Oral mucosal melanoma in situ: a case report and review of the literature.

Oral mucosal melanoma is a rare presentation of malignant melanoma with a 5-year survival rate of only 15%. Oral mucosal melanoma in situ (OMMIS) is its assumed precursor. This report describes one of only 20 documented cases of OMMIS and outlines how early clinical recognition resulted in prompt histopathological diagnosis and subsequent complete surgical excision. A literature review of existing reported cases, their management, and latest outcomes was also performed, highlighting this rare condition for consideration in the differential diagnosis of pigmented oral pathologies.

Simultaneous detection and image capture of biological evidence using a combined 360° camera system with single wavelength laser illumination.

Forensic investigators frequently utilise light sources to detect and presumptively identify biological evidence. The instrumentation typically deploys single or multiple wavelength exposures at various intensities, which interact with constituents of biological material, initiating fluorescence or improving contrast between the material and substrate. Documentation using sketches and/or photographic approaches follows detection, which are essential for scene reconstruction. Recent research has demonstrated the simultaneous detection and capture of biological evidence using a 360° camera system combined with an alternate light source exhibiting broad wavelength ranges of light. Single wavelength light sources reportedly offer enhanced sensitivity, due to the increased light intensity and narrower bandwidth of light, although their combined use with a 360° camera system has not yet been explored. Samples of human blood, semen, saliva, and latent fingermarks were deposited on to a variety of substrates. A 360° camera system combined with a laser light source was used to detect and capture the samples. Ten participants were asked to detect the samples on images of the substrates without ground truth knowledge. It was possible to detect and capture biological evidence, although success varied according to substrate colour and light intensity. Advantageously, presumptive screening for biological fluids and the simultaneous location and visualisation of such evidence as part of a 360° panorama of the scene for contextual purposes was permitted. There was no fluorescent response from the fingermarks, although the oblique lighting effects appeared sufficient to aid mark detection in some circumstances. The use of single wavelength illumination clearly facilitates identification of a range of forensically important material. When coupled with a 360-degree camera, this allows for simultaneous identification and recording of such evidence in the context of the whole environment.

On the Hydrodynamics of Anomalocaris Tail Fins.

Anomalocaris canadensis, a soft-bodied stem-group arthropod from the Burgess Shale, is considered the largest predator of the Cambrian period. Thanks to a series of lateral flexible lobes along its dorso-ventrally compressed body, it is generally regarded as an efficient swimmer, well-adapted to its predatory lifestyle. Previous theoretical hydrodynamic simulations have suggested a possible optimum in swimming performance when the lateral lobes performed as a single undulatory lateral fin, comparable to the pectoral fins in skates and rays. However, the role of the unusual fan-like tail of Anomalocaris has not been previously explored. Swimming efficiency and maneuverability deduced from direct hydrodynamic analysis are here studied in a towing tank facility using a three-vane physical model designed as an abstraction of the tail fin. Through direct force measurements, it was found that the model exhibited a region of steady-state lift and drag enhancement at angles of attack greater than 25° when compared with a triangular-shaped reference model. This would suggest that the resultant normal force on the tail fin of Anomalocaris made it well-suited for turning maneuvers, giving it the ability to turn quickly and through small radii of curvature. These results are consistent with an active predatory lifestyle, although detailed kinematic studies integrating the full organism, including the lateral lobes, would be required to test the effect of the tail fin on overall swimming performance. This study also highlights a possible example of evolutionary convergence between the tails of Anomalocaris and birds, which, in both cases, are well-adapted to efficient turning maneuvers.

On the high-lift characteristics of a bio-inspired, slotted delta wing.

