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Endometriosis is characterized by infertility and pelvic pain in 10–15% of women of reproductive age. The genetic events involved in endometriotic cell expansion remain in large part unknown. To identify genomic changes involved in development of this disease, we examined a panel of 18 selected endometriotic tissues by comparative genomic hybridization (CGH), a molecular cytogenetic method that allows screening of the entire genome for chromosomal gains and/or losses. The study was performed on native, nonamplified DNA extracted from manually dissected endometriotic lesions. Recurrent copy number losses on several chromosomes were detected in 15 of 18 cases. Loss of chromosome 1p and 22q were detected in 50% of the cases. Additional common losses occurred on chromosomes 5p (33%), 6q (27%), 7p(22%), 9q (22%), 16 (22%) as well as on 17q in one case. Gain of DNA sequences were seen at 6q, 7q and 17q in three cases. To validate the CGH data, selective dual-color FISH was performed using probes for the deleted regions on chromosomes 1, 7 and 22 in parallel with the corresponding centromeric probes. Cases showing deletion by CGH all had two signals at 1p36, 7p22.1 and 22q12 in less than 30% of the nuclei in comparison to the double centromeric labels found in more than 85% of the cells. These findings indicate that genes localized to previously undescribed chromosomal regions play a role in development and progression of endometriosis. [ABSTRACT FROM AUTHOR]

A human epithelial-like cell line derived from peritoneal implants from a patient with gonadotrophin-releasing hormone (GnRH) agonist-resistant endometriosis graded as stage IVd according to the American Fertility Society classification was established in vitro. This cell line, designated FbEM-1, exhibited an epithelial-like morphology, grew in suspension and was immunoreactive for cytokeratins 8, 18, 19, vimentin and human leukocyte class I antigens. The cultured cells were negative for various haematopoietic cell markers, including the lymphoid cell antigens CD3, CD20 and CD45, von Willebrandt factor, carcinoembryonic antigen and the carcinoma antigen-125 (CA-125). In addition, the FbEM-1 cells were found to be moderately positive for periodic acid Schiff's (PAS) solution but were negative for α-naphthyl acetate esterase, peroxidase and chloroacetate esterase activities. Using specific antibodies against the progesterone, androgen and oestrogen receptors, 40% and 5-10% of the cells immunostained for progesterone and androgen receptors respectively, while oestrogen receptors were not detected. On cytogenetic analysis using R-banding, these cells showed numerous chromosomal aberrations, including loss of one chromosome X, 4q+, 5q+, trisomy 7, 8 and 10 and tetrasomy of chromosomes 17, 18, 19 and 20. These data show that the continuously growing FbEM-1 cell line established from endometriotic implants may be useful in achieving better understanding of the histogenesis of endometriosis. [ABSTRACT FROM PUBLISHER]

The effects of a short-term oral treatment with captopril or enalapril, two converting enzyme inhibitors (CEIs) administered in equipotent antihypertensive doses, on the systemic vasopressor and on the renal, mesenteric and hind-limb vascular responses to cirazoline and UK 14304, respectively alpha1- and alpha2- adrenoceptor specific agonists, were investigated in the adult pithed SHR. Cirazoline and UK 14304 induced vasoconstrictor responses in the three investigated territories, demonstrating the location and a functional role at these levels of the two sub-types of alpha-adrenoceptors. Both captopril and enalapril reduced, to the same extent, the systemic pressor and the regional vasoconstrictor responses, especially in the renal and mesenteric territories, elicited by cirazoline and UK 14304, demonstrating that both subtypes of alpha-adrenoceptors are involved in the CEIs-induced attentuation of sympathetic responses. [ABSTRACT FROM PUBLISHER]

Whole-blood cells of obligate carriers of the X-linked Wiskott-Aldrich syndrome (WAS) exhibit nonrandom inactivation of the X-chromosomes. However, because of the limited polymorphism of the probes available, the X-methylation pattern can only be determined in a restricted proportion of females. We thus analysed a large set of normal females and members of WAS families, using the recently described marker M27β, which detects the hyperpolymorphic locus DXS255. The probe was used to detect differences in methylation between the active and inactive X-chromosome, and the findings were compared with the pattern obtained using the well-documented probes from the 5′ end of the PGK and HPRT genes. All the normal females were found to use either X-chromosome randomly, and there was complete correlation between the three probes in the populations studied. Segregation analysis performed with M27β and other related markers in the WAS families was fully in accordance with the X-inactivation data. The use of M27β, for both X-inactivation and segregation analysis of WAS kindreds, provides a basis for genetic counselling in the majority of families, including those with no surviving males. [ABSTRACT FROM AUTHOR]