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Biomedical subjects

J Shearer

Publications and source records attributed to J Shearer.

16 recordsLinked to original sources

Macrophage arginine metabolism and the inhibition or stimulation of cancer.

The potential of the immune system to inhibit or stimulate tumor growth is a vivid example of the "two-edged sword" nature of immune responses. Our results provide evidence that this dual capacity can be attributed, in part, to the dual pathways of arginine metabolism exhibited by intratumor macrophages. Specifically, i.p. tumor rejection in P815-preimmunized mice is accompanied by an upshift in intratumor macrophage arginine metabolism to the nitric oxide (NO) synthase pathway that yields citrulline and NO. A rapid and marked local increase in IFN-gamma (both mRNA and protein) in preimmunized mice during tumor rejection suggests that this cytokine plays a role in up-regulating nitric oxide production in vivo. Unlike tumor rejection, progressive i.p. P815 tumor growth in naive mice is associated with a marked decline in the production of citruline/NO by intratumor macrophages. Examination of macrophage arginine metabolism via arginase revealed a pattern opposite that of NO synthase. The local production of ornithine/urea markedly increases during progressive tumor growth whereas arginase activity decreases during tumor rejection. Inasmuch as nitric oxide inhibits tumor cell replication whereas ornithine is the precursor of polyamines required for cell replication, these results are consistent with the conclusion that the pathway macrophages use to metabolize arginine can influence the type of host immune responses against cancer and other conditions.

Animals

Healing of residual screw holes after plate removal.

A single photon absorptiometric method of imaging residual screw holes after plate removal is described. Application of this technique to seven patients demonstrated that ingrowth into these defects is a protracted process which remained incomplete at 18 weeks in all seven patients. Bone mass at the site of the screw holes was, however, close to normal at 18 weeks in four young adults, lending support to the AO-ASIF recommendation that athletic activity should be avoided for 4 months after plate removal.

Absorptiometry, Photon

Bone weakness after the removal of plates and screws. Cortical atrophy or screw holes?

Bone weakness leading to refracture is a recognised complication of the removal of rigid fixation plates. We have used partially demineralised rabbit tibiae to simulate atrophic changes and to determine whether weakness is due to atrophy or to residual screw holes. Partial demineralisation and a screw hole each reduced maximum bending moment. However, energy absorbing capacity was little affected by demineralisation, but was reduced to 50% by a single drill hole. Residual screw holes are a considerably more important cause of bone weakness after plate removal than is cortical atrophy.

Animals

Financial comparison of three testing strategies for detection of estrus in dairy cattle.

Three commercial tests that measure progesterone content in milk were evaluated for accuracy of estrus detection. The tests were evaluated on 96 milk samples collected from Holstein cows at a commercial dairy farm in central Florida. The test results were compared with the results of radioimmunoassay on the same sample. Comparisons were made by calculating the sensitivities, specificities, and predictive values. The significance of the statistical association between the tests and the radioimmunoassay was evaluated by use of the McNemar chi 2 test. Decision-tree analysis was used to determine the most useful testing strategy, considering both cost and accuracy. The cowside progesterone assay on estrus-mount detector-positive cows was more profitable than use of estrus-mount patches alone. The return on investment was higher with the cowside test, making it preferred as a field test for detecting estrus.

Animals

Influence of young maternal age and parity on term and preterm low birthweight.

Data on 4496 singleton births to young women (19 years or less) are reported by maternal age and parity with birthweight and gestation cross-classified to yield rates of preterm and term low birthweight. After adjustment, the risk of preterm low birthweight was increased with very young maternity (15 years or less); preterm low birthweight and term low birthweight were each increased with young multiparity. These data suggest that the identification of factors associated with preterm birth and their incorporation into the prenatal care regimen may be important in improving pregnancy outcome in young women.

Adolescent

Pulmonary metabolism of reactive oxygen species.

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.

Adaptation, Physiological

Glutamine metabolism in rat skeletal muscle wounded with lambda-carrageenan.

Wounding with lambda-carrageenan results in a marked decrease in the intracellular-free glutamine content of rat skeletal muscle. The potential mechanisms for this finding, including alterations in glutamine release, glutamine utilization, and glutamine synthesis, were investigated in rats under pentobarbital anesthesia. Wounding did not increase glutamine release from muscle during incubation or isolated hindlimb perfusion. Wounded muscle utilized more glutamine than nonwounded muscle, as measured both by the production of [14C]O2 and of -glutamate from labeled glutamine. Maximal glutamine synthetase activity was increased by wounding. The increase in glutamine synthetase activity in wounded muscle was prevented by adrenalectomy and restored by replacement doses of corticosterone in wounded adrenalectomized animals. The decrease in muscle free glutamine induced by wounding is therefore not mediated by an increase in the release of this amino acid, nor by a reduction in the tissue capacity for glutamine synthesis, but by an increase in glutamine utilization at the site of injury. This difference is apparently determined by the utilization of glutamine by the cellular components of the inflammatory infiltrate, which were shown to be capable of active glutaminolysis.

Adrenalectomy

Prenatal care adequacy and the outcome of adolescent pregnancy: effects on weight gain, preterm delivery, and birth weight.

A prospective study of 757 adolescents who gave birth to singleton live-born infants was undertaken to assess effects of prenatal care on pregnancy outcome. The analysis indicated that the odds of low pregnancy weight gain for gestation was reduced by a factor of two (odds ratio = 0.50, P less than .05) for adolescents with adequate prenatal care; the risk of preterm delivery was reduced with both adequate (odds ratio = 0.34, P less than .01) and intermediate prenatal care (odds ratio = 0.46, P less than .05). Birth weight was increased by an average of 157 g with adequate care (P less than .05) and 107 g with intermediate care (P less than .05). After adjusting for pregnancy weight gain and preterm delivery, differences in birth weight were much smaller and no longer statistically significant, suggesting indirect effects of care on birth weight (ie, improvements in weight gain adequacy and in preterm delivery).

