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Prolonged exposure of the developing neonatal ovine uterus to a progestin from birth prevents uterine gland development and creates an adult endometrial phenotype characterized by the absence of glandular epithelium, the uterine gland knockout (UGKO) phenotype. This study used endometrium from normal and UGKO sheep to identify messenger RNAs (mRNAs) expressed differentially in the endometrial epithelium using the molecular techniques of mRNA differential display PCR (DD-PCR) and suppression subtractive complementary DNA (cDNA) hybridization (SSH). Sequence analyses of DD- and SSH-identified and cloned cDNAs indicated similarity of some to known mRNAs, including beta-lactoglobulin, alkaline phosphatase, type B and D endogenous sheep retroviruses, gp330/megalin, matrix Gla protein, and others. Other cDNAs were not similar to any known sequences and are considered novel, although some of these match human expressed sequence tags. In situ hybridization analyses of uteri from cyclic and pregnant ewes indicated that all DD-PCR- and SSH-identified mRNAs were expressed in either the endometrial lumenal and/or glandular epithelium, although some were also expressed in other uterine cell types. Northern and in situ hybridization analyses revealed that patterns of mRNA expression for most clones were affected by the day of the estrous cycle and pregnancy in a manner consistent with regulation by progesterone. Studies demonstrate the utility of the ovine UGKO model as a tool with which to identify known and novel uterine epithelial-specific genes. Cloned cDNAs identified here are expressed sequence tags useful for comparative and physical genetic mapping and may be used to reveal new factors and pathways regulating endometrial function.

CD66a (human homolog of rat cell-cell adhesion molecule, also known as biliary glycoprotein) is a cell surface protein of the immunoglobulin family. CD66a has been shown to mediate homotypic cell adhesion. Aside from this, no other functions of this molecule have been demonstrated. We have observed previously that CD66a protein expression is lost in most prostate tumors, suggesting that the down-regulation of CD66a is associated with the abnormal growth of prostate cells. CD66a is homologous (65% identity) to rat cell-cell adhesion molecule, which has been shown to have tumor-suppressive activity. This homology suggests the possibility that CD66a might also be a tumor suppressor. In this report, we show that restoring CD66a expression in DU145 human prostate cancer cells by adenovirus (Ad)-mediated gene transfer dramatically altered the malignant phenotype of these cells, as evidenced by their reduced ability to form tumors in a xenograft animal model. This result suggests that loss of CD66a protein plays an important role in the development of prostate cancer, and that restoring CD66a expression might provide an effective treatment for prostate cancer. We further explored the possibility of using Ad vectors to deliver CD66a as a potential therapeutic agent for prostate cancer. Direct injection of Ad-CD66a, an Ad vector carrying the CD66a gene, into DU145 tumors in mice significantly suppressed the growth of these tumors. This antitumor activity of CD66a was found to be dose-dependent. These results suggest that CD66a has tumor-suppressive activity and that Ad-CD66a is a potential therapeutic agent for prostate cancer treatment.

We use remote-sensing reflectance from particulate R(rs) to determine the volume absorption coefficient a of turbid water in the 400 < lambda < 700-nm spectral region. The calculated and measured values of a(lambda) show good agreement for 0.5 < a < 10 (m(-1)). To determine R(rs) from a particulate, we needed to make corrections for remote-sensing reflectance owing to surface roughness S(rs). We determined the average spectral distribution of S(rs) from the difference in total remote-sensing reflectance measured with and without polarization. The spectral shape of S(rs) showed an excellent fit to theoretical formulas for glare based on Rayleigh and aerosol scattering from the atmosphere.

These studies were undertaken to assess the relative expression and autocrine activation of the epidermal growth factor receptor (EGFR) in normal and transformed prostatic epithelial cells and to determine whether EGFR activation plays a functional role in androgen-stimulated growth of prostate cancer cells in vitro. EGFR expression was determined by Western blot analysis and ELISA immunoassays. Immunoprecipitation of radiophosphorylated EGFR and evaluation of tyrosine phosphorylation was used to assess EGFR activation. The human androgen-independent prostate cancer cell lines PC3 and DU145 exhibited higher levels of EGFR expression and autocrine phosphorylation than normal human prostatic epithelial cells or the human androgen-responsive prostate cancer cell line LNCaP. PC3 and DU145 cells also showed higher levels of autonomous growth under serum-free defined conditions. Normal prostatic epithelial cells expressed EGFR but did not exhibit detectable levels of EGFR phosphorylation when cultured in the absence of exogenous EGF. Addition of EGF stimulated EGFR phosphorylation and induced proliferation of normal cells. LNCaP cells exhibited autocrine phosphorylation of EGFR but did not undergo significant proliferation when cultured in the absence of exogenous growth factors. A biphasic growth curve was observed when LNCaP cells were cultured with dihydrotestosterone (DHT). Maximum proliferation occurred at 1 nM DHT with regression of the growth response at DHT concentrations greater than 1 nM. However, neither EGFR expression nor phosphorylation was altered in LNCaP cells after androgen stimulation. In addition, DHT-stimulated growth of LNCaP cells was not inhibited by anti-EGFR. These studies show that autocrine activation of EGFR is a common feature of prostatic carcinoma cells in contrast to normal epithelial cells. However, EGFR activation does not appear to play a functional role in androgen-stimulated growth of LNCaP cells in vitro.

C-CAM1 is an epithelial adhesion molecule of immunoglobulin supergene family and has been implicated in the growth suppression of prostate cancer cells. Here we show that C-CAM1 can also suppress the tumorigenicity of breast cancer cells. These observations suggest that C-CAM1 may be a general growth suppressor in epithelial cells. In addition, we have identified the cytoplasmic domain, but not the extracellular adhesion domain, of C-CAM1 as critical for the growth suppression. Thus, the adhesion and the growth suppression functions of C-CAMI are independent of each other. Furthermore, mutation at the tyrosine phosphorylation site in the cytoplasmic domain of C-CAM1 did not obliterate C-CAM1's growth suppression function, suggesting that tyrosine phosphorylation is not involved in the signal transduction pathway leading to cell growth suppression. These studies provide the structural basis for future development of therapeutics that may selectively activate C-CAM1's growth suppression function.

Traditionally, morphometric studies have relied on statistical analysis of distances, angles or ratios to investigate morphometric variation among taxa. Recently, geometric techniques have been developed for the direct analysis of landmark data. In this paper, we offer a summary (with examples) of three of these newer techniques, namely shape coordinate, thin-plate spline and relative warp analyses. Shape coordinate analysis detected significant craniofacial variation between 4 modern human populations, with African and Australian Aboriginal specimens being relatively prognathous compared with their Eurasian counterparts. In addition, the Australian specimens exhibited greater basicranial flexion than all other samples. The observed relationships between size and craniofacial shape were weak. The decomposition of shape variation into affine and non-affine components is illustrated via a thin-plate spline analysis of Homo and Pan cranial landmarks. We note differences between Homo and Pan in the degree of prognathism and basicranial flexion and the position and orientation of the foramen magnum. We compare these results with previous studies of these features in higher primates and discuss the utility of geometric morphometrics as a tool in primatology and physical anthropology. We conclude that many studies of morphological variation, both within and between taxa, would benefit from the graphical nature of these techniques.

We report two cases of transitional cell carcinoma of the urinary tract that consist of optically clear cells rich in glycogen. We propose that transitional cell carcinoma may exhibit a clear cell morphologic variant that should be distinguished from clear cell adenocarcinoma.