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Proliferative activity of the anterior pituitary gland in 10 week-old male and female rats under normal conditions was investigated by counting mitotic figures and using single and double immunostaining of 5-bromo-2'-deoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and six pituitary hormones. To determine which proliferative changes depend on the estrous cycle and circadian changes, respectively, six groups of female and two groups of male rats were studied at various times of day. Additionally, BrdU-incorporated cells were further classified by the six types of hormones they contained, or as immunonegative cells. Cell proliferative activity in the females fluctuated drastically with the highest activity in estrus and the lowest in diestrus. In the males, proliferative activity was at a relatively low level, and was similar to that in females in proestrus or early estrus, with the greater activity at night. Identified by their pituitary hormones, the distribution of the proliferating cells was almost the same in each sex, with prolactin (PRL) cells accounting for the highest proportion, followed by growth hormone (GH) cells, and adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) cells. These percentages agreed well with previously reported levels of cell types among all pituitary cells of the rat. It is therefore suggested that the life span and cycle of rat pituitary cells does not differ among cell types. In another test, male and female rats were given BrdU continuously via an osmotic pump for 8 days to compare cell proliferative activity between sexes, exclusive of the influence of estrous cycle and circadian changes. In this way, we were able to demonstrate that the cumulative incorporation of BrdU in females was consistently twice as high as in males over a constant period of time, and to conclude that cell renewal occurs at a doubled rate in the pituitary of female rat.
Anat Rec 1993 Jan
PMID:Cellular proliferation in the anterior pituitary gland of normal adult rats: influences of sex, estrous cycle, and circadian change. 841 18

Previous studies of colonic epithelial cell kinetics in mice and rats revealed a pattern similar to small intestine, where basally located stem cells proliferate, differentiating as they migrate towards the surface epithelium. Vacuolated and goblet cells are assumed to co-migrate at the same rate. The present study indicates that rabbit distal colon has more complicated epithelial cell kinetics. The zone of proliferation was detected immunohistochemically using proliferating cell nuclear antigen (PCNA) and confirmed with the use of colchicine to arrest dividing cells in metaphase. Migrating cells were tracked from the zero-hour position (PCNA labeling, mitosis) to positions 24, 48, 72 hrs by monitoring cell migration with the thymidine analog 5-Bromo-2-Deoxyuridine (BrdU). PCNA revealed a major proliferative zone in the upper third of the crypt column and the presence of mitotic figures after colchicine corroborated these results. Differentiated vacuolated cell proliferation was detected at three crypt sites: base, middle, and top of the crypt, while columnar cells arose from a population of dividing cells at the top of the crypt. Turnover of columnar and vacuolated cells occurred within 72 hrs. Goblet cells exhibited maximal proliferation at the crypt base and migrated at a much slower rate than the other cell types. In rabbit distal colon, populations of proliferating cells exist at multiple levels of the crypt column. Vacuolated and goblet cells differ in their labeling indices and migration rates, suggesting that the two cell types arise and migrate independently.
Anat Rec 1998 09
PMID:Proliferation of goblet cells and vacuolated cells in the rabbit distal colon. 973 43

Grafted periosteum is known to have potential for heterotopic bone formation by endochondral ossification. Although osteochondrogenic cells have been thought to originate from the osteogenic layer in grafted periosteum, no histological report has yet demonstrated this. The present study was designed to elucidate the origin of chondrogenesis preceding bone formation in grafted periosteum. Periostea harvested from young Japanese white rabbits' tibiae were grafted into suprahyoid muscles and examined radiographically and histologically at postoperative days 1, 7, 9, 14, 21, and 35. Normal periostea and tibial graft site were also examined. Surgical harvesting of the periosteum split and damaged its osteogenic layer but retained the fibrous layer intact. Most of the osteoblasts remained on the tibial bone surface, and only few cells of the osteogenic layer were present in grafted tissue. By the seventh day after grafting, the fibrous layer had thickened. The fibroblastic cells in the fibrous layer had significantly increased in number (P < 0.01) and were positively stained for proliferating cell nuclear antigen. These cells exhibited alkaline phosphatase activity at day 9. The differentiated chondrocytes had formed cartilage at postoperative day 14. Cells in the osteogenic layer appeared necrotic and subsequently disappeared. Following postoperative day 21, cartilage was replaced by trabecular bone. Bone formation was completed by 35 days. An X-ray analysis at this time also revealed new bone formation. These findings indicate that grafted periosteum forms bone by endochondral ossification and that the cells of the fibrous layer play essential roles in chondrogenesis that precedes such bone formation.
Anat Rec 2001 12 01
PMID:Cellular origin of endochondral ossification from grafted periosteum. 1174 90

