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Biomedical subjects

J C Young

Publications and source records attributed to J C Young.

At least 91 records · Page 5Linked to original sources
PubMed1991

Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line.

Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation. Pre-B cells transformed by a variety of oncogenes including those of the ABL protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v-abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants analyzed contained elevated IL-7 transcripts. None of the cell lines secreted detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7-dependent pre-B cell line to assess the potential for autocrine growth stimulation and malignant transformation. We achieved dramatic deregulation of IL-7 translational suppression by removing portions of the 5' flanking region. Levels of IL-7 expression much greater than those needed to establish factor-independent growth did not induce colony formation in agar by IL-7-expressing pre-B cell lines, and the majority of these lines were nontumorigenic in syngeneic mice. The same pre-B cell line transformed by v-abl displayed a highly malignant phenotype while containing dramatically lower IL-7 transcript levels. We conclude that endogenous IL-7 expression is not a necessary event in transformation of pre-B cells, nor is it sufficient to explain the malignant phenotype in v-abl-transformed cells. Up regulation of endogenous IL-7 expression in some transformed pre-B cells may be one of several synergistic events which can lead to malignant conversion.

Abelson murine leukemia virus↗
PubMed1991

BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias.

The c-abl proto-oncogene encodes a cytoplasmic tyrosine kinase which is homologous to the src gene product in its kinase domain and in the upstream kinase regulatory domains SH2 (src homology region 2) and SH3 (src homology region 3). The murine v-abl oncogene product has lost the SH3 domain as a consequence of N-terminal fusion of gag sequences. Deletion of the SH3 domain is sufficient to render the murine c-abl proto-oncogene product transforming when myristylated N-terminal membrane localization sequences are also present. In contrast, the human BCR/ABL oncogene of the Philadelphia chromosome translocation has an intact SH3 domain and its product is not myristylated at the N terminus. To analyze the contribution of BCR-encoded sequences to BCR/ABL-mediated transformation, the effects of a series of deletions and substitutions were assessed in fibroblast and hematopoietic-cell transformation assays. BCR first-exon sequences specifically potentiate transformation and tyrosine kinase activation when they are fused to the second exon of otherwise intact c-ABL. This suggests that BCR-encoded sequences specifically interfere with negative regulation of the ABL-encoded tyrosine kinase, which would represent a novel mechanism for the activation of nonreceptor tyrosine kinase-encoding proto-oncogenes.

Animals↗
PubMed1991

Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle.

Glucose transport in muscle is activated by contractile activity, an effect that persists in the postexercise state. Polymyxin B, a cyclic decapeptide antibiotic, inhibits the stimulation of glucose uptake in isolated muscle by contractile activity but also decreases tension development in electrically stimulated muscle. The purpose of this study was to determine whether polymyxin B also inhibits contraction-stimulated glucose uptake after in vivo administration of the drug and to examine the relationship between the effects of polymyxin B on tension development and its effects on contraction-stimulated glucose uptake. When polymyxin B was administered to rats in vivo, glucose uptake in muscle after electrical stimulation was decreased, despite the same amount of tension developed as in control rats, indicating an effect of polymyxin B on glucose transport independent of tension development. Our results also indicate that the postexercise increase in glucose uptake is a function of the tension developed by prior contractions. When muscles were perfused with medium containing polymyxin B, this relationship was disrupted. These results provide evidence that polymyxin B causes a decrease in muscle glucose uptake independent of its effects on tension development. The extent to which its effects on glucose uptake are also the result of a diminution in contractile force is uncertain.

Animals↗
PubMed1991

Electrical stimulation of the thigh muscles after reconstruction of the anterior cruciate ligament. Effects of electrically elicited contraction of the quadriceps femoris and hamstring muscles on gait and on strength of the thigh muscles.

The effects of neuromuscular electrical stimulation on the strength of the thigh muscles and on gait were examined in ten patients after reconstruction of the anterior cruciate ligament. The patients were randomly assigned to one of two treatment groups: neuromuscular electrical stimulation and volitional exercise, or volitional exercise alone. A four-week course of electrically elicited co-contraction of the thigh muscles resulted in significant attenuation of the characteristic loss of strength of the quadriceps as compared with volitional exercise. There was no significant difference between groups in any measure of performance of the hamstring muscles. In the group that received neuromuscular electrical stimulation, the values for cadence, walking velocity, stance time of the involved limb, and flexion-excursion of the knee during stance were significantly different from those of the volitional exercise group. Flexion-excursion of the knee during stance was directly and significantly correlated with strength of the quadriceps femoris muscle. Flexion of the knee during stance was qualitatively different in the involved extremity as compared with the uninvolved extremity in all patients. There is a rapid flexion of the knee at weight acceptance that is maintained throughout stance and probably reflects stabilization of the joint by muscular coactivation to compensate for weakness of the quadriceps. The patients who received neuromuscular electrical stimulation had stronger quadriceps muscles and more normal gait patterns than those in the volitional exercise group.

