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Biomedical subjects

L A Perry

Publications and source records attributed to L A Perry.

At least 55 records · Page 3Linked to original sources
PubMed1991

Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy.

Insulin-like growth factor-binding protein-1 (IGFBP-1) has been purified from amniotic fluid by anion exchange, hydrophobic interaction and gel filtration chromatography. The overall recovery of the purification process was 12.2%. The purified IGFBP-1 yielded a single band on SDS-PAGE gel but showed two bands (34 kDa and 68 kDa) on Western blot under non-reducing conditions. Polyclonal antisera were raised by immunization of sheep using the purified IGFBP-1. The best antiserum bound 50% of 125I-labelled IGFBP-1 at a final dilution of 1:500,000. A radioimmunoassay for IGFBP-1 was developed. This assay had a minimum detection limit of 5 micrograms/l, and was used to determine serum levels in non-pregnant and pregnant women. There was no cross-reaction with a wide variety of materials tested. Serum IGFBP-1 levels in non-pregnant individuals (33 +/- 16 (S.D.) micrograms/l) were found to be significantly lower than those in the second (96 +/- 64 micrograms/l) and third trimesters (95 +/- 60 micrograms/l) of pregnant women. During pregnancy, circulating IGFBP-1 levels increased rapidly in the first trimester and reached a peak at 12-13 weeks of gestation (107 +/- 75 micrograms/l). The level then remained at 80 +/- 53 to 103 +/- 70 micrograms/l until term.

Adolescent↗
PubMed1990

Female pseudohermaphroditism due to a maternal adrenocortical tumor.

A 15-yr-old, apparently male, patient presented with a 2-yr history of gynecomastia and poor genital development. A normally formed, but small, penis with a phallic urethra was present, and testes were impalpable. The karyotype was 46,XX, and at laparotomy a uterus, Fallopian tubes, and ovaries were found, but there was no testicular tissue. The mother had had regular periods ever since menarche at 14 yr. She had complained of hirsutism since the birth of the child, and on examination 15 yr later had marked clitoromegaly. Serum androgens were elevated: testosterone, 4.5 nmol/L (normal, 0.5-3); dehydroepiandrosterone sulfate, 18 mumol/L (normal, 3-12); and androstenedione, 35 nmol/L (normal, 3-8). All failed to suppress with dexamethasone. Abdominal computed tomographic scan revealed a 9 X 6-cm mass in the position of the left adrenal gland. This was removed at laparotomy and found to be an adrenocortical tumor. Postoperatively, the androgens returned to normal. Virilization of a female fetus due to androgens secreted by a maternal adrenal tumor has only been described three times previously, and the presentation has never been delayed so long.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Free and serum testosterone levels in 276 males: a comparative study of rheumatoid arthritis, ankylosing spondylitis and healthy controls.

A cross-sectional study of testosterone levels in 276 males was undertaken. Of these 87 were RA patients, 48 males with AS and 141 were healthy controls. Free and serum testosterone levels were significantly lower in the RA males than in either the AS group or the healthy controls (p less than 0.001). This difference was unaffected by age. No differences were seen in testosterone levels between DR1 or DR4 RA patients compared to those without these antigens. No evidence of hyperandrogenicity was seen in the AS group. The finding that males with RA have lower androgen levels than both normal controls and a disease group with inflammatory spondarthritis supports the hypothesis that male sex hormones may be a protective factor against the development of RA.

Adult↗
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

Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life.

The relationships between plasma insulin, insulin-like growth factor I (IGF-I) and dehydroepiandrosterone sulfate (DHEAS) concentrations in normal subjects have not been defined. We performed iv glucose tolerance tests on 102 normal subjects, aged 5-20 yr. The subjects were divided into 4 groups according to pubertal stage (Tanner): A, stage 1 (n = 22); B, stages 2 and 3 (n = 17); C, stages 4 and 5 (n = 20); and D, adult, greater than 17 yr (n = 43). The basal plasma IGF-I and insulin concentrations and incremental 0-60 min insulin areas in response to glucose rose significantly throughout puberty (P less than 0.001 for all parameters) and declined to prepubertal levels by the third decade of life. There was a strong positive correlation between log fasting plasma insulin vs. log plasma IGF-I (r = 0.625; P less than 0.001) and log incremental 0-60 min insulin areas vs. log plasma IGF-I (r = 0.572; P less than 0.001). Plasma DHEAS concentrations were measured in groups A-C (n = 59); these also rose throughout puberty. There was strong correlations between log plasma DHEAS and log basal or stimulated (incremental 0-60 min areas) insulin responses (P less than 0.001). To assess the relationship between plasma DHEAS and insulin before puberty, we analyzed the data from group A separately. Plasma DHEAS concentrations tended to be higher in children 9 yr of age or older than in those less than 9 yr old, whereas basal and stimulated plasma insulin levels were similar. We found no correlation between log plasma insulin (fasting or stimulated responses) and log plasma DHEAS concentrations in group A (P greater than 0.05). In conclusion, we found a strong relationship between plasma insulin and IGF-I throughout childhood and puberty and during adult life. This finding suggests that insulin may be important for normal growth during childhood. There was no correlation between plasma insulin and DHEAS concentrations in prepubertal children, which suggests that adrenarche does not influence insulin levels.

