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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 145 records · Page 8Linked to original sources

Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 in early human pregnancy.

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) were measured in amniotic fluid, extraembryonic coelomic fluid and maternal serum from 23 women with apparently normal first trimester pregnancies prior to termination. The levels of IGF-1 and IGFBP-1 were significantly higher in coelomic fluid than amniotic fluid (IGF-1, P = 0.006; IGFBP-1, P = 0.0008 (paired t-test)). The levels of IGFBP-1 were lower in amniotic fluid than in maternal serum (P = 0.017), a finding in sharp contrast to the situation in the second and third trimesters of pregnancy. There was a significant relation between levels of IGF-1 and IGFBP-1 in amniotic fluid (r = 0.43; P = 0.04) and in coelomic fluid (r = 0.81; P less than 0.001) but not in maternal serum. The finding that both the absolute levels of IGFBP-1 and the ratio to IGF-1 were low in amniotic fluid implies that there is a very high level of unbound, biologically active IGF-1 in this compartment in the first trimester. Thus, the regulatory role of IGFBP-1 may change as pregnancy advances.

Amniotic Fluid↗

Pregnancy tests: a review.

Pregnancy tests are widely used both by the public and by healthcare professionals. All tests depend on the measurement of human chorionic gonadotrophin (HCG) in urine. Other pregnancy-specific materials have been proposed as pregnancy tests but none can better the sensitivity and convenience offered by immunoassay of HCG. Ultrasound detection is also not as sensitive as HCG measurement. The current generation of tests is based on monoclonal antibodies to the beta-subunit of HCG; these virtually eliminate the possibility of cross-reaction with pituitary luteinizing hormone (LH) and it is this feature which permits the high sensitivity. However, it is important to recognize that the 'beta-subunit' antibody reacts with both intact HCG, which is the major component in pregnancy serum, and with fragments of the beta-subunit (beta-core), which are the major form in urine. Both the blood and urine of non-pregnant subjects contain small amounts of HCG. HCG from the implanting blastocyst first appears in maternal blood around 6-8 days following fertilization; the levels rise rapidly to reach a peak at 7-10 weeks. With most current pregnancy test kits (sensitivity 25 units per litre) urine may reveal positive results 3-4 days after implantation; by 7 days (the time of the expected period) 98% will be positive. A negative result 1 week after the missed period virtually guarantees that the woman is not pregnant. With the present generation of test kits, false positive results due to interfering materials are extremely unlikely. Pregnancy tests have now reached a level of sensitivity and specificity which is unlikely to be surpassed either by better tests or alternative technology.

Chorionic Gonadotropin↗

Erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy.

OBJECTIVE: The aim was to measure erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid from 7-12 weeks' gestation. SUBJECTS: Twenty healthy women with ultrasonographically normal first trimester pregnancies prior to surgical termination. METHODS: Paired samples of amniotic fluid and extraembryonic coelomic fluid were collected by transvaginal ultrasound guided needling. Erythropoietin was measured in both pregnancy fluids using a radioimmunoassay. RESULTS: There was a highly significant difference between erythropoietin levels in extraembryonic coelomic fluid (median level 15.45 mU/ml; range 6.8-32.1 mU/ml) and those in amniotic fluid (median 5.0 mU/ml; range < 5.0-5.8 mU/ml) (P < 0.0001; Mann-Whitney U-test). The levels of erythropoietin in maternal serum (median 15.4 mU/ml; range 5.6-29.4 mU/ml) were similar to those in the extra-embryonic coelom (P = 0.81; Mann-Whitney U-test). No relation was demonstrated between erythropoietin levels in amniotic fluid or coelomic fluid and stage of gestation. CONCLUSION: High levels of erythropoietin in coelomic fluid suggests that the hormone is involved in the process of human extraembryonic erythropoiesis. The exact regulatory role remains unknown.

Amniotic Fluid↗

Biochemical composition of amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy.

