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Biomedical subjects

J A Davis

Publications and source records attributed to J A Davis.

At least 127 records · Page 7Linked to original sources
PubMed1991

Effect of work rate increment on peak oxygen uptake during wheelchair ergometry in men with quadriplegia.

The purpose of this study was to determine the effect of work rate increment on peak oxygen uptake (VO2 peak) during wheelchair ergometry (WCE) in men with quadriplegia due to cervical spinal cord injuries (CSCI). Twenty-two non-ambulatory subjects (aged 20-38 years) with CSCI were divided into two groups based on wheelchair sports classification (n = 12 for IA group and n = 10 for IB/IC group). Subjects underwent three different, continuous graded exercise tests (spaced at least 1 week apart) on an electronically braked wheelchair ergometer. Following a 3-min warmup, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min-1 for the IB/IC group. Ventilation and gas exchange were measured breath-by-breath with a computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2 peak in the IA group (P greater than 0.05). The mean (SD) VO2 peak values (ml.kg-1.min-1) were 9.3 (2.4), 9.4 (3.2), and 8.4 (2.6) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2 peak (P less than 0.05). The mean (SD) VO2 peak values (ml.kg-1,min-1) were 15.1 (4.0), 14.1 (4.4), and 12.7 (4.0) for the 4, 6, and 8 W.min-1 protocols, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of men with quadriplegia due to CSCI, using WCE, should employ work rate increments between 2 and 6 W.min-1 and that work rate increments of 8 W.min-1 or greater will result in an underestimate of VO2 peak.

Adult↗
PubMed1991

A classification of developmental activities of academic family medicine supported by federal grants.

Substantial funds have been awarded to academic departments of family medicine through the federal Establishment of Departments of Family Medicine grants program, initiated in 1980 under the Public Health Service Act. In 1989 the authors analyzed the successful grant applications in a sample of 61 institutions variously funded or re-funded for the grant cycles from 1980 through 1986 in order to classify the supported developmental activities. Three dimensions for explicating this activity emerged: (1) the functional area of the activity (e.g., curricular development); (2) the objectives of the activity (e.g., improving relevance of instruction); and (3) the strategies to be used to attain the objectives (e.g., addition of specialized faculty). This classification scheme provides a tentative but useful framework for characterizing departmental development.

Academic Medical Centers↗
PubMed1991

Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules.

Metabolism and cellular levels of glycine, alanine, and other relevant amino acids in proximal tubules were studied during models of acute injury and protection by glycine. Freeze-clamped, normal rabbit renal cortex was very rich in glycine (66.8 nmol/mg protein) and glutamate and also had substantial levels of taurine, alanine, glutamine, serine, and aspartate. Isolated proximal tubules were severely depleted of all these amino acids (glycine, 2.1 nmol/mg protein). During 37 degrees C incubation in presence of alanine, tubules recovered only glutamate to a level approximating that in vivo (38.8 nmol/mg protein, 15.2 mM). Glycine added to medium at levels ranging from 0.25 to 2 mM was actively concentrated four- to sixfold by tubule cells. Two millimolar glycine potently protected tubules from lethal cell injury induced by hypoxia, antimycin A, or ouabain. Glycine levels of injured tubules rapidly equilibrated with medium, irrespective of whether glycine was loaded by preincubation or was added concomitantly with the injury maneuver. Metabolism of glycine during protection, assessed by changes in total levels, gas chromatography-mass spectroscopy determination of the fate of [13C]glycine, and redistribution of label from [3H]glycine was minimal. The data suggest that glycine plays an essential, constitutive role in maintenance of tubule cell structural integrity independently of common metabolic pathways. Intracellular amino acid content is sufficiently labile for depletion of structurally essential amino acids to potentially occur in a variety of settings, but, even with severe ATP depletion or Na+ pump inhibition, supplemental glycine is readily available to intracellular sites of action.

Amino Acids↗
PubMed1991

Role of increased cytosolic free calcium in the pathogenesis of rabbit proximal tubule cell injury and protection by glycine or acidosis.