Adolescent↗
PubMed1988

Low free testosterone levels in rheumatoid arthritis.

The androgen status of 25 male patients with rheumatoid arthritis (RA) was assessed and compared with that of age matched controls with osteoarthritis (OA). Significantly reduced levels of serum free testosterone were found in the RA group. Within that group free testosterone was unrelated to all indices of disease activity measured, though it was strongly related to latex positivity. These results support the hypothesis that male sex hormones may have a protective role in RA, though prospective studies would be necessary to determine whether the relation was one of cause or effect.

Adult↗
PubMed1988

Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses.

Plasma cortisol and adrenocorticotropin (ACTH) were measured in fetal blood samples obtained by cordocentesis from 61 appropriate for gestational age (AGA) and in 41 small for gestational age (SGA) fetuses at 18-38 weeks gestation. Fetal plasma cortisol (mean 74 nmol/l) did not change but plasma ACTH increased between 18 and 36 weeks gestation and the two were not significantly correlated. Plasma cortisol in cord blood samples after vaginal delivery at term (mean 305 nmol/l) was higher than in samples at elective cesarean section (mean 151 nmol/l), and there was a significant correlation between fetal and maternal levels. The findings suggest that in human fetuses a late gestational rise in plasma cortisol may not be necessary for organ maturation and that the high fetal plasma cortisol in spontaneous labor at term is probably the result rather than the cause of labor. In SGA fetuses, plasma cortisol was higher and ACTH lower than in AGA fetuses, and plasma cortisol was inversely correlated to fetal hypoglycemia, suggesting that in the chronically hypoglycemic SGA fetus the fetal pituitary is under negative inhibition.

Adrenocorticotropic Hormone↗
PubMed1988

Ultra rapid blood sampling for the determination of short-term variations in the circulating concentration of oestradiol in man.

Blood was taken from three healthy female and three healthy male volunteers every 20 s for 15 min. The serum level of oestradiol was measured and the pattern of variation assessed by a cusum plot of the sequential data, by autocorrelation of the detrended serial data, and by looking for pulses. In two cases the variation in oestradiol values was greater than that which could be attributed to variation in the assay. Both these subjects showed a significant overall change in values during the sampling period (an increase and a decrease). There was no trend in the remaining four subjects. In two of the six subjects there was significant autocorrelation of detrended sequential levels. Defining a 'pulse' as three times the assay coefficient of variation no more pulses were identified than was expected from random fluctuations. By frequency analysis the two subjects with significant autocorrelation showed periodic fluctuations of approximately 70/h and 9/h respectively. It is apparent that both the rate of sampling and the method of analysis greatly influence the evaluation of pulsatile release of oestradiol.

Adult↗
PubMed1988

Development of a direct [125I]radioimmunoassay for serum levels of 17-hydroxyprogesterone.

We describe a direct, rapid, sensitive and highly specific radioimmunoassay for determining serum levels of 17-hydroxyprogesterone. It is based on the use of highly specific sheep antiserum, 125I-labelled tracer, dextran-coated charcoal to separate the antibody bound and free fractions, and sodium salicylate to eliminate interference from endogenous binding proteins in serum. Intra- and interassay coefficients of variation are less than 8% and recovery is satisfactory. Sensitivity is 3.5 fmol per assay tube (0.14 nmol/l). Results correlate closely with those of an established technique using 3H-labelled steroid after initial solvent extraction and column chromatography of samples (y = 1.02x - 0.16; r = 0.998). The values found for serum from normal adult subjects ranged from 1.0 to 12.1 nmol/l while those from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were 1.4-18.4 and 27.3-650 nmol/l, respectively.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Evidence for similarity in testosterone levels in haplotype identical brothers.

An analysis of 89 male sibling pairs from multicase rheumatoid arthritis families demonstrated an association between HLA and serum testosterone levels. In sibling pairs that were haplotype identical, the mean inter-pair difference in testosterone level expressed as a log ratio was significantly less than sibling pairs sharing neither haplotype (p = 0.03). This difference was independent of the RA status of the pairs. These results suggest the presence of a gene(s) controlling testosterone levels linked to the Major Histocompatibility Complex (MHC) on chromosome 6. These findings may aid understanding of the roles of HLA antigens and sex hormones in the susceptibility to RA and other autoimmune disease.

Arthritis, Rheumatoid↗
PubMed1987

The production and characterisation of antisera to 17-hydroxyprogesterone.