OBJECTIVE: To determine the biochemical composition of amniotic fluid and extraembryonic coelomic fluid between 8 and 12 weeks gestation. DESIGN: Prospective observational study. SUBJECTS: 40 women with a normal pregnancy between 7 and 12 weeks gestation having termination of pregnancy. INTERVENTIONS: Before termination the women had a transvaginal ultrasound guided amniocentesis. Pure samples of amniotic fluid and extraembryonic coelomic fluid were obtained from each woman and standard biochemical variables were measured in each fluid sample immediately after collection. RESULTS: Levels of sodium, potassium and bicarbonate were significantly higher in amniotic fluid whilst chloride, urea, bilirubin, protein, albumin, glucose, creatinine, calcium and phosphate were present in higher concentrations in extraembryonic coelomic fluid. All differences in concentration were significant (P less than 0.05; unpaired t-test). No relation was demonstrated between electrolyte concentrations in amniotic fluid or coelomic fluid and stage of gestation. CONCLUSIONS: Amniotic fluid and extraembryonic coelomic fluid have a widely differing biochemical composition. The biological significance of these differences remains unexplained.

Amnion↗

Role of the ovary in the synthesis of placental protein-14.

Women with absent ovarian function provide an opportunity to investigate the ovarian contribution to secretion of placental proteins (PP), such as PP14, in early pregnancy. We present data on serum PP14 levels in 12 women (median age, 30.5 yr; range, 26-37 yr) with premature ovarian failure (POF) who conceived after ovum donation and embryo transfer with exogenous sex steroid support using transdermal (n = 5) or oral (n = 7) estradiol and vaginal (n = 8) or im (n = 4) progesterone. The women were closely monitored throughout early pregnancy, with measurement of serum levels of estradiol (E2), progesterone (P4), and PP14. Levels of E2 and P4 were entirely normal. Levels of PP14 were significantly subnormal (P = 0.008) in all 12 agonadal women compared with levels of PP14 in a control group of women with normal ovarian function between 6-12 weeks gestation. Basal and peak levels for subjects with absent ovarian function were 40 and 124 micrograms/L, respectively. For each week between 6-12 weeks of pregnancy, the mean serum levels of PP14 for women with normal ovarian function were between 706-940 micrograms/L. These observations support the concept that PP14 arises from the ovary in early pregnancy or that factors under the control of the maternal ovary are involved in its production by the endometrium.

Adult↗

Chromatographic characterization of insulin-like growth factor-binding proteins in human pregnancy serum.

Insulin-like growth factor-binding proteins (IGFBPs) in maternal and umbilical cord sera have been analysed by combinations of gel filtration chromatography, affinity cross-linking and electrophoresis. On gel filtration chromatography, the majority of circulating IGF-I in non-pregnant and pregnant women was present in the large molecular mass (150 kDa) binding proteins (IGFBP-3). In umbilical cord serum, by contrast, most IGF-I was present in the 40 kDa binding proteins (consisting of IGFBP-1 and IGFBP-2). Western blots demonstrated an apparent progressive attenuation of IGFBP-3 and IGFBP-2 in serum from pregnant women with an increase in IGFBP-1. After prior cross-linking with disuccinimidyl suberate, the 150 kDa fractions (IGFBP-3) from non-pregnant and pregnant serum showed a similar pattern on SDS-PAGE (several bands at different molecular masses). However, IGFBP-2 (one of the components of the 40 kDa fractions) was undetectable, even after cross-linking, in serum from pregnant women later than 8 weeks of gestational age and in a mixture of maternal serum at term delivery and serum from non-pregnant women. This suggests that serum IGFBP-2 was degraded by specific proteases present in pregnancy serum. Following acid treatment, the 150 kDa fractions from pregnancy serum were split into smaller subunits or fragments while the 40 kDa fractions remained unchanged, suggesting that the 40 kDa binding proteins, are acid-stable. The present data demonstrate that IGFBP-3 is the principal IGFBP in pregnancy serum even though there is an apparent reduction in serum IGFBP-3 activity as revealed on Western blots. The absence of IGFBP-2 in serum from pregnant women may be due to degradation by proteases. In the fetal circulation IGFBP-1 and IGFBP-2 appear to be the major binding proteins for IGF-1.