The large intestine of mammals has long been viewed as an osmoregulatory organ, and evidence suggests that fluid and solute transport mechanisms within the intestine are heterogeneous, varying depending on the particular segment involved. Variations in function are often matched by morphological correlates, but despite the widespread use of rabbit large intestine as an experimental model, there is a lack of knowledge about the cellular makeup and dynamics in the colonic mucosal epithelium. The presence of mitotic figures and immunohistochemical localization of proliferating cell nuclear antigen (PCNA) were used to identify the proliferative zone(s). Cellular migration patterns were determined through the use of the thymidine analog 5-bromo-2-deoxyuridine (BrdU) over a 24-, 48-, and 72-hr period. Apoptotic nuclei were identified utilizing terminal deoxynucleotidyl transferase d-UTP nick-end labeling (TUNEL). Both cecum and the initial portion of the proximal colon (P1) exhibited a proliferative zone at or near the crypt base, and migration proceeded upwards toward the surface epithelium lining the intestinal lumen, where apoptosis occurred Turnover time of crypt columnar cells was determined to be about 3 days; that of mucous cells was estimated to be about 5 weeks. Rabbit cecum and proximal colon P1 are similar in their cellular morphology and epithelial cell kinetics. In both, the major proliferative zone is located at or near the crypt base, from which crypt columnar cells migrate toward the lumenal surface epithelium over a period of 3 days. Goblet cell turnover rate is much slower than that of columnar cells.
Anat Rec 2001 12 01
PMID:Epithelial cell dynamics in rabbit cecum and proximal colon P1. 1174 97

The cell kinetics of the developing central nervous system (CNS) is determined by both proliferation and apoptosis. In the human neocortex at week 6 of gestation, proliferation is confined to the ventricular zone, where mitotic figures and nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA) are detectable. Cell division is symmetric, with both daughter cells reentering mitosis. At week 7, the subventricular zone, a secondary proliferative zone, appears. It mainly gives rise to local circuit neurons and glial cells. Around week 12, the ventricular and subventricular zones are thickest, and the nuclear PCNA label is strongest, indicating that proliferation peaks at this stage. Thereafter, asymmetric division becomes the predominant mode of proliferation, with one daughter cell reentering mitosis and the other one migrating out. Towards late gestation, the ventricular and subventricular zones almost completely disappear and proliferation shifts towards the intermediate and subplate zones, where mainly glial cells are generated. A remnant of the subventricular zone with proliferative activity persists into adulthood. In general, proliferation follows a latero-medial gradient in the neocortex lasting longer in its lateral parts. Apoptotic nuclei have been detected around week 5, occurring in low numbers in the ventricular zone at this stage. Apoptotic cell death increases around midgestation and then spreads throughout all cortical layers, with most dying cells located in the ventricular and subventricular zones. This spatial distribution of apoptosis extends into late gestation. During the early postnatal period, most apoptotic cells are still located in the subcortical layers. During early embryonic development, proliferation and apoptosis are closely related, and are probably regulated by common regulators. In the late fetal and early postnatal periods, when proliferation has considerably declined in all cortical layers, apoptosis may occur in neurons whose sprouting axons do not find their targets.
Anat Rec 2002 Aug 01
PMID:Proliferation and apoptosis in the developing human neocortex. 1212 4

Smad 3 is a signaling intermediate for the transforming growth factor beta (TGFbeta) family; however, little is known about the role this protein plays in the regulation of the ovarian surface epithelium (OSE). Using a transgenic mouse model, we found that in the absence of Smad 3 there was a distinct morphological alteration of OSE cells. Wild-type (WT) OSE was flat with thin cells, while Smad 3-deficient (Smad 3 -/-) OSE was thick with plump cuboidal cells. WT OSE had less immunostaining for proliferating cell nuclear antigen (PCNA) and estrogen receptor alpha (ERalpha) than Smad 3 -/- OSE. However, there were no differences in the number of apoptotic cells or Bax and Bcl-2 levels between WT and Smad 3 -/- OSE. Although WT mice had higher levels of serum estradiol than Smad 3 -/- mice, WT and Smad 3 -/- mice had similar levels of progesterone. These data suggest that Smad 3 regulates OSE morphological appearance and proliferation in the absence of high serum estradiol levels or alterations in progesterone levels.
Anat Rec A Discov Mol Cell Evol Biol 2003 Aug
PMID:Smad 3 regulates proliferation of the mouse ovarian surface epithelium. 1284 4

