Search PubMed⌕ Search

Biomedical subjects

J S Robinson

Publications and source records attributed to J S Robinson.

At least 37 records · Page 2Linked to original sources

Circulating insulin-like growth factor (IGF)-I and IGF binding proteins -1 and -3 and placental development in the guinea-pig.

Restricting maternal nutrition before and throughout pregnancy in the guinea-pig restricts foetal growth in part by altering placental structural determinants of substrate transfer function. The insulin-like growth factors have been implicated in mediating these changes. To assess the role of IGF-I in placental adaptation to maternal undernutrition, we examined the associations of circulating IGF-I and IGF binding proteins -1, -3 and -4 in the mother with placental structural development. In both mid- and late pregnancy, maternal food restriction reduced maternal plasma IGF-I by 56 per cent (P<0.0005) and 50 per cent (P<0.0005) respectively, and plasma IGFBP-3 by 47 per cent (P=0.03) and 55 per cent (P=0.002), respectively. Maternal plasma IGFBP-4 was reduced by 45 per cent (P=0.041) in food restricted guinea-pigs in mid-pregnancy but not late in pregnancy, while IGFBP-1 was unaltered at both stages. Late in pregnancy, food restriction reduced the ratio of maternal circulating IGF-I to IGFBP-1 by 52 per cent (P=0.011) and increased the ratio of IGF-I to IGFBP-3 in maternal plasma by 10 per cent (P=0.011). The relationships between the maternal IGF axis and structural correlates of placental function were assessed using pooled data from both ad libitum fed and food restricted animals. In mid-pregnancy, the volume density of the maternal blood space in the placental labyrinth correlated positively with both maternal plasma IGF-I and IGFBP-3, while maternal blood space volume correlated negatively with maternal plasma IGFBP-1. In late pregnancy, placental weight correlated positively with both maternal plasma IGF-I and IGFBP-4, while the surface area of syncytiotrophoblast and weight of trophoblast correlated positively, and mean syncytiotrophoblast thickness negatively, with maternal plasma IGF-I. Late in pregnancy, the volume density and weight of syncytiotrophoblast, the surface density and total surface area of trophoblast and the volume of the maternal blood space each correlated positively, and syncytiotrophoblast thickness correlated negatively with maternal plasma IGFBP-3. Concomitantly, placental weight, placental diameter, placental volume, volume density and weight of syncytiotrophoblast, weight of foetal capillaries, syncytiotrophoblast surface density and total syncytiotrophoblast surface area in the placental labyrinth, each correlated positively with the ratio of IGF-I to IGFBP-1 in maternal plasma, while syncytiotrophoblast thickness correlated negatively with this ratio. In late pregnancy therefore, increased trophoblast abundance and placental vascularity, and a reduced barrier to diffusion between maternal and foetal blood, occurs in association with increased abundance of IGF-I and its major carrier, IGFBP-3, and a reduction in that of IGFBP-1 in maternal blood in the guinea-pig. This suggests that systemic IGF-I and modulation of its bioavailability by IGFBPs -1 and -3 within the mother may influence placental growth and differentiation in an endocrine fashion, particularly when nutrition is limited.

Animals↗

Perinatal growth and plasma GH profiles in adolescent and adult sheep.

Poor prenatal growth is associated with limited evidence of GH deficiency in adult humans, which may contribute to their increased risk of cardiovascular and metabolic disease. We therefore examined the effects of placental restriction of fetal growth (PR) on size at birth, neonatal fractional growth rate (FGR) and the circulating GH profile in adolescent and young adult sheep of both sexes. Moderate or severe PR decreased birth size and increased neonatal FGR of weight, crown-rump length and abdominal circumference. In adolescent males, mean and baseline GH concentrations correlated negatively and independently with birth weight and FGR of weight, and mean GH concentrations correlated negatively with current weight. In young adult males, mean GH concentrations correlated negatively and independently with birth shoulder height and FGR of shoulder height whilst, in young adult females, these correlations were positive. This suggests that restricted fetal growth and reduced neonatal growth rate in sheep are followed by elevated circulating GH in adolescent and adult males, but GH deficiency or increased GH clearance in adult females.

