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Biomedical subjects

J A Brasel

Publications and source records attributed to J A Brasel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of training and growth hormone suppression on insulin-like growth factor I mRNA in young rats.

The growth hormone (GH)-insulin-like growth factor I (IGF-I) axis plays a role in the adaptation to exercise training, but IGF-I gene expression in response to exercise training and GH suppression has not been studied. Twenty female rates underwent a 4-wk treadmill training program begun in the prepubertal period (day 14 of life). In 10 of the training rats, GH production was suppressed by anti-GH-releasing hormone antibodies (GH suppressed). IGF-I mRNA and protein levels were measured in liver and hindlimb skeletal muscle. GH suppression reduced IGF-I mRNA expression in the liver to a much greater extent than in the muscle. In the GH control rats, training induced significant increases in hepatic exon 1-derived IGF-I mRNA (mean increase 30%; P < 0.05) and muscle exon 2-derived mRNA (mean increase 35%; P < 0.05). In the GH-suppressed rats, only muscle exon 1-derived transcripts were significantly increased by training (55%; P < 0.05) and this was associated with a significant increase in muscle IGF-I protein levels (P < 0.05). We speculate that the anabolic response to training may involve both GH-dependent increases in IGF-I mRNA in the liver and GH-independent increases in the muscle.

Actins↗
PubMed1994

Effect of brief exercise on circulating insulin-like growth factor I.

An acute insulin-like growth factor I (IGF-I) response to 10 min of above-lactate threshold cycle ergometer exercise was studied in 10 subjects (age 22-35 yr). Each subject exercised on three separate mornings after ingesting one of two isocaloric isovolemic liquid meals high in either fat or glucose or an isovolemic noncaloric placebo. The high-fat meal attenuated the growth hormone (GH) response (Cappon et al., J. Clin. Endocrinol. Metab. 76: 1418-1422, 1993). In contrast, IGF-I increased equally for all protocols [e.g., after the placebo meal IGF-I increased from 21,716 (SE) ng/ml preexercise to 25,316 ng/ml at 10 min of exercise; P < 0.05]. IGF-I peaked by the 10th min of exercise, like GH, and remained significantly elevated for only 20 min of recovery. We tested for possible GH-dependent mechanisms in which circulating IGF-I would increase 12-24 h after exercise. Ten subjects (age 23-32 yr) performed 10 min of above-lactate threshold exercise at 9, 10, and 11 A.M. GH was elevated after the first exercise bout (peak GH 6.05 +/- 1.45 ng/ml; P < 0.001) but was significantly reduced for the second and third bouts (peak GH 2.52 +/- 0.76 and 1.50 +/- 0.40 ng/ml, respectively). No increase in IGF-I was observed by 8 A.M. on the following day. Heavy ergometer exercise led to brief and small increases in circulating IGF-I that were independent of circulating GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of growth hormone suppression on exercise training and growth responses in young rats.

Exercise training improves maximal oxygen uptake and endurance times in adult human beings and other animals. The mechanism of this improvement results in part from anabolic effects of exercise and may be mediated by growth hormone (GH). Little is known about the role of GH in the adaptation to exercise in younger, still-developing organisms. To examine this role, we began a 4-wk treadmill exercise training protocol in 14-d-old female rats. GH was suppressed by passive immunization with anti-GH releasing hormone antisera. There were four experimental groups: 1) GH-control (normal GH secretory capacity), untrained (n = 21); 2) GH-suppressed, untrained (n = 13); 3) GH-control, trained (n = 14); and 4) GH-suppressed; trained (n = 11). At the end of the training period, maximal oxygen uptake and treadmill endurance running time were measured. Serum GH and IGF-I were assessed using RIA, and whole hind limb musculature succinate dehydrogenase (an indicator of mitochondrial function) was measured with standard fluorometric technique. Body weight gain was markedly reduced in GH-suppressed rats (mean, 54% of GH-controls in untrained rats and 55% in trained; p < 0.05). No apparent effect of training on linear growth was observed. As expected, serum IGF-I was markedly reduced by GH suppression, but no exercise-induced increase occurred in IGF-I as a result of training in either the GH-control or GH-suppressed rats. In GH-control rats, maximal oxygen uptake and succinate dehydrogenase were 69% and 25% greater, respectively, in trained compared with untrained rats (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Acute effects of high fat and high glucose meals on the growth hormone response to exercise.