A bio-inspired, slotted delta wing was abstracted from a multi-vane propulsor geometry ubiquitous in nature, and analysed to investigate aerodynamic performance during acceleratory and steady-state motions. Evolutionary convergence of slotted geometries in nature suggests an aerodynamic benefit in manoeuvrability, as exemplified in the fins and wings of a broad range of extant and extinct swimmers and flyers, respectively. Through direct force measurements and stereoscopic particle image velocimetry, it was found that the abstracted, slotted geometry exhibited a region of steady-state lift and drag enhancement at angles of attack greater than 25° when compared to a reference profile based on a delta-wing plate. At an angle of attack of 30°, the lift and drag measured on the abstracted model were 15.3% and 17.0% higher than the delta-wing model, respectively. In contrast, these shapes showed little difference in performance during an acceleration-from-rest manoeuvre. It was found that the secondary and tertiary vanes of the abstraction encouraged the formation of additional leading-edge vorticity. The formation of these additional leading-edge vortices was confirmed by an increase in streamwise circulation measured near each effective leading edge along the length of the chord. As such, this configuration provides lift augmentation appropriate for the development of high-performance control surfaces.

[Total laryngopharyngectomy and reconstruction with a jejunum speech siphon : A case report]. / Totale Laryngopharyngektomie und Rekonstruktion mit Jejunumsprechsiphon : Fallbericht.

Advanced laryngeal and hypopharyngeal carcinomas are associated with a poor prognosis and a pronounced loss of quality of life due to impairment of the swallowing and voice function. The fundamental therapeutic challenge is successful tumor control with concomitant rehabilitation of swallowing and voice functions. Further objectives are a low complications rate (fistula, aspiration) and prompt transfer to the adjuvant radio-oncologic therapy. With these factors in mind, the microvascular anastomosed jejunum speech siphon with a biventer rein has proven to be an effective method of reconstruction following extensive circular laryngopharyngeal resections. In this case report, a typical operative and postoperative course is presented, as are the functional results.

Prenatal programming by testosterone of hypothalamic metabolic control neurones in the ewe.

Ewes treated prenatally with testosterone develop metabolic deficits, including insulin resistance, in addition to reproductive dysfunctions that collectively mimic polycystic ovarian syndrome (PCOS), a common endocrine disease in women. We hypothesised that metabolic deficits associated with prenatal testosterone excess involve alterations in arcuate nucleus (ARC) neurones that contain either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC). Characterisation of these neurones in the ewe showed that immunoreactive AgRP and POMC neurones were present in separate populations in the ARC, that AgRP and POMC neurones co-expressed either neuropeptide Y or cocaine- and amphetamine-regulated transcript, respectively, and that each population had a high degree of co-localisation with androgen receptors. Examination of the effect of prenatal testosterone exposure on the number of AgRP and POMC neurones in adult ewes showed that prenatal testosterone excess significantly increased the number of AgRP but not POMC neurones compared to controls; this increase was restricted to the middle division of the ARC, was mimicked by prenatal treatment with dihydrotestosterone, a non-aromatisable androgen, and was blocked by co-treatment of prenatal testosterone with the anti-androgen, flutamide. The density of AgRP fibre immunoreactivity in the preoptic area, paraventricular nucleus, lateral hypothalamus and dorsomedial hypothalamic nucleus was also increased by prenatal testosterone exposure. Thus, ewes that were exposed to androgens during foetal life showed alterations in the number of AgRP-immunoreactive neurones and the density of fibre immunoreactivity in their projection areas, suggestive of permanent prenatal programming of metabolic circuitry that may, in turn, contribute to insulin resistance and an increased risk of obesity in this model of PCOS.

Feeding motivation on the incidence of floor eggs and extraneously calcified eggs laid by broiler breeder hens.

