running and bicycling performance.
Seven men and five women triathletes ran 10 km and bicycled 40 km at race pace for the purpose of studying changes in plasma, blood, and red blood cell volumes. A second trial followed 1 wk later with the order of exercise counterbalanced (running first-cycling second; cycling first-running second). Water consumption was measured by providing water bottles on the bike phase, at 3.2 and 6.7 km on the run phase, and at the transition area. Body weight was obtained at the start and end of each phase. A 10-ml blood sample was obtained just before starting and immediately upon finishing each phase. Changes in plasma volume, blood volume, and red cell volume were calculated from hematocrit and hemoglobin values. Changes in blood volume, plasma volume, and red cell volume did not differ between the sexes; therefore, results were combined. Sequential cycling and running caused significant hemoconcentration (-6 to -8% blood volume; -8 to -10% plasma volume) with moderate dehydration (-3 to -4% body weight) despite ad libitum fluid replacement. More severe fluid compartment shifts occurred on the initial phase regardless of exercise mode. Blood volume and plasma volume changes during the second mode of exercise were minor in extent with the major differences occurring in red cell volume. When fluid changes were calculated on a per hour basis, shifts were greater during running than during cycling.
Studies on the large subunit ribosomal RNA genes and intergenic spacer regions of non-proteolytic Clostridium botulinum types B, E and F.
The large-subunit ribosomal ribonucleic acid (23S rRNA) genes of non-proteolytic (group II) strains of Clostridium botulinum toxin types B, E and F were amplified using the polymerase chain reaction (PCR), and cloned in Escherichia coli. Sequence determination showed that the 23S rRNA genes were 2910 nucleotides in length, and comparative analysis revealed approximately 99.5% sequence similarity. The 23S rRNA gene sequence of a strain phenotypically resembling non-proteolytic C. botulinum, except in not producing botulinal neurotoxin, was also determined and displayed 99.5% sequence similarity with those from toxigenic strains. A diagnostic sequence within the 23S rRNA characteristic for non-proteolytic C. botulinum was identified and used for the design of an oligonucleotide probe. Molecular hybridizations with PCR-amplified rDNA targets provided a precise and reliable method of identifying non-proteolytic (or Group II) C. botulinum and closely related non-toxigenic strains.