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Biomedical subjects

B H Breier

Publications and source records attributed to B H Breier.

At least 109 records · Page 6Linked to original sources
PubMed1992

Growth allometry of organs, muscles and bones in mice from lines divergently selected on the basis of plasma insulin-like growth factor-I.

Growth allometry was examined over the range 6 to 112 days of age in male and female mice from lines selected for low (L) or high (H) plasma concentrations of insulin-like growth factor-I (IGF-I). Plasma IGF-I concentrations were greater in the H line than in L line mice from 28 days of age. H line mice also had greater liveweights and weights of the heart, kidneys, pancreas, lungs, liver, brain and testes from 21-28 days of age. Changes in weights of these organs reflected the general pattern of body growth, there being no consistent effects of selection line on allometric growth coefficients. Ovarian weights were not different between the lines. For muscle weights, (gastrocnemius, quadriceps femoris), the weights or lengths of bones (tibia, femur) and the nose-anus and anus-tail lengths, allometric growth coefficients were generally higher (P less than .05) in L line females than in L line males or H line mice of either sex. The allometric growth coefficient for spleen was significantly (P less than .05) greater in H line mice than in L line mice with the result that spleen weights were 30% higher in H line mice from 28 days of age. This is consistent with results from mice treated with, or transgenic for, IGF-I and suggests a specific effect of this hormone on growth of the spleen. Thymus weights were also greater in H line than in L line mice and developmental patterns of thymus weight closely paralleled those of circulating IGF-I.

Animals↗
PubMed1991

The circulating molecular weight forms of infused recombinant insulin-like growth factor-I and effects on glucose and fat metabolism in lambs.

We have investigated the relationship between the plasma distribution of infused recombinant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism. The studies were performed in 24-h fasted ram lambs which received primed constant infusions of 3H labelled glucose tracer. When isotopic equilibrium had been reached, the animals received 90-min infusions of human insulin-like growth factor-I at various doses (2.5, 20, 40 and 120 micrograms.kg-1.h-1, n = 3 for each dose). Total plasma insulin-like growth factor-I was significantly elevated by infusion at a rate of 40 micrograms.kg-1.h-1 (from 185 +/- 14 micrograms/l to 442 +/- 41 micrograms/l, p less than 0.05) and 120 micrograms.kg-1.h-1 (from 181 +/- 2 micrograms/l to 953 +/- 39 micrograms/l, p less than 0.005). The plasma concentrations of insulin-like growth factor-I not associated with binding proteins remained undetectable (less than 15 micrograms/l) at the end of the 2.5 and 20 micrograms.kg-1.h-1 doses, but were significantly elevated at the end of the 40 and 120 micrograms.kg-1.h-1 infusions (to 71 +/- 14 micrograms/l, p less than 0.05 and 176 +/- 55 micrograms/l, p less than 0.01 respectively). The infused insulin-like growth factor-I associated primarily with 35-60 kilodalton binding proteins. Glucose kinetics were significantly altered only by the highest dose infusion, during which there was a fall in plasma glucose concentration from 3.5 +/- 0.2 mmol/l to 1.9 +/- 0.2 mmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of the frequency of subcutaneous insulin-like growth factor-1 administration on weight gain in growth hormone deficient mice.

To ascertain the frequency of subcutaneous IGF-1 administration necessary to promote growth we examined the weight gain of male homozygous lit/lit mice in response to either sc. IGF-1 or bovine GH administration. Lit/lit mice showed a dose dependent response to treatment with GH. Bovine GH induced a response in body weight gain within 3 days of the start of treatment. Following a single subcutaneous injection of IGF-1, plasma IGF-1 levels were elevated for 4-6 hours. Three treatment schedules for IGF-1 were used (once daily, twice daily and four times daily), each employing the same total daily dose of IGF-1 (30 micrograms). With IGF-1 treatment, a significant effect on body weight gain was obtained when administered four times daily. The growth rate with IGF-1 treatment 6 hourly was similar to that observed following treatment with bGH (10 micrograms sc daily). Twelve hourly IGF-1 administration only had a significant effect on body weight gain when weight was measured in the evening. Lit/lit mice treated once daily with 30 micrograms IGF-1 had no weight gain response and became severely hypoglycaemic. Frequent subcutaneous IGF-1 administration is one approach to growth enhancement in GH deficiency; higher doses administered less frequently do not promote growth and may cause hypoglycaemia.