Blotting, Western↗

Immunoreactive beta-core-like material in normal postmenopausal urine: human chorionic gonadotrophin or LH origin? Evidence for the existence of LH core.

Material with the immunochemical properties of the beta-core of human chorionic gonadotrophin (hCG) can be found in the urine of normal postmenopausal women. However, we have been unable to detect intact hCG (using an assay which is specific for the alpha-beta heterodimer of intact hCG) in serum of such subjects. The levels of serum LH and urinary beta-core were compared in matched samples from 28 women (serum LH: median 27 U/l, range 4-70 U/l, urinary beta-core: median 0.27 microgram/l, range less than 0.05-0.645 microgram/l). Urine (4 litres) from three postmenopausal women was concentrated, dialysed and subjected to gel exclusion chromatography on Sephadex G-100. Fractions were analysed by specific assays for LH, intact hCG, total beta-hCG (free beta-subunit and intact hCG), free alpha-subunit and beta-core. Material eluting at the expected position of the beta-core fragment of hCG was detected in all three samples by the beta-core, beta-hCG and LH assays, despite the fact that the LH antibody does not recognize the authentic beta-core of pregnancy. Electrophoresis and Western blotting of the concentrated urines revealed that material of the same molecular size as beta-core was recognized by the antibody to LH but not by a monoclonal antibody raised to free beta-hCG which also recognizes the beta-core molecule of hCG. We conclude that the predominant core-like material identified in postmenopausal urine is probably derived from the beta-subunit of LH.

Aged↗

Human chorionic gonadotrophin and subunit composition of maternal serum and coelomic and amniotic fluids in the first trimester of pregnancy.

Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total beta-hCG (free beta-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6.73 kIU/l) and 2.8 times greater than in MS (median 141.5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1.73 kIU/l) and 1.6 times greater than in MS (median 157 kIU/l). Free alpha-subunit levels in EECF (median 17.3 mg/l) were 66 times greater than in AF (median 0.262 mg/l) and 12 times greater than in MS (median 1.3 mg/l). Virtually all of the total beta-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total beta-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free alpha-subunit was a major constituent; on a molar basis the ratio of free alpha:free beta:intact hCG was 1:1.2:0.3 in AF, 1:0.6:0.5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Multi-parameter flow cytometric quantitation of the expression of the tumor-associated antigen SM3 in normal and neoplastic ovarian tissues. A comparison with HMFG1 and HMFG2.

SM3 is a monoclonal antibody that reacts with a peptide epitope in the core protein of polymorphic epithelial mucin. Multi-parameter flow cytometry was used to characterize the expression of SM3 and compare it with two related tumor-associated antigens, HMFG1 and HMFG2, in cell suspensions of 44 malignant ovarian tumors, 15 benign ovarian tumors, and 16 normal ovaries. Tumor-associated antigen expression was significantly higher in malignant ovarian neoplasms than in benign neoplasms (P less than 0.001 for all three antigens). SM3 was expressed more specifically in malignant than benign tumors but had a lower affinity than HMFG1 and HMFG2. Multi-parameter flow cytometric evaluation of a panel of monoclonal antibodies can be used to help in choosing the best antibody for immunohistochemistry, imaging, and eventually treatment of ovarian tumors.

Antibodies, Monoclonal↗

Sonographic depiction of postmenopausal endometrium with transabdominal and transvaginal scanning.

The thickness of the endometrium was measured in postmenopausal women by both the transvaginal and transabdominal ultrasound approaches in two separate groups of patients. The first group consisted of 90 women who received a transabdominal scan of the endometrium before dilatation and curettage or hysterectomy for either postmenopausal bleeding or uterine prolapse. The second group consisted of 111 women who underwent a transvaginal scan of the endometrium for similar postmenopausal conditions. Both methods suggested that an endometrial thickness of 5 mm may be used as a cut-off level in the conservative management of patients with postmenopausal bleeding or in a screening program for endometrial carcinoma. Patient acceptance and image quality were better in the group examined transvaginally. The proximity of the transvaginal probe to the endometrium, in the absence of a full bladder compressing the endometrium, revealed a unique group of patients with atrophic endometrium but thick endometrial cavity caused by intracavity fluid. In the presence of uterine fibroids distorting the uterine cavity, transvaginal scanning was better than transabdominal scanning for visualizing the endometrium. The transabdominal full-bladder technique can be of value in detecting asymptomatic bladder pathology.

