Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy

The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.     

Aspects of psychological and social morbidity in patients awaiting coronary artery bypass grafting.

OBJECTIVES--To assess anxiety, depression, and social adjustment in patients awaiting coronary artery bypass surgery. DESIGN--Patient completed questionnaire study. SETTING--Regional cardiothoracic centre. PATIENTS--109 questionnaires were sent to patients on the waiting list of two cardiothoracic surgeons. Sixty eight (62%) were returned and 15 (22%) of the respondents were women. There was no difference in the response rates for men (53/84) 63% and women (15/25) 60%. MAIN OUTCOME MEASURES--Anxiety and depression were assessed by the hospital anxiety and depression (HAD) scale. Social functioning was assessed by several nine point rating scales on which patients indicated how their work, family relationships, social activities, private leisure activities, and home management were impaired. Patients also indicated the severity of their cardiac symptoms on a questionnaire based on the New York Heart Association classification for the assessment of the functional state of patients with heart disease. RESULTS--On the HAD scale 19 (28%) patients scored in the clinically significant range for anxiety. Time spent on the waiting list was positively and significantly related to anxiety (p = 0.05). Thirty two (47%) patients scored in the clinically significant range for depression. Time spent on the waiting list was positively and significantly related to depression (p = 0.005). Positive and significant relations were found between time spent on the waiting list and impairment of work (p = < 0.0001), family relationships (p = < 0.0001), private leisure activities (p = < 0.0001), and social activities (p = 0.004). No correlation was found between any of the above variables and the indicated level of clinical symptoms. CONCLUSIONS--This study documents previously unreported associations between the time patients wait for coronary artery surgery and levels of anxiety, depression, and social functioning. Conclusions regarding the causes of these symptoms cannot be made from this small population of patients but these results do suggest that these associations should be studied further.     

The production of monoclonal antibodies to human chorionic gonadotrophin and its subunits

The difficulties encountered in producing highly specific antisera to human chorionic gonadotrophin (hCG) were overcome by the use of hybridoma technology. A panel of monoclonal antibodies directed toward hCG and its subunits was produced. Of the four antibodies which were fully characterized, one recognized the intact hCG molecule only, a second recognized only the free beta-subunit, a third recognized only the free alpha-subunit and the fourth bound to the beta-subunit of hCG both when it was in the free form and when it was associated with the alpha-subunit forming the intact hCG molecule. There was no significant cross-reaction of any of these antibodies with the pituitary glycoprotein hormones. The four antibodies had high binding affinities which should permit their use in immunoassays for measurement of circulating levels of hCG and its subunits.     

The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45

Summary The presence, densities, and patterns of distribution of melanocytes in the epidermis of human embryos and fetuses, ranging in age from 40 d to 140 d estimated gestational age (EGA), were studied using the HMB-45 monoclonal antibody that recognizes an antigen in melanoma cells and fetal melanocytes. Immunostained sections of skin and epidermal sheets revealed dendritic melanocytes within the basal or intermediate layers of 50 d EGA and older skin. Melanocytes could not be identified by immunostaining or electron microscopy in younger (40–50 d EGA) epidermis or in cultured epidermal cells from these specimens. However, skin from a 45 d EGA embryo grown in organ culture for 11 d stained positively with HMB-45, suggesting that melanocytes are present at that age either in the epidermis or dermis of the explant. Double-labeling experiments using ATPase and HMB-45 confirmed the specificity of HMB-45 for melanocytes and demonstrated that melanocytes and Langerhans cells are nonoverlapping populations. Melanocytes were present in the embryonic epidermis in relatively high numbers (mean value of 1050 cells/mm²); they increased in density to 2300 cells/mm² during the late first trimester and early second trimester, then declined during later stages of development to a density of 800 cells/mm², within the range of values for the newborn child and young adult. Equivalent numbers of melanocytes were recognized by silver staining and with the HMB-45 antibody in an 87 d EGA test sample, indicating that HMB-45 reacted with the total melanocytic population. Melanocytes appeared to be distributed in epidermal sheets in a regular pattern. Statistical tests used to evaluate the randomness of a population revealed a tendency toward a non-random distribution in specimens younger than 80 d EGA, just prior to appendage formation and epidermal stratification into multiple layers, however there was variability in the degree of randomness for any given age. The results of this study have closed the gap in timing between the conclusion of neural crest formation and migration (around 6 weeks) and the appearance of melanocytes in the skin between 40–50 d EGA.Portions of this work were presented at the annual meeting of the Society for Investigative Dermatology, May, 1987 and at the 37th Annual Symposium on the Biology of Skin, October, 1987