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Biomedical subjects

J D Teale

Publications and source records attributed to J D Teale.

At least 19 recordsLinked to original sources
PubMed1992

The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer.

Tamoxifen treatment of women with advanced breast cancer has previously been reported to reduce plasma insulin-like growth factor-type I (IGF-I) concentrations. In this study we have examined the effect of treatment with Tamoxifen, medroxyprogesterone acetate (MPA) or 4-hydroxyandrostenedione (4-OHA) on plasma IGF-I and IGF-II concentrations. As IGF-binding proteins (IGFBPs) can modulate the biological effects of IGF-I, plasma IGFBP-I levels were also measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but significant, decrease in IGF-I levels, but increase in the plasma concentration of IGFBP-I. In contrast, treatment with MPA increased levels of IGF-I, but significantly reduced plasma IGFBP-I concentrations. Treatment with 4-OHA had no significant overall effect on plasma IGF-I or IGFBP-I levels, although changes were detected for some subjects. Plasma IGF-II concentrations were not altered by treatment with Tamoxifen, MPA or 4-OHA. It is concluded that although treatment with Tamoxifen or MPA produced significant changes in plasma IGF-I concentrations, any physiological effects of such changes are likely to be modulated by the corresponding alterations in plasma IGFBP-I concentrations.

Aged↗
PubMed1992

Alleviation of non-islet cell tumour hypoglycaemia by growth hormone therapy is associated with changes in IGF binding protein-3.

The hypoglycaemia caused by non-islet cell tumours is often associated with an increase in plasma insulin-like activity. In many cases there is a relative if not always absolute increase in plasma insulin-like growth factor II (IGF-II). Growth hormone (GH) secretion is almost invariably depressed as is the plasma insulin response to oral glucose. Despite the high concentration of IGFs (i.e. IGF-I and IGF-II) normally found in the plasma of healthy people their potential hypoglycaemic effect is not manifest due to the tightness with which they are bound to specific binding proteins (IGFBPs). Plasma levels of the major binding protein (IGFBP-3), which is GH-dependent, were depressed in three patients with tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to levels which were approximately equimolar to total plasma IGF concentrations, alleviated the hypoglycaemia and restored the plasma insulin responses to oral glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated IGFBP-3 in association with a pre-existing acid-labile subunit to form high molecular weight complexes which prevent IGF-II gaining access to tissues receptors through which it exerts its hypoglycaemic effects.

Aged↗
PubMed1991

Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer.

We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically.

Animals↗
PubMed1990

Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells.

We showed previously that insulin-like growth factor I (IGF-I) is detectable in small cell lung cancer (SCLC) tumor biopsies and cell lines and that recombinant human IGF-I stimulates DNA synthesis in SCLC cells. Here we report further studies on the role of IGF-I in 2 SCLC cell lines: HC12, classic; and ICR-SC17, variant. Immunoreactive IGF-I was detected in medium conditioned by HC12 but not ICR-SC17. Both HC12 and ICR-SC17 bound IGF-I with 100-fold greater affinity than insulin. Scatchard analysis revealed two classes of IGF-I binding site of high (Kd 0.1 nM, n = 2,300) and lower (Kd 3 nM, n = 28,000) affinity. In both cell lines [3H]thymidine incorporation was enhanced by recombinant human IGF-I, 100-1000 ng/ml. ICR-SC17 also showed growth enhancement as measured by increase in cell numbers. There was no response in HC12, probably due to endogenous IGF-I production. 125I-IGF-I binding and basal and IGF-I-stimulated mitogenesis were inhibited by monoclonal antibodies to IGF-I (SM1.20B, SM1.25) or the type I IGF receptor alpha IR3 but not an isotypic control monoclonal antibody. Antiproliferative effects were manifest in [3H]thymidine incorporation assays in serum-free conditions and growth of serum-supplemented liquid cultures. We also tested fresh or newly cultured tumor cells obtained by fine needle aspiration of metastases in three previously untreated and four relapsed patients with SCLC. IGF-I binding sites were demonstrable on fresh SCLC cells, and specific binding was inhibited by SM1.20B. All seven samples showed stimulation of [3H]thymidine incorporation in the presence of recombinant human IGF-I, 100-500 ng/ml. As in cultured cells, basal and IGF-I-stimulated DNA synthesis was inhibited by monoclonal antibodies SM1.20B, SM1.25, and alpha IR3 but not the isotypic control. These results confirm the findings of previous studies and suggest that IGF-I can function as an autocrine growth factor in SCLC in vitro and possibly also in vivo.