The health promoting, anabolic effects of physical activity may be mediated, in part, by an exercise-associated increase in GH. However, little is known about the acute effects of diet on exercise-induced GH release. We hypothesized that a single meal could attenuate the GH response to exercise by modulating substances like somatostatin, insulin, or glucose. Eleven healthy young adults performed 10 min of high intensity, standardized cycle ergometry in the morning following an overnight fast. On separate days they ingested a noncaloric placebo liquid meal or an isovolemic, isocaloric liquid meal high in either fat or glucose. Venous blood samples were obtained before and for 90 min after exercise began, whereas gas exchange data were measured breath by breath. Peak mean oxygen consumption (VO2) was, on average, 9-fold greater than preexercise levels in all groups. Although there was no difference in preexercise GH levels, mean peak, postexercise GH was 54% lower after the high-fat meal compared with placebo (P < 0.01). Modest decreases in GH response to exercise after the high-glucose meal were not statistically significant. Mean serum somatostatin was significantly higher after the high-fat meal compared with both high glucose and placebo meals. This study demonstrates that exercise-induced GH release can be significantly attenuated by the contents of a single preexercise meal. The high fat meal increased circulating somatostatin and was associated with an inhibition of the GH secretion. The data provide a possible specific mechanism to explain how diet can acutely modulate the anabolic effects of exercise.

Adult↗
PubMed1992

Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome.

Seventy girls with Turner syndrome, verified by karyotype, were randomly assigned to observation or treatment with human growth hormone (hGH), oxandrolone, or a combination of hGH plus oxandrolone for a period of 12 to 24 months, to assess the effect of treatment on growth velocity and adult height. Subsequently, all subjects received either hGH alone or hGH plus oxandrolone. Data are presented for 62 subjects treated for a period of 3 to 6 years. When compared with the anticipated growth rate in untreated patients, the growth rate after treatment with hGH, both alone and in combination with oxandrolone, showed a sustained increase for at least 6 years. Treatment is continuing in over half of the subjects; at present, 14 (82%) of 17 girls receiving hGH alone and 41 (91%) of 45 girls receiving combination therapy exceeded their expected adult heights. Thirty girls have completed treatment; mean height for these 30 patients is 151.9 cm, compared with their mean original projected adult height of 143.8 cm. We conclude that therapy with hGH, alone and in combination with oxandrolone, can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome.

Age Determination by Skeleton↗
PubMed1992

Effect of low and high intensity exercise on circulating growth hormone in men.

We hypothesized that circulating GH would increase only if a threshold of work intensity [corresponding to the anaerobic or lactate threshold (LT)] was exceeded. Ten healthy male volunteers (18-35 yr) first performed ramp-type progressive cycle-ergometer exercise to determine the LT and the maximal oxygen uptake. On subsequent mornings after an overnight fast, each subject performed bouts of 1, 5, and 10 min constant work rate exercise of either high intensity (above LT) or low intensity (below LT). A 1-h interval separated exercise bouts. Gas exchange (breath-by-breath), GH, immunoreactive insulin, glucose, lactate, pyruvate, and epinephrine and norepinephrine were measured at regular intervals. After the 10-min bouts of high compared with low intensity exercise, lactate was 7.2 +/- 3.7 mmol/L vs. 1.4 +/- 1.3, P less than 0.05; epinephrine was 1,113 +/- 519 pmol/L vs. 496 +/- 273, P less than 0.05; and norepinephrine was 7.89 +/- 3.45 nmole/L vs. 2.83 +/- 1.34, P less than 0.05. GH did not increase significantly from preexercise baseline during low intensity exercise (e.g., GH after 10-min low intensity exercise changed from baseline values by 1.5 +/- 2.0 micrograms/L, NS). Although lactate was elevated after 5-min of high intensity exercise, peak GH was significantly elevated (mean increase above baseline of 7.7 +/- 2.4 micrograms/L, P less than 0.05) only after 10 min of high intensity exercise (increases in 9 of 10 subjects). The GH increase occurred despite simultaneous increases in both IRI and glucose. A minimum duration of 10 min, high intensity exercise consistently increased circulating GH in adult males.

Adolescent↗
PubMed1990

Effects of tumor necrosis factor alpha on skeletal muscle and Walker 256 carcinosarcoma protein metabolism studied in vivo.