1. Commercial broiler breeder hens lay many eggs on the floor rather than in nest boxes provided. A study was conducted to determine whether feeding feed-restricted broiler breeder hens during the sitting phase of nesting results in a higher incidence of floor eggs and/or retained eggs. 2. Sixty broiler breeder females (Ross 308) were randomly assigned to 6 deep litter pens containing 10 nest-boxes. At 35 weeks of age and for 9 weeks, feed was distributed to all pens at lights-on every second day (fed normally, FN). On alternate days (feeding delay, FD), feed was distributed when 2-3 hens/pen were sitting in a nest box. Behaviour was sampled at 41 weeks of age, for 26 d. Eggs and egg location data were collected daily, and eggs were scored for extra-cuticular calcium. 3. Of 81 instances in which the hen was sitting firmly in a nest box at the time of feeding, on 80 instances the hen left the nest-box to feed, and on one instance the hen laid her egg then exited to the feeder. Of these 80 instances, on 58 occasions the hen returned to a nest-box to lay her egg; on 12 the hen returned to the nest-box but laid no egg; on 7 the hen did not return to the nest box and laid no egg; and on three the hen laid her egg on the floor. 4. Mean floor egg percentage was 13·3 ± 3·2% on FN and 13·3 ± 4·7% on FD days; these did not differ significantly. 5. The mean extra-cuticular calcium score over all pens was 0·9 ± 0·06 on FN days and 1·2 ± 0·06 on FD days; these differed significantly. 6. In conclusion, feeding broiler breeder hens during nesting results in a conflict between feeding and nesting motivation and higher numbers of extraneously calcified eggs, but does not result in a significant increase in floor eggs even though nesting hens will leave the nest box for food.

The lived experience of depression among culturally Deaf adults.

Culturally Deaf adults lost hearing at early ages, communicate primarily in American Sign Language (ASL), and self-identify as culturally Deaf. Communication barriers lead to isolation, low self-esteem, abuse, and inadequate health care. Screening Deaf patients for depressive symptoms poses challenge. Nurses are rarely familiar with ASL, and depression screening tools aren't easily translated from English to ASL. Consequently, Deaf adults are not adequately screened for depression. Qualitative interviews were conducted with culturally Deaf adults, and certified interpreters helped to enhance understanding. Text was generated from interview transcriptions and researcher observations. No novel depressive symptoms were described. Various ASL signs were used to represent depression; two participants used a unique gesture that had no meaning to others. Childhood experiences leading to depression included sexual or physical abuse, feeling ostracized from family and like a burden. Suicidal gestures communicated severity of depression. Adults felt interpreters were unwelcome during mental health encounters. No participants were asked about depressive symptoms despite frank manifestations of depression. Study describes antecedents and consequences of depressive symptoms among Deaf adults. Understanding symptom manifestations and challenges experienced by Deaf patients helps identify those at risk for depression, thereby reducing morbidity and mortality.

Take action to prevent diabetes--the IMAGE toolkit for the prevention of type 2 diabetes in Europe.

When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.

One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Novel nuclear corticosteroid binding in rat small intestinal epithelia.

When small intestinal epithelial cells are incubated with [(3)H]corticosterone, nuclear binding is displaced neither by aldosterone nor RU-28362, suggesting that [(3)H]corticosterone is binding to a site distinct from mineralocorticoid receptor and glucocorticoid receptor. Saturation and Scatchard analysis of nuclear [(3)H]corticosterone binding demonstrate a single saturable binding site with a relatively low affinity (49 nM) and high capacity (5 fmol/microg DNA). Competitive binding assays indicate that this site has a unique steroid binding specificity, which distinguishes it from other steroid receptors. Steroid specificity of nuclear binding mirrors inhibition of the low 11beta-dehydrogenase activity, suggesting that binding may be to an 11beta-hydroxysteroid dehydrogenase (11betaHSD) isoform, although 11betaHSD1 is not present in small intestinal epithelia and 11betaHSD2 does not colocalize intracellularly with the binding site. In summary, a nuclear [(3)H]corticosterone binding site is present in small intestinal epithelia that is distinct from other steroid receptors and shares steroid specificity characteristics with 11betaHSD2 but is distinguishable from the latter by its distinct intracellular localization.

Corticosteroid receptors and 11beta-hydroxysteroid dehydrogenase isoforms in rat intestinal epithelia.

