Sweat Gland Ducts Research Articles

Quick Review: Cystic Fibrosis

Quick Review: Cystic Fibrosis

Spatially confined and temporally resolved refractive index and scattering evaluation in human skin performed with optical coherence tomography.

In the present applications of optical coherence tomography (OCT), parameters besides pure morphology are evaluated in skin tissue under in vivo conditions. Spatially mapped refractive indices and scattering coefficients may support tissue characterization for research and diagnostic purposes in cosmetics/pharmacy and medicine, respectively. The sample arm of our OCT setup has been arranged to permit refractive index evaluation with little mechanical adjustment of a lens within the objective. A simple algorithm has been derived. Known from atmospheric work, the Klett algorithm [J. D. Klett, "Stable analytical inversion solution for processing LIDAR returns," Appl. Opt. 20(2), 211-220 (1981)] has been applied to the same data set for retrieval of scattering coefficients. Both parameters have been measured in layered structures in skin like stratum corneum, epidermis and dermis. Significant water content in a localized sweat gland duct has been observed by refractive index evaluation. Time studies over 1.5 h permitted a first understanding about physiological changes in skin which are not obtainable by intrusive methods.

100 MHz sonography in the visualization of the palmar stratum corneum after application of various creams and ointments

To visualise the effects of different topically applied substances on the stratum corneum in vivo by means of sonography, it is necessary to have an ultrasound unit with a much higher resolution than provided for by the 20 MHz scanners currently used in dermatology. We developed a workstation with a highly focussed transducer with a large bandwidth, providing a resolution of 9 microns axially and 27 microns laterally. Using this ultrasound unit, we investigated the effects of different creams and ointments in 10 persons on the palmar side of the distal finger segments (vaseline, a water-in-oil-emulsion, an oil-in-water-emulsion, 10% urea in an oil-in-water-emulsion and water). Sonograms were taken after an occlusion period of 0, 30, 60, 120, 180 and 240 min. In 100 MHz sonograms of palmar skin, the stratum corneum is represented as an echo-poor band below the echo-rich entry echo--the correlate of the interface between the coupling water and the horny layer. The echo-poor band is traversed by echo-rich coils, representing eccrine sweat gland ducts. It is separated by an echo-rich line from the viable epidermis, which is echo-poor as well. The topically applied substances differ in the time course of the swelling of the stratum corneum. After longer application all externals cause a significant thickening of the stratum corneum (p < 0.005) and a reduction of the echogenicity of the skin entry echo due to altered impedance. 100 MHz sonography is well suited to visualise and quantify the effects of externals on the stratum corneum in vivo.

Sonography of the Skin at 100 MHz Enables In Vivo Visualization of Stratum Corneum and Viable Epidermis in Palmar Skin and Psoriatic Plaquesy1

A main drawback of 20-25 MHz ultrasound units for skin imaging is their limited resolution. We used a transducer with a center frequency of 95 MHz and a resolution of 8.5 microm axially and 27 microm laterally - an almost 10-fold increase compared with 20 MHz. By means of a new scanning technology we reached a depth of field of 3.2 mm. We examined normal palmar skin, normal glabrous skin on the abdomen, the upper back, the calf and the dorsal forearm, and 35 lesions of psoriasis vulgaris. From 11 psoriatic plaques biopsies were taken for correlation with the sonograms. In normal palmar skin, the horny layer is represented as an echopoor band below the skin entry echo, traversed by echorich coils, which correspond to eccrine sweat gland ducts. The thickness of this band significantly increases after occlusive application of petrolatum. Its lower border is defined by an echorich line, representing the stratum corneum/stratum Malpighii-interface. Underneath, a second echopoor band is visible, which corresponds to the viable epidermis plus the papillary dermis, bordered by the scattered echo reflexes of the reticular dermis. This band is also visible in glabrous skin; however, the stratum corneum cannot be detected. In psoriatic lesions, the thickened horny layer appears echorich; after application of petrolatum, its echodensity decreases. Below, the acanthotic epidermis plus the dermis with the inflammatory infiltrate are represented as an echopoor band. There is an excellent correlation between the sonometric thickness of this band and the histometric thickness of the acanthosis plus the infiltrated dermis. Our results show that 100 MHz sonography is a valuable tool for in vivo examination of the upper skin layers.

