The potential value of CA125 as a tumour marker in small volume, non-evaluable epithelial ovarian cancer.

Seventy four consecutive patients with epithelial ovarian cancer have been followed up longitudinally with serial serum CA125 for up to 48 months. From this database, the CA125 changes in small volume disease have been evaluated. For long term complete responders (n = 12), the mean plateau level of CA125 was 7.2 U/ml (95% confidence interval; 5.6 to 9.2 U/ml). The natural half-life of CA125 at 5.1 days (range 3.8 to 7 days) was calculated from five patients with Stage I and II disease who underwent complete surgical excision. A mean lead time of 99 days (range 14 to 255 days) was demonstrated between marker detection of disease progression and clinically apparent progressive disease in 12 out of 13 patients (92%) who relapsed after chemotherapy induced complete remission. The threshold of tumour volume detection with CA125 is unlikely to be determined by an arbitrary cut-off level. The kinetics of CA125 provide more useful information and the potential to define complete response or indeed cure with CA125 parameters requires further investigation.     

Brain corticosteroid receptor gene expression and neuroendocrine dynamics during aging

The present study examined the stress responsiveness of the hypothalamic-pituitary-adrenal axis in relation to the properties of corticosteroid receptors in the brain and pituitary in old (30 months) and young (3 months) male Brown Norway rats. The data demonstrate that circulating ACTH rather than the corticosteroid plasma level was elevated under basal conditions and following stress. Furthermore, a reduction of mineralocorticoid receptor (MR) number in the hippocampus and of glucocorticoid receptor (GR) number in the hypothalamus and the pituitary correspond to increased neuroendocrine responsiveness and negative feedback following stress. The changes in receptor binding do not parallel the changes in the amount of MR and GR mRNA measured with in situ hybridization. This suggests that the processing rather than the receptor gene expression is affected in senescence.     

Tamoxifen and oestrogen both protect the rat muscle against physiological damage

Tamoxifen (TX), an oestrogen antagonist, was used to characterize the protective effect of oestradiol (E2) on exercise-related creatine kinase (CK) release from skeletal muscle of the rat. Subcutaneous administration of TX for 3 weeks in female rats had a profound antioestrogen effect as evidenced by a reduced weight of the uterus. The CK release after electrical stimulation of the isolated soleus muscle, previously shown to be E2-dependent, was markedly reduced (30–50%) after treatment with TX; this observation points to an E2-like protective action of TX instead of E2-antagonism. This effect was dose-dependent (0.25–1.00 mg/kg) and was not seen when TX was given shortly (24 h) before the experiments. In ovariectomized females, that show more CK leakage due to the lack of circulating E2, both E2- and TX-treatment resulted in a 60% reduction of the CK leakage. Muscles from male rats, treated with TX, showed a similar response: after contractions the CK release was significantly lower. We conclude that TX, like E2, reduces contraction-induced muscle damage in the rat and, thus, has E2-agonistic properties on skeletal rat muscle.     

Uptake, distribution and binding of vertebrate and invertebrate steroid hormones and time-dependence of ponasterone A binding in Calliphora vicina. Comparisons among cholesterol, corticosterone, cortisol, dexamethasone, 5 alpha-dihydrotestosterone, 1,25-dihydroxyvitamin D3, ecdysone, estradiol-17 beta, ponasterone A, progesterone, and testosterone.

The presence of specific binding sites for radiolabelled vertebrate-type and arthropod-type steroid hormones was investigated in several organs including salivary gland, and central nervous system of third instar Calliphora vicina larvae by thaw-mount autoradiography. Ponasterone A, a 20-hydroxyecdysone agonist and 20-hydroxyecdysone are the only steroids which bind to nuclear high affinity binding sites. These binding sites are DNA associated while nucleoli show no tracer binding. Ecdysone, an endogenous 20-hydroxyecdysone precursor, is taken up by target cells but no significant nuclear binding occurs. 1,25-Dihydroxyvitamin D3 concentrates in cytoplasm only and its uptake is highest compared to all other steroids. Progesterone and testosterone show weak accumulation in the cytoplasm, while for cholesterol, corticosterone, cortisol, dexamethasone, dihydrotestosterone and estradiol-17 beta, no noticeable uptake occurs. For ponasterone A, a clear time dependence of uptake and intracellular distribution is visible, suggesting the existence and involvement of specific ecdysteroid uptake and transport mechanisms. These results suggest the presence of binding sites for various mammalian steroids in insects. Whether vertebrate steroid hormones or metabolites of them play a role in insects or whether the uptake and binding is based on chemical similarities alone without biological significance remains to be further investigated.     

Maternal serum alpha-fetoprotein screening activities of state health agencies: a survey.

Maternal serum alpha-fetoprotein (MSAFP) screening has been demonstrated to be cost-effective on a population basis and is becoming standard practice. The American Society of Human Genetics has twice published policy statements to define the essential elements of a quality screening program. The present study reviewed the impact of these policy statements on state public-health agencies with respect to regulation or provision of MSAFP screening in their jurisdictions. With a few exceptions, states have not elected to play a major role in provision or regulation of this test. There is need to address issues of funding, standards, and data collection in a collaborative effort, if policy statements on genetic services are to be translated into effective state population screening.