To assess the role of increased cytosolic free calcium (Caf) in the pathogenesis of acute proximal tubule cell injury and the protection afforded by exposure to reduced medium pH or treatment with glycine, fura-2-loaded tubules were studied in suspension and singly in a superfusion system. The Ca2+ ionophore, ionomycin, increased Caf to micromolar levels and rapidly produced lethal cell injury as indicated by loss of lactate dehydrogenase to the medium by suspended tubules and accelerated leak of fura and failure to exclude Trypan blue by superfused tubules. Decreasing medium Ca2+ to 100 nM prevented the ionomycin-induced increases of Caf and the injury. Reducing medium pH from 7.4 to 6.9 or adding 2 mM glycine to the medium also prevented the cell death, but did not prevent the increase of Caf to micromolar levels. Cells treated with 1799, an uncoupler of oxidative phosphorylation which produced severe adenosine triphosphate (ATP) depletion, did not develop increases of Caf until just before loss of viability. Preventing these increases of Caf with 100 nM Ca2+ medium did not protect 1799-treated cells. Reduced pH and glycine protected 1799-treated cells without ameliorating the increases of Caf. These data demonstrate the toxic potential of increased Caf in the proximal tubule and show that Caf does sharply increase prior to loss of viability in an ATP depletion model of injury, but this increase does not necessarily contribute to the outcome. The potent protective actions of decreased pH and glycine allow the cells to sustain increases of Caf to micromolar levels in spite of severe, accompanying cellular ATP depletion without developing lethal cell injury.

Acidosis↗
PubMed1991

Metabolic aspects of protection by glycine against hypoxic injury to isolated proximal tubules.

To clarify the roles of butyrate and acylglycine formation in hypoxic proximal tubule cell injury and protection by glycine and to test the contribution of iodoacetate-suppressible metabolism to protection, (1) it was determined whether protection by glycine is fully expressed when glucose, lactate, alanine, and butyrate are replaced by alpha-ketoglutarate as the sole substrate for the tubules, (2) butyrate metabolism and acylglycine formation were directly measured in control and hypoxic preparations, and (3) it was assessed whether injury produced by iodoacetate, a potent inhibitor of glycolytic metabolism, is subject to protection by glycine. Susceptibility to hypoxic injury in medium with alpha-ketoglutarate as the sole substrate was similar to that seen in medium containing glucose, lactate, alanine, and butyrate. Tubules in alpha-ketoglutarate medium showed high degrees of protection by glycine against injury produced by 30-min of hypoxia, by iodoacetate alone, and by iodoacetate combined with hypoxia. Protection did not require preservation of cell ATP or glutathione. In glucose-lactate-alanine-butyrate medium, butyrate, measured by gas chromatography, was rapidly metabolized by oxygenated tubules and fully accounted for basal rates of oxygen consumption. Butyrate utilization stopped during hypoxia. Neither aspect of butyrate metabolism was altered by glycine. Formation of acylglycines was assessed by gas chromatography/mass spectroscopy. In preparations treated with glycine, butyrylglycine was detected under both oxygenated and hypoxic conditions; the quantities, however, were small and no other acylglycines were found. These observations indicate that protective effects of glycine are independent of short-chain acylglycine formation and glycolytic metabolism.

Animals↗
PubMed1991

Effect of heterosis on performance of mice across three environments.

Performance of six genetic groups of mice was studied in three different environments in order to determine the effect of heterosis on consistency of performance in varied environments. Designed as a 3 x 6 factorial, data were analyzed using least squares analyses of variance. Genetic group effects, environmental effects, genetic group x environment interaction, and heterosis were examined for 42-d weight, age and weight at vaginal opening, age and weight at puberty, ovulation rate (determined by total corpora lutea), number of implantations, and number of fetuses at 10 d of gestation. Weight at vaginal opening, ovulation rate, implantation rate and total number of fetuses exhibited significant heterosis. Regression of these traits against an environmental index (mean performance of all genetic groups over environments) provided an estimate of stability of performance. In general, genetic groups exhibiting heterosis expressed more consistent performance across environments than pure lines did. We conclude that a stability model could be used to aid in identification of lines with consistent performance for production traits in variable environments.

Analysis of Variance↗
PubMed1991

Modification to the RITARD surgical model.

The Removable Intestinal Tie-Adult Rabbit Diarrhea (RITARD) procedure is the surgical model of choice for studying pathogenesis of diarrheas of Campylobacter, Escherichia coli, and Aeromonas origin. Other than nonhuman primates, the RITARD rabbit is the only model that closely resembles human infection. Classically, the RITARD model is created by isolating the terminal ileum using umbilical tape placed in a slipknot fashion, and injecting the occluded segment with the organism of choice. The slipknot is removed at 4 h postinoculation and patency of the gut reestablished. We found removal of the umbilical tape to be extremely difficult, usually requiring a second surgery to gently untie the material and prevent destruction of the fragile intestinal tissue. This complication of the described procedure appeared to be related to the absorptive and abrasive nature of the tape material. The modification described uses the same idea, but a different material and a different knot pattern. The tubing was easily removed at the prescribed 4 h postsurgery, without an additional surgery. The tubing did not adhere to or damage the gut, yet did provide the occlusive seal required for a 4-h static gut. Histologically, no evidence of pressure could be found at the tie site.