Palmoplantar pustulosis: a clinical and immunohistological study.

Pustulosis palmoplantaris (PPP) is a common chronic skin disease, which is very resistant to treatment. It is not known why the lesions are located in the palms and soles. There are few studies of the disease and in particular studies of the histology. Fifty-nine patients with PPP answered a questionnaire concerning their medical history and 39 of them were clinically examined. Biopsy specimens were taken from involved skin in 22 of the 39 patients and studied immunohistologically for tryptase+ mast cells, EG2+ eosinophils, lipocalin+ neutrophils and CD3+ T lymphocytes. The sweat gland and sweat duct were visualized with AE1/AE3 antibody (cytokeratins 1-8, 10, 14/15, 16, 19). In addition to neutrophils in the pustule and lymphocytes in the upper dermis, there were also large numbers of mast cells and eosinophils in the subpustular area. Numerous eosinophils were present in the pustule. The epidermal part of the eccrine duct was not detectable in any of the specimens from patients with PPP but was present in all of the nine control persons (including two smokers). The results indicate that the acrosyringium is involved in the inflammation and also that mast cells and eosinophils participate in a hitherto unknown way. Of the 39 patients clinically examined, two had previously diagnosed thyroid disease and two had gluten hypersensitivity. Seventeen had one or several abnormal serum concentrations of thyroid-stimulating hormone, thyroxin, antibodies against thyroglobulin or thyroperoxidase and 10 had immunoglobulin (Ig) A antibodies to gliadin. The mean +/- SD for serum IgA and for eosinophil cationic protein was increased. From the questionnaire the most notable finding was that 56 of the 59 patients had been or still were smokers, all of whom had started smoking before the first signs of PPP. We hypothesize that the acrosyringium might be the target for the inflammation and that PPP is linked to autoimmune thyroid disease and smoking.

Regulation of ion content in primary cultures from reabsorptive ducts of human sweat glands studied by X-ray microanalysis.

X-ray microanalysis was used to investigate whether cAMP- and/or Ca2+-activated regulation of chloride and potassium efflux is expressed in primary cultures of sweat gland duct cells. The effects of extracellular UTP and ATP on the duct cells, and the signalling system involved in the response to ATP was also studied. Primary cultures from duct cells of human sweat glands responded to 1 microM carbachol, 2 microM of the Ca2+ ionophore A23187, or 5 mM 8-bromo-cAMP stimulation for 5 min, resulting in a decrease in cellular Cl and K concentrations. 50 microM 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB), a Cl- channel blocker, can inhibit the decrease in Cl concentration induced by cAMP. Extracellular (200 microM) ATP caused a decrease of Cl and K in cultured duct cells, while (200 microM and 2 mM) UTP was ineffective. Both the phosphoinositidase C inhibitor U73122 (10 microM) and the absence of extracellular Ca2+ abolished the ATP-induced decrease in Cl and K content. Alloxan (1.25 mM), an adenylate cyclase inhibitor, had an inhibitory effect on the response to ATP. The decrease in K, but not in Cl, content in the cells elicited by ATP was blocked by prior incubation with 100 ng/ml pertussis toxin, indicating the coupling of ATP to pertussis toxin-sensitive G-proteins. In conclusion, both Ca2+- and cAMP-dependent Cl- permeability is present in primary cultures from duct cells of human sweat gland. The response to ATP can be mediated both by Ca2+- and by cAMP-dependent pathways, and is coupled to pertussis toxin-sensitive G-proteins.

Colocalization of 11 beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia.