Animals↗
PubMed1991

Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs.

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.

Animals↗
PubMed1991

Photoperiod associated changes in insulin-like growth factor-I in reindeer.

Insulin-like growth factor-I (IGF-I) concentrations were measured in the plasma of reindeer calves exposed to a manipulated photoperiod, indoors, of either 16 h light followed by 8 h dark each day (16L:8D) (n = 3) or 8L:16D (n = 3) from about the autumnal to the vernal equinox, to determine whether the seasonal growth spurt normally seen in spring is associated with a photoperiod-induced rise in IGF-I. A high quality concentrate diet was available ad libitum, and individual food intake was recorded daily. The animals were weighed, bled, and the diameters of their testes were measured every 2 weeks. Plasma samples were assayed for IGF-I by RIA. Six to 8 weeks after the start of the study those calves exposed to 16L:8D showed a significant increase in plasma IGF-I concentration, which was maintained until the close 24 weeks after the start. In contrast, IGF-I plasma concentrations in those calves exposed to a day length of 8L:16D did not significantly alter during the study. The elevated IGF-I in the 16L:8D group was associated with rapid weight gain, higher food intake, and decreased testes size compared with the 8L:16D group. We have shown that the seasonal growth spurt is preceded by an elevation in plasma IGF-I concentration. Further, this elevation in IGF-I is day length dependent. This is the first account of any growth factor secretion being regulated by photoperiod.

Animals↗
PubMed1991

Chronic treatment with bovine growth hormone upregulates high-affinity hepatic somatotropic receptors in sheep.

We evaluated the effect of chronic bovine growth hormone treatment on the hepatic somatotropic receptor. Growing lambs were treated with bGH at 0, 0.05, 0.15, 0.25 or 0.55 mg.kg-1.day-1 daily (N = 5/group) for 56 days. The binding of ovine GH to hepatic membranes washed with 4 mol/l MgCl2 and prepared in the presence of aprotinin was examined. The specific binding of oGH was increased (p less than 0.01) from 7.1 +/- 1.2% in saline-treated controls to 17.4 +/- 1.5% in the 0.55 mg.kg-1.day-1 group. Scatchard analysis showed curvilinear plots that best fitted a two-site model in 22/25 livers. The two sites had estimated dissociation constants (Kd) of 3 to 13 nmol/l for the low-affinity site and a Kd ranging from 0.17 to 0.31 nmol/l for the high-affinity site. Treatment with bGH had no consistent effect on the affinity of either binding site. However, bGH therapy was associated with a dose-dependent increase (p less than 0.01) in the number of high-affinity somatotropic receptors. There was no effect of bGH therapy on the concentration of low-affinity binding sites. The concentration of high-affinity receptors correlated with weight gain (r = 0.54, p less than 0.01), fat content (r = -0.54, p less than 0.01), protein content (r = 0.40, p less than 0.05), and plasma IGF-I (r = 0.57, p less than 0.005). The concentrations of low-affinity binding sites showed no such correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Influence of nutrition and bovine growth hormone (GH) on hepatic GH binding, insulin-like growth factor-I and growth of lambs.