Animals↗
PubMed1991

Amino acid protection of cultured kidney tubule cells against calcium ionophore-induced lethal cell injury.

Treatment of two cultured renal tubule epithelial cell lines, MDCK and LLC-PK1, with ionomycin produced rapidly evolving models of lethal cell injury characterized by increases of cytosolic free calcium to the microM level within 15 minutes followed by lactate dehydrogenase release and failure to exclude vital dyes that began between 30 and 60 minutes and became extensive after 60 minutes. The pattern of injury was similar when the mitochondrial uncoupler, carbonyl cyanide-m-chlorophenylhydrazone, was added to ionomycin. Carbonyl cyanide-m-chlorophenylhydrazone alone produced severe ATP depletion but not lactate dehydrogenase release. Inclusion of glycine in the experimental medium at concentrations ranging from 0.25 mM to 5 mM did not affect the increases of cytosolic free calcium or ATP depletion but was protective against enzyme release and failure to exclude vital dyes for 180 minutes. Maximal protection was achieved at glycine concentrations between 1 and 5 mM. Several other small neutral amino acids including alanine, beta-alanine, L-serine, 1-aminocyclopropane-1-carboxylic acid, and alpha-aminoisobutyric acid also had protective effects but, glucose, pyruvate, glutamate, glutamine, leucine, valine, and taurine did not. These data indicate that potent protective effects of glycine and other small neutral amino acids previously shown in fresh tubule preparations are fully expressed in cultured tubule cells of diverse origin when appropriate acute injury models are used and the protective effects are sustained for long durations. The suitability of cultured cell lines for prolonged exposure studies will provide a powerful way of further exploring mechanisms of these effects.

Adenosine Triphosphate↗
PubMed1991

Protocol dependency of VO2max during arm cycle ergometry in males with quadriplegia.

The purpose of this study was to determine whether maximal oxygen uptake (VO2max) is protocol dependent during arm cycle ergometry (ACE) for quadriplegic males with spinal cord injuries (SCI). Twenty-four non-ambulatory subjects (aged 20-38 yr) with cervical SCI were divided into two groups based on wheelchair sports classification (IA group = 14; IB/IC group = 10). They underwent three different, continuous graded exercise tests spaced at least 1 wk apart on an electronically braked arm cycle ergometer. Following a 3-min, unloaded warm-up at 60 rpm, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min-1 for the IB/IC group. Ventilation and gas exchange were measured breath-by-breath with a SensorMedics 4400 computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2max in the IA group (P greater than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 10.8 (+/- 3.4), 11.0 (+/- 2.7), and 10.2 (+/- 2.9) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2max (P less than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 16.8 (+/- 4.5), 15.3 (+/- 4.3), and 14.6 (+/- 4.3) for 4, 6, and 8 W.min-1, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of SCI persons with quadriplegia, using ACE, should employ work rate increments between 2-6 W.min-1 and that work rate increments of 8 W.min-1 or greater will underestimate VO2max.

Adult↗
PubMed1991

Effects of warm-up on muscle glycogenolysis during intense exercise.

This study investigated the effects of preliminary exercise (warm-up) on glycogen degradation and energy metabolism during intense cycle ergometer exercise. After determination of VO2max, six male subjects were randomly assigned to perform warm-up (WU) and no warm-up (NWU) trials incorporating a 2 min standardized sprint ride (SR) at 120% of the power output attained at VO2max (POmax). Muscle biopsies and temperature (Tm) recordings were obtained from the vastus lateralis muscle. Tm was elevated above the resting level prior to the SR during the WU trial (37.7 +/- 0.1 vs 35.4 +/- 0.4 degrees C; P less than 0.05) and remained higher than the NWU trial after the SR (38.6 +/- 0.2 vs 37.1 +/- 0.4 degrees C; P less than 0.05). Similar trends existed for rectal temperature (Tr). The increases in Tm and Tr during the SR were both greater in the NWU trial (P less than 0.05). Muscle glycogen degradation was similar for the WU and NWU trials (30.8 +/- 3.7 vs 25.6 +/- 3.7 mmol.kg-1, respectively). When blood and muscle lactate concentrations after the SR were expressed relative to values before the SR, the WU trial resulted in a lower accumulation of blood lactate (6.5 +/- 0.9 vs 10.7 +/- 0.8 mEq.l-1; P less than 0.01) and muscle lactate (20.1 +/- 0.1 vs 23.4 +/- 2.2 mEq.kg-1 wet wt.; P less than 0.05). Furthermore, oxygen consumption during the 1st min of the SR was higher in the WU trial (2.3 +/- 0.2 vs 1.9 +/- 0.2 l.min-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of warm-up on blood gases, lactate and acid-base status during sprint swimming.

