Tissue remodeling in Guinea pig lateral prostate at different ages after estradiol treatment

Estrogen seems to have an essential role in the fibromuscular growth characteristic of benign prostatic hyperplasia (BPH). This paper describes the effects of chronic estradiol treatment on Guinea pig prostatic stroma at different ages. Tissues from experimental animals were studied by histological and histochemical procedures, morphometric-stereological analysis and transmission electron microscopy (TEM). Marked fibromuscular hypertrophy was observed after estradiol treatment in animals of pre-pubertal and adult ages. Increases in the density and thickness of the collagen and elastic fibers were observed by histochemistry. TEM revealed wide distributions of collagen fibrils and large elastic fibers adjacent to the epithelial basal lamina and between the stromal cells, establishing contacts between them. These results indicate that the Guinea pig prostate simulates the stromal modifications observed in BPH in some aged animals after estrogen treatment at different ages, making it a good model for this disease.     

Metabolic engineering of new fatty acids in plants

Metabolic engineering of plants to express high levels of new fatty acids that are of nutritional and industrial importance has proven to be highly challenging. Significant advances have been made recently, however, particularly in the development of the first plant oils to contain long-chain polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Methods of increasing the accumulation of Delta12-modified fatty acids synthesized by transgenically expressed FAD2-like enzymes have also been investigated. Biochemical analyses of plants that express these introduced fatty-acid metabolic pathways have highlighted the central importance of ensuring the removal of novel fatty acids from their site of synthesis on phosphatidylcholine to enable their further modification, exclusion from membrane lipids and accumulation in seed triacylglycerols.     

Structure-activity relationships of 1-alkyl-5-(3,4-dichlorophenyl)-5-{2-[3-(substituted)-1-azetidinyl]-ethyl}-2-piperidones. Part 2: Improving oral absorption

A series of piperidone analogues of 1b-q, seeking replacements for the polar sulfamide moiety in clinical candidate UK-224,671 1a, possessing reduced H-bonding potential as a strategy to improve oral absorption, were prepared. These studies led to the successful identification of 1n, which demonstrated equivalent pharmacology and metabolic stability to 1a, and greatly improved oral absorption as assessed in rat PK studies.     

Induction of transplantation tolerance in non-human primate preclinical models

Short-term outcomes following organ transplantation have improved considerably since the availability of cyclosporine ushered in the modern era of immunosuppression. In spite of this, many of the current limitations to progress in the field are directly related to the existing practice of relatively non-specific immunosuppression. These include increased risks of opportunistic infection and cancer, and toxicity associated with long-term immunosuppressive drug exposure. In addition, long-term graft loss continues to result in part from a failure to adequately control the anti-donor immune response. The development of a safe and reliable means of inducing tolerance would ameliorate these issues and improve the lives of transplant recipients, yet given the improving clinical standard of care, the translation of new therapies has become appropriately more cautious and dependent on increasingly predictive preclinical models. While convenient and easy to use, rodent tolerance models have not to date been reliably capable of predicting a therapy's potential efficacy in humans. Non-human primates possess an immune system that more closely approximates that found in humans, and have served as a more rigorous preclinical testing ground for novel therapies. Prior to clinical adaptation therefore, tolerance regimens should be vetted in non-human primates to ensure that there is sufficient potential for efficacy to justify the risk of its application.     

4-D micro-CT of the mouse heart

PURPOSE: Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control. MATERIALS AND METHODS: Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function. RESULTS: Contrast enhancement with Isovue-370 increased over time with a maximum of approximately 500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of approximately 620 HU (aorta) and approximately 90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was approximately 250 HU for Isovue-370 and approximately 500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output. CONCLUSION: Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.     

Rbm19 is a nucleolar protein expressed in crypt/progenitor cells of the intestinal epithelium

Intestinal development and homeostasis rely on the coordination of proliferation and differentiation of the epithelium. To better understand this process, we are studying Rbm19, a gene expressed in the gut epithelium that is essential for intestinal morphogenesis and differentiation in the zebrafish (Development 130, 3917). Here we analyzed the expression of Rbm19 in several biological contexts that feature proliferation/differentiation cell fate decisions. In the undifferentiated embryonic gut tube, Rbm19 is expressed throughout the epithelium, but then becomes localized to the crypts of Lieberkühn of the adult intestine. Consistent with its expression in adult crypt/progenitor cells, expression is widespread in human colorectal carcinomas and dividing Caco-2 cells. Its expression in Caco-2 cells recapitulates the in vivo pattern, declining when the cells undergo confluence-induced arrest and differentiation. Rbm19 protein localizes to the nucleolus during interphase and to the perichromosomal sheath during mitosis, in accordance with the pattern described for other nucleolar proteins implicated in ribosome biogenesis. Interestingly, the loss of nucleolar rbm19, nucleolin/C23, and nucleophosmin/B23 in confluent Caco-2 cells did not signify loss of nucleoli as detected by electron microscopy. Taken together, these data point to the nucleolus as a possible locus for regulating the proliferation/differentiation cell fate decision in the intestinal epithelium.     

Fine structure of boar spermatozoa

Summary The fine structure of epididymal spermatozoa of boars was studied, with special regard to the head cytoplasm, the neck, and the axial filament. Epon embedding and staining with heavy metals was used.The acrosome consists of a moderately opaque, homogeneous substance bounded by a single membrane. Within the distinct equatorial segment, the acrosome is very thin and separated from the nuclear membrane by a narrow rim of moderately dense material, which may be related to the perforatorium of rat spermatozoa.The postnuclear cap consists of a dense, homogenous substance inside the cell membrane and is stainable with phosphotungstic acid.The fibre structures of the neck are surrounded by folded extensions of the nuclear membrane. Two short, dark rods appear in the centre of the neck. The light segments of the coarse, peripheral fibres are merely deep notches in the fibre substance. The coarse peripheral fibres reach their maximal thickness at the anterior end of the middle piece. They taper rapidly anteriorly from this point and more gradually posteriorly. Irregular bridges connect them with each other in the anterior middle piece.The central 9+2 fibrils of the axial filament have distinct arms and spokes in the middle piece and main piece. The subfibrils connected with the arms and spokes appear to be solid, except in the neck and end pieces. The two central fibrils run through the neck to the wall of the proximal centriole. Acknowledgements. We wish to express our sincere gratitude to Dr. B. Afzelius, the Wenner-Gren Institute, Stockholm, for helpful discussions regarding tail fine structure, and to Dr. J. Luft, Department of Anatomy, University of Washington, Seattle, Wash., U.S.A., for the generous supply of ingredients for the Epon embedding procedure.