It has been proposed that the inactivation of glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) is an obligatory step in the kidney, permitting binding of aldosterone to the mineralocorticoid receptor, and in the placenta, protecting the fetus from high circulating levels of maternal glucocorticoids. Both low and high affinity isoforms of 11 beta HSD are known to exist, with evidence accumulating that the former species (11 beta HSD1) does not fulfill criteria that would allow it to perform these physiological functions. We have recently cloned a high affinity isoform of the enzyme (11 beta HSD2) from a human kidney library and have shown this species to possess all of the characteristics predicted from whole cell studies. In the present study we have raised a polyclonal antibody (HUH23) to a synthetic peptide deduced from the carboxy-terminus of the protein. The immunopurified antibody recognized a single band at 41,000 daltons on Western blots of mammalian cells transfected with an expression plasmid containing 11 beta HSD2, slightly smaller than the predicted 44,140 daltons protein. A single band of identical size was also seen in blots of human kidney and placenta, suggesting post-translational processing of the enzyme. Immunohistochemical studies on frozen sections of human kidney showed strong 11 beta HSD2 immunoreactivity in the cortical distal convoluted tubules and collecting ducts. Strong staining was also observed in medullary tubules, which had the appearance of collecting ducts and the thick ascending limb of Henle's loop. Staining of medium intensity was observed in vascular smooth muscle cells. Epithelial cells of glomeruli showed weak but detectable reactivity with HUH23. In the placenta, HUH23 antibody immunoreactivity was restricted to syncytial trophoblast cells in which strong staining was observed. These results suggest that the 11 beta HSD2 enzyme colocalizes with the mineralocorticoid receptor in the distal nephron where it allows aldosterone to occupy its physiological receptor. Furthermore, 11 beta HSD2 is also ideally situated in the placenta to protect the fetus from high circulating levels of maternal glucocorticoids.

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The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) confers specificity on the renal mineralocorticoid receptor by inactivating glucocorticoids. Mutations in this gene give rise to the syndrome of apparent mineralocorticoid excess, a congenital condition characterized by sodium retention, severe hypertension, and often by growth retardation. It is not known whether 11 beta HSD2 or another enzyme confers specificity in nonrenal sodium transporting epithelia, such as those in the sweat gland, salivary gland, and gastrointestinal tract. We previously have used the HUH23 antibody to localize 11 beta HSD2 in the human kidney, vascular smooth muscle cells, and placenta. In the present study, we have examined a range of human epithelia for the presence of 11 beta HSD2. In the skin, staining was seen in eccrine sweat glands and arterioles, whereas weak HUH23 immunostaining was observed in the epidermis. Staining was absent from sebaceous glands and hair follicles. In the parotid gland, the 11 beta HSD2 enzyme was present in striated and excretory ducts, whereas in the submandibular gland, it was found in striated and interlobular ducts. Acini, adipocytes, and associated tumor tissue did not stain with the HUH23 antibody. In the gastrointestinal tract, HUH23 stained ileal enterocytes, colonic absorptive cells, and epithelial goblet cells, whereas the rectum contained areas of staining and nonstaining absorptive cells. Gastrointestinal structures, such as the lamina propria, Peyer's patch, and goblet cells within the crypts of Lieberkuhn did not stain with the antibody. This study demonstrates the presence of 11 beta HSD2 in nonrenal sodium-transporting epithelia and describes a range of tissues affected in the syndrome of apparent mineralocorticoid excess.

The "Applied Simulations and Integrated Modelling for the Understanding of Harmful Algal Blooms" (Asimuth) project sought to develop a harmful algal bloom (HAB) alert system for Atlantic Europe. This was approached by combining, at a national or regional level, regulatory monitoring phytoplankton and biotoxin data with satellite remote sensing and other information on current marine conditions, coupled with regional scale models that included a representation of HAB transport. Synthesis of these products was achieved by expert interpretation within HAB risk alert bulletins that were prepared on a regular basis (typically weekly) for use by the aquaculture industry. In this preface to the Asimuth Special Issue we outline the main HAB species of concern in the region and the strengths and limitations of different methodologies to provide early warning of their blooms.

The findings of increased gene and protein expression of PDGF in renal biopsies from patients with diabetic nephropathy imply a potential role for this prosclerotic growth factor in the development of the progressive fibrosis that characterizes human diabetic kidney disease.