Human tumor necrosis factor alpha (TNF) inhibits tumor growth, but its effects on tumor and skeletal muscle protein metabolism in vivo have not been adequately studied. Walker 256 carcinosarcoma growth rate was followed over an 11-day period in Sprague-Dawley rats. Tumor-bearing rats received either saline or 50 micrograms of TNF (Genentech, Inc.) s.c. on day 8 of tumor growth. This single dose of TNF reduced tumor protein growth during a 2-day posttreatment period from 27.6 +/- 4.4 to 10.5 +/- 3.7%/day (mean +/- SE; P less than 0.01). The rate of in vivo incorporation of L-[1-14C]leucine into skeletal muscle protein was significantly increased (P less than 0.05) from 5.1 +/- 0.2%/day in the saline-treated tumor-bearing rats to 7.7 +/- 1.3%/day in the TNF-treated tumor-bearing rats. The latter value was not statistically different from the 9.2 +/- 0.9%/day observed in the tumor-free control animals. TNF administration significantly increased both the total and individual acid-soluble skeletal muscle amino acid concentrations in tumor-bearing rats by an average of 86 +/- 7%, compared to values in saline-treated tumor-bearing rats. Similarly, acid-soluble skeletal muscle 3-methyl-histidine concentrations increased from 66 +/- 14 to 113 +/- 19 pmol/g protein (P less than 0.05). Tumor protein synthesis in the TNF-treated group was 50% greater than in the saline-treated group, whether expressed as %/day (72.7 +/- 9.1 versus 47.9 +/- 4.8; P less than 0.05) or was micrograms/g tumor/min (58.7 +/- 7.7 versus 40.7 +/- 4.5; P less than 0.05). In contrast, estimated tumor protein degradation rates were increased by over 200% in the TNF-treated rats, compared to the values in the saline-treated rats [62.1 +/- 10.7 versus 20.3 +/- 6.0%/day (P less than 0.01) and 50.0 +/- 8.9 versus 17.5 +/- 5.4 micrograms/g tumor/min (P less than 0.01)]. Thus, TNF appears to stimulate tumor protein degradation more than protein synthesis, explaining the overall decrease in tumor growth.

Amino Acids↗
PubMed1989

Growth hormone secretory dynamics in subjects with normal stature.

To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.

Adolescent↗
PubMed1988

The source of urinary epidermal growth factor in humans.

To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118 +/- 12 vs 105 +/- 6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5 +/- 0.25 vs 1.5 +/- 0.18 ng/ml in males and females respectively p less than 0.05). Urine EGF excretion averaged 1641 +/- 233 ng/h in males and 1507 +/- 191 ng/h in females (p greater than 0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98, p less than 0.01) and female (r = 0.94, p less than 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 micrograms/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.

Adult↗
PubMed1988

Three-year results of a randomized prospective trial of methionyl human growth hormone and oxandrolone in Turner syndrome.

Seventy girls with Turner syndrome, 4 to 12 years of age, participated in a prospective, randomized study to determine the effects on growth of methionyl human growth hormone (met-hGH) or oxandrolone. Subjects were randomly assigned to receive either no treatment (control) or met-hGH (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination met-hGH plus oxandrolone. At the end of an initial period of 12 to 20 months, patients in the original control and oxandrolone groups were given combination met-hGH plus oxandrolone. At that time the dosage of oxandrolone was lowered to 0.0625 mg/kg/day. Sixty-five subjects have now completed the first 3 years of the study. Compared with the control growth rate for year 1 (3.8 cm/yr), significant increases in growth rate were seen in all 3 years of combination therapy (9.8, 7.4, and 6.1 cm/yr, respectively) and in the first 2 years of treatment with met-hGH alone (6.6, 5.4, and 4.6 cm/yr). When growth velocity was expressed as standard deviation for age in girls with Turner syndrome, significant increases relative to the control group for year 1 (-0.1 SD) were seen in all three years of both combination therapy and met-hGH alone (combination, +6.6, +4.3, +3.0 SD; met-hGH, +3.1, +2.0, +1.4 SD). After 3 years of treatment, predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group.

Body Height↗
PubMed1987

Anogenital ratio: measure of fetal virilization in premature and full-term newborn infants.

To provide normative data, we measured anogenital distances in 115 infants of 25 to 42 weeks gestational age and 10 pregnant women, including anus to fourchette (AF), anus to base of the clitoris (AC), and fourchette to base of the clitoris (FC). All infant measurements showed positive and significant correlations with body surface area, weight, length, and gestational age (P less than 0.001). However, the anogenital ratio (AF/AC) followed a normal distribution and did not correlate with any of the anthropometric variables or age. Mean (+/- SD) value in infants was 0.37 +/- 0.07, and in adults, 0.36 +/- 0.07. An anogenital ratio greater than 0.50 falls outside the 95% confidence limits, suggests labioscrotal fusion, and indicates a need for further evaluation. Because it is independent of body size and gestational age, the anogenital ratio should be useful in diagnosing androgen-induced labioscrotal fusion in both premature and full-term female infants.

Adult↗
PubMed1987

Diet composition and lipoprotein lipase (EC 3.1.1.34) activity in human obesity.