Adolescent

Amino acid metabolism after lambda-carrageenan injury to rat skeletal muscle.

To evaluate whether the alterations in amino acid (AA) metabolism that follow the lambda-carrageenan injury are direct consequences of wounding and are therefore independent of food intake, plasma AA, in vivo muscle intracellular free AA, and AA release during isolated hindlimb perfusions were determined in pentobarbital-anesthetized rats with lambda-carrageenan-induced hindlimb muscle wounds (W) and in pair-fed (PFC) and ad libitum-fed (ALC) non-wounded controls. Both PFC and W animals showed different plasma and muscle intracellular AA composition that ALC. The alterations observed in these compartments in W animals may not have resulted exclusively as a consequence of the wound. Wounded hindlimbs released more AA during perfusion than either control group. The marked increase in net protein catabolism of W muscle appeared to be related to wounding and not a consequence of partial starvation. The normalized release (amino acid/phenylalanine ratio) of glutamine (W less than ALC), alanine (W less than PFC and ALC), and the branched-chain amino acids (W greater than PFC and ALC) differed among groups, suggesting an alteration in the metabolism of these AA in W tissue.

Alanine

A macrophage-mediated factor that increases the high energy phosphate content of skeletal muscle.

A marked cellular infiltrate accompanies wounding. The phagocytic and bacteriocidal activities of this infiltrate require increased substrate and O2 consumption. This rapid utilization of available oxygen and substrates could jeopardize an already compromised resident cellular component of a wound. Recent studies have demonstrated macrophage-mediated cell stimulatory agents which induce proliferation of nonlymphoid mesenchymal cells. This study was designed to examine macrophage-resident tissue interactions and their possible significance in wounded tissue. A reconstituted wound system was designed which combines the major components of a lambda-carrageenan skeletal muscle wound (muscle + macrophages). The extensor digitorum longi (EDL) of male Fisher rats were incubated in a standardized fashion. The groups of EDL were muscle incubated alone, muscle with the addition to the incubate of activated peritoneal macrophages or muscle with the addition of a conditioned supernatant from the incubation of activated or nonactivated peritoneal macrophages. Muscle ATP and CP content were noted to be increased 46 and 22%, respectively, when macrophages and skeletal muscle were coincubated. Macrophage-conditioned media from activated or nonactivated macrophages increased the ATP and CP muscle content 44 and 37%, respectively. Preliminary characterization of this high energy phosphate (HEP) promoting factor demonstrates it to be heat and cold stable and less than 10,000 Da. Therefore, a macrophage-mediated transferable factor is capable of increasing the HEP content of skeletal muscle in an in vitro system. This may have important consequences in maintaining host cell integrity following injury.

Adenosine Triphosphate

Macrophage interaction with skeletal muscle: a potential role of macrophages in determining the energy state of healing wounds.

A decrease in ATP and creatine phosphate (CP) is characteristic of local injury to skeletal muscle. Recent data have suggested adequate potential for high-energy phosphate production in the wounded tissue. Thus, an adequate explanation for the deficit in the high-energy tissue content in wounds was lacking. Since the wound has multiple components (muscle + cellular infiltrate), the tissue content represents the summation of these components. Therefore, a technique to separate these components was designed. Using a 0.5% solution of lambda-carrageenan as the wounding agent, the extensor digitorum longus muscles (EDL) of male Fisher rats were unilaterally wounded with intramuscular injections. Five days later, both wounded and contralateral nonwounded muscles were incubated in a standardized fashion. The groups of EDL were: wounded as described, contralateral nonwounded, or contralateral nonwounded with the addition to the incubate of 6 X 10(6)/ml lambda-carrageenan elicited peritoneal macrophages. Following incubation, the individual component parts of the system (muscle and macrophage) were rapidly frozen and assayed for high-energy phosphate and DNA content. Examination of the high-energy phosphate content of the separate components of a wound demonstrated that macrophages increased the ATP and CP content of normal skeletal muscle. Yet when total high-energy phosphate content was normalized for total DNA (muscle + macrophages) in the reconstituted system, the values approximated those of wounded muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

The description of structural and temporal characteristics of tonic electrophysiological activity during sleep.

The structural and temporal characteristics of tonic variation among electrophysiological measures during sleep are examined from the point of view of sleep stage scoring procedures and the digital quantification and statistical analysis of these measures. Sleep stage scoring procedures are nominally scaled and therefore less able to index structural and temporal characteristics than are measures derived from digital methods of quantification having the properties of interval or ratio scales. These arguments are illustrated using principal components analysis to describe the structure of tonic covariation among 36 variables derived from the computer analysis of EEG, EMG, and EOG. Three components resulting from the analysis are tentatively named 'slow-fast', 'hemispheric-shift' and 'eyes-activation'. They appear across variations in experimental manipulations such as night time awakenings and also across differences in age and species. The periodic characteristics of the vectors associated with the three components are specified by means of the Fast Fourier transform in combination with digital low pass and band pass filtering. Cycles are found which are both slower and faster than the paradigmatic 90 min ultradian rhythm. These results indicate that currently available techniques of digital and statistical analysis provide new possibilities for research on the electrophysiology and psychophysiology of sleep.

Adolescent