The effect on young lambs of 0.25 mg recombinant bovine GH (bGH)/kg per day on plasma concentrations of insulin-like growth factor-I (IGF-I), glucose, specific hepatic GH binding and body composition changes was examined at two levels of nutrition (lucerne pellets; 3 and 1.7% of body weight/day). Lambs on low levels of nutrition had low plasma IGF-I (P less than 0.001). Plasma concentrations of IGF-I were increased by bGH treatment at both levels of nutrition, with the high nutrition group showing the greatest IGF-I response after 3 and 40 days of bGH treatment. Plasma glucose, after 40 days, was higher overall (P less than 0.05) in lambs on high nutrition. bGH treatment increased plasma glucose, with the response being greater in the well-fed lambs. Specific binding of GH to liver membranes was highest in lambs on high nutrition and on bGH treatment; no significant interaction between nutrition and bGH treatment was detected, indicating that specific binding of GH was increased proportionally by bGH at both nutritional levels. The major change in body composition was the reduced level of fatness in lambs treated with bGH. There was no significant effect of bGH on body weight although bGH treatment tended to increase weight gain of well-fed lambs and decreased weight loss of poorly nourished lambs. The results show that, although there was a significant (P less than 0.05) bGH/nutrition interaction for IGF-I there was no such interaction for body weight/components or specific GH binding to the liver. The results indicate that an increase in plasma IGF-I does not necessarily result in increases in growth or changes in carcass composition.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Radioimmunoassay for insulin-like growth factor-I: solutions to some potential problems and pitfalls.

This report describes essential requirements for the validation of a radioimmunoassay (RIA) for insulin-like growth factor-I (IGF-I) and presents solutions to some problems and pitfalls commonly observed. The preparation of IGF-I to be used as radioligand or standard has to be selected carefully since some IGF-I preparations are contaminated with variants which demonstrate different potencies for different antisera used in the RIA. Accurate assessment of IGF-I levels in blood plasma requires an efficient extraction method for the IGF-binding proteins (IGFBPs). Extraction methods to remove the influence of IGFBPs in the RIA were compared using blood plasma of considerable differences in IGF-I/IGFBP ratios. Acidification of plasma before column chromatography on Sephadex G-75 (G75) is generally considered to be the most reliable extraction method, but it is very time-consuming. The acid-ethanol extraction (AE) of plasma is not valid in many situations. Non-parallel displacement to the IGF-I standard was observed with AE-extracted plasma samples in the RIA. In addition, a comparison of IGF-I values obtained in the RIA after AE or G75 extraction of fetal ovine plasma has shown no significant correlation. We report an extraction technique based on a modified AE extraction followed by cryo-precipitation (AEC). AEC extraction on blood plasma reduced residual IGFBPs to a level that did not interfere in the assay. Furthermore, AEC-extracted plasma samples showed parallel displacement in the RIA to highly purified preparations of authentic IGF-I. We observed high correlations, with a slope close to unity, of IGF-I values obtained in the RIA using the AEC or G75 extraction for plasma from different species including adult and fetal sheep, rat, mouse and man. The AEC extraction provides a rapid and simple alternative to G75 extraction for blood plasma from a variety of species provided that high-affinity antisera are used for the RIA.

Animals↗
PubMed1991

Physiological responses to somatotropin in the ruminant.

The physiological responses to somatotropin supplementation of ruminants are reviewed with particular reference to the dairy industry. Exogenous somatotropin improves lactational performance by altering the partitioning of absorbed nutrients. Lipid accretion is reduced, lipid mobilization is increased, and glucose uptake by peripheral tissues and whole body oxidation of glucose and amino acids are reduced. The net effect of these changes is that the limited supply of glucose and amino acids is spared for synthesis of milk components, and lipid reserves are preferentially used as an energy source. The increase of cardiac output and mammary blood flow are prominent physiological responses to somatotropin by the dairy cow. These responses permit a greater share of nutrient input to the mammary gland. The lack of evidence for functional membrane receptors for somatotropin in mammary tissue demands the involvement of endocrine mediators to explain the increase of mammary gland metabolism with somatotropin treatment. An increase of high affinity somatotropic receptors in the liver and increased plasma insulin-like growth factor-I and -II appear to be one of the most prominent endocrine responses to somatotropin treatment. However, the relative role of the insulin-like growth factors and the multiple forms of their plasma-binding proteins and receptors remain to be resolved.