We evaluated the relationship among proliferation, death and migration of granule cells in lobules VI-VIII of vermis, in comparison with lobule III, during cerebellar development. To this aim, a single injection of cisplatin, i.e., a cytostatic agent that is known to induce death of proliferating granule cells, was given to 10-day-old rats. Histochemical markers of proliferating (PCNA immunoreaction) and apoptotic (TUNEL staining) cells were used; the variations of the external granular layer (EGL) thickness were evaluated in parallel. After PCNA and TUNEL reactions, evident changes of the whole EGL were found on PD11 (1 day after treatment), when a reduction of the thickness of this layer was found in treated rats, mainly in consequence of the high number of apoptotic cells in all the cerebellar lobules. On PD17 (7 days after treatment), a thick layer of proliferating cells was observed in lobules VI-VIII of treated rats, while the peculiar pattern of the normal development showed a thin EGL. At the same time, in treated rats, the number of apoptotic cells in EGL was low. In all developmental stages of treated rats, after GFAP immunoreaction, glial fibers appeared twisted, thickened, and with an irregular course; intensely labeled end-feet were present. The damage of radial glia suggests an alteration of migratory processes of granule cells, which is also evidenced by the decreased thickness of the premigratory zone of the EGL. Injured radial glia fibers were restricted to lobules VI-VIII and they persisted at PD30, leading to the presence of ectopic granule cells in the molecular layer, as we previously described.
Anat Rec A Discov Mol Cell Evol Biol 2005 Dec
PMID:Proliferation and migration of granule cells in the developing rat cerebellum: cisplatin effects. 1624 1

The proximal and distal growth plates of the principal long bones do not contribute equally to longitudinal growth. Most forelimb elongation occurs at the shoulder and wrist, while most hindlimb growth occurs at the knee. This study examined whether insulin-like growth factor-I (IGF-I), a potent growth regulator, could underlie this variation via differential receptor expression. The spatiotemporal distribution of the IGF-I receptor (IGF-IR) was mapped in hindlimb growth plates (overall and within regional zones) from immature mice using immunohistochemistry. Growth activity was assessed by size/morphology of the growth plate and proliferating cell nuclear antigen (PCNA) expression. Both IGF-IR and PCNA staining declined considerably with age in the proximal femur and distal tibia (hip and ankle), but expression remained high in the more active distal femur and proximal tibia (knee) throughout growth. Growth plate size decreased with age in all sites, but the absolute and relative decline in IGF-IR in the hips and ankles of older mice indicated a site-specific loss of IGF-I sensitivity in these less active regions. These results suggest that regulation of the IGF-IR may at least partially mediate differential long bone growth, thereby providing a local mechanism for altering skeletal proportions absent modification of systemic hormone levels.
Anat Rec (Hoboken) 2007 Apr
PMID:Age- and site-specific decline in insulin-like growth factor-I receptor expression is correlated with differential growth plate activity in the mouse hindlimb. 1751 62

The goal of the study was to investigate participation of bone marrow (BM) cells in the process of airway epithelial restoration after naphthalene-induced injury. We transplanted sex-mismatched green fluorescent protein (GFP) -tagged BM-derived cultured plastic-adherent mesenchymal stem cells into 5Gy-irradiated C57BL/6 recipients. After 1 month of recovery, experimental animals were subjected to 250 mg/kg naphthalene IP. Animals were killed at 2-30 days after naphthalene. By immunofluorescence, immunohistochemistry, and by in situ hybridization for the Y-chromosome, we observed patches of donor-derived cells in the large and small conducting airways, mostly at 2-6 days after injury. GFP(+) cells in the epithelium of airways were positive for pancytokeratin and some other epithelial markers. Although rare, GFP(+) cells formed clear isolated patches of the bronchial epithelium, consistent with clonal formation; as some cells were also positive for proliferating cell nuclear antigen, a marker of proliferating cells. After day 12, only occasional GFP(+) cells were present in the epithelium. These data confirm that bone marrow-derived cultured mesenchymal cells can participate in the recovery of the injured airway epithelium after naphthalene-induced injury with minimal long-term engraftment.
Anat Rec (Hoboken) 2007 Sep
PMID:Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice. 1766 77

The interactions between steroid and nonsteroid hormones in the prostate are of special interest during the growth phase of the gland. The purpose of this work is to study the influence of prolactin (PL), with or without androgenic blockade, on epithelial cells from peripubertal rat ventral prostate. Twenty male peripubertal Sprague-Dawley rats were grouped as controls, or treated with cyproterone acetate (CA), CA plus PL (CA-PL), or PL. The total number (N total) of epithelial cells, and their labeling indices to proliferative cell nuclear antigen (LI PCNA), apoptosis (LI apoptosis) and androgen receptors (LI AR) were measured. CA and PL treatment significantly decrease the N total, but the LI PCNA was unchanged. We have observed a greater LI apoptosis in pharmacologically castrated animals without PL than in the rats with androgenic blockade with PL. The LI AR does not change with CA treatment in the ventral region, but the PL significantly increases it. Androgenic blockade and PL decrease the number of epithelial cells from the ventral prostate. These changes are not attributable to the decrease of cell proliferation, rather to the increase of epithelial apoptosis. The increase of cells expressing AR after treatment with PL might be attributed to the decrease of testosterone secretion caused by the hyperprolactinemia. PL does not modulate the size of the ventral prostate in prepubertal rats.
Anat Rec (Hoboken) 2009 May
PMID:Effect of prolactin on the population of epithelial cells from ventral prostate of intact and cyproterone acetate-treated peripubertal rats: stereological and immunohistochemical study. 1930 35


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