Analysis of Variance↗

Determination of water concentration in brain tissue by Raman spectroscopy.

Brain edema is one of the most common morbidity factors in patients with intracranial neoplasms and cerebrovascular pathology. Monitoring of intracranial pressure gives only an indirect and global measure of brain swelling. We have made an assessment of the applicability of Raman spectroscopy as an alternative method for assessing brain edema, which measures the water concentration in the tissue directly. Partial least-squares models were developed on the basis of Raman spectra measured in the 2600-3800-cm(-1) region, which predict the water fraction of brain tissue in the 0.75-0.95 range, with an accuracy better than 0.01.

Animals↗

The contribution of maternal smoking to preterm birth, small for gestational age and low birthweight among Aboriginal and non-Aboriginal births in South Australia.

OBJECTIVES: To determine the contribution of maternal smoking to preterm birth (< 37 weeks' gestation), small for gestational age (SGA, birthweight < 10th percentile for gestational age) and low birthweight (< 2500 g) among Aboriginal and non-Aboriginal births in South Australia. DESIGN: Retrospective cohort analysis of population-based perinatal data. SETTING: The State of South Australia, population 1.5 million. PARTICIPANTS: 36059 women (of whom 851 were Aboriginal women) who had singleton births in 1998-1999. MAIN OUTCOME MEASURES: Relative risks and population-attributable risks of preterm birth, SGA and low birthweight from smoking in the second half of pregnancy, by age and Aboriginality. RESULTS: Aboriginal women had a higher rate of smoking in pregnancy than non-Aboriginal women (57.8% v 24.0% at the first antenatal visit) and high rates for all age groups, while the rates decreased with age among non-Aboriginal women. Heavy smoking increased with age, and Aboriginal women were heavier smokers. Women who smoked had elevated relative risks of preterm birth (1.64), SGA (2.28) and low birthweight (2.52), and all these showed a dose-response relationship. Among Aboriginal (versus non-Aboriginal) births, population-attributable risks were significantly higher for SGA (48% v 21%, and 59% for births to Aboriginal teenagers), low birthweight (35% v 23%) and preterm birth (20% v 11%). CONCLUSIONS: Health promotion programs, with a focus on smoking cessation and reducing uptake of smoking, need to be implemented in an appropriate cultural context, especially among young Aboriginal women. Such a program is being developed in South Australia.

Adult↗

The impact of fetal size and length of gestation on 6-sulphatoxymelatonin excretion in adult life.

Recent studies have shown that intrauterine growth retardation or fetal distress in human infants is associated with a pronounced reduction in melatonin secretion during the first 3 months of life. It is not known whether these associations persist beyond infancy. We have therefore examined the relationship between birthsize and melatonin secretion in 159 men and women aged 20, born in Adelaide, South Australia. Melatonin secretion was estimated by analysing the overnight urinary excretion of 6-sulphatoxymelatonin. The overnight excretion ranged from 1.7 to 128.9 nmoles/subject, was higher in women than in men (46.5 vs 34.1 nmoles, P = 0.003) and was significantly negatively correlated with the body mass index (P = 0.006). Excretion correlated with both birthweight and ponderal index at birth (P = 0.04 and P = 0.01 respectively after adjustment for gestational age) and also fell with increased duration of gestation (P = 0.007). The effects of adult body mass index added to that of low birthweight in predicting 6-sulphatoxymelatonin excretion. These data suggest that urinary 6-sulphatoxymelatonin excretion was impaired in adults who were growth restricted prenatally or were delivered after 40 weeks gestation.

Adult↗

Restriction of fetal growth has a differential impact on fetal prolactin and prolactin receptor mRNA expression.