Amino Acids↗
PubMed1990

Developmental patterns of plasma insulin-like growth factor-1 concentrations in sheep.

A study was undertaken to examine the ontogeny of circulating insulin-like growth factor-1 (IGF-1) concentrations in sheep. The trial was a balanced 2 x 2 factorial design incorporating the effects of sex and rearing rank with a total of 48 animals. Blood sampling was initiated four weeks post-weaning (about 3 months of age) and continued every 2 weeks for 6 months and then every 4 weeks for 7 months. Fecal egg counts and plasma concentrations of non-esterified fatty acids (NEFA) were also determined. IGF-1 concentration was positively related to live weight throughout the trial, even when adjusted to common sex and rearing rank. Sex of lamb had a significant effect on plasma IGF-1 concentrations with concentrations in males being greater than those in females. Puberty in females, as determined by date of first estrus, was associated with an increase in plasma IGF-1 concentrations. Although puberty in males was not measured, a surge in plasma IGF-1 concentrations around the approximate time of puberty in males resulted in a marked divergence between the sexes which remained throughout the study. Rearing rank did not influence plasma IGF-1 concentrations beyond 7 months of age. Plasma IGF-1 concentrations tended to be negatively associated with plasma NEFA concentrations and fecal egg counts but relationships were only occasionally significant. IGF-1 levels were highly repeatable, concentrations at the first sample being significantly correlated with those at all subsequent samples. Implications of these results in relation to potential use of plasma IGF-1 concentration as a genetic marker for productivity are discussed.

Animals↗
PubMed1990

The effect of maternal starvation on plasma insulin-like growth factor I concentrations in the late gestation ovine fetus.

In view of the suggested relationship between substrate availability, fetal growth and circulating fetal IGF-I concentrations, we investigated the effect of maternal starvation on plasma IGF-I levels in the late gestation ovine fetus. Ten fetuses aged 125-130 d gestation were sampled daily from indwelling arterial catheters. Ewes were starved for 72 h. Starvation was terminated with an intravenous infusion of 10% glucose to the ewe. Food was then replaced 4 h later. Fetal IGF-I concentrations fell from 176.1 +/- 15.2 ng/mL before starvation to 124.5 +/- 10.3 ng/mL after 72 h starvation (p less than 0.05, n = 10). The fall in IGF-I concentrations was reversed by 4 h of maternal glucose infusion. In five fetuses, where samples were obtained 24 h after terminating the starvation, fetal IGF-I concentrations were comparable to those seen before starvation (180.0 +/- 37.7 ng/mL). This study demonstrates that acute maternal starvation causes a reversible decrease in fetal plasma IGF-I levels. These studies suggest that nutrient and in particular glucose availability is a significant determinant of fetal IGF-I secretion and support the hypothesis that IGF-I may play a role in the regulation of fetal growth.

Animals↗
PubMed1990

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I.

A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P less than 0.05) but not by sex. Significant (P less than 0.001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P less than 0.001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of long-term administration of pituitary-derived bovine growth hormone and estradiol on growth in steers.