A standardized 200-m front crawl sprint swim (SpS) was used to evaluate the effects of warm-up on pH, blood gases, and the concentrations of lactate ([La-]) and bicarbonate ([HCO3-]) in arterialized and venous blood. Eight trained male swimmers performed two randomly assigned 200-m front crawl swims at previously determined intensities corresponding to 120% VO2max. One swim was preceded by a warm-up (WU trial) which consisted of a 400-m front crawl swim (82% VO2max), 400-m flutter kicking (45% VO2max), and 4 x 50-m front crawl sprints (111% VO2max). The second was performed without warm-up (NWU trial). Blood was sampled from a hyperemized earlobe and an antecubital vein before the warm-up, 9 min after the warm-up (1 min before the swim), immediately following the SpS, and at 2, 5, 10, and 20 min after the SpS. The warm-up exercise resulted in a higher pre-SpS [La-] in arterialized blood (3.1 +/- 0.4 and 1.7 +/- 0.4 mmol x l-1, p less than 0.05), a higher hydrogen ion concentration ([H+]) in venous blood (45.9 +/- 0.9 and 42.2 +/- 0.8 nmol x l-1, p less than 0.001), and a lower arterialized blood [HCO3-] (25.1 +/- 0.9 and 22.2 +/- 0.8 mmol x l-1, p less than 0.05). The SpS was accompanied with higher heart rates during the WU trial (178 +/- 3 and 169 +/- 3 bpm; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules.

Kidney proximal tubules are resistant to hypoxic injury if glycine or L-alanine is present in their incubation medium. Protection does not depend on the concentration or turnover of ATP in cells. We have investigated structure-function relationships that govern this protective activity. Among more than 45 amino acids and analogs examined, only glycine, L-alanine, D-alanine, beta-alanine, and the neuronal glycine binding site agonist, 1-aminocyclopropane-1-carboxylic acid, were active. The protective effect could not be explained by amino acid metabolism. Ultrastructural features in protected cells were preserved to a degree which suggested that processes responsible for degradation during hypoxia were retarded. These results are consistent with stringent requirements of amino acid molecular structure for protection against hypoxia, and suggest the involvement of highly specific, acceptor-ligand effects on a process critical for maintaining cellular integrity.

Adenosine Triphosphate↗
PubMed1990

The relationship between 'normal' fluid retention in women and idiopathic oedema.

A sample of women attending a gynaecological outpatient clinic were examined for symptoms and objective signs of fluid retention. Patients completed a questionnaire on symptoms suggesting fluid retention and recorded daily weight and abdominal girth variation. Daily weight variation varied from 0-9 pounds (mode 2 pounds) with no discernable difference between premenstrual and intermenstrual variation. Daily girth variation varied from 0-6 inches (mode 1 inch). Symptoms of breast swelling were more common premenstrually, finger/hand and ankle swelling intermenstrually and abdominal swelling occurred with equal frequency in both periods. No correlation between symptoms and weight variation was seen although abdominal swelling and girth variation were associated (P less than 0.04). The results indicate that symptoms of mild fluid retention and of diurnal weight and abdominal girth variation are part of the everyday experience of our study population. There is no clear-cut separation between 'normal' and 'abnormal' fluid retention (idiopathic oedema, periodic oedema, fluid retention syndrome); the latter may be an exaggeration of normal fluid-retaining mechanisms common to most women or may represent a pathological state. An approach which evaluates individual risk factors and the severity of fluid retention in each patient is recommended.

Adolescent↗
PubMed1990

Protection by glycine of proximal tubules from injury due to inhibitors of mitochondrial ATP production.

We have determined whether glycine or glutathione can protect rabbit proximal tubules damaged by chemical inhibitors of oxidative phosphorylation: antimycin A, rotenone, cyanide, oligomycin, or carbonyl cyanide m-chlorophenylhdrazone (CCCP). All the agents severely depleted cell ATP levels within 15 min and caused lethal cell injury, as quantified by lactate dehydrogenase (LDH) release. Glycine and glutathione largely prevented this injury without altering the primary effects of the inhibitors on tubule respiration or the depletion of ATP. Buthionine sulfoximine and 1,3-bis(2-chloroethyl)-1-nitrosourea decreased cell glutathione but did not prevent the protective effects of either glycine or glutathione in tubules treated with rotenone. Protection was sustained during both a 15-min exposure and a 45-min postwash period irrespective of whether the wash removed the agent or mitochondrial function recovered. Cysteine uniquely induced a dramatic recovery of mitochondrial function in tubules washed after treatment with CCCP. These data 1) demonstrate that the cytoprotective effects of glycine previously seen during hypoxia extend to other tubule lesions characterized by severe ATP depletion, 2) emphasize the actions of glycine to preserve cell structural integrity in spite of sustained severe impairment of ATP-generating processes in proximal tubules, and 3) indicate that it is glycine rather than intracellular or extracellular glutathione which mediates protection.