To evaluate the potential roles that both receptors and enzymes play in corticosteroid regulation of intestinal function, we have determined glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) expression in intestinal epithelial cells. GR and MR mRNA and receptor binding were ubiquitously expressed in epithelial cells, with receptor levels higher in ileum and colon than jejunum and duodenum. RNase protection analysis showed that 11beta-HSD1 was not expressed in intestinal epithelial cells, and enzyme activity studies detected no 11-reductase activity. 11beta-HSD2 mRNA and protein were demonstrated in ileal and colonic epithelia; both MR and GR binding increased when enzyme activity was inhibited with carbenoxolone. Duodenal and jejunal epithelial cells showed very little 11beta-HSD2 mRNA and undetectable 11beta-HSD2 protein; despite minor (<7%) dehydrogenase activity in these cells, enzyme activity did not alter binding of corticosterone to either MR or GR. These findings demonstrate the ubiquitous but differential expression of MR and GR in intestinal epithelia and that 11beta-HSD2 modulates corticosteroid binding to both MR and GR in ileum and proximal and distal colon but not in duodenum or jejunum.

Transcriptional activation by NF-kappaB requires multiple coactivators.

Nuclear factor-kappaB (NF-kappaB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-kappaB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-kappaB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-kappaB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-kappaB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.

The type I and type II 11beta-hydroxysteroid dehydrogenase enzymes.

Local tissue concentrations of glucocorticoids are modulated by the enzyme 11beta-hydroxysteroid dehydrogenase which interconverts cortisol and the inactive glucocorticoid cortisone in man, and corticosterone and 11-dehydrocorticosterone in rodents. The type I isoform (11beta-HSD1) is a bidirectional enzyme but acts predominantly as a oxidoreductase to form the active glucocorticoids cortisol or corticosterone, while the type II enzyme (11beta-HSD2) acts unidirectionally producing inactive 11-keto metabolites. There are no known clinical conditions associated with 11beta-HSD1 deficiency, but gene deletion experiments in the mouse indicate that this enzyme is important both for the maintenance of normal serum glucocorticoid levels, and in the activation of key hepatic gluconeogenic enzymes. Other important sites of action include omental fat, the ovary, brain and vasculature. Congenital defects in the 11beta-HSD2 enzyme have been shown to account for the syndrome of apparent mineralocorticoid excess (AME), a low renin severe form of hypertension resulting from the overstimulation of the non-selective mineralocorticoid receptor by cortisol in the distal tubule of the kidney. Inactivation of the 11beta-HSD2 gene in mice results in a phenotype with similar features to AME. In addition, these mice show high neonatal mortality associated with marked colonic distention, and remarkable hypertrophy and hyperplasia of the distal tubule epithelia. 11Beta-HSD2 also plays an important role in decreasing the exposure of the fetus to the high levels of maternal glucocorticoids. Recent work suggests a role for 11beta-HSD2 in non-mineralocorticoid target tissues where it would modulate glucocorticoid access to the glucocorticoid receptor, in invasive breast cancer and as a mechanism providing ligand for the putative 11-dehydrocorticosterone receptor. While previous homologies between members of the SCAD superfamily have been of the order of 20-30% phylogenetic analysis of a new branch of retinol dehydrogenases indicates identities of > 60% and overlapping substrate specificities. The availability of crystal structures of family members has allowed the mapping of conserved 11beta-HSD domains A-D to a cleft in the protein structure (cofactor binding domain), two parallel beta-sheets, and an alpha-helix (active site), respectively.

A prospective study of two intravenous catheter securement techniques in a skilled nursing facility.

A prospective, controlled study was undertaken in a skilled nursing facility to determine whether a sterile catheter securement device (StatLock i.v., Venetec International, Mission Viejo, CA) would provide better intravenous therapy outcomes than a standard securement technique. The StatLock-device resulted in significantly longer average catheter dwell times (3.95 days versus 2.45 days) and significantly fewer total complications (65 versus 155). In addition, the securement device reduced the total time spent managing a vascular access device by 13.5 minutes per patient. Thus, the StatLock i.v. device improved overall clinical outcomes of i.v. therapy and the quality of care.

Nuclear integration of glucocorticoid receptor and nuclear factor-kappaB signaling by CREB-binding protein and steroid receptor coactivator-1.

