Prevalence of prediabetes and type 2 diabetes in children with obesity and increased transaminases in European German-speaking countries. Analysis of the APV initiative.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes mellitus are known to be closely linked with obesity as early as during childhood. OBJECTIVES: The study aimed to determine the prevalence of prediabetes and T2DM in children with obesity with or without increased transaminases. METHODS: Data from the observational multicentre (n = 51), cross-sectional Adipositas Patienten Verlaufsbeobachtung registry were analyzed. Mild increase (mild group) was defined by alanine transaminase (ALT) >24 to ≤50 U/L and moderate to severe increase (advanced group) by ALT > 50 U/L. Prediabetes and T2DM were defined according to recent IDF/ISPAD guidelines. RESULTS: The prevalence of prediabetes and T2DM was 11.9% (95% CI: 11.0-12.8) and 1.4% (95% CI: 1.1-1.7) among all participants (n = 4932; male = 2481; mean age 12.9 ± 2.7 years; BMI-SDS 2.1 ± 0.5; Tanner stage 3.2 ± 1.5). The prevalence of impaired glucose metabolism (prediabetes and T2DM) was 13.8% (95% CI: 12.1-15.4) in the mild, 21.9% (95% CI: 18.8-25.1) in the advanced group, 10.7% (95% CI: 9.4-11.9) in the control group. Mild and advanced groups had greater odds ratios for prediabetes [1.42; 95% CI: 1.17-1.72, 2.26-fold; (1.78-2.86), respectively], the advanced group also for T2DM [2.39 (1.36-4.21)] compared to controls. While an increase in transaminases predominantly affected boys, girls within the advanced group had a higher T2DM prevalence than males (5.4 vs. male 2.1%). CONCLUSIONS: Children with obesity and increased liver transaminases as surrogates of NAFLD should be screened for T2DM.

Vitamin D levels in patients admitted to the intensive care unit and the association with organ dysfunction and glutamine levels.

BACKGROUND: Vitamin D deficiency is common in intensive care unit (ICU) patients (50 - 82%) and is associated with multi-organ dysfunction. Vitamin D deficiency alters pathways of glutamine metabolism in critical illness, but the impact of vitamin D status on glutamine levels is poorly characterised. OBJECTIVES: To assess the prevalence of vitamin D deficiency and its association with organ dysfunction and glutamine levels in a South African (SA) ICU. METHODS: Records of 103 adult patients admitted to the Wits Donald Gordon Medical Centre ICU, Johannesburg, SA were retrospectively reviewed. 25-hydroxyvitamin D (25(OH)D) and glutamine levels were measured on admission. The association between admission vitamin D levels and glutamine levels, illness severity scores, organ support and outcomes was examined. RESULTS: On ICU admission, 66% (68/103) of patients were vitamin D deficient (<20 ng/mL) (95% confidence interval (CI) 56 - 75). Vitamin D deficiency was significantly associated with mechanical ventilation (40% v. 14%) (p=0.013) and a higher median sequential organ failure assessment (SOFA) score on admission (6 (interquartile range (IQR) 3 - 8) v. 4 (IQR 2 - 6)) (p=0.047) and on day 7 (5 (IQR 2 - 10) v. 2 (IQR 1 - 4)) (p=0.017). Median admission serum glutamine levels were 481 µmol/L, with 38% deficient (<420 µmol/L) (95% CI 28 - 48). Vitamin D deficiency status on admission was not significantly associated with median admission glutamine levels (p=0.66). CONCLUSIONS: Vitamin D deficiency is common in ICU patients in SA. Deficient patients were more severely ill and required more respiratory support. No significant relationship between deficiency and median glutamine levels was noted.

Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact).

BACKGROUND AND AIMS: Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients. METHODS: In this double-blind, randomised study, patients (n = 75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22 g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables. RESULTS: 68 patients completed the study (n = 35 SG, n = 33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8 ± 13.9 years (SG) versus 55.7 ± 14.8 (CG) (p = 0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p = 0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p = 0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r = -0.4047, p = 0.018). Days on mechanical ventilation (1.24 ± 0.83 days in SG versus 0.88 ± 1.63 days in CG, p = 0.385) and ICU LOS (9.5 ± 7.09 days in SG versus 10.7 ± 7.6 days in CG, p = 0.490) were not different between groups. CONCLUSION: PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes.

Paediatric liver transplantation in Johannesburg revisited: 59 transplants and challenges met.