Prolactin is present in the fetal circulation and prolactin receptors are expressed in a wide range of fetal tissues. The factors which regulate the synthesis and secretion of prolactin, and the expression of its receptors before birth, are poorly understood. We have investigated whether experimental restriction of placental growth in the sheep has an impact on the prolactin axis in the growth restricted fetus. The majority of uterine endometrial caruncles were removed before pregnancy in 10 ewes (placental restriction; PR group). Placental, fetal liver and kidney weights were reduced in the PR compared to the control group (n = 10). The ratio of fetal prolactin mRNA : 18S rRNA was significantly lower (P < 0.01) in the PR group (1.83 +/- 0.45, n = 6) than in the control group (4.11 +/- 0.54, n = 6). The ratio of prolactin mRNA : 18S rRNA in the fetal pituitary was positively correlated with fetal and with placental weight. Using stepwise linear regression, it was determined that the level of fetal prolactin mRNA : 18S rRNA expression was best described (as judged by the maximum adjusted R2) by prolactin mRNA: 18 S rRNA = - 3.0378 + 0.17 PO2 + 2.772 glucose (adjusted R2 = 0.765, F = 17.53, P < 0.001). Fetal plasma prolactin concentrations were significantly reduced (P < 0.05) in the PR group compared to control animals between 109 and 141 days gestation. Fetal prolactin receptor (PRLR) mRNA transcripts encoding long (PRLR1) and short forms (PRLR2) of PRLR were present in the liver and kidney of animals in the PR and control groups at 140-141 days gestation. PR did not alter the levels of PRLR1 or PRLR2 mRNA in the fetal liver or kidney. The suppression of the synthesis and secretion of prolactin in the growth restricted fetus may limit the action of prolactin on the growth and metabolism of key fetal organs during suboptimal intrauterine conditions

Animals↗

Fetoplacental growth in sheep administered progesterone during the first three days of pregnancy.

We have previously shown that administration of progesterone during early pregnancy in sheep enhances fetal weight and crown-rump length. The present study examined the effect of this treatment on individual fetal organ weights and on placental growth and structure. Embryos that had been exposed to either a normal or a high concentration of progesterone on days 1-3 in initial recipient ewes were transferred at random to final recipient ewes that had or had not been treated with progesterone on days 1-3. Embryos in an additional group of ewes were exposed to progesterone on days 1-3 with oviducts of the ewes ligated. An increase in fetal weight was observed in the final recipient group that had been treated with progesterone (P< 0.01) but not in the initial group treated with progesterone. Fetal weight was increased (P< 0.05) in the initial recipients treated with progesterone plus ligation. Placental weight did not differ between any of the treatments in either initial or final recipients, while placental volumes of chorionic membrane and maternal crypts were increased by progesterone, with and without ligation, in initial recipients (P< 0.05). The responses of fetal weight in final recipients were associated with increases in the weight and linear dimensions of specific fetal components (e.g. brain, kidney, heart, spleen, total gut, head width, thorax circumference). Proportionate increases were observed for most parameters with the exception of brain, heart and M tibialis anterior weight; adjusted least squares means indicated disproportionate increases in these of 5 per cent, 32 per cent and 26 per cent respectively. Enhanced fetal weight in the progesterone plus ligation group was associated with increased (P< 0.05) heart weight; a disproportionate increase of 39 per cent was recorded. Increased fetal weight and fetal heart, skeletal muscle and brain weight were correlated with increased volumes and surface area of the fetal trophectoderm and maternal fetomaternal syncytium in the final recipients treated with progesterone. It is concluded that alteration of the embryo's environment during the first few days of development enhances fetal growth disproportionately, in close association with increased abundance of the exchange epithelia in the placenta.

Animals↗

Altered placental structure induced by maternal food restriction in guinea pigs: a role for circulating IGF-II and IGFBP-2 in the mother?

