Lee W. Evans

Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair

Recently we demonstrated a strong induction of activin expression after skin injury, suggesting a function of this transforming growth factor‐β family member in wound repair. To test this possibility, we generated transgenic mice that overexpress the activin βA chain in the epidermis under the control of a keratin 14 promoter. The transgenic mice were significantly smaller than control littermates, and they had smaller ears and shorter tails. In their skin, the fatty tissue was replaced by connective tissue and a severe thickening of the epidermis was found. The spinous cell layer was significantly increased, and the epidermal architecture was highly disorganized. These histological abnormalities seem to result from increased proliferation of the basal keratinocytes and abnormalities in the program of keratinocyte differentiation. After skin injury, a significant enhancement of granulation tissue formation was detected in the activin‐overexpressing mice, possibly as a result of premature induction of fibronectin and tenascin‐C expression. These data reveal novel activities of activin in the regulation of keratinocyte proliferation and differentiation as well as in dermal fibrosis and cutaneous wound repair.

Maternal serum total activin A and follistatin in pregnancy and parturition

Objective To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour

Characterization of serum activin-A and follistatin and their relation to virological and histological determinants in chronic viral hepatitis

BACKGROUND/METHODS Hepatocyte proliferation in viral hepatitis is regulated by a number of growth factors. Activin-A inhibits hepatocyte DNA synthesis while follistatin, a potent activin-A antagonist, promotes liver regeneration. We report the first study of activin-A and follistatin in human viral hepatitis. Sera from 15 normal subjects, 22 hepatitis B and 47 hepatitis C patients were analysed for activin-A and follistatin and correlated with serological and histological markers of liver injury and with specific immunohistochemistry. RESULTS All groups showed immunoreactivity for activin with hepatocyte localisation. Serum activin-A was significantly increased in viral hepatitis patients compared to controls, was greater in hepatitis B compared to hepatitis C, and correlated with serum aminotransferase and hepatitis B viral replication. A concurrent rise in serum follistatin was not observed in either group, but serum follistatin correlated inversely with hepatitis B DNA levels. Although hepatocyte apoptosis in hepatitis C and proliferation in both groups was significantly elevated compared to controls, there was no correlation with serum activin-A or follistatin. CONCLUSIONS Activin-A and follistatin are constitutively expressed in human liver and serum concentrations are increased in viral hepatitis. Dysregulation of the activin/follistatin axis may be linked to hepatitis B replication but does not correlate with hepatocyte apoptosis.

Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators.

Objective: To determine the effects of inflammatory mediators on the production of activin A, inhibin A, and the binding protein follistatin in term amnion and chroidecidual tissues. Methods: The effects of interleukin-1β (IL-1β; 1 ng/mL), tumor necrosis factor-α (TNF-α; 10 ng/mL), and bacterial lipopolysaccharide (LSP; 5 μg/mL) on production rates of activin A, inhibin A, and follistatin by term choriodecidual and amnion membranes in explant culture were determined using specific enzyme-linked immunoabsorbent assays. Results: All explants (n = 6 placentas) produced detectable amounts of activin A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were more than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1β and TNF-α to 450 ± 155.4% and 531 ± 170.8% of control, respectively (mean ± standard error of the mean; P < .05 by analysis of variance), whereas production of inhibition and follistatin was stimulated to a much more modest extent. Similar responses were observed in the choriodecidual explants. Lipopolysaccharide had no significant effect on amnion activin A production, but stimulated choriodecidual production to 290 ± 34% of control. Lipopolysaccharide exerted only limited effects on inhibin A and follistatin production. Conclusions: Treatment with proinflammatory mediators resulted in a preferential increase in activin A production compared with that of inhibin A or follistatin. These findings suggest that inflammation of the gestational membranes could result in increased local activin. A production and bioactivity.

Serum inhibin, activin and follistatin in postmenopausal women with epithelial ovarian carcinoma

Objective To investigate the role of serum inhibin A, inhibin pro‐αC immunoreactivity, activin A, and follistatin in postmenopausal women with epithelial ovarian cancer.

Amniotic fluid levels of dimeric inhibins, pro‐αC inhibin, activin A and follistatin in Down's syndrome

In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Downs syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro‐αC inhibin, activin A and the binding protein follistatin in amniotic fluid in Downs syndrome and control pregnancies.

Using clinical indicators in emergency medicine: documenting performance improvements to justify increased resource allocation.

OBJECTIVES: To demonstrate how emergency department triage scale and thrombolysis indicator data can be used to document the impact of a substantial increase in resource allocation. METHODS: Descriptive study in an emergency department of an adult tertiary hospital in Perth, Australia during similar periods of the year both before and after a substantial increase in emergency department staff, equipment, and system resources. The study group comprised a total of 11,048 emergency department attendances and all cases of emergency department initiated thrombolysis or acute angioplasty. Outcome was measured using numbers seen and percentage seen within indicator threshold time together with admission rates in each of the five triage categories as well as by using time from presentation to initiation of reperfusion treatment in acute myocardial infarction. RESULTS: The proportion of patients seen within the prescribed indicator time increased by 16.4% (95% confidence interval 14.4% to 18.2%). The increase was most pronounced in triage category 2 (32.7%). Median time to thrombolysis fell by 30 minutes to 37 minutes (p = 0.0002). CONCLUSIONS: Use of the Australasian national triage scale and time to thrombolysis clinical indicator data allows a quantitative assessment of the impact of increased emergency department resource allocation.

Ultrasensitive Enzyme Immunoassays for Inhibins and Activins

The “Monash” radioimmunoassay for inhibin (1) provided a tool for numerous physiological studies (2). However, it gradually became apparent that this assay was unable to discriminate between dimeric bioactive inhibin forms and various forms of the free alpha subunit that occur in large amounts in body fluids (3). It became popular in publications to refer to the material measurable by the Monash assay as “immunoreactive” inhibin to acknowledge the possibility that the assay might not accurately measure the levels of bioactive inhibin.