Antibodies, Monoclonal↗
PubMed1990

The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects.

IGF-1 concentrations were measured in plasma from 20 obese patients and 20 age- and sex-matched control subjects all of whom were fasting. Plasma IGF-1 concentrations were lower (p less than 0.05) in the obese individuals than in the controls. Plasma GH and insulin responses to stimulation with oral glucose were measured in 7 healthy normal weight individuals and both before and after energy restriction in 7 obese individuals. Before treatment the obese individuals were hyperinsulinaemic (fasting and integrated stimulated concentrations p less than 0.05) and showed attenuation of the plasma GH response to stimulation (peak and integrated stimulated values p less than 0.05 and less than 0.005, respectively) following oral glucose when compared to normal weight controls. Plasma insulin levels fell (both fasting and integrated concentrations p less than 0.05 and less than 0.005, respectively) and stimulated plasma GH responses increased (both peak and integrated values p less than 0.01 and less than 0.05, respectively) in the obese individuals following 3 wk treatment with a synthetic very low energy diet. Plasma IGF-1 concentrations remained unchanged during energy restriction. These results fail to support an endocrine IGF-1 mediated feedback inhibition on the hypothalamic-pituitary axis as the cause of the attenuated release of GH in obesity.

Adult↗
PubMed1990

Inappropriately elevated plasma insulin-like growth factor II in relation to suppressed insulin-like growth factor I in the diagnosis of non-islet cell tumour hypoglycaemia.

The diagnosis of non-islet cell tumour (hypoinsulinaemic) hypoglycamia has been complicated by contradictory biochemical evidence. Although insulin-like growth factor II (IGF-II) has been identified as the hypoglycaemic agent, plasma levels are often not elevated. In this study specific radioimmunoassay procedures for the measurement of IGF-I and IGF-II are described. Reference data on plasma IGF-II concentrations in relation to a wide range of IGF-I levels have been accumulated using plasma samples from acromegalic, hypopituitary and insulinoma (i.e. hyperinsulinaemic hypoglycaemia) patients as well as normal subjects from all age groups. The reference data indicate that a low plasma IGF-I value is normally associated with a relatively low plasma IGF-II level. Within a group of hypoinsulinaemic hypoglycaemia patients, a small number, invariably with evidence of a neoplasm, had low plasma IGF-I concentrations but apparently normal IGF-II levels. We propose that, in such cases, an apparently normal plasma IGF-II value is inappropriately high for the low plasma IGF-I level and, in association with non-ketotic hypoinsulinaemia and suppressed plasma growth hormone (GH), is diagnostic of a non-islet cell tumour as the cause of hypoglycaemia.

Adult↗
PubMed1989

Growth hormone secretion in Turner's syndrome and influence of oxandrolone and ethinyl oestradiol.

We investigated 24 hour growth hormone secretion by intermittent 20 minute blood sampling in 34 prepubertal patients with Turner's syndrome, aged 4.3-12.4 years. Growth hormone profiles were analysed by the PULSAR programme and results expressed as the sum of growth hormone pulse amplitudes. Six patients had abnormal growth hormone pulse frequencies. In the remaining 28, growth hormone pulse amplitudes declined significantly with increasing age, but there was no correlation between growth hormone pulse amplitudes and growth rates. Concentrations of insulin like growth factor-1 (IGF-1) rose with age but did not correlate with either growth rates or growth hormone secretion. Fifteen patients were given oxandrolone and 11 low dose ethinyl oestradiol. Both agents increased height velocity without increasing growth hormone secretion. We conclude that the relation between growth hormone secretion and growth in Turner's syndrome is less certain than in normal children. End organ resistance is probably due to a skeletal dysplasia. Both oxandrolone and low dose ethinyl oestradiol improve the growth of girls with Turner's syndrome, but their mechanism of action remains uncertain.