BACKGROUND: A paediatric liver transplant programme was started at the Wits Donald Gordon Medical Centre, Johannesburg, South Africa (SA), in November 2005. We reported on the first 29 patients in 2012. Since then we have performed a further 30 transplants in 28 patients, having met the major challenge of donor shortage by introducing a living related donor programme and increasing the use of split liver grafts. OBJECTIVE: To review the Wits Donald Gordon Medical Centre paediatric liver transplant programme to date. We describe how the programme has evolved and specifically compare the outcomes of the first cohort with the most recent 28 patients. METHODS: Case notes of all paediatric liver transplants performed between 14 November 2005 and 30 June 2014 were retrospectively reviewed. Data were analysed for age and weight at transplantation, indication and type of graft. Morbidity and mortality were documented, specifically biliary and vascular complications. Comparison was made between Era 1 (November 2005 - October 2012) and Era 2 (November 2012 - June 2014). RESULTS: A total of 59 transplants were performed in 57 patients. Age at transplantation ranged from 9 months to 213 months (mean 82.39 months) and weight ranged from 5 kg to 62 kg (mean 21 kg). A total of 23 whole livers, 10 reduced-size grafts, 14 split liver grafts and 12 living donor liver transplants (LDLTs) were performed. Eight patients were referred with fulminant hepatic failure (FHF), all in Era 2. Of these, three patients were successfully transplanted. Of the 57 patients, 45 are alive and well with actuarial 1-year patient and graft survival of 85% and 84% and 5-year patient and graft survival of 78% and 74%, respectively. Sixteen (25.42%) biliary complications occurred in 15 of our 59 transplants. Seven patients developed significant vascular complications. Comparing Era 1 with Era 2, mean age at transplant decreased from 100.86 months to 64.73 months, mean weight from 25.2 kg to 16.9 kg, and type of graft utilised changed with a trend away from the use of whole livers and reduced-sized grafts to split livers and segment 2,3 LDLT grafts. CONCLUSION: Initially limited by a shortage of donor organs, we aggressively explored optimal utilisation, splitting liver grafts from deceased donors as often as possible and establishing an LDLT programme. This increased access to donor livers allowed us to include patients with FHF and to perform retransplantation in recipients with early graft failure. It remains to offer liver transplantation to the entire paediatric community in SA, in conjunction with the only other established paediatric liver transplant unit, at Red Cross War Memorial Children's Hospital in Cape Town.

Procalcitonin and C-reactive protein levels in HIV-positive subjects with tuberculosis and pneumonia.

Pulmonary tuberculosis (PTB) and pneumococcal community-acquired pneumonia (PCAP) are common causes of lower respiratory tract infections in HIV-seropositive patients and may have similar clinical and radiological features. This study aimed to assess the value of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in HIV-seropositive patients with pneumonia, and to investigate their potential role in differentiating pneumococcal from mycobacterial infections. HIV-seropositive patients admitted with pneumonia were evaluated prospectively, 34 with PTB and 33 with PCAP. All 33 patients in the PCAP group and 20 of 34 patients in the PTB group had elevated PCT levels (>0.1 ng x mL(-1)). All patients in both groups had elevated CRP levels (>10 mg x L(-1)). The PTB group had significantly lower CD4 T-lymphocyte counts, lower CRP levels, lower white cell counts, and lower PCT levels than the PCAP group. Receiver operating characteristic analysis showed that optimal discrimination between PTB and PCAP could be performed at a cut-off point of 3 ng x mL(-1) for PCT (sensitivity 81.8%; specificity 82.35%) and 246 mg x L(-1) for CRP (sensitivity 78.8%; specificity 82.3%). In conclusion, HIV-seropositive patients with pneumococcal community-acquired pneumonia had significantly higher procalcitonin and C-reactive protein levels than those with pulmonary tuberculosis. A procalcitonin level >3 ng x mL(-1) and a C-reactive protein level >246 mg x L(-1) were both highly predictive of pneumococcal infection.

CD4 T-lymphocyte subset counts in HIV-seropositive patients during the course of community-acquired pneumonia caused by Streptococcus pneumoniae.

Total lymphocyte counts, CD4 T-lymphocyte counts and CD4/CD8 ratios were measured in 30 anti-retroviral-naive HIV-seropositive patients upon hospital admission for acute community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, and again 1 month after resolution of infection. There was a significant depression of the total lymphocyte count (p < 0.005) and CD4 T-lymphocyte count (p < 0.001) in the acute stage of CAP caused by S. pneumoniae, with a subsequent increase in 90% (27/30) of cases after resolution of the infection. There was no significant difference in the CD4/CD8 T-lymphocyte ratio on admission compared with 1 month later (p 0.9).

Dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in HIV-seropositive patients with community acquired pneumonia.