Journal Article↗

Human chorionic gonadotrophin and alpha-fetoprotein levels in matched samples of amniotic fluid, extraembryonic coelomic fluid, and maternal serum in the first trimester of pregnancy.

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound-guided amniocentesis from 32 women between 7 and 12 weeks of pregnancy were analysed for human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). There was a highly significant difference between the hCG levels in amniotic fluid (median level 6.3 U/ml; range 1.6-310.0 U/ml) and those in extraembryonic coelomic fluid (median level 400.0 U/ml; range 135.0-2250.0 U/ml) (p less than 0.001; Mann-Whitney U-test). The levels of AFP were very similar in amniotic fluid (median 26.0 kU/ml; range 10.0-116.5 kU/ml) and extraembryonic coelomic fluid (median level 24.1 kU/ml; range 12.4-94.4 kU/ml).

Abortion, Therapeutic↗

Some observations on the development of a 'scoring system' in an expert system for prediction of ovulation.

As part of the construction of an expert system for the diagnosis of infertility we have developed a scoring system for the identification of conditions which can interfere with ovulation. The scores were obtained from a group of clinicians, and the arithmetic means of these scores were used in the actual system. Correlation between the scores obtained from individual clinicians was very poor (r = 0.345 +/- 0.134). Correlation improved when groups of clinicians were compared. Thus scores derived from a group of clinicians will reflect more reliably the 'general medical opinion'. Scores derived from the opinion of clinicians should be regarded with caution until probabilities or weighting factors derived from real clinical data become available.

Expert Systems↗

Multiparameter flow-cytometric quantitation of epidermal growth factor receptor and c-erbB-2 oncoprotein in normal and neoplastic tissues of the female genital tract.

A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein on 85 cryopreserved normal tissues (30 ovary, 29 endometrium, 16 cervix) and 67 carcinomas (31 ovarian, 18 cervical, 15 endometrial, 3 vulvar). Overexpression of the EGFR and c-erbB-2 oncoproteins was found in respectively 3/31 (9%) and 10/31 (32%) ovarian carcinomas, 13/18 (72%) and 7/18 (38%) cervical carcinomas, and 2/15 (13%) and 2/15 (13%) endometrial carcinomas. Oncoprotein expression was significantly higher in the malignant tumors (for all tumor sites) than in the corresponding normal tissues (P less than 0.034 for all combinations). Aneuploid tumors expressed levels of EGFR and c-erbB-2 oncoprotein significantly higher than those of DNA diploid tumors (P = 0.042 and P = 0.048, respectively). Oncoprotein could be detected in nearly all normal tissues: expression was higher in premenopausal than in postmenopausal patients (EGFR, P = 0.07; c-erbB-2, P less than 0.001). The present study supports the idea that EGFR and c-erbB-2 may play an important role in the autocrine, paracrine, and/or endocrine growth control and differentiation of normal tissues. Alteration in the expression of these oncoproteins is probably involved in malignant transformation and tumorigenesis.

Carcinoma↗

The concentrations of transferrin, beta 2-microglobulin, and albumin in seminal plasma in relation to sperm count.

A number of studies have shown a relationship between transferrin levels in seminal plasma and sperm count. In the present study, the levels of transferrin, beta 2-microglobulin and albumin were measured in 171 samples of seminal plasma (50 subjects with normal sperm count; 32 with azoospermia; 49 with oligozoospermia; 10 with polyzoospermia; and 31 vasectomized). All three proteins were related to sperm count. It is concluded that there is a general relationship between seminal plasma proteins and sperm numbers and that some products of the sperm themselves must control the entry of plasma proteins into seminal plasma.

Humans↗