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) has been shown to confer specificity on mineralocorticoid receptors (MR) by inactivating glucocorticoids. In the present study we examined the colocalization of 11 beta HSD2 and MR in various exocrine and secretory glands by immunostaining of serial mirror tissue sections with subsequent computerized image analysis. Both 11 beta HSD2 and MR proteins were expressed in the same cells in the distal convoluted tubules, Henle's loop, and collecting tubules of the kidney and the absorptive epithelia of duodenum, jejunum, ileum, colon, and excretory ducts of anal and esophageal glands. Significantly, 11 beta HSD2 and MR immunoreactivity also colocalized in the respiratory tract, in collecting ducts of the tracheal and bronchial glands, ciliated bronchial epithelial cells, and type II alveolar epithelial cells, suggesting important and unexpected roles for mineralocorticoids in the lung. In the skin, 11 beta HSD2 and MR were present only in excretory ducts of eccrine sweat glands, but not in sebaceous or apocrine glands. In eccrine glands, MR immunoreactivity was present in the basal cells of excretory ducts, while 11 beta HSD2 immunoreactivity was localized in the luminal cells. Neither 11 beta HSD2 nor MR proteins were expressed in the lacrimal gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, or ureter. These results indicate that 11 beta HSD2 protein colocalizes with MR protein in the great majority of sodium-transporting epithelia involved in serous secretion and supports the proposal that 11 beta HSD2 is a pivotal determinant of mineralocorticoid receptor occupancy in man. Furthermore, our demonstration of colocalization in discrete areas of the lung suggests that mineralocorticoid agonists or antagonists, and/or inhibitors of 11 beta HSD2, may have unexpected applications in respiratory disease.

The cystic fibrosis transmembrane conductance regulator as a marker of human pancreatic duct development

BACKGROUND & AIMS: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance adenosine 3',5'-cyclic monophosphate (cAMP)-activated chloride ion channel found in the apical membranes of epithelia within the pancreas, airway, intestine, bile duct, sweat gland, and male genital ducts. Pancreatic insufficiency is a feature of about 85% of patients with cystic fibrosis and is believed to be caused by pancreatic autolysis after pancreatic duct obstruction. The aim of this study was to investigate the expression of CFTR in the pancreas from early development to postnatal life to establish whether the CFTR plays a key role in development of the pancreatic duct epithelium. METHODS: Expression of CFTR from the start of the mid- trimester of human development through term to adult life by messenger RNA (mRNA) in situ hybridization was examined. RESULTS: CFTR mRNA is detected throughout the pancreatic duct epithelium and its pattern of expression follows the differentiation of the duct system. CONCLUSIONS: CFTR is a valuable marker of human pancreatic duct cell development and differentiation. (Gastroenterology 1997 Sep;113(3):914-9)

Localization of monocyte chemotactic and activating factor ( [formula omitted]) in psoriasis

The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic factor towards monocytes, is produced by several cell types present in the skin. The in situ presence of MCAF MCP-1 protein in the skin has, however, not yet been established. Using immunohistochemical techniques we have investigated the distribution of MCAF in skin from patients with different types of psoriasis and normal healthy volunteers. We report the novel finding that psoriasis has strong positive immunostaining for MCAF located to all the layers of the epidermis, except the stratum granulosum, in pustular, guttate and chronic plaque psoriasis. In the dermis, infiltrating cells in the perivascular aggregates and the blood vessels stained positive for MCAF. No significant differences were observed between the different subtypes of psoriasis except that strongly positive infiltrating cells were observed in the epidermal pustules in pustular psoriasis. In normals positive staining was observed in all the layers of the epidermis and in a few perivascular cells and blood vessels in the dermis. Where present in normal and diseased skin, eccrine ducts of sweat glands and sebaceous glands stained positive for MCAF. Arrector pili muscles were in all cases negative. These findings are consistent with a role for MCAF in attracting inflammatory cells, including monocytes, into the skin in psoriasis.

Porocarcinoma of the heel: A case report with unusual histologic features

BACKGROUND Eccrine porocarcinoma is an uncommon neoplasm of the intraepidermal sweat gland duct. METHODS A case of porocarcinoma of the right heel in a male age 51 years is described with a review of pertinent literature. The surgically excised neoplasm was evaluated by routine histology and transmission electron microscopy. RESULTS The porocarcinoma showed extensive nuclear pleomorphisms with frequent, multinucleated tumor giant cells, focal epidermotrophic spread within the epidermis, a peripheral, eccrine syringofibroadenoma-like growth pattern, and an origin in a contiguous eccrine poroma. Ultrastructurally, the squamous tumor cells contained rare intracytoplasmic lumens. CONCLUSIONS The extensive nuclear pleomorphism with frequent tumor giant cells was an unusual feature of the porocarcinoma. Its epidermotrophic spread within the epidermis and its origin in a contiguous eccrine poroma supported the diagnosis of porocarcinoma. The eccrine syringofibroadenoma-like growth pattern in the periphery of the tumor was a unique and previously undescribed feature of the porocarcinoma. The presence of intracytoplasmic lumens in squamous tumor cells mimicked embryonic development of the intraepidermal sweat gland duct. Cancer 1996;78:751-7.