Adenosine Triphosphate↗
PubMed1990

Ouabain-induced lethal proximal tubule cell injury is prevented by glycine.

Exposure to 1 mM ouabain for greater than 30 min caused lethal cell injury to isolated rabbit proximal tubules as measured by increased lactate dehydrogenase release. Addition of 2 mM glycine or glutathione to the incubation medium prevented this injury and a sharp fall of cell ATP that accompanied it. Glycine and glutathione did not alter rapid, early effects of ouabain to deplete cell K+ and inhibit respiration. Preservation of cellular glutathione was not required for protection. Glycine did not ameliorate ouabain-induced increases of cell water and did not prevent lethal cell injury associated with cell swelling produced by incubation in a high K+ concentration medium. In contrast, 100 mM mannitol, which at least partially ameliorated swelling in both ouabain and high-K+ medium, prevented lethal injury in high-K+ medium and decreased it in the presence of ouabain. The combination of glycine and mannitol completely prevented ouabain-induced lethal injury and cell water increases. These observations indicate that glycine, unlike mannitol, does not protect against primary volume-induced insults. Ouabain-induced lethal cell injury results from a process that includes both a volume component ameliorated by mannitol and a volume-independent component that is prevented by glycine and is closely associated with accelerated ATP depletion.

Glutathione↗
PubMed1990

Effects of exercise mode on muscle glycogen restorage during repeated days of exercise.

The purpose of this study was to examine differences in muscle glycogen storage during three successive days of running or cycling. In a crossover design, seven male subjects performed two 3-d trials of either running (trial R) or cycling (trial C) for 60 min at 75% VO2max. Biopsy samples were obtained before and after each day's exercise from the gastrocnemius (trial R) or vastus lateralis (trial C) muscle. Diets in the 2 d preceding and during each trial contained 5 g carbohydrate.kg-1.d-1 and 14,475 +/- 402 kJ.d-1. Mean pre-exercise glycogen content (mmol.kg-1 wet wt.) was significantly reduced in both trials on day 3 (103.4 +/- 6.0) when compared to day 1 and day 2 (119.9 +/- 6.8 and 116.4 +/- 5.7, respectively). Day 1 glycogen reduction was significantly greater in trial C (P less than 0.03), and glycogen restorage was greater (P less than 0.02) only in trial C between the 1st and 2nd d. On day 3, spectrophotometric analysis of PAS strains showed that pre-exercise glycogen content in either muscle group was significantly (P less than 0.01) less in Type I as compared to Type II fibers. This difference in fiber glycogen storage did not appear to be attributable to muscle damage as negligible leukocyte infiltration and low blood CK levels were obtained. No difference between modes were observed for CK values throughout the trials. These data suggest that the depressed glycogen storage before the 3rd d of exercise was due to the moderate carbohydrate intake.

Adult↗
PubMed1990

The influence of exercise intensity on heat acclimation in trained subjects.

Low-intensity exercise (less than or equal to 50% VO2max) has been demonstrated to produce heat acclimation (HA) in trained subjects. The purpose of this study was to determine whether shorter-duration, moderate-intensity exercise would also result in HA. Nine trained runners performed two 9-d exercise heat-stress protocols. Each protocol consisted of a 90-min heat tolerance test on days 1 (HTT1) and 9 (HTT2). On days 2-8 the subjects exercised at 50% VO2max for 60 min.d-1 (T50) or at 75% VO2max for 30-35 min.d-1 (T75). Final HTT2 heart rate and rectal temperature (Tr) were significantly (P less than 0.001) reduced, as compared to HTT1, with no differences between T50 and T75. Both protocols resulted in significant (P less than 0.05) reductions in HTT2 pre-exercise Tr and total exercising caloric expenditure, both of which are known to contribute to HA. No changes in resting plasma volume, osmolality, protein, post-HTT aldosterone, and exercising sweat rate were observed. These results demonstrate that equal levels of HA were obtained with T50 and T75, which suggests that moderate-intensity, short-duration exercise in the heat can produce HA in trained subjects.

Acclimatization↗