Maternal feed restriction may restrict fetal growth in part indirectly by impairing placental functional development. Such actions could be mediated by the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonstrated, less is known of the influence, if any, of that in the mother. This study aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restriction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal weight (r = 0.65, P = 0.008, n = 17), volume of the maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of syncytiotrophoblast (r = 0.65, P = 0.023, n = 17), were positively correlated, and syncytiotrophoblast thickness was negatively correlated, with maternal plasma IGF-II concentration (r = -0.69, P = 0.014, n = 17). Late in gestation, fetal weight, placental weight and total exchange surface area in the placenta were each negatively correlated with maternal plasma IGFBP-2 concentration (all P < 0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental weight (r = 0.52, P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per cent (P = 0.001) and this ratio was positively correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental weight (r = 0.59, P = 0.006), placental diameter (r = 0.621, P = 0.003), placental volume (r = 0.57, P=0.009), weight of trophoblast (r = 0.51, P=0.037), weight of fetal capillaries (r = 0.49, P = 0.046), syncytiotrophoblast surface density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy, maternal circulating IGF-II promotes placental structural development, while later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term.

Animals↗

Fetal growth and the fetal origins hypothesis in twins--problems and perspectives.

Although there is substantial evidence from studies of singletons that small size at birth is linked with long-term adverse health effects, until recently little was known as to whether these associations extend to twins. A review of published studies suggests that at present there is little consistent evidence that birthsize in twins is associated with increased morbidity or morality. While, these findings may reflect methodological limitations, it is also argued that they arise as a consequence of the substantially different biology of fetal growth in twins.

Birth Weight↗

Fetal growth restriction: adaptations and consequences.

A range of pathophysiological factors can result in a perturbation or restriction of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The critical importance of these physiological adaptations for both immediate survival and long-term health outcomes has provided an impetus for experimental studies of the nature and consequences of specific fetal adaptations to a poor intrauterine environment. This review summarizes data from recent studies that have focused on the responses of the fetal cardiovascular, sympathoadrenal, hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental restriction of placental function in the sheep and discusses the consequences of these adaptations for fetal, neonatal and adult health.

Adaptation, Physiological↗

Origins of fetal growth restriction.

Regulation of growth of the fetus and its placenta begins before pregnancy. Early in pregnancy the mother sets the rate of growth of the fetus on a trajectory, which may be modified by events later in pregnancy. Low maternal weight for height, history of previous small babies, maternal undernutrition, pregnancy disorders, e.g. pre-eclampsia, are associated with low birthweight. Maternal smoking is a major factor in developed countries; infections and undernutrition in developing countries.Recently, there has been emphasis on adverse long-term outcomes including ischaemic heart disease, hypertension and diabetes associated with poor fetal growth. Experimental studies in animals show that some of these outcomes can readily be induced by restriction of fetal growth. Progress in determining successful treatments to improve the growth of the fetus has lagged behind these epidemiological and experimental findings. However, nutrient supplements improve growth in undernourished women and smoking cessation also improves fetal size and outcome.

Animals↗

Alcohol consumption and insulin resistance in young adults.

BACKGROUND: Alcohol may have a cardioprotective effect. One possible mechanism is by reducing insulin resistance, a known cardiovascular risk factor. The aim of this study was to assess the relationship between alcohol consumption, insulin resistance and other parameters determining glucose tolerance in 154 young men and women. SUBJECTS AND METHODS: Subjects completed a questionnaire documenting weekly alcohol consumption. Insulin sensitivity and glucose tolerance were measured using the intravenous glucose tolerance test with minimal model analysis. Height, weight, usual level of exercise, smoking habits and socio-economic status were also recorded. RESULTS: Insulin sensitivity correlated inversely with body mass index (r = - 0.529, P < 0.001) but not with level of physical fitness. Women were significantly less insulin sensitive than men (4.19 and 5.63 104 min-1 pmol-1 L-1, respectively; P < 0.001). Insulin sensitivity correlated positively with alcohol consumption and this trend remained significant allowing for body mass index and gender (beta = 0.17, P < 0.014). First-phase insulin secretion showed a weak but non-significant trend in the opposite direction. Fasting glucose, fasting insulin and glucose tolerance showed no relationships with alcohol consumption. CONCLUSION: These data suggest a close relationship between alcohol consumption and insulin resistance in young adults. Regular alcohol consumption is associated with decreased insulin resistance and this may partly explain the cardioprotective effect of alcohol.

