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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 199 records · Page 11Linked to original sources
PubMed1989

Maternal serum alpha-fetoprotein levels in anembryonic pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were determined in 21 women with threatened miscarriage in whom an ultrasound diagnosis of anembryonic pregnancy was confirmed. Fourteen of the 21 patients had normal AFP levels; the remaining seven had levels above the 95th centile of the reference range. This is in contrast to earlier findings of an association between low levels of AFP in anembryonic pregnancy. It is concluded that most anembryonic pregnancies are pregnancies in which the fetus has been lost rather than pregnancies in which the fetus was never present.

Abortion, Threatened↗
PubMed1989

Circulating levels of placental protein 12 and chorionic gonadotrophin following RU 38486 and gemeprost for termination of first trimester pregnancy.

First trimester termination of pregnancy was successfully induced in ten patients with RU 38486 followed 2 days later by a prostaglandin (Gemeprost) pessary. Human chorionic gonadotrophin (HCG) values remained unaltered until after the abortion. The levels of placental protein 12 (PP12) showed an immediate and significant fall following RU 38486, then rose to values substantially higher than those at the initial visit after 2 days. These findings show that RU 38486 has a direct inhibitory effect on tissues producing PP12 and confirm the progesterone dependency of this protein.

Abortifacient Agents↗
PubMed1989

Maternal serum alpha-fetoprotein levels in ectopic pregnancy.

Maternal serum alpha-fetoprotein (AFP) was measured at the time of presentation in 44 women with histologically proven ectopic pregnancy. Serum AFP levels were within the reference range in 32 women. Eleven women (25%) had AFP levels above the 90th centile of the normal range, including five women with a live fetus seen ultrasonically preoperatively. The two women with a ovarian pregnancy and a cornual pregnancy had levels below the median value for gestational age.

Female↗
PubMed1989

Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-I. A synchronized approach to pubertal development?

In a cross-sectional study of 69 normal adolescents we have found sex hormone-binding globulin (SHBG) levels to fall in both males and females throughout the pubertal period. Multiple regression analysis revealed a close negative correlation with insulin in both sexes. Weaker correlations were also found between SHBG and circulating androgen concentrations, in both males and females. Similar results were also obtained for a second circulating binding protein of primarily hepatic origin. This low molecular weight insulin-like growth factor (IGF) binding protein I (IBP-I) is one of two distinct classes of IGF binding proteins which bind IGF-I and IGF-II. IGF-I in turn mediates, at least in part, the actions of growth hormone. IBP-I also fell throughout puberty, correlating with the increasing insulin levels. In addition IBP-I correlated with androgen levels in both sexes. These similarities between SHBG and IBP-I, together with a strong correlation across puberty between the levels of the two binding proteins themselves (r = 0.737, P less than 0.001), suggest common mechanisms of control over the circulating levels of these two binding proteins. The association with insulin raises the possibility of a synchronized modulation of the actions of sex steroids and IGFs by nutritional intake. Thus pubertal growth and sexual development may occur over the same time with both modulated according to nutritional intake, linked through pancreatic insulin release, to hepatic production of SHBG and IBP-I.

Adolescent↗
PubMed1989

Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer.

Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.

Adult↗
PubMed1989

Inhibition of binding of gonadal steroids to serum binding proteins by non-esterified fatty acids: the influence of chain length and degree of unsaturation.

The effect of non-esterified fatty acids (NEFA) on the in vitro binding of testosterone, 5-alpha dihydrotestosterone and estradiol E2 to sex hormone binding globulin (SHBG) was examined using pooled normal female serum, and SHBG and albumin fractions obtained from the partial purification of late pregnancy serum. A range of saturated and unsaturated fatty acids were examined for their effect on steroid-protein binding. In normal female serum, NEFA added at physiological concentrations disrupted steroid-protein binding. The shorter chain (C8-C12) saturated acids and the poly-unsaturated acids proved to be more effective inhibitors than the longer chain saturated or mono-unsaturated acids. The greatest inhibition was obtained with E2 whereas the binding of dihydrotestosterone was least affected. With partially purified SHBG, the same concentrations of NEFA were less effective at inhibiting the binding of dihydrotestosterone and testosterone but elicited the same effect with E2. The binding of steroids to albumin appeared to be unaffected by these concentrations of NEFA.

