Extended pelvic lymphadenectomy is associated with a high rate of lymph node metastasis outside of the fields of standard lymphadenectomy in cases of clinically localized prostate cancer. Lymphadenectomy including the internal iliac lymph nodes should be performed in all patients with prostate cancer who are at high risk for lymph node involvement, as indicated by PSA greater than 10.5 ng./ml. and biopsy Gleason sum 7 or greater. In the low risk group pelvic lymphadenectomy can be omitted.
The Nodal and Hedgehog signaling pathways influence dorsoventral patterning at all axial levels of the CNS, but it remains largely unclear how these pathways interact to mediate patterning. Here we show that, in zebrafish, Nodal signaling is required for induction of the homeobox genes nk2.1a in the ventral diencephalon and nk2.1b in the ventral telencephalon. Hedgehog signaling is also required for telencephalic nk2.1b expression but may not be essential to establish diencephalic nk2.1a expression. Furthermore, Shh does not restore ventral diencephalic development in embryos lacking Nodal activity. In contrast, Shh does restore telencephalic nk2.1b expression in the absence of Nodal activity, suggesting that Hedgehog signaling acts downstream of Nodal activity to pattern the ventral telencephalon. Thus, the Nodal pathway regulates ventral forebrain patterning through both Hedgehog signaling-dependent and -independent mechanisms.
Extended pelvic lymphadenectomy is associated with a high rate of lymph node metastasis outside of the fields of standard lymphadenectomy in cases of clinically localized prostate cancer. Lymphadenectomy including the internal iliac lymph nodes should be performed in all patients with prostate cancer who are at high risk for lymph node involvement, as indicated by PSA greater than 10.5 ng./ml. and biopsy Gleason sum 7 or greater. In the low risk group pelvic lymphadenectomy can be omitted.
Hedgehog signaling is required for formation and patterning of the anterior pituitary gland. However, the role of Hedgehog in pituitary precursor cell specification and subsequent placode formation is not well understood. We analyzed pituitary precursor cell lineages and find that pitx3 and distal-less3b (dlx3b) expression domains define lens and pituitary precursor positions. We show that pitx3 is required for pituitary pre-placode formation and cell specification, whereas dlx3band dlx4b are required to restrict pituitary placode size. In smoothened mutant embryos that cannot transduce Hedgehog signals,median pituitary precursors are mis-specified and form an ectopic lens. Moreover, overexpression of sonic hedgehog (shh) blocks lens formation, and derivatives of lens precursors express genes characteristic of pituitary cells. However, overexpression of shh does not increase median pituitary placode size nor does it upregulate patched(ptc) expression in pituitary precursors during early somitogenesis. Our study suggests that by the end of gastrulation, pitx3-expressing cells constitute an equivalence domain of cells that can form either pituitary or lens, and that a non-Hedgehog signal initially specifies this placodal field. During mid-somitogenesis, Hedgehog then acts on the established median placode as a necessary and sufficient signal to specify pituitary cell types.
Because of the relative ease of embryonic manipulation and observation, the ability to produce a great number of genetic mutations, efficient screening methods, and the continued advance of molecular genetic tools, such as the progress in sequencing and mapping of the zebrafish genome, the use of zebrafish (Danio rerio) as a biomedical model organism continues to expand. However, studies involving zebrafish husbandry and veterinary care struggle to keep pace with scientific progress. This article outlines some of the current, acceptable methods for providing anesthesia and euthanasia and provides some examples of how performance-based approaches can be used to advance the relatively limited number of anesthetic and euthanizing techniques available for zebrafish.
Zebrafish, Danio rerio, are frequently handled during husbandry and experimental procedures in the laboratory, yet little is known about the physiological responses to such stressors. We measured the whole-body cortisol levels of adult zebrafish subjected to net stress and air exposure at intervals over a 24 h period; cortisol recovered to near control levels by about 1 h post-net-stress (PNS). We then measured cortisol at frequent intervals over a 1 h period. Cortisol levels were more than 2-fold higher in net stressed fish at 3 min PNS and continued to increase peaking at 15 min PNS, when cortisol levels were 6-fold greater than the control cortisol. Mean cortisol declined from 15 to 60 min PNS, and at 60 min, net-stressed cortisol was similar to control cortisol. Because the age of fish differed between studies, we examined resting cortisol levels of fish of different ages (3, 7, 13, and 19 months). The resting cortisol values among tanks with the same age fish differed significantly but there was no clear effect of age. Our study is the first to report the response and recovery of cortisol after net handling for laboratory-reared zebrafish.
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