Adult↗

Differential effects of placental restriction on IGF-II, ACTH receptor and steroidogenic enzyme mRNA levels in the foetal sheep adrenal.

We have investigated the effects of restriction of placental growth on foetal adrenal growth and adrenal expression of mRNAs for Insulin-like Growth Factor II (IGF-II), the IGF binding protein IGFBP-2, Steroidogenic Factor 1 (SF-1) and adrenocorticotrophic hormone (ACTH) receptor (ACTH-R) and the steroidogenic cytochrome P-450 enzymes: cholesterol side chain cleavage (CYP11A1), 17alpha-hydroxylase (CYP17) and 21-hydroxylase (CYP21A1); and 3beta-hydroxysteroid dehydrogenase/Delta5Delta4 isomerase (3betaHSD). Endometrial caruncles were removed from non-pregnant ewes before mating (placental restriction group; PR). The total adrenal: foetal weight ratio was higher in PR (n=6 foetuses) than in control foetuses (n=6 foetuses). There was no difference in plasma ACTH concentrations between the PR and control foetuses between 130 and 140 days gestation. Adrenal IGF-II mRNA levels were lower (P<0.05) in the PR group, however, adrenal IGFBP-2 mRNA levels were not different between the PR and control groups. Adrenal ACTH-R mRNA levels were also lower whilst CYP11A1 mRNA levels were increased (P<0.005) in the PR group. We conclude that foetal adrenal growth and steroidogenesis are stimulated as a consequence of foetal growth restriction and that factors other than ACTH are important in foetal adrenal activation during chronic, sustained hypoxaemia.

Adrenal Glands↗

Pump-regulated lumbar subarachnoid drainage.

OBJECTIVE: The diversion of cerebrospinal fluid (CSF) has been widely used in the prevention and treatment of CSF fistulae. A common method is the use of a lumbar drainage system. Although it is effective, several serious complications can develop, which can be avoided by regulating the flow of CSF with a standard intravenous infusion pump. TECHNIQUE: We present a simple, inexpensive, and accurate method of flow-controlled lumbar subarachnoid drainage that minimizes patient discomfort and the unpredictability of a gravity-dependent system. This system uses a standard lumbar drain connected to an intravenous infusion pump to provide drainage of CSF in a constant and predictable manner. RESULTS: A total of 42 patients from two institutions were treated with this method. CSF fistulae occurred secondary to trauma in 9 patients, after spinal surgery in 11 patients, after transsphenoidal surgery in 10 patients, and after cranial base surgery in 12 patients. Resolution of the fistula was attained in 36 of 42 patients. There were no deaths, no cases of deep venous thrombosis, and no incidence of meningitis. One patient developed tension pneumocephalus, and two patients developed headache with nausea and vomiting. All patients were ambulatory, and only three patients required narcotic analgesia for headaches. CONCLUSION: Pump-regulated lumbar subarachnoid drainage is safe and effective in the treatment of CSF fistulae, as reported elsewhere in the literature. The advantage of this method is that the drainage of CSF can be carefully controlled and titrated in a predictable fashion. Because the system is independent of gravity to produce drainage of CSF, patients are not confined to bed and serious complications of overdrainage can be avoided.

Adult↗

Fetal growth and the physiological control of glucose tolerance in adults: a minimal model analysis.