Production of Heparin-Binding Epidermal Growth Factor–like Growth Factor (HB-EGF) at Sites of Thermal Injury in Pediatric Patients

Fluids that accumulate at wound sites may be an important reservoir of growth factors that promote the normal wound healing response. The presence of heparin-binding growth factors was studied in burn wound fluid (BWF) from 45 pediatric patients who had sustained partial thickness burns. One of the growth factors present was similar to platelet-derived growth factor (PDGF) based on its heparin affinity, inhibition of bioactivity by a PDGF antiserum, and detection in a PDGF-AB enzyme-linked immunosorbent assay. A second growth factor was identified as heparin-binding epidermal growth factor-like growth factor (HB-EGF) based on its heparin affinity, competition with 125I-labeled epidermal growth factor (EGF) for EGF receptor binding, and recognition in biological assays and Western blots by two HB-EGF antisera. Amino acid sequence analysis of one form of this second growth factor verified its identity as an N-terminally truncated form of HB-EGF. Immunohistochemical analysis of partial thickness burns demonstrated the presence of HB-EGF in the advancing epithelial margin, islands of regenerating epithelium within the burn wound, and in the duct and proximal tubules of eccrine sweat glands. HB-EGF in the surface epithelium of burn wounds was uniformally distributed, whereas it was restricted to the basal epithelium in nonburned skin. These data support a role for PDGF and HB-EGF in burn wound healing and suggest that the response to injury includes deposition of HB-EGF and PDGF into blister fluid and a redistribution of HB-EGF in the surface epithelium near the wound site.

Epidermal cell proliferation and terminal differentiation in skin organ culture after topical exposure to sodium dodecyl sulphate

Epidermal cell proliferation and differentiation were investigated in vitro after exposure to the anionic surfactant sodium dodecyl sulfate (SDS). Human skin organ cultures were exposed topically to various concentrations of SDS for 22 h, after which the irritant was removed. Cell proliferation was measured immunohistochemically by incorporation of bromodeoxyuridine (BrdU) into the DNA of cells during S-phase, while the expression of transglutaminase and involucrin were used as markers of differentiation. Cell proliferation was moderately increased at concentrations of SDS that did not affect the histomorphology (0.1% and 0.2% SDS). A marked increase of cell proliferation was observed 22 to 44 h after removal of SDS at a concentration (0.4%) that induced slight cellular damage. Exposure of human skin organ cultures to a toxic concentration of SDS 91.0% led to decreased cell proliferation. Transglutaminase and involucrin were expressed in the more basal layers of the epidermis after exposure to 0.4% or 1.0% SDS. Moreover, intra-epidermal sweat gland ducts were positive for transglutaminase at these irritant concentrations. These in vitro data demonstrate that SDS-induced alterations of epidermal cell kinetics, as described in vivo are at least partly due to local mechanisms and do not require the influx of infiltrate cells. However, we were unable to relate to altered cell kinetics to the release of interleukin-1 alpha or interleukin-6. Furthermore, supplementation of the culture medium with 12-hydroxyeicosantetraenoic acid did not affect epidermal cell proliferation. Rabbit skin cultures appeared more sensitive to SDS than human skin. At nontoxic doses, the irritant induced an increase of epidermal cell proliferation, similar to that observed in human skin discs.

Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase.

