Characterization of 17B-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate

In the present study, expressions of 17B-hydroxysteroid dehydrogenase (17HSD) types 1, 2 and 3, 5α-reductase type 2 and human androgen receptor mRNAs were determined in 12 benign prostatic hyperplasia and 17 prostatic carcinoma specimens. 17HSD type 2 was found to be the principal isoenzyme expressed in the prostate. Significantly higher expressions of 17HSD type 2 and 5α-reductase type 2 were detected in benign prostatic hyperplasia compared with the carcinoma specimens. Expression of the androgen receptor in the 2 groups was not significantly different. 17HSD type 3 mRNA was not detected in any of the specimens investigated. Only low constitutive expression of the 2.3 kb mRNA of 17HSD type I was seen. Immunohistochemical analyses indicated that this did not lead to significant enzyme expression, only faint staining for the enzyme protein being detected, mainly in uroepithelial cells. No significant correlation was found between any of the mRNAs analyzed, but the data on 5α-reductase type 2 mRNA support the presence of an increased proportion of 5α-dihydrotesterone in the hyperplastic prostate. In cultured PC-3 prostatic cancer cells and in transiently transfected human embryonic kidney 293 cells, 17HSD type 2 was found exclusively to convert 5α-dihydrotestosterone and testosterone into the less potent 17-keto compounds 5α-androstanedione and 4-androstenedione, respectively. We suggest that the 17HSD type 2 isoenzyme plays a part in the metabolic pathway, resulting in the inactivation of testosterone and 5α-dihydrotestosterone locally in the prostate. The enzyme expressed in the prostate could, therefore, protect cells from excessive androgen action. © 1996 Wiley-Liss, Inc.     

Maternal origin of transferrin receptor positive cells in venous blood of pregnant women

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti-CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti-alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.     

IGF‐I concentrations are positively associated with carotid artery atherosclerosis in women

BACKGROUND. Alterations in the growth hormone (GH)/insulin‐like growth factor I (IGF‐I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF‐I levels.

AIMS. To investigate whether IGF‐I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery.

METHODS. Fasting plasma IGF‐I concentrations (n = 1008) were measured in a large population‐based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method.

RESULTS. Low IGF‐I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C‐reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF‐I concentrations were positively associated with the mean IMT of women (ß = 0.127, P = 0.009) whereas the association in men was weaker and negative (ß = ?0.088, P = 0.034). The 1169A allele was associated with low low‐density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women.

CONCLUSIONS. IGF‐I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF‐I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.     

Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor alpha 2

Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) alpha 1 and alpha 2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFR alpha 2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFR alpha 2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFR alpha 2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data suggest that GDNF and NRTN may modulate seizure susceptibility by altering the function of hilar neuropeptide Y-containing interneurons and entorhinal cortical afferents at dentate granule cell synapses.     

Development of the standard reference plane for the Heidelberg retina tomograph

Background: Topometry of the optic disc is the quantitative assessment of the structure of the optic nerve head by means of three- dimensional parameters. The parameter values depend on definitions of intraocular reference planes. Purpose: To describe the development of intraocular reference planes in laser scanning tomography for the Heidelberg Retina Tomograph (HRT) using image intrinsic data with a fixed offset reference plane (320 μm) and to present a contour-line-based ”flexible” standard reference plane (”SRP”) for calculation of intrapapillary stereometric parameters taking the interindividual variability of optic disc topography into account.Methods: Ten-degree triple images were obtained by laser scanning tomography from 99 glaucoma eyes and 180 normal eyes. The images were evaluated to assess the variability of height measurements of an optic disc border contour-line segment (6° width) corresponding to the site of the papillo-macular bundle as indicated by the average optic disc surface inclination angle. Results: The average optic disc surface inclination angle was –7°±3° below the horizontal meridian (0°). The 6° wide contour-line segment for the SRP was chosen according to the average surface inclination angle (–10° to –4°). The reproducibility of the SRP-segment height measurements was 16.0±10.8 μm for normal eyes and 23.4±18.0 μm for glaucoma eyes. To ensure that the automatic reference level determination for intrapapillary parameters remained below the disc border height, we defined the SRP level at a 50 μm offset (>2 SD of average segment height reproducibility in glaucoma) added to the individual height position of the 6° contour line segment. Conclusion: The flexible standard reference plane allows for automatic determination of intrapapillary variables once a disc border contour line is interactively defined. In contrast to a fixed offset reference plane (e.g. 320 μm below the mean retina height), the interindividual variability of optic disc topography (oblique insertion, glaucomatous surface flattening) is respected at the cost of the need for an accurate optic disc border outline. Received: 9 March 1999 Revised: 26 August 1999 Accepted: 29 September 1999     

Optical coherence tomography and localized defects of the retinal nerve fiber layer

PURPOSE: To test the capability of the optical coherence tomography (OCT) to demonstrate and quantitate retinal nerve fiber layer (RNFL) defects. METHODS: The authors examined 6 eyes of 6 chronic open angle glaucoma patients with the OCT. The patients had abnormal Humphrey 30-2 visual fields which corresponded to RNFL defects visible in monochromatic fundus images taken with a digital imaging system. The RNFL images were used for directing the OCT scans to areas where most information was believed to be obtainable. Several linear scans of different lengths across healthy and abnormal RNFL regions were made. RESULTS: When the OCT images were compared to RNFL photographs, the defective areas showed reduced backscattering with the OCT, being distinctly different from the adjacent normal RNFL. Except for one case the RNFL thickness values were smaller in the areas of abnormal appearance compared to areas of normal appearance. CONCLUSION: This preliminary study suggests that the OCT examination results of the RNFL are in good agreement with the RNFL appearance in monochromatic fundus images.     

Randomized Controlled Trial of Back School With and Without Peer Support

The aim of this trial was to determine whether social interaction between patients with long-lasting nonspecific back pain reduces subjective or objective disability. The participants were selected from persons visiting an occupational health care unit because of back pain. After a clinical examination in a university clinic, subjects without a specific diagnosis and having no disabilities preventing active rehabilitation were selected for study. The subjects (n = 108) were randomized into treatment (n = 54) and control groups (n = 54). Altogether 18 study groups, 9 treatment groups and 9 groups for controls, were formed. Before starting the back schools altogether 15 subjects dropped out. Both the treatment groups (n = 47) and the controls (n = 46) attended a back school consisting of 10 lessons and demonstrations supervised by a physiotherapist. The participants in treatment groups, but not the controls, had physical exercise and social intercourse with other members within the group. The clinical examination was repeated after 6 and 12 months. Both the treatment groups and the controls showed improvement in perceived functional capacity (assessed with Oswestry disability questionnaire) and in perceived life quality (assessed with 15D score). At the 6-month follow-up life quality had improved statistically significantly more among the participants in treatment groups than among the controls, and at the 12-month follow-up the Oswestry index showed corresponding improvement. Among subjects suffering from nonspecific back pain, social support improves the results of active rehabilitation.     

Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P=.023 and.043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N=56; P=.033) and all the diabetics (n=6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P=.014), diastolic blood pressure (P=.009), and sagittal diameter (P=.032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.