Annual antler renewal presents the only case of epimorphic regeneration (de novo formation of a lost appendage distal to the level of amputation) in mammals. Epimorphic regeneration is also referred to as a blastemabased process, as blastema formation at an initial stage is the prerequisite for this type of regeneration. Therefore, antler regeneration has been claimed to take place through initial blastema formation. However, this claim has never been confirmed experimentally. The present study set out to describe systematically the progression of antler regeneration in order to make a direct histological comparison with blastema formation. The results showed that wound healing over a pedicle stump was achieved by ingrowth of full-thickness pedicle skin and resulted in formation of a scar. The growth centers for the antler main beam and brow tine were formed independently at the posterior and anterior corners of the pedicle stump, respectively. The hyperplastic perichondrium surmounting each growth center was directly formed in situ by a single type of tissue: the thickening distal pedicle periosteum, which is the derivative of initial antlerogenic periosteum. Therefore, the cells residing in the pedicle periosteum can be called antler stem cells. Antler stem cells formed each growth center by initially forming bone through intramembranous ossification, then osseocartilage through transitional ossification, and finally cartilage through endochondral ossification. There was an overlap between the establishment of antler growth centers and the completion of wound healing over the pedicle stump. Overall, our results demonstrate that antler regeneration is achieved through general wound healing-and stem cell-based process, rather than through initial blastema formation. Pedicle periosteal cells directly give rise to antlers. Histogenesis of antler regeneration may recapitulate the process of initial antler generation.

At the pre-pedicle stage, the frontal lateral crest (under 5 mm in height) consisted horizontally of antlerogenic periosteum and underlying cancellous bone. Both the cellular layer (3.74 times, P < 0.01) and the fibrous layer of the antlerogenic periosteum were much thicker than those of the margin of the antlerogenic region or the facial periosteum. The crest was formed through intramembranous ossification. When the pedicle began to develop (5-15 mm in height), some discrete clusters of mature chondrocytes appeared in the bony trabeculae, which signified the beginning of the transition of the ossification pattern from the intramembranous to the endochondral. The pedicle consisted of three portions from distal to proximal, periosteum/perichondrium, osseocartilaginous tissue, and osseous tissue. When the pedicle became visible (about 20 mm in height), it consisted of the same three portions as the pedicle initiation stage, but the osseocartilaginous portion was expanded compared to the initiation stage and the cartilaginous proportion increased distally. When the pedicle grew to 25-40 mm in height, continuous cartilaginous trabeculae appeared under the apical perichondrium. The pedicle consisted of four portions from distal to proximal: perichondrium, cartilaginous tissue, osseocartilaginous tissue, osseous tissue. It was formed through endochondral ossification. All these ossification pattern changes could not be seen externally as the overlying integument was characterised by typical scalp skin. When the pedicle grew to about 60 mm in height, antler tissue was visually apparent at the apex as the hair type changed from scalp hair to the velvet-like hair of growing antler. However, this transformation could not be distinguished internally as the inside tissues were all continuous between pedicle and antler. Therefore, the histogenesis of the deer pedicle and the first antler originated from the antlerogenic cells and covered two phases: an internal phase through which pedicle was formed and an external phase which signalled the beginning of antlerogenesis.

The Cxbladder Monitor test significantly outperforms current Food and Drug Administration-approved urine-based monitoring tests, as well as cytology, in a large representative population undergoing surveillance for recurrent UC. This supports using Cxbladder Monitor as a confirmatory negative adjunct to cystoscopy or to justify postponing cystoscopic investigations in patients with a low risk of recurrence.

The acute and long term effects of dietary restrictions on gonadotropin secretion were studied in ovariectomized female lambs. Nutritionally growth-restricted lambs which were chronically maintained at a body weight comparable to that at weaning (approximately 20 kg) became hypogonadotropic, exhibiting a low frequency of episodic LH discharges. Repeated administration of physiological doses of GnRH to these females at hourly intervals produced corresponding LH pulses, leading to the hypothesis that the dietary-induced hypogonadotropism arises from a deficiency in endogenous GnRH release, rather than an inability of the pituitary gland to secrete gonadotropins in response to hypothalamic stimulation. In such growth-restricted females receiving a single meal daily, initiation of ad libitum feeding led to a spontaneous LH pulse within 1 h. After 14 days of increased food intake, hourly LH pulses were evident; a marked reduction in LH pulse frequency was associated with the return to limited nutrition. No effects on pulse amplitude were evident. Changes in circulating FSH followed a pattern similar to that for LH, namely an increase in concentration with improved nutrition and a decrease with reduced nutrition. The rate of response of FSH secretion to these alterations in nutrition was slower than that for LH. PRL levels were not altered by changes in nutrition, and a clear annual rhythm of secretion was observed. GH concentrations changed inversely with the level of nutrition; high secretion was associated with periods of restricted feeding, and low secretion with increased nutrition. These findings indicate that dietary restriction in the developing female lamb depresses gonadotropin secretion without reducing other anterior pituitary gland secretions, such as PRL and GH. That these changes occur in the absence of the ovaries implies that metabolic and growth-related modulation of neuroendocrine function can occur independently of changes in sensitivity to the feedback actions of ovarian steroids and polypeptides.

The utilization of a deer antler model to study gene expression in tissues undergoing rapid growth has been hampered by an inability to sample the different tissue types. We report here a standardized procedure to identify different tissue types in growing antler tips and demonstrate that it can help in the classification of expressed sequence tags (ESTs). The procedure was developed using observable morphological markers within the unstained tissue at collection, and was validated by histological assessments and virtual Northern blotting. Four red deer antlers were collected at 60 days of growth and the tips (top 5 cm) were then removed. The following observable markers were identified distoproximally: the dermis (4.86 mm), the subdermal bulge (2.90 mm), the discrete columns (6.50 mm), the transition zone (a mixture of discrete and continuous columns) (3.22 mm), and the continuous columns (8.00 mm). The histological examination showed that these markers corresponded to the dermis, reserve mesenchyme, precartilage, transitional tissue from precartilage to cartilage, and cartilage, respectively. The gene expression studies revealed that these morphologically identified layers were functionally distinct tissue types and had distinct gene expression profiles. We believe that precisely defining these tissue types in growing antler tips will greatly facilitate new discoveries in this exciting field. Anat Rec 268: 125-130, 2002.