Body Height↗
PubMed1989

Insulin-like growth factor-I in the parenterally fed low birth weight infant.

Postnatal change in insulin-like growth factor-1 (IGF-I) was studied longitudinally in 9 very low birth weight infants (less than 1,200 g, less than 30 weeks at birth) who were receiving 85% or more of their nutrient intake via the parenteral route. There was no apparent relationship between IGF-I, nitrogen intake, energy intake, or nitrogen retention. In 6/9 infants IGF-I decreased with postnatal age. A low IGF-I may reflect the poor nutritional status and growth rate commonly seen in sick preterm infants.

Energy Intake↗
PubMed1989

The measurement and effect of growth hormone in the presence of growth hormone-binding antibodies.

We have developed methods for measuring the concentrations of free GH in plasma using a polyethylene glycol (PEG) separation procedure to remove antibody-bound GH within 1 h of collection. Total GH concentrations were obtained by acidification of the GH-antibody complex to release the GH followed by PEG precipitation of the antibody. The plasma GH assay had a within-assay coefficient of variation (C.V.) of 6.8% at 4.6 mU/l and a between-assay C.V. of 9.2% at 4.0 mU/l. The PEG-modified assay had a within-assay C.V. of 4.3% at 6.3 mU/l and a between-assay C.V. of 10.9% at 5.3 mU/l. Both assays had a sensitivity of 1.3 mU/l. There was good correlation between plasma and free GH concentrations in 24-h profiles in two tall children (r = 0.98; P less than 0.001) and between total and free GH in the same profiles (r = 0.97; P less than 0.001). GH antibodies were measured using a highly sensitive radioimmunoassay. In children who did not develop GH antibodies there was no difference between total, plasma and free GH concentrations. In contrast, in those who developed GH antibodies both total and plasma GH concentrations were markedly increased compared with free GH concentrations. The presence of GH antibodies did not affect the growth, plasma insulin-like growth factor-I concentrations or fasting serum insulin concentration responses to 1 year of therapy with biosynthetic human GH.

Autoantibodies↗
PubMed1988

Postoperative positive nitrogen balance with intravenous hyponutrition and growth hormone.

11 patients having major gastrointestinal surgery were allocated at random to receive either biosynthetic human growth hormone (BSHGH) 0.1 mg/kg or placebo daily for the first 7 postoperative days. All patients received the same intravenous feeding regimen, which contained 2.09 MJ glucose, 1.88 MJ fat, and 7 g N daily. Patients receiving BSHGH were in positive nitrogen balance throughout the study (mean 1.8 [SEM 0.4] g N/day) and those receiving placebo were in negative nitrogen balance (mean -0.9 [0.7] g N/day). Resting energy expenditure progressively increased in the patients receiving BSHGH (115.7% [14.8] on day 7) but remained unchanged in patients receiving placebo (99.35% [1.4]). Fat oxidation was nearly three times higher in the patients on BSHGH (4.09 [0.38] MJ/day) than in controls (1.38 [0.50]). Carbohydrate oxidation remained about the same in both groups. Whole-body protein turnover, synthesis, and breakdown were increased in the patients receiving growth hormone.

Aged↗
PubMed1987

Thyroid dysfunction in institutionalised Down's syndrome adults.

This study of 111 institutionalised Down's syndrome subjects and 74 controls found a relatively low risk of hypothyroidism in both groups compared with certain other studies of Down's subjects, which found very high rates of thyroid hypofunction. However, the Down's syndrome group had a significantly raised risk of hypothyroidism (9%), hyperthyroidism (1.8%) and the presence of thyroid microsomal antibodies (29%) compared with the controls and with laboratory reference data. It is recommended that thyroid function testing should be routine in older Down's syndrome subjects, with special attention being given to the clinical status of those with microsomal antibodies present.

Adult↗