The expression of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11HSD) activity has been investigated in the epidermis and appendages of the human skin. Aldosterone binds to MR and regulates sodium transport in tight epithelia. Mineralocorticoid selectivity is achieved through coexpression of MR and 11HSD, which prevents permanent MR occupancy by glucocorticoids. Some forms of hypertension may involve abnormalities of MR and/or 11HSD. However, their direct assessment in humans remains difficult in the kidney or colon. This led us to explore this system in human skin easily accessible to biopsy. In situ hybridization with specific MR complementary ribonucleic acid probes and immunohistochemistry using three different anti-MR antibodies showed that MR was expressed at both the messenger ribonucleic acid and protein levels in the keratinocytes of the epidermis, in the sweat and sebaceous glands, and in the hair follicles. A significant 11HSD activity was found in isolated sweat gland ducts (5 fmol/3-mm length.10-min incubation with 10 nmol/L corticosterone as substrate) and was very low in the epidermis. In both structures, reductase activity was 10 times lower than that of dehydrogenase. Studies on the cofactor specificity of the enzyme showed a nicotinamide-adenine-dinucleotide preference in sweat glands, contrasting with a nicotinamide-adenine-dinucleotide phosphate dependence in epidermis. Human skin appears as a new target for aldosterone because it coexpresses MR and 11HSD. Our findings present the possibility to explore the functionality of the MR system in human tissue and its implications in various physiopathological situations.

Immunocytochemical Localization of Androgen Receptors in the Scalp of the Stumptail Macaque Monkey, a Model of Androgenetic Alopecia

The purpose of this study was to identify the distribution of androgen receptors in the bald and hairy scalp of adult male and female stumptail macaque monkeys by light microscopic biotin-avidin immunocytochemistry with a highly purified rat monoclonal antibody against the cloned human androgen receptor. Consistent, intense nuclear and minimal cytoplasmic immunostaining was observed in several distinct cell populations of the pilosebaceous unit including the dermal papilla, hair epithelium, outer root sheath, dermal sheath, and sebaceous gland. A similar distribution of androgen receptors was found in miniaturized and terminal anagen and telogen follicles of the bald and hairy scalp, respectively. Binding of androgen receptor antibody was also detected in dermal fibroblasts, basal and intermediate layers of the interfollicular epidermis, and duct and glandular cells of eccrine sweat glands. This investigation demonstrates the presence of androgen receptors in the pilosebaceous unit of the scalp of the stumptail macaque and also shows that their distribution is comparable to that previously reported for humans.

5'-Adenylylimidodiphosphate does not activate CFTR chloride channels in cell-free patches of membrane.

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel requires both phosphorylation of its R domain and the presence of nucleoside triphosphates for activation. Our previous work suggested that hydrolysis of nucleoside triphosphates may be required to support channel activity. However, recent studies have suggested that the nonhydrolyzable adenosine triphosphate analogue, 5'-adenylylimidodiphosphate (AMP-PNP), may support some Cl- channel activity in sweat gland duct epithelia in the presence of low ATP concentration and in Cl- channels associated with expression of the P-glycoprotein multidrug resistance transporter. To examine the effect of AMP-PNP, we applied it to the cytosolic surface of phosphorylated CFTR Cl- channels contained in excised, cell-free patches of membrane. We found that preparations of 10 mM AMP-PNP opened phosphorylated CFTR Cl- channels. However, this effect was due to contaminating ATP: high-pressure liquid chromatography analysis of AMP-PNP demonstrated that 10 mM AMP-PNP could contain up to 50 microM ATP, which could account for the observed stimulation of CFTR Cl- channel activity. When contaminating ATP was hydrolyzed with hexokinase, AMP-PNP was unable to support CFTR channel activity. AMP-PNP (10 mM) also failed to attenuate or potentiate the current induced by 0.3 mM ATP. These results suggest that AMP-PNP has no direct effect on CFTR Cl- channels.

Glycosyl phosphatidylinositol membrane anchoring of melanotransferrin (p97): apical compartmentalization in intestinal epithelial cells

Melanotransferrin (p97) is an iron-binding membrane glycoprotein with 40% homology to transferrin and lactoferrin. It was first identified on the basis of its high level of expression in melanoma cells, as compared to normal melanocytes. It is also present in many cultured cell types. In normal tissues, p97 is expressed in fetal intestine, umbilical cord, sweat gland ducts and liver sinusoidal lining cells. Kinetic studies in melanoma cells have suggested that p97 plays a role in iron metabolism. We have examined expression of p97 in cell lines derived from human colorectal carcinomas which express a differentiated phenotype. When polarized, these cells showed a preferred apical distribution of p97, as demonstrated by immunohistochemistry, immune electron microscopy and domain-selective biotinylation. Correspondingly, p97 was only found on the apical brush border of epithelial cells in the fetal intestine. p97 was shown to be anchored to the membrane through a glycosyl phosphatidylinositol moiety by treatment with phophatidylinositol-specific phospholipase C (PI-PLC) and labeling with [14C]ethanolamine. These observations provide a basis for the elucidation of the physiological role of p97 in iron metabolism and its possible role in cell proliferation and malignant cell transformation.

