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Suniiriary. Skin collagcn conlcnt a~~d skin thickness in a g r o u p of postinenopausal wonicn w h o had been treated with sex h o r m o n c implants were c o m p a r e d with those in a n untreated g r o u p of similar w o m e n . Both skin collagen content and thickness were found t o b e significantly greater in the treated than in the untreated group. In the untreated women skin collagen content declined in re1 a 1' ion to m e n opausal age but not t o chronological age. No correlation was found with menopausal age, chronological age or duration of therapy in t h e trcated group. These data suggest that skin collagen is influenced by t h c sex h o r m o n e status arid declines after t h e menopause. contributing t o t h e increase in urinary liydroxyproline excretion that has been reportcd to occur a t this time.Alhright ct nl. (1940) first postulated that loss of oestrogens leads to bone loss after the menopause. but the effects of oestrogcn deficiency on the skin collagen content and skin thickness have not been reported. Although it has been suygested that there is a link between the quality of the skin and bone mass. (McConkey et ul. 1069; tiordon 19771, the possible effect of sex hormones on skin has not been adequately investigated. Brincat el al. (l983), in a study comparing 29 postmenopausal women with 26 women of similar age, who had been on sex hormone replacement for between 2 and 10 years, showed that the treated group had a higher skin collagen content than the untreated group. thus suggesting that sex hormones have a direct effect on the skin. Shuster et al. (1Y70) wggested'that it is an increase in androgen levels that gives hirsute women their higher skin collagen and skin thickness.In order to investigate the effects of sex hormones on the skin. we have studied the skin collagen content and the skin thickness in a large number of women treated with sex hormones and in untreated women at various stages after the menopause. Patients and methodsThe skin collagen content was measured in 52 postmenopausal women, who had been treated with oestradiol and testosterone implants for 2 to 10 years, and compared with that in a group of 66 postmenopausal women who had never received sex hormone therapy.The two groups were similar in age. the mean age was 50.5 years in the treated group and 50.3 years in the untreated group. The treated group of women were maintained on implants of 50 mg of oestradiol (&,) and 100 mg of testosterone (Tlo,,) (Brincat et al. 1984) administered every 6 nionths. Those women who had a uterus were given 5 mg of norethisterone for 7 days to produce a regular bleed and to prevent endometrial hyperplasia (Thorn et (11. 1979). The mean duration of therapy in the treated group was 5-2 years. The mean number of years since the menopause was 8.8 in the treated group and 8-1

Objectives The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum. Design and methods The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants. Results In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples. In addition, positive correlations, (R2 0.67–0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts. Conclusions We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications.

BMD in children with chronic cholestatic liver disease improves remarkably by 12 months after LT. Catch-up growth in children can account for the different effect of LT on bone density between adult and pediatric populations in the first year after surgery.

Parathyroid hormone-related peptide (PTHrP) has been detected in fetal serum and amniotic fluid. Using a combination of immunocytochemistry and molecular biology we have detected the peptide and its mRNA in a variety of fetal tissues throughout gestation. Tissue-specific mRNA isoforms were observed, the pattern of hybridization of which changed throughout gestation. In addition, the intensity and pattern of immunocytochemical localization of the peptide was found to vary over the time-period studied (8-30 weeks). PTHrP is expressed by a variety of tumours associated with the syndrome of humoral hypercalcaemia of malignancy and probably accounts for the hypercalcaemia by virtue of its limited amino acid homology with parathyroid hormone. These data demonstrate for the first time that PTHrP, a tumour-related peptide, is expressed during normal human fetal development, and suggest the possibility that it may function to regulate fetal calcium balance and growth in utero.