Pulmonary infections with more than one organism are common in human immunodeficiency virus (HIV) seropositive patients. We describe nine cases of dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in HIV-seropositive patients presenting with community acquired pneumonia (CAP). It is important to exclude pulmonary tuberculosis in HIV-seropositive patients with CAP who fail to respond appropriately to initial antibiotic therapy, even if another etiological pathogen has been found.

Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1: identification of a novel mutation in the human mineralocorticoid receptor in one sporadic case and no mutations in two autosomal dominant kindreds.

Pseudohypoaldosteronism type 1 (PHA1) is characterized by neonatal salt wasting resistant to mineralocorticoids. There are 2 forms of PHA1: the autosomal recessive form with symptoms persisting into adulthood, caused by mutations in the amiloride-sensitive luminal sodium channel, and the autosomal dominant or sporadic form, which shows milder symptoms that remit with age. Mutations in the gene encoding the human mineralocorticoid receptor (hMR) are, at least in some patients, responsible for the latter form of PHA1. We here report the results of a genetic study in a sporadic case and in 5 affected patients from 2 families with autosomal dominant PHA1. In the sporadic case we identified a new frameshift mutation, Ins2871C, in exon 9 of the hMR gene. Family members were asymptomatic and had no mutation. This mutation is the first described in exon 9 and impairs the last 27 amino acids of the hormone-binding domain. In 2 kindreds with autosomal dominant PHA1 we found no mutation of the hMR gene. Our results confirm the hypothesis that autosomal dominant or sporadic PHA1 is a genetically heterogeneous disease involving other, as yet unidentified, genes.

Impaired rapid mineralocorticoid action on free intracellular calcium in pseudohypoaldosteronism.

Earlier observations on impaired in vitro effects of aldosterone on lymphocytic sodium and potassium pointed to the involvement of a defective nongenomic rather than genomic effector in pseudohypoaldosteronism. In this study, we investigated nongenomic aldosterone action in five patients with pseudohypoaldosteronism with regard to a rapid increase of free intracellular calcium [Ca2+]i in cultured nasal epithelial cells, assumably reflecting calcium influx through calcium channels. Patients were defined by episodes of salt loss despite high plasma aldosterone and renin levels. Four unaffected members of the families and four independent subjects served as controls. Considering an aldosterone-induced increase of [Ca2+]i by at least 10 nm as positive response, only 12% of cells from patients were responsive compared with 25% in normal subjects (P < 0.05). In terms of absolute changes, mean increase of [Ca2+]i was 1.6 +/- 1.1 nm in the patients (range-1-4) and 9.5 +/- 2.7 nm (P < 0.025) in the controls (range 1-25). Basal [Ca2+]i was not different between both groups (167 +/- 5 vs. 169 +/- 8 nm, mean +/- SE). These findings show an impaired nongenomic mineralocorticoid effector in patients with pseudohypoaldosteronism, which is in line with a defective sodium channel as shown recently by molecular cloning, and also with the fact that the classical, genomic intracellular receptor is structurally normal in these patients.

Immunohistochemical detection of immature Sertoli cell markers in testicular tissue of infertile adult men: a preliminary study.

Testicular biopsy specimens from oligozoospermic infertile patients are characterized by different types of spermatogenic impairment in adjacent seminiferous tubules, a phenomenon called mixed atrophy. In order to evaluate possible involvement of the state of Sertoli cell differentiation, the distribution pattern of anti-Müllerian hormone (AMH), vimentin and cytokeratin intermediate filament proteins was investigated by means of immunohistochemistry. AMH immunoactivity occurs in Sertoli cells of the normal postnatal prepubertal testis, but it is absent in the adult testis with normal spermatogenesis. In the case of mixed atrophy, AMH immunoactivity was found in Sertoli cells of tubules showing spermatogenic arrest at the level of spermatogonia and in tubules showing Sertoli-cell-only (SCO) syndrome. Vimentin was expressed regularly in Sertoli cells independent of spermatogenic impairment or the state of Sertoli cell differentiation. Cytokeratin immunoactivity occurs in Sertoli cells of the normal postnatal prepubertal testis. Furthermore, cytokeratin expression was found in Sertoli cells of tubules showing spermatogenic arrest at the level of spermatogonia and in some SCO tubules. Co-expression of AMH and cytokeratin suggests that spermatogenic impairment such as spermatogenic arrest and SCO syndrome in human seminiferous tubules is associated with a population of Sertoli cells showing a prepubertal stage of development. The different pattern of AMH and cytokeratin expression in SCO tubules indicates that Sertoli cells in SCO syndrome show a mosaic pattern of differentiation.

1,25(OH)2 vitamin D3 binding sites in male sex organs of the Siberian hamster (Phodopus sungorus). An autoradiographic study.