The p65 (RelA) component of nuclear factor-kappaB (NF-kappaB) and the glucocorticoid receptor (GR) mutually repress each other's ability to activate transcription. Both of these transcriptional activators depend upon the coactivators CREB-binding protein (CBP) and steroid receptor coactivator-1 (SRC-1) for maximal activity. Here we show that increased levels of CBP relieves the inhibition of glucocorticoid-mediated repression of NF-kappaB activity and the NF-kappaB-mediated repression of GR activity. SRC-1 can relieve the NF-kappaB-mediated repression of GR activity. We propose that cross-talk between the p65 component of NF-kappaB and glucocorticoid receptors is due, at least in part, to nuclear competition for limiting amounts of the coactivators CBP and SRC-1, thus providing a novel mechanism for decreasing expression of genes involved in the inflammatory response.

Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11betaHSD.

Recently, we identified a novel putative nuclear receptor in colonic crypt cells distinct from both mineralocorticoid receptor and glucocorticoid receptor, with high affinity for 11-dehydrocorticosterone (11-DHB) (33). In the present study, competitive nuclear binding assays demonstrated that this site has a unique steroid binding specificity that distinguishes it from other steroid receptors. Western blot analysis showed the presence of 11beta-hydroxysteroid dehydrogenase-2 (11betaHSD2) but not 11betaHSD1 in colonic crypt cells and showed that 11betaHSD2 was present in the nuclear pellet. Differences in steroid specificity between the putative DHB receptor and inhibition of 11betaHSD activity indicate that binding is not to the enzyme. Furthermore, modified Chinese hamster ovary cells transfected with the 11betaHSD2 gene express nuclear 11betaHSD2 but not a nuclear DHB binding site. In conclusion, these data support the existence of a novel nuclear DHB receptor in rat colon that is distinct from the classic steroid receptors and from both 11betaHSD1 and 11betaHSD2.

Decreased apparent affinity of corticosterone for colonic crypt glucocorticoid receptors is dependent on the cellular milieu and is distinct from corticosterone metabolism.

[3H]Steroid binding in intact colonic crypt cells and cytosol was compared to determine if 11beta hydroxysteroid dehydrogenase (11betaHSD) activity modulates access of corticosterone (B) to both glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Cytosol from non-adrenalectomized rat colonic crypt cells showed no 11betaHSD activity, and B bound with high affinity to both MR (Kd=0.47+/-0.03 nM; Bmax=177+/-34 fmol/mg protein) and GR (Kd=4.5+/-0.3 nM; Bmax=279+/-40 fmol/mg protein). In contrast, intact colonic crypt cells incubated with 25-30 nM [3H]B for 90 min converted 62% of B to 11-dehydrocorticosterone, with little binding to MR (14+/-3 fmol/mg protein) and GR (22+/-5 fmol/mg protein). When 11betaHSD activity was inhibited with carbenoxolone, and the same concentration of [3H]B used, binding of [3H]B to MR increased 10-fold to 122+/-12 fmol/mg protein, not significantly different from MR levels in colonic crypt cytosol. In contrast, [3H]B binding to GR in intact cells increased only 1.6-fold to 36+/-9 fmol/mg protein, significantly less than to GR in cytosol (212+/-24 fmol/mg protein). Scatchard analysis showed both lower levels of GR and an apparently lower affinity for [3H]B in colonic crypt cells (Kd=31+/-3 nM; Bmax=130+/-21 fmol/mg protein) compared with cytosol (Kd=4.5+/-0.3 nM; Bmax=279+/-40 fmol/mg protein. [3H]Dexamethasone similarly showed an apparently lower affinity and capacity for GR (Kd=8.8+/-1.3 nM; Bmax=232+/-32 fmol/mg protein) in intact cells compared with cytosol (two separate determinations, Kd=2.6 and 2.9 nM; Bmax=369 and 300 fmol/mg protein). In contrast, [3H]aldosterone displayed similar affinity and capacity for MR in both intact cells (Kd=2.0 nM; Bmax=121 fmol/mg protein) and cytosol (Kd=1.5 and 1.4nM; Bmax=115 and 93 fmol/mg protein). These findings demonstrate not only that 11betaHSD modulates binding to both MR and GR in colonic crypt cells, but also that an additional mechanism(s) operating in whole cells but not in cytosol selectively reduces the affinity and capacity of colonic GR for both natural and synthetic ligands.