Sixty-three Friesian steers (9 mo old, 257 kg; n = 15 or 16/treatment) were employed in a 2 x 2 factorial to test bovine growth hormone (bGH) and estradiol (Compudose implant). Steers received daily subcutaneous injections of vehicle or bGH (40 micrograms/kg body weight) for 22 wk. Steers were slaughtered 8 wk after the end of bGH treatment (wk 30). Steers had ad libitum access to silage plus a fixed amount (4 to 5.5 kg/d) of concentrate. Average daily gain (ADG) and feed conversion efficiency (FCE) improved (P less than .05) in response both to bGH and to estradiol during wk 0 to 22. Although bGH did not affect ADG or FCE during wk 23 to 30, estradiol improved (P less than .05) them; bGH and estradiol appeared additive (nonsignificant interactions) during wk 0 to 22. At slaughter, estradiol increased (P less than .05) carcass weight and carcass and leg length while decreasing (P less than .05) conformation score and percentage of kidney, knob and channel fat (KHP); bGH decreased (P less than .05) KHP. Although both bGH and estradiol increased (P less than .01) plasma GH, their effects were not additive. Both bGH and estradiol increased (P less than .01) plasma somatomedin-C and decreased (P less than .01) plasma urea nitrogen concentrations; effects were additive. Estradiol, but not bGH, increased (P less than .05) plasma glucose, whereas neither bGH nor estradiol altered plasma creatinine and nonesterified fatty acids. In summary, both bGH and estradiol improved growth and FCE, and their effects appeared to be additive. It is likely that some of their effects were mediated by somatomedin-C.

Animals↗
PubMed1990

Disappearance of labelled IGF-2 from plasma of the ovine fetus in late gestation.

The role of IGF-2 in the fetus and its possible influence on fetal growth remains speculative. We investigated the size distribution of unsaturated binding sites for labelled oIGF-2 in ovine fetal plasma. In addition, the disappearance of each form of protein bound IGF-2 in the late gestation ovine fetus (125-135 days, n = 5) was estimated. One minute after injection into the fetal femoral vein, 125IoIGF- circulated in the fetal femoral artery bound primarily to a 50 kDa binding protein. Only a small amount of binding to a 150 kDa binding protein was seen with little to no free IGF-2 present. IGF-2 also circulated in association with a large molecular weight complex (ca. 250 kDa) presumed to be circulating receptor bound IGF-2. The half life of the 250 kDa form of IGF-2 was 385.9 +/- 65.4 min, for the 150 kDa form 308.0 +/- 65.0 min, for the 50 kDa form was 35.5 + 2.6 min and for the free form of IGF-2 was 1.6 +/- 0.6 min. There was no apparent movement of intact IGF-2 out of the fetal circulation into any of the fetal fluids or into the maternal circulation. Similarly there was no consistent placental uptake of IGF-2 from the fetal circulation.

Animals↗
PubMed1990

Plasma clearance of radiolabelled IGF-1 in the late gestation ovine fetus.

We investigated the distribution of radiolabelled IGF-1 in the late gestation ovine fetus by exclusion gel chromatography following intravenous injection of 125I rh (recombinant human) met-IGF-1 into the chronically instrumented fetal lamb (120-130 days, n = 7). One minute after injection of 125I rh met-IGF-1 into the fetal femoral vein, 20.9 +/- 3.1% of the counts circulated in the 150K binding protein region, 55.0 +/- 3.7% in the 50K binding protein region and 18.7 +/- 0.6% in the free or 7K region. The chromatographic profiles obtained in the fetus were in general similar to those previously seen in the adult sheep. After an initial equilibration phase the half life of IGF-1 associated with the 150K binding fractions were 412.1 +/- 103.6 min. Two phases of clearance were observed for IGF-1 in association with the 50K binding fractions, an initial phase with a half life of 30.6 +/- 4.5 min followed by a second phase with a half life of 202.3 +/- 10.3 min. The 7K or 'free' form of IGF-1 had an initial half life of 12.6 +/- 5.1 min. Chromatography of samples of fetal tracheal fluid, fetal urine, amniotic fluid, maternal uterine venous plasma and maternal systemic plasma showed no movement of intact IGF-1 out of the fetal circulation into the fetal fluids or into the maternal circulation. However, when simultaneous samples were obtained from the fetal femoral artery and umbilical vein, higher radioactivity was consistently observed in the fetal femoral artery raising the possibility of placental uptake of IGF-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