Adolescent↗
PubMed1991

Defining the major trauma patient and trauma severity.

Criteria for defining the major trauma patient have been specified by physicians using Injury Patient Management Categories (PMCs), a computerized classification that can be used effectively with routinely collected discharge abstract data from non-trauma center hospitals as well as trauma centers. These criteria for major trauma not only include the more severe and complex single injuries, but also include criteria for identifying combinations of injuries that require tertiary level care. Major trauma patients identified as tertiary using PMCs are compared with existing and frequently used measures of injury severity such as AIS and ISS. Analyses suggest that the Injury PMCs identify major trauma patients accurately and more specifically than other indicators of severity that are commonly used. In addition, unlike other measures that are generally limited to registries, PMC tertiary patient criteria differentiate major trauma patients at both trauma centers and non-trauma centers without additional data collection. Using this method thus facilitates trauma systems evaluation and patient outcome assessment.

Databases, Factual↗
PubMed1990

Failure of prior low-intensity exercise to potentiate the thermic effect of glucose.

We have previously shown that following recovery from 45 min exercise at 67% maximum oxygen consumption (VO2max) the thermic effect of a glucose load is increased by 65% over that observed on a non-exercise day (Young et al. 1986). The purpose of this study was to determine if potentiation of the thermic effect of glucose by prior exercise is dependent on exercise intensity. The thermic response to a 1674 kJ glucose load was measured in five subjects in the absence of exercise (control) and following recovery from 45 min cycling exercise at each of three intensities: low (34% VO2max), moderate (54% VO2max), and high (75% VO2max). The average percentage increase in oxygen consumption over baseline due to glucose ingestion was similar for the control (9.9%, SE 2.0%), and the low- (10.2%, SE 0.9%) and moderate- (12.6%, SE 1.2%) intensity exercise conditions, while a significant increase in average VO2 was observed after the high-intensity condition (18.0%, SE 2.3%, P less than 0.05). The total energy expenditure (kJ) over baseline for 3 h was also similar for the control (84.5, SE 11.7), and the low-(100.0, SE 9.2) and moderate- (118.8, SE 5.0) intensity exercise conditions. The thermic response following high-intensity exercise (146.4 kJ, SE 13.4) was significantly greater than that observed in the control (P less than 0.01) or low-intensity (P less than 0.05) exercise conditions. These findings demonstrate that unlike prior high-intensity exercise (75% VO2max), low- or moderate-intensity exercise (i.e., 34% or 54% VO2max) fails to potentiate the thermic effect of a glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Identifying injuries and trauma severity in large databases.

In order to assess the cost and effectiveness of inpatient trauma care, trauma patients and their levels of severity must first be identified accurately using data from all hospitals, not just trauma centers. The present study provides the methodology to identify injuries and trauma severity using discharge abstract data collected routinely by all hospitals. In this study, the validity of defining trauma patients using routinely collected abstract data and two computerized patient classifications--Diagnosis Related Groups (DRGs) and Patient Management Categories (PMCs)--was tested using the trauma registry data of one major trauma center as the gold standard. Medical records were reviewed to assess whether patients were accurately classified as having injuries by each of the two systems and whether patients were incorrectly omitted from the registry. Results indicated that trauma patients are more accurately identified by PMCs (95.1% accuracy) than by either DRGs (44.4% accuracy) or the registry standard itself (91.8% accuracy). Because patients identified by DRGs as trauma were not likely to be injured (21.2% specificity), and many true injuries were not identified as such by DRGs (47.9% sensitivity), per case payments to hospitals are unpredictable, and management based on DRG data is misleading. By contrast, PMCs (97.8% sensitivity; 77.7% specificity) can be used to improve injury surveillance methods, to monitor outcomes in terms of morbidity and mortality, and to make hospital payment systems more equitable.

Databases, Bibliographic↗
PubMed1990

Acute obstructive jaundice in the multiple trauma patient.

The appearance of acute jaundice in the multiple trauma patient may result from obstruction of the common bile duct by clot. Management of this problem may be hindered by a delay in diagnosis, especially where alterations in pigment load and hepatic clearance may have produced the jaundice. A high index of suspicion combined with the judicious use of various noninvasive imaging modalities may be helpful in making the diagnosis. The progression of jaundice in a patient suspected of having acute obstructive hemobilia should prompt rapid operative intervention. At laparotomy, cholangiography or common bile duct exploration should be done. Persistent bleeding should be managed initially with angiographic localization and transcatheter embolization; its failure would necessitate surgical control of the source.

