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Biomedical subjects

J C Young

Publications and source records attributed to J C Young.

At least 19 recordsLinked to original sources

Supercritical fluid chromatography of Fusarium mycotoxins.

Capillary- and packed-column supercritical fluid chromatography has been used for the separation of Fusarium mycotoxins of various structure types such as the trichothecenes including deoxynivalenol and its acetylated derivatives and T-2 toxin, as well as butenolide, culmorin, sambucinol and zearalenone. The effect of modifier concentration and column temperature and pressure was also studied. Retention indices based on alkylphenones were determined for these mycotoxins on two of the capillary columns employed.

Capillary Action

The role of the N region in signal sequence and signal-anchor function.

To determine the role of sequences other than the hydrophobic core in mediating signal sequence function, we examined the behavior of fusion proteins and deletion mutants in cell-free systems. We demonstrate that neither the N nor the C region of the preprolactin signal sequence is necessary for translocation. However, insertion of sequences with either a net charge of +2.5 or -6.0 between the N region and the hydrophobic core of the signal converted it into a signal-anchor. The topologies adopted (types I and II, respectively) were opposite those predicted from the distribution of charges surrounding the hydrophobic core of the signals. When these mutant signals were located in the interior of an otherwise secreted protein, both sequences functioned as stop-transfer sequences. Related mutations were assayed in fusion proteins in which the IgM transmembrane domain functioned as an amino-terminal signal-anchor. For these molecules, the distribution of charged residues surrounding the hydrophobic core had no influence on the topology adopted. Our results suggest that features other than simple charge distribution play an important role in determining membrane topology in vitro.

Amino Acid Sequence

The effect of prior exercise on oral glucose tolerance in late gestational women.

Glucose tolerance deteriorates over the course of a normal human pregnancy as a result of increased peripheral insulin resistance. In contrast, physical exercise has been shown to improve glucose tolerance and blunt the insulin response to a glucose load in insulin-resistant individuals. The purpose of this study was to determine the effect of exercise on glucose tolerance and the insulin response in healthy women during the third trimester of pregnancy (33 weeks of gestation). Five subjects underwent oral glucose tolerance tests (a) 30 min following a 30-min exercise bout on a cycle ergometer at a relative intensity of 50% maximal aerobic capacity, and (b) on a control day without prior exercise. The area under the glucose concentration curve was not different between trials, while the area under the insulin concentration curve was decreased by 23% in the exercise trial compared with the control trial (P less than 0.05). These results suggest that the insulin response to a glucose load is improved in late gestational women by a single bout of moderate intensity exercise.

Administration, Oral

Skeletal muscle glucose uptake following overload-induced hypertrophy.

While endurance exercise training has been shown to enhance insulin action in skeletal muscle, the effects of high resistance strength training are less clear. The purpose of this study was to determine the rate of glucose uptake in skeletal muscle in which compensatory hypertrophy was induced by synergist muscle ablation. Basal and insulin mediated [3H] 2-deoxyglucose uptake were measured in soleus and EDL muscles using the perfused rat hindquarter preparation. Neither basal nor insulin mediated glucose uptake, when expressed per gram muscle, were enhanced in hypertrophied soleus muscles compared with control muscles, despite a twofold increase in mass (P less than 0.01). In the EDL, muscle mass increased 60% with synergist ablation (P less than 0.01), however insulin mediated glucose uptake was not different from that of control muscles. The basal rate of glucose uptake in hypertrophied EDL muscles was increased twofold over that of control muscles (P less than 0.05), possibly due to changes in neural input and/or loading. These results suggest that the stimulus for development of increased muscle mass is different from that for metabolic adaptations.

Analysis of Variance

Adaptation in synergistic muscles to soleus and plantaris muscle removal in the rat hindlimb.

Although the soleus muscle comprises only 6% of the ankle plantar flexor mass in the rat, a major role in stance and walking has been ascribed to it. The purpose of this study was to determine if removal of the soleus muscle would result in adaptations in the remaining gastrocnemius and plantaris muscles due to the new demands for force production imposed on them during stance or walking. A second purpose was to determine whether the mass or the fiber type of the muscle(s) removed was a more important determinant of compensatory adaptations. Male Sprague-Dawley rats underwent bilateral removal of soleus muscle, plantaris muscle, or both muscles. For comparison, compensatory hypertrophy was induced in soleus and plantaris muscles by gastrocnemius muscle ablation. After forty days, synergist muscles remaining intact were removed. Mass, and oxidative, glycolytic, and contractile enzyme activities were determined. Despite its role in stance and slow walking, removal of the soleus muscle did not elicit a measurable alteration in muscle mass, or in citrate synthase, lactate dehydrogenase, or myofibrillar ATPase activity in gastrocnemius or plantaris muscles. Similarly, removal of the plantaris muscle, or soleus and plantaris muscles, had no effect on the gastrocnemius muscle, suggesting that this muscle was able to easily meet the new demands placed on it. These results suggest that amount of muscle mass removed, rather than fiber type, is the most important stimulus for compensatory hypertrophy. They also suggest that slow-twitch motor units in the gastrocnemius muscle play an important role during stance and locomotion in the intact animal.

Adaptation, Physiological

The use of transesophageal echocardiography in the evaluation of chest trauma.