Lectin‐binding profiles for normal skin appendages and their tumors

A histochemical investigation of lectin-binding sites was carried out on formalin-fixed paraffin-embedded sections of 60 skin appendage tumors and adjacent normal skin appendages, using four different biotinylated lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), and Ulex europaeus agglutinin-1 (UEA-1), and avidin-biotin-horseradish peroxidase labeling. In the secretory segments of eccrine sweat glands, the superficial dark cells showed strong cytoplasmic staining with UEA-1, whereas DBA and SBA strongly stained the plasma membranes of basal clear cells. The acinar cells of apocrine sweat glands revealed sporadic apical membrane staining with all four lectins. In some cases, the luminal membranes of sweat gland ducts showed apical membranous staining with all four lectins. In the hair follicles, the inner root sheath was positive for all four lectins, and the outer root sheath was stained by PNA. The sebaceous ducts, as well as the outer root sheath at the level of sebaceous duct insertion, were also labeled by all four lectins. Sebaceous lobules showed cytoplasmic and membrane staining of mature sebocytes with PNA and SBA. Although sweat gland tumors revealed differences in lectin binding when compared to their corresponding normal tissues, the lectin-binding pattern of pilosebaceous tumors was analogous to the pilosebaceous apparatus.

Perianal Paget's disease: report of five cases

Paget's disease of the anus is a rare perianal disorder. The condition is often associated with underlying invasive carcinoma. The prognosis is poor when rectal adenocarcinoma is present. Five own cases of perianal Paget's disease are presented. In two of our cases an underlying adenocarcinoma was found in the anorectum. Adenocarcinoma is sweat gland ducts was found in one case. One patient developed an adenocarcinoma in the anorectal junction four years after the Paget diagnose. In only one of our cases no underlying adenocarcinoma was found.

Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages.

Biotinylated hyaluronan (HA) binding complex (HABC) from bovine articular cartilage proteoglycan was used as a histological probe to study the localization of HA in human skin. The distribution of HA was compared with its presumptive cell surface receptor, CD44, using monoclonal antibodies. In epidermis both HA and CD44 were found in the basal and spinous cell layers, but neither was present in the stratum granulosum and stratum corneum. In the keratinizing parts of hair follicles, i.e. in the outer and inner epidermal root sheath, pilosebaceous duct and the actual hair, HA and CD44 were found between the vital but not the terminally differentiated cells. In the sebaceous glands a small amount of HA was found around all cells, whereas CD44 was restricted to the basal cell layer. The secretory acini of the sweat glands stained intensively with anti-CD44 antibodies but only weakly with HABC. In the sweat gland, CD44 was localized on the basal and lateral surfaces of the clear cells, whereas the dark cells and the myoepithelial cells were negative. Both the lower and upper layers of the sweat gland ducts showed a faint but constant staining for CD44 and only minor amounts of HA. While in the keratinizing skin epithelia both HA and its CD44 receptor showed an intense staining with a close co-distribution, in the sweat and sebaceous glands their distribution patterns were not similar. It is suggested that in epithelia with divergent differentiation programs the functions of CD44 and HA may be different.

Expression of the cystic fibrosis gene in human development

The specialised epithelia lining the respiratory tract, pancreatic ducts, male genital ducts and sweat gland ducts are defective in the severe inherited disease, cystic fibrosis (CF). We have looked at the expression of the CF gene in human fetal tissues to throw light on the development of function in specialised ductal epithelia and to determine the age of onset of the CF disease process. The CF gene is already seen to be transcribed in mid-trimester fetal lung, pancreas and male genital ducts. Hence, by this developmental stage, and before they are fully differentiated, these epithelia have the capability to perform important transport functions. Epithelial cell cultures derived from fetal pancreas and male genital ducts maintain expression of the CF gene in vitro and so form good models for analysing CF gene function and differentiation of these specialised epithelia.