Accidents, Traffic↗
PubMed1990

Inhibition of beta-glucuronidase in human urine by ascorbic acid.

The effects of oral supplementation of ascorbic acid (1500 mg d-1) on urinary beta-glucuronidase (beta-G) activity was assessed in a double-blind crossover study design over a 3-week period. The subjects on ascorbic acid treatment displayed a statistically significant (P less than 0.05) decrease in beta-G with an approximate decrease of 25%.

Adult↗
PubMed1990

Comparison of anterior laxity measurements in anterior cruciate deficient knees with two instrumented testing devices.

We measured anterior tibial displacements in 21 anterior cruciate ligament deficient patients using two instrumented testing devices, the KT-1000 and the KSS. A comparison of values obtained from testing was done using statistical analysis. The two tests common to both devices were the 20 lb pull and the manual maximum. The involved normal (I-N) values showed that there was no significant difference between the two devices for both the manual maximum and the 20 lb force level. There was also no significant difference between devices for the manual maximum absolute values. The significant difference between the absolute values for the 20 lb force level is probably due to the different testing techniques for both devices. When testing with the KSS, the patella remains free; testing with the KT-1000 requires that the examiner maintain pressure to hold the patella down. The manual maximum absolute values showed no significant difference because the testing techniques for both devices were identical. Comparable data for both devices are the I-N values for the 20 lb and manual maximum values.

Adolescent↗
PubMed1989

Variations of heavy metals and arsenic in fish and other organisms from the Calcasieu River and Lake, Louisiana.

The edible parts of several species of fish and other marine organisms inhabiting the Calcasieu River/Lake, Louisiana were analyzed for Cd, Cr, Cu, Pb, Hg, Ag, Zn and As. Concentrations of all metals measured in both intra and interspecies showed no significant variation with sample location. Differences in elemental concentrations were related to organism mobility and not to site-specific variations in metal loadings. Different species of finfish contained only trace amounts of Cd (0.02-0.08), Ag (less than 0.01-0.3), Pb (less than 0.2-0.5), and As (less than 0.1-0.3) mg kg(-1). Concentrations of Cu and Cr were highly variable, in contrast to Zn, which was present in relatively constant amounts across all species (28 +/- mg kg(-1). Sessile organisms such as oysters had the highest concentrations of heavy metals, including Cd. Periphyton and zooplankton were the only groups that showed differences in metal concentrations with sampling location.

Animals↗
PubMed1989

Percutaneous cardiopulmonary bypass for the treatment of hypothermic circulatory collapse.

Environmentally induced hypothermia has a very high mortality. Cardiopulmonary bypass affords the best chance of survival from hypothermia but can be time-consuming to institute. We have utilized percutaneous cardiopulmonary bypass with recently developed bypass catheters to resuscitate a patient with profound hypothermia complicated by circulatory collapse. Percutaneous cardiopulmonary bypass appears to be the treatment of choice for profound hypothermia.

Cardiopulmonary Bypass↗
PubMed1989

Exercise intensity and glucose tolerance in trained and nontrained subjects.

The improved glucose tolerance and increased insulin sensitivity associated with regular exercise appear to be the result, in large part, of the residual effects of the last bout of exercise. To determine the effects of exercise intensity on this response, glucose tolerance and the insulin response to a glucose load were determined in seven well-trained male subjects [maximal O2 uptake (VO2max) = 58 ml.kg-1.min-1] and in seven nontrained male subjects (VO2max = 49 ml.kg-1.min-1) in the morning after an overnight fast 1) 40 h after the last training session (control), 2) 14 h after 40 min of exercise on a cycle ergometer at 40% VO2max, and 3) 14 h after 40 min of exercise at 80% VO2max. Subjects replicated their diets for 3 days before each test and ate a standard meal the evening before the oral glucose tolerance test. No differences in the 3-h insulin or glucose response were observed between the control trial and before exercise at either 40 or 80% VO2max in the trained subjects. In the nontrained subjects the plasma insulin response was decreased by 40% after a single bout of exercise at either 40 or 80% VO2max (7.0 X 10(3) vs. 5.0 X 10(3), P less than 0.05; 3.8 X 10(3) microU.ml-1.180 min-1, P less than 0.01). The insulin response after a single bout of exercise in the nontrained subjects was comparable with the insulin responses found in the trained subjects for the control and exercise trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Decreased glucose uptake in the fetus after maternal exercise.