Using autoradiography, binding sites for 1,25(OH)2 vitamin D3 are found in certain genital organs of male Siberian hamsters (Phodopus sungorus), in particular in basal epithelial cells and fibroblasts of the lamina propria of prostate glands. Scattered labeled cells are also present in the epithelium of coagulation and urethral glands. In contrast to the findings in mice, under the conditions of the experiment, 1,25(OH)2 vitamin D3 binding sites are not recognizable in other accessory sex glands and gonads. The frequency of basal epithelial cells with [3H]1,25(OH)2 vitamin D3 nuclear binding is higher in regressed dorsal prostate glands of animals living in short photoperiods. The data suggest that 1,25(OH)2 vitamin D3 may promote proliferation and differentiation in basal epithelial cells, modulated by the seasonal and functional status of the animal.

Progestagen nuclear binding sites in the male genital tract of the mouse, studied by autoradiography.

Autoradiograms were prepared after injection of 125I progestagen (sp. act. 2200 Ci/mmol) to prepubertal and young adult mice. Nuclear concentration of radioactivity was found in smooth muscle cells at the beginning and the end of the deferent duct and in fibroblasts around the fusion of the deferent duct with the urethra. Nuclear labeling was enhanced in adult animals pretreated with oestradiol-valerate. In prepubertal mice nuclear labeling was more abundant than in adult mice and found in all smooth muscle cells of the deferent duct. No nuclear labeling was observed in other accessory sex organs. Nuclear labeling was prevented by injection of excess of unlabeled R5020. The presence of progestin receptors in smooth muscle cells of the deferent duct suggests a regulatory effect of progestin on contractions in analogy to progestin effects on oviductal and uteral smooth muscle cells. The presence of nuclear progestin receptors in the periurethral region may indicate an involvement of progestins in the etiology and regulation of benign prostate hyperplasia.

Differential nuclear binding of [3H]testosterone and its metabolites to androgen and estrogen receptors in brain, pituitary, heart, kidney and accessory sex glands of the mouse: an autoradiographic study.

Nuclear binding of [3H]testosterone ([3H]T) was studied by autoradiography in brain and peripheral tissues of normal male mice and androgen receptor (AR) deficient Tfm (testicular feminized) mice at various time points after injection. All tissues examined contain AR and estrogen receptors (ER). Nuclear binding (accumulation of radioactive hormone) was characterized by competition with excess of dihydrotestosterone (DHT) or estradiol (E2) and by inhibition of aromatization (AI). 2 h after injection of [3H]T, nuclear binding is found in certain regions of the forebrain of male and Tfm mice, but only in area postrema of hindbrain and in accessory sex glands of males. In pituitary, heart and kidney no nuclear binding is observed. In brain, except for area postrema, binding is inhibited by competition with E2 or by AI. DHT has no effect. This indicates predominant binding to ER. In the area postrema and in accessory sex glands binding is inhibited by DHT but not by E2, indicating binding only to AR. After [3H]T together with E2 or AI, additional nuclear binding is found in certain regions of the brain and in pituitary, unlabeled after [3H]T alone and after [3H]T with DHT. It suggests binding to AR which becomes detectable by an increased amount of androgen available for AR. Up to 1 h after [3H]T in the brain, binding is detectable at more sites than after 2 h. This additional binding is not suppressible by E2, indicating binding to AR. Since this additional binding is found only within the first hour after injection, a difference in binding to AR between brain and accessory sex glands after [3H]T is suggested.

Differentiation between androgen and estrogen receptor mediated effects of testosterone on FSH using androgen receptor deficient (Tfm) and normal mice.

The comparison of normal and androgen receptor (AR) deficient Tfm-mice allows distinction between AR mediated and estrogen receptor (ER) mediated effects of testosterone (T)--the latter after aromatization of T to estrogens--on serum and pituitary FSH. Normal male and female as well as Tfm mice were gonadectomized after 8 days and treated for 11 days with either T, estradiol (E2) or vehicle. Serum and pituitary FSH was determined by RIA for rat FSH. In Tfm mice T caused a suppression of serum FSH, indicating an ER mediated effect. Lower serum FSH levels after T in normal mice than Tfm mice indicate an additional AR mediated suppression. Lower serum FSH values in E2 treated Tfm than in T treated Tfm mice--where T acts only through ER--suggest two classes of estrophilic cells: one which aromatizes, thus being susceptible for both T and E2, and the other which does not aromatize. Only AR but not ER mediated T effects on pituitary FSH could be demonstrated.