Although there is now substantial evidence linking low birthweight with impaired glucose tolerance and type 2 diabetes in adult life, the extent to which reduced fetal growth is associated with impaired insulin sensitivity, defective insulin secretion, or a combination of both factors is not clear. We have therefore examined the relationships between birth size and both insulin sensitivity and insulin secretion as assessed by an intravenous glucose tolerance test with minimal model analysis in 163 men and women, aged 20 yr, born at term in Adelaide, South Australia. Birth size did not correlate with body mass index or fat distribution in men or women. Men who were lighter or shorter as babies were less insulin sensitive (P = 0.03 and P = 0.01, respectively), independently of their body mass index or body fat distribution. They also had higher insulin secretion (P = 0.007 and P = 0.006) and increased glucose effectiveness (P = 0.003 and P = 0.003). Overall glucose tolerance, however, did not correlate with birth size, suggesting that the reduced insulin sensitivity was being compensated for by an increase in insulin secretion and insulin-independent glucose disposal. There were no relationships between birth size and insulin sensitivity or insulin secretion in women. These results show that small size at birth is associated with increased insulin resistance and hyperinsulinemia in young adult life but that these relationships are restricted to the male gender in this age group.

Adult↗

In vivo proton magnetic resonance spectroscopy of brain tumors.

The ability of magnetic resonance spectroscopy (MRS) to differentiate neoplastic brain cells and their metabolic and structural characteristics is evaluated. We examined 120 patients with brain tumors using a 1.5-tesla MRI unit and MRS. The peak areas of N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr), choline-containing compounds (Cho), lactate, lipids, myoinositol, amino acids and the ratios of NAA/Pcr-Cr, NAA/Cho and Cho/Pcr-Cr were calculated by a standard integral algorithm. In normal brain tissue, the following metabolites were identified: NAA at 2.0 ppm, Pcr-Cr at 3.0 ppm and Cho at 3.2 ppm. The different concentrations of the metabolites examined and their role in the biochemical profile of different types of tumors are discussed. The confidence interval of the MRS versus pathology was between 0.9 and 0.954, while it was between 0.52 and 0.631 for MRI versus pathology. The Cho/Pcr-Cr ratio is a very important malignancy marker for histologic tumor grading of astrocytomas. The greater this ratio, the higher the grade of the astrocytoma. NAA/Pcr-Cr together with Cho/Pcr-Cr help specify the presence or absence of a neoplasm. Proton MRS is a useful and promising diagnostic modality not only in diagnosing but also in grading solid brain tumors.

Adult↗

Impact of restriction of placental and fetal growth on expression of 11beta-hydroxysteroid dehydrogenase type 1 and type 2 messenger ribonucleic acid in the liver, kidney, and adrenal of the sheep fetus.

We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD-1) and 11betaHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. Fetal liver, kidney, and adrenals were collected from normally grown fetuses at 90 days (n = 6), 125 days (n = 6), and 141-145 days (n = 7) and from PR fetuses at 141-145 days (n = 6). Expression of 11betaHSD-1 mRNA in the fetal liver increased significantly between 125 days (7.4+/-0.8) and 141-145 days gestation (27+/-5.3). There was also an approximately 2-fold increase in the ratio of 11betaHSD-1 mRNA/18S rRNA expression in the PR group (53.8+/-7.9) compared with that in control animals at 141-145 days gestation. There was a significant decrease in 11betaHSD-2 mRNA in fetal adrenals between 125 days (41.6+/-2.4) and 141-145 days (26.7+/-1.1) gestation, but there was no effect of PR on the expression of adrenal 11betaHSD-2 mRNA. 11betaHSD-2 mRNA expression in the fetal kidney increased between 90 days (16.8+/-1.7) and 141-145 days gestation (31.7+/-4.3), but there was no effect of PR on the levels of 11betaHSD-2 mRNA in the fetal kidney. In summary, 11betaHSD-2 mRNA is differentially regulated in the fetal adrenal and kidney in the sheep fetus during late gestation. There is also a specific increase in the expression of 11betaHSD-1 mRNA in the liver of growth-restricted fetuses in late gestation. This suggests that there is increased hepatic exposure to cortisol in the growth-restricted fetus, which may be important in the reprogramming of hepatic physiology that occurs after growth restriction in utero.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