Sheep were immunised with 11-deoxycortisol-21-hemisuccinate-bovine serum albumin (11-deoxycortisol-21-HS-BSA) or with 17-hydroxyprogesterone-7 alpha-carboxyethyl thioether-keyhole limpet haemocyanin (17-OHP-7 alpha-CETE-KLH) or with 17-OHP-3-(O-carboxymethyl)oxime-KLH (17-OHP-3-CMO-KLH). The resultant antisera were assessed using [3H]17-OHP and dextran-coated charcoal to separate the antibody bound and free fractions. All sheep produced antisera with an apparent affinity constant of from 1.4 to 6.6 X 10(9) 1/mol. Those raised against 11-deoxycortisol-21-HS-BSA had titres ranging from 1:12,000 to 1:78,000 but showed significant cross-reactivity with many of the steroids tested. Sheep immunised with 17-OHP-7 alpha-CETE-KLH had antisera titres of from 1:102,000 to 1:180,000 and only 17-hydroxypregnenolone cross-reacted significantly (10-20%). The best antisera were raised in sheep immunised with 17-OHP-3-CMO-KLH. Titres ranged from 1:168,000 to 1:390,000 and there were about 8 g/l of specific antibodies which cross-reacted 5.7% or less with 17-hydroxypregnenolone, and less than 0.5% with progesterone, 11-deoxycortisol and the other steroids studied. The antisera to 17-OHP-3-CMO-KLH were further assessed using [125I]17-OHP; titres ranged from 1:5,700,000 to 1:18,000,000 with affinity constants of from 1.67 to 2.5 X 10(10) 1/mol. They showed minimal or no cross-reactivity with the steroids studied. Reimmunisation after an 8-month interval produced antisera with a higher affinity constant and even lower cross-reactivity with other steroids.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Saliva levels of oestradiol and progesterone in relation to non-protein-bound concentrations in blood during late pregnancy.

Serum and saliva samples were obtained from 25 women in the last eight weeks of pregnancy. The concentrations of oestradiol and progesterone were measured by radioimmunoassay. The proportion of each hormone which was not bound to protein in serum was measured by centrifugal ultrafiltration: for progesterone the unbound fraction was 2.5% (2.13--2.78%) and for oestradiol 1.27% (1--1.83%). There was only a weak relationship between the free hormone concentrations estimated in blood and the levels measured in saliva. We conclude that, for the situation examined here, saliva does not provide a useful measure of unbound, biologically active steroid.

Estradiol↗
PubMed1987

Androgen suppression by hydrocortisone without aminoglutethimide in orchiectomised men with prostatic cancer.

The effects of hydrocortisone (HC) alone and in combination with aminoglutethimide (AG) have been studied on circulating blood levels of androgens in orchiectomised men with metastatic prostatic cancer. Serum testosterone levels were significantly lower in both early and late hydrocortisone-treated patients compared with pre-treatment levels. The regimen of HC + AG increased serum testosterone almost back to pre-treatment levels. Similar observations were noted with serum androstenedione, dehydroepiandrosterone sulphate and sex hormone binding globulin (SHBG) levels. Clinical responses to hydrocortisone alone have been observed in this series of patients. It is concluded that aminoglutethimide has no place in the therapy of prostatic cancer and that physiological doses of hydrocortisone represent the best second hormonal manoeuvre for prostatic cancer patients.

Aged↗
PubMed1987

A relationship between sex hormone binding globulin and dehydroepiandrosterone sulfate in normally menstruating females.

Blood samples were collected from 120 normally menstruating women throughout the menstrual cycle. Serum was assayed for sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2) and testosterone (T). There was an inverse relationship between SHBG and DHEAS, but no relationship between T or E2 and SHBG levels. There is at present no model which readily explains this inverse relationship between SHBG and DHEAS in normal subjects.

Adolescent↗
PubMed1986

Early diagnosis of 11 beta-hydroxylase deficiency in two siblings confirmed by analysis of a novel steroid metabolite in newborn urine.

Plasma and urinary steroid measurements are reported in 2 normotensive newborn female siblings with virilized external genitalia due to 11 beta-hydroxylase deficiency. Plasma 11-deoxycortisol concentrations were markedly elevated whereas 17OH-progesterone concentrations were not raised. Plasma renin activity was suppressed, but increased to levels characteristic of infancy within 4 weeks of treatment. The enzyme defect was confirmed by measurement of increased urinary excretion of tetrahydro-11-deoxycortisol. A more polar steroid metabolite, 6 alpha-hydroxytetrahydro-11-deoxycortisol was also determined by gas chromatographic and mass spectrometric analysis. Analysis of metabolites in urine is an additional specific marker to plasma 11-deoxycortisol measurement for the diagnosis of 11 beta-hydroxylase deficiency in early infancy.

17-Hydroxycorticosteroids↗