Distribution of soltriol [1,25(OH)2-vitamin D3] binding sites in male sex organs of the mouse: an autoradiographic study.

After injection of [3H]-1,25(OH)2-vitamin D3 (soltriol), nuclear labeling is found in Sertoli cells of testes, being highest at the stage of spermiosis, in epithelium of efferent ductules and caput epididymidis and in connective tissue cells of epididymis, in lamina propria and muscular sheath of deferent duct, and in epithelium and muscular sheath of dorsal and ventral prostate of the mouse. This labeling pattern is characteristic for [3H]-soltriol and differs from that for [3H]-dihydrotestosterone and [3H]-estradiol, although with overlap. The nuclear labeling with [3H]-soltriol suggests an action of the hormone on certain processes during spermatogenesis, on sperm maturation, on epididymal fluid resorption, and on secretion and transport of spermatozoa.

True hermaphroditism with bilateral ovotestis: a case report.

A true hermaphrodite with a 46 XX/47 XXY karyotype, gynaecomastia, hypospadia and scrotal gonads was investigated. Gonadectomy performed at 14 years of age revealed bilateral ovotestes. The ovarian portion contained follicles of all developmental stages. The testicular portion was immature consisting of seminiferous cords with Sertoli cells at various steps of differentiation and few germ cells within massive aggregates of collagenous connective tissue. Leydig cells as well as germ cells remained in an embryonic stage of development. Sections of a differentiated Wolffian duct (ductuli efferentes, epididymis, vas deferens) as well as of a Müllerian duct (hypoplastic fallopian tube) were found adjacent to both gonads. Postoperative treatment consisted of androgen substitution therapy leading to progression of puberty.

[Thromboembolism as a complication of Pudenz-Heyer drainage with cardiac shunt]. / Die Thromboembolie als Komplikation bei Pudenz-Heyer-Drainage mit kardialer Ableitung.

We report the case of a 2.7 year old boy with ventriculoatrial Pudenz Heyer shunt for hydrocephalus internus presenting with symptoms suggestive of shunt infection. 2D-echocardiography showed a pedunculated right atrial thrombus that prolapsed through the tricuspid valve in diastole. Scintigraphy of the lungs showed multiple defects suggestive of embolism. The thrombus was excised after exploratory surgery with cardiopulmonary bypass. No organisms could be isolated from the thrombus. In ventriculo-atrial Pudenz Heyer shunt thrombi and embolism are possible complications. The regular use of 2D-echocardiography in order to detect these thrombi at a very early stage is discussed.

No evidence for aromatization of [3H]testosterone in oestrogen receptor containing cells of the epididymis.

Oestrogen receptors are found in the principal cells of the caput and in apical and clear cells of the epididymis of the mouse. The distribution pattern of oestrogen receptors is different from that of androgen receptors and suggests a physiological role for oestrogens in the epididymis. We examined by competition experiments and thaw-mount autoradiography to see whether aromatization of [3H]testosterone is the source of oestrogens in the epididymis. After injection of [3H]testosterone we found the same labeling pattern as after non-aromatizable [3H]dihydrotestosterone. In particular, apical and clear cells showed a low or no nuclear concentration of radioactivity as with [3H]dihydrotestosterone. Competition with oestradiol had no effect on the binding pattern of [3H]testosterone in the epididymis in contrast to its effects in the brain of the same animals. Competition with dihydrotestosterone abolished labeling in contrast to the brain, where no effect was observed. Thus no aromatization of [3H]testosterone to oestrogens but conversion to dihydrotestosterone seems to occur in the epididymis.

Androgen receptor-deficient Tfm cells in the mosaic epididymis of sex-reversed mice heterozygous for Tfm: an autoradiographic study with [3H]-dihydrotestosterone and [3H]-estradiol.

Testicular feminization (Tfm) in the mouse is characterized by androgen insensitivity of the target cells. We describe the presence of androgen-insensitive Tfm cells in the epididymis of mosaic mice produced by converting female carriers of the Tfm mutation (XTfm/X+) to males via the sex reversal factor (Sxr). The mosaic arises by random X-inactivation. In the epididymal duct, flat undifferentiated Tfm cells are interspersed between high columnar wild-type cells. By thaw-mount autoradiography we show that after injection of [3H]dihydrotestosterone, radioactivity is concentrated in the nuclei of high columnar wild-type cells, whereas the nuclei of the low cuboid Tfm cells remain free of nuclear radioactivity. After injection of [3H]estradiol, both Tfm and wild-type cells show nuclear labeling. Our observations demonstrate that Tfm cells in the mosaic epididymis selectively lack nuclear dihydrotestosterone-binding sites, whereas estradiol-binding sites are intact.