1. Adipose tissue lipoprotein lipase (EC 3.1.1.34; AT-LPL), a rate-limiting enzyme in triglyceride storage in adipose tissue, is hormonally regulated and may be important in the maintenance of obesity. 2. In twelve obese women, AT-LPL activity was measured before weight loss, during weight loss and after 1 and 2 weeks of weight maintenance on either a high-carbohydrate or a high-protein diet. 3. When related to tissue weight, AT-LPL activity during the 2 weeks of weight maintenance was higher than the initial AT-LPL activity; there was no difference when activity was expressed per cell. 4. Changes in AT-LPL activity were not affected by diet composition. AT-LPL activity correlated with insulin levels and a change in insulin sensitivity of AT-LPL was observed after weight loss.

Adipose Tissue↗
PubMed1987

Continuing physician education: the Health Learning Systems approach.

In the past 10 years, Jack Filer has served as executive editor for a series of five separate national education programs on infant nutrition. Four of these have been directed towards physicians and the last been developed for mothers. He was assisted by a group of associate editors with expertise in various areas, as needed, depending on the material to be developed. The educational programs have included closed-circuit live telecasts, films and slides for use in a visiting faculty program, monographs and newsletters, and videotapes for maternal instruction. The nutritional guidelines for infant feeding emphasized throughout the recommendations of the Committee on Nutrition of the American Academy of Pediatrics to promote breast-feeding with commercial infant formula as an alternative if breast-feeding is not elected or stopped early. Delayed introduction of solid food and cow milk was also recommended.

Education, Medical, Continuing↗
PubMed1986

Methionyl human growth hormone and oxandrolone in Turner syndrome: preliminary results of a prospective randomized trial.

Seventy girls with Turner syndrome, 4 to 12 years of age, were randomly assigned to receive either no treatment (control) or methionyl human growth hormone (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination hGH plus oxandrolone therapy. Baseline growth rates averaged 4.3 cm/yr, and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome. Sixty-seven girls remained in the study for a minimum of 1 year. Growth rates and growth velocity (in standard deviations for age in girls with Turner syndrome) were control 3.8 cm/yr (-0.1 SD), hGH 6.6 cm/yr (+2.3 SD), oxandrolone 7.9 cm/yr (+3.7 SD), and combination therapy 9.8 cm/yr (+5.4 SD). Mean bone ages advanced 1.0 years (hGH), 1.3 years (oxandrolone), and 1.6 years (combination). However, median increments in height age/bone age (delta HA/delta BA) ratios ranged from 1.0 to 1.1 for treatment groups, compared with 0.8 for the controls. Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or oxandrolone alone, and 3.2 cm for combination treatment. These data indicate that both hGH and oxandrolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome, and potentially increase final adult height.

Adolescent↗
PubMed1986

Meal-induced changes in lipoprotein lipase activity in brown fat and other tissues of rats.

Brown fat thermogenesis is increased after a single test meal. This study was conducted to determine whether lipoprotein lipase activity is higher in brown adipose and other tissues after a single large meal. Rats were trained to eat two large meals per day. Two hours after consuming a test meal, lipoprotein lipase activity was measured in interscapular brown adipose tissue, retroperitoneal and epididymal white adipose tissue, gastrocnemius and soleus skeletal muscles and heart. After a high carbohydrate test meal, lipoprotein lipase activity in white adipose tissue pads was higher (P less than 0.05) and that in brown adipose tissue was lower (P less than 0.05) than in these tissues from the meal-deprived group. Muscle lipoprotein lipase did not change significantly. A high fat test meal did not significantly alter lipoprotein lipase activity in brown adipose tissue, white adipose tissue, gastrocnemius or soleus when compared to the meal-deprived control, but heart lipoprotein lipase activity was significantly elevated. These findings indicate that after a single test meal lipoprotein lipase activity in brown adipose tissue is not higher than that from the meal-deprived group and therefore, lipoprotein lipase may not play a rate-limiting role in moving free fatty acids into this tissue in the postprandial state.

Adipose Tissue, Brown↗
PubMed1986

Adipose tissue thymidine kinase activity in man.

Thymidine kinase activity was studied during human adipose tissue development. Adipose tissue was obtained from the groin in 81 persons, aged 7 wk through 60 yr. None had a metabolic or growth disorder. Adipose tissue thymidine kinase activity was highest in infants and lowest in adults. Peak thymidine kinase activity was seen in the early postnatal period and a lesser elevation was found in the preadolescent years, coinciding with hypothesized periods of proliferation of preadipocytes in man. In contrast, during adulthood, a time of stable lipid-laden cell number, thymidine kinase activity was lower. Although these adipose tissue samples include both stromal and fat cells, the data support the hypothesis that adipose tissue growth in early infancy is primarily the result of cellular proliferation, and that little cellular proliferation occurs after infancy, except possibly for a brief period prior to adolescence.

Adipose Tissue↗