Glucose uptake by muscle is stimulated by exercise. However, during pregnancy, insulin resistance develops in maternal skeletal muscle as a mechanism to spare glucose for use by the developing fetus. The purpose of this study was to determine whether a bout of exercise adversely affects glucose availability to the fetus by increasing glucose uptake in maternal muscle tissue. Pregnant (P) and nonpregnant (NP) rats were divided into rest and exercise groups. Immediately following a 50-min treadmill run, a bolus of glucose (1 g.kg-1) and tracer [1-3H]2-deoxyglucose was injected i.v., and rats underwent a 60-min i.v. glucose tolerance test (IVGTT), after which they were sacrificed. Although glucose levels were lower for P vs NP rats at all time points, prior exercise did not affect glucose levels in either P or NP rats. Plasma insulin levels were augmented in P compared with NP rats and were not significantly altered by prior exercise. Glucose/tracer accumulation was enhanced in red and white gastrocnemius in both P and NP rats, and in soleus of NP rats, by exercise. However, glucose/tracer accumulation in the fetus was decreased by 40% (P less than 0.01) in the exercised dams. These results indicate that uptake of glucose by the fetus is compromised following exercise, as a result of increased glucose uptake by maternal skeletal muscles.

Animals↗
PubMed1988

Periventricular white matter changes and dementia. Clinical, neuropsychological, radiological, and pathological correlation.

Forty-three patients with computed tomographic scan findings of decreased attenuation in the periventricular white matter (PVWM) region were studied. Clinical evaluation revealed presence of hypertension in 36 patients (84%) and cerebrovascular risk factors in 41 patients (95%). Unilateral or bilateral neurological deficits were present in 40 patients (93%). Neuropsychological evaluation in 27 of them revealed features of subcortical dementia. Magnetic resonance imaging in seven cases demonstrated high-intensity areas in the deep white matter region on T2-weighted imaging. Pathological evaluation in four patients revealed demyelination without inflammatory cells and infarctions in the PVWM region, lacunar infarctions in the basal ganglia and brain stem, and marked arteriosclerosis. The study indicated that most (95% in this series) of the patients with computed tomographic scan findings of decreased attenuation in the PVWM region had cerebrovascular risk factors and various neurological and neuropsychological features of subcortical dementia. Pathologically, these lesions represented areas of infarction and demyelination, along with diffuse arteriosclerosis.

Adult↗
PubMed1988

A host-dependent temperature-sensitive mutant of Rous sarcoma virus: evidence for host factors affecting transformation.

We have characterized a host range mutant of Rous sarcoma virus in order to identify host cell factors involved in transformation. This mutant, tsLA33-1, which was isolated from a stock of the temperature-sensitive mutant tsLA33, is not temperature-sensitive for transformation of chicken embryo fibroblasts, as judged by its ability to induce morphological changes and agar colony formation at both 36 and 41.5 degrees. In Rat-3 cells, however, this mutant induced a temperature-dependent transformation: infected Rat-3 cells were transformed at 34 degrees but not at 39.5 degrees. Retransformants were isolated from tsLA33-1-infected Rat-3 cells by growth in agar suspension at 39.5 degrees. Virus rescued from these retransformants induced a temperature-dependent transformation when reintroduced into rat cells. The level of expression of pp60v-src at 39.5 degrees was unchanged in the retransformants. When the retransformants were treated with herbimycin, an antibiotic which induces turnover of certain protein-tyrosine kinases, they reverted to a normal phenotype, indicating that the transformed phenotype of the retransformants was dependent on continued expression of pp60v-src. The retransformants are therefore pseudorevertants in which a cellular alteration has occurred that allows transformation at 39.5 degrees by the mutant pp60v-src. Thus the temperature-dependence of transformation by tsLA33-1 is affected by the cellular environment, and is suppressed or complemented both in chicken cells and in the rat cell pseudorevertants. No clear correlation between levels of phosphorylation at tyrosine and transformation was observed. In Rat-3 cells the pp60v-src encoded by tsLA33-1 may be defective in its interaction with low abundance substrates that are critical for transformation; alternatively the nonpermissive cells may require a higher threshold dose of pp60v-src for transformation.

Animals↗
PubMed1988

The utility of physiological status, injury site, and injury mechanism in identifying patients with major trauma.

It has been suggested that if triage criteria are to identify accurately patients with major trauma, not only physiologic status, but also anatomic site and injury mechanism must be assessed. This study examined the influence of physiologic, injury site, and injury mechanism criteria on the diagnosis of major trauma in 2,057 trauma patients. Because the Trauma Score was found to be a highly specific indicator of major trauma (98.7%), the strategy adopted for isolating the factors that minimize inappropriate triage was to determine which, alone or in combination, are the most effective in identifying patients with major trauma among those with high Trauma Scores (greater than 12). Based on this analysis, a set of triage guidelines was developed. The application of these guidelines to the study population indicated an undertriage rate of 4.1 to 6.3% and an overtriage rate of 16.8 to 21.3%, depending on the definition of major trauma.

Adolescent↗