Transesophageal echocardiography (TEE) has been used over the last 10 years (1982-1992) to study the heart and thoracic aorta. We set out to evaluate the diagnostic applications of TEE in patients with thoracic trauma. Specifically, TEE was performed on patients suspected of having either a cardiac contusion or an injury of the thoracic aorta. Fifty-eight patients admitted with thoracic trauma underwent TEE. Fifty of those patients suspected of having a cardiac contusion also underwent transthoracic echocardiography (TTE). The two diagnostic modalities were compared. In 21 of these patients a wide mediastinum was apparent on admission chest x-ray films. Nineteen of this latter group underwent thoracic angiography in addition to TEE. Two patients underwent post-mortem examination. Of the 50 patients undergoing both TEE and TTE, a cardiac contusion was detected by TEE in 26 patients. Transthoracic echocardiography detected only six contusions in this group. Of the 21 patients with a wide mediastinum, TEE detected three obvious aortic disruptions. These findings were confirmed in each case by angiography. In 16 cases TEE showed the aorta to be normal. This was confirmed on the angiogram in 14 cases and by autopsy in two cases. Transesophageal echocardiography revealed an aortic intimal irregularity distal to the left subclavian artery in two cases. The results of aortography were normal in these last two cases. As a diagnostic modality, TEE more accurately detected cardiac contusions than TTE (p less than 0.001) and was a very sensitive screening tool in the early evaluation of patients with a wide mediastinum.

Adolescent

Effect of prior exercise and insulin on potential thermogenic systems in rat skeletal muscle.

We previously reported that insulin stimulates oxygen consumption by the perfused rat hindquarter after high-intensity exercise. The purpose of the present study was to examine whether fructose 6-phosphate-fructose 1,6-bisphosphate cycling or an uncoupling of mitochondrial respiration contributes to this phenomenon. Hindquarter skeletal muscle was analyzed after perfusion in the absence or presence of insulin (150-200 microU/ml) for high-energy phosphate content, fructose 6-phosphate-fructose 1,6-bisphosphate cycling of glucose before incorporation into glycogen, and mitochondrial respiratory control. Muscle from exercised rats perfused with insulin did not display greater rates of glucose cycling or mitochondrial uncoupling; in fact, insulin decreased the rate of fructose 6-phosphate cycling and tended to increase respiratory control in skeletal muscle mitochondria. In addition, the concentrations of ATP and creatine phosphate and the calculated free ADP level in muscle of previously exercised rats perfused with insulin were similar to those of control rats. The results do not exclude the possibility that localized subcellular changes in ADP occurred, however. In conclusion, the results suggest that insulin-induced increases in other substrate cycles, ion transport systems, and/or as yet unidentified energy-requiring processes account for the 25-30% increase in hindquarter oxygen consumption after intense exercise.

Animals

Ageing, exercise and food restriction: effects on skeletal muscle glucose uptake.

We investigated the effects of ageing, exercise and food restriction on glucose uptake by muscles perfused with physiological concentrations of insulin and glucose in male Long-Evans rats. The rate of glucose uptake by hindlimb muscles perfused with medium containing 50 microU@ml insulin and 8 mM glucose was the same in 9-10 month-, 18 month-, and 24-month-old rats. Rats exercised by means of swimming 3 h/day, 5 days/week, had significantly higher rates of muscle glucose uptake than did the sedentary freely eating rats. Paired-weight sedentary rats, that were food restricted so as to keep their weights in the same range as those of the swimmers, had a hindlimb glucose uptake rate similar to that of the swimmers, and greater than that of the sedentary freely eating rats. The 24-month-old sedentary freely eating rats showed a trend toward a higher plasma glucose response and a lower plasma insulin response to a glucose tolerance test. The 24-month-old swimmers showed no deterioration in glucose tolerance compared to the 9-10 month-old rats. Our findings argue against the concept that ageing results in skeletal muscle insulin resistance in rats.

Aging

Skeletal muscle atrophy in old rats: differential changes in the three fiber types.

This study was undertaken to reevaluate the effects of ageing on skeletal muscle mass and on mitochondrial and glycolytic enzyme levels in the different types of skeletal muscle in rats. It was found that some muscles atrophy with ageing, while others do not, in male rats. Atrophy appears to occur in weight-bearing muscles, and is most marked in those with a high proportion of type IIb fibers. The muscles that did not atrophy are non-weight-bearing, and include the epitrochlearis (predominantly type IIb fibers) and the adductor longus (predominantly type I fibers). The average cross-sectional area of muscle fibers in the plantaris muscles of 28-30-month-old rats was approximately 30% smaller than that of 9-10-month-old animals, providing evidence that the approximately 30% lower weight of the plantaris in the old group was entirely due to fiber atrophy. The proportion of type IIa fibers was decreased and the proportion of type I fibers was increased in the plantaris of the old rats. The respiratory capacity of the soleus muscle (predominantly type I fibers), and the glycolytic capacity of the superficial, white (type IIb) and deep, red (predominantly type IIa) portions of the vastus lateralis, were reduced in the old rats. Our results provide evidence that ageing has differential effects on the three types of skeletal muscle fiber, and on weight-bearing and non-weight-bearing muscles, in the rat.

Aging

Transesophageal echocardiographic examination of a patient with traumatic aortic transection from blunt chest trauma: a case report.

Traumatic aortic disruption is an injury associated with high mortality. Early recognition, diagnosis, and surgical repair are important in order to salvage patients with this injury. We report a case in which transesophageal echocardiography, a rapid, minimally invasive diagnostic technique, was used to identify an acute disruption of the proximal descending aorta in a patient with blunt chest trauma.

Adult

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

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

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

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

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