Dihydrotestosterone↗
PubMed1989

Immunochemical analysis of the human chorionic gonadotrophin-like material secreted by 'normal' and neoplastic urothelial cells.

Material with the immunochemical characteristics of human chorionic gonadotrophin (hCG) is produced by bladder tumour cells in vitro and in vivo. In order to characterize this material further, media were collected from 17 cell cultures (three choriocarcinomas, seven bladder carcinomas and seven 'normal' urothelium). The hCG-like material was compared with pregnancy hCG and purified alpha-and beta-subunits by specific radioimmunoassays. Media were also submitted to affinity chromatography and the fractions further analysed by SDS-PAGE and Western blotting. It was shown that both the neoplastic and normal urothelium produced only free beta-subunit-like material. This urothelial 'beta-hCG' has the same molecular weight and electrophoretic mobility as that present in the intact hCG of pregnancy.

Cell Line↗
PubMed1989

Amplification or rearrangement of the beta-human chorionic gonadotrophin (beta-hCG)--human LH gene cluster is not responsible for the ectopic production of beta-hCG by bladder tumour cells.

The beta-subunit of human chorionic gonadotrophin (hCG) is coded on chromosome 19 by the beta-hCG-hLH gene cluster. Genomic DNA has been isolated from bladder tumour cell lines which ectopically express beta-hCG. The beta-hCG-hLH gene cluster was probed for possible rearrangement or amplification and cells karyotyped for chromosome 19 abnormalities. No rearrangement or amplification of the gene cluster and no consistent abnormalities of chromosome 19 were found. The expression of beta-hCG by bladder tumours is therefore likely to be the result of altered gene regulation and not a rearrangement or amplification of this gene cluster.

Cell Line↗
PubMed1989

Levels of the small insulin-like growth factor-binding protein are strongly related to those of insulin in prepubertal and pubertal children but only weakly so after puberty.

We have looked at the relationship between fasting levels of insulin and a small insulin-like growth factor (IGF)-binding protein (IBP-1) in a cross-sectional study of 116 normal subjects aged 5-48 years. The relationship between IBP-1 and insulin was also examined within individual normal children in overnight profiles of IBP-1 and insulin obtained from two children at each stage of puberty (Tanner stages 1-5). In the cross-sectional study high levels of IBP-1 were found in early childhood and these fell throughout puberty as fasting levels of insulin rose. Multiple regression analysis revealed that both these changes were predominantly due to pubertal development rather than to age. After the age of 16 IBP-1 levels remained low despite fasting insulin levels returning to prepubertal levels. A strong negative correlation was obtained between IBP-1 and insulin in children of 5-16 years (r = -0.63; n = 60; P less than 0.001), no such relationship being found after the age of 16. In the second study, IBP-1 underwent a marked circadian variation in all cases and an inverse correlation with insulin, measured at the same time, was obtained at pubertal stages 1 to 4, but not at stage 5 (pooled data stages 1-4, r = -0.69; n = 53; P less than 0.001). We have demonstrated that a potential inhibitor of IGF-activity is inversely related to insulin throughout the period of active GH-related growth and that this relationship weakens after puberty.

Adolescent↗
PubMed1989

Enhancement of ectopic beta-human chorionic gonadotrophin expression by interferon-alpha.

Treatment of three beta-human chorionic gonadotrophin (beta-hCG)-expressing bladder tumour cell lines with interferon-alpha (IFN-alpha) (5000 U/per 10(6) cells) enhanced the rate of beta-hCG secretion from 34.2 +/- 0.9 to 102.5 +/- 0.1 mIU/10(6) cells per 72 h in cell line 5637; 111.15 +/- 11.75 to 261.8 +/- 51.75 mIU/10(6) cells per 72 h in cell line RT112 and 503.25 +/- 28.55 to 1361.65 +/- 110.3 mIU/10(6) cells per 72 h in cell line SCaBER. IFN-gamma had no effect on the rate of beta-hCG secretion. Both interferons reduced the growth rate of the cells: incorporation of radiolabelled thymidine was reduced by 15-45% in the presence of IFN-alpha and by 20-53% with IFN-gamma. Enhancement of beta-hCG secretion by IFN-alpha was dose-dependent over the range 5-50,000 U/10(6) cells. Analysis of cell cycle profiles by flow cytometry showed no increase in the proportion of cells in the G0G1 phase in cultures treated with IFN-alpha. The conceptus of some species produces substances which are either luteotrophic or anti-luteolytic. In sheep, the corpus luteum is maintained by ovine trophoblast protein-I, which has been shown to have structural homology with human IFN-alpha. In primates and a few other higher mammals, early pregnancy is maintained by chorionic gonadotrophin. IFN-alpha is also an early product of the human conceptus. We have now shown that IFN-alpha enhances the ectopic production of the beta-subunit of hCG by bladder tumour cells. This study suggests a direct transcription/translational effect of this cytokine on the expression of a reproductive endocrine gene.

Cell Line↗
PubMed1989

Placental proteins 12 and 14 in pre-eclampsia.

The concentrations of circulating placental protein 12 (PP12) and placental protein 14 (PP14) were measured in 41 patients with pre-eclampsia and in 17 control subjects. The levels of PP12 were significantly elevated in patients with severe preeclampsia, whereas PP14 levels were unaffected. There was a negative correlation between the levels of both PP12 and PP14 and birthweight. PP12 and PP14 appear therefore to have different control mechanisms and, possibly, different cellular origins within the decidua.

Birth Weight↗
PubMed1989

Interferon in pregnancy.

The cells of the immune system exchange information by a complex network of molecules referred to as lymphokines: these include the interferons. The physiology of the interferons, both in terms of control and function, is poorly understood. However, there is ample evidence that production of alpha-interferon is characteristic of the fetoplacental unit in both the human and other species. Indeed, the major trophoblast protein in early pregnancy in the sheep is alpha-interferon and in this species the molecule appears to have an important anti-luteolytic effect. The function of the interferons in human pregnancy is not known but, by analogy with information from other experimental systems, it might reflect aspects of the immune relationship between the mother and the fetus.

Animals↗
PubMed1988

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

Chorionic Gonadotropin↗
PubMed1988

Serum alphafetoprotein levels in subjects infected with hepatitis B virus.

Serum alphafetoprotein (AFP) levels were measured using a sensitive radioimmunoassay in 108 hepatitis B surface antigen (HBsAg)-positive subjects and 695 controls. The concentrations were significantly higher in the HBsAg-positives. Within this group, the highest levels were found in those with active HBV infection. In those without evidence of acute infection, the levels were higher in the high-risk than in the low-risk subjects. It is concluded: 1) that measurement of serum AFP might be a useful additional index of infectivity and prognosis in HBsAg-positive subjects; and 2) that in the light of the association between chronic HBV infection, hepatocellular carcinoma, and raised AFP in non-European populations, consideration should be given to regular monitoring of AFP levels in HBsAg-positive subjects in the United Kingdom.

Hepatitis B↗
PubMed1988

Changes in circulating alphafetoprotein and human chorionic gonadotrophin following chorionic villus sampling.

Chorionic villus sampling (CVS) is rapidly becoming established as a routine procedure for first-trimester fetal diagnosis. The technique can result in fetomaternal haemorrhage and this might sensitize Rhesus-negative mothers and on occasion lead to spontaneous abortion. Serial sampling indicates that there is a rapid rise in alphafetoprotein (AFP) levels following CVS; however, this is not reflected by raised levels at 16-18 weeks and does not influence the subsequent pregnancy outcome. Unlike AFP, alterations in hCG levels are small and variable. Anti-D prophylaxis for non-sensitized Rhesus negative mothers should be given after CVS and the procedure may be contra-indicated in patients who are already sensitized.

Chorionic Gonadotropin↗