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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of gamma-interferon (gamma-IFN) on three cellular parameters: cell membrane fluidity and expression of two antigens that have been associated with cell proliferation, namely transferrin receptor (Tf-R: a cell surface protein) and Ki-67 antigen (Ki-67: a nuclear protein). We observed small, yet significant changes in the first two parameters, but not the third parameter. These were investigated in K562 cells, a human chronic myelocytic leukemia cell line. These results suggest that the microviscosity changes and the surface Tf-R density were closely associated, and that gamma-IFN was involved in increasing proliferative activity of the cells by decreasing membrane fluidity and upregulating Tf-R expression.
Res Commun Mol Pathol Pharmacol 1996 May
PMID:Gamma-interferon upregulates transferrin receptors and decreases membrane microviscosity in K562 cells. 877 72

The quantitative distribution pattern of Ki-67 protein and proliferating cell nuclear antigen (PCNA) immunoreactivity was studied in human testis biopsies. In normal seminiferous epithelium Ki-67 is expressed in nuclei of spermatogonia, while PCNA additionally occurs in nuclei of primary spermatocytes. The staining pattern of spermatogonia is as follows (Ki-67-positive/PCNA-positive): 26.6 +/- 12.4%/46.3 +/- 9.5%. No stage-dependent differences were found. Biopsies with mixed atrophy (score < or =7) showed a significant (P < 0.05) decrease of immunopositive spermatogonia to 19.9 +/- 3.0%/31.4 +/- 5.7% (score 1) with minimal variation between different samples (score 7 to 1). Associated with defined histological defects such as hypospermatogenesis (hyp), spermatogenic arrest at the level of spermatids (sda), spermatocytes (sca) or spermatogonia (sga), however, there was a significant (P < 0.05) decrease of Ki-67 staining in tubules showing hyp (28.6 +/- 8.8%), sda (25.6 +/- 9.3%), sca (23.7 +/- 9.3%) and sga (16.2 +/- 6.0%) and of PCNA staining in sca (32.2 +/- 11.8%) and sga (20.0 +/- 9.5%), respectively. The decrease of immunoreactive spermatogonia did not correspond to elevation of follicle stimulating hormone (FSH). These data demonstrate that the low spermatogenic efficiency in infertile men is not only due to postmeiotic events, but also to a decrease in the meiotic activity of spermatogonia, and is not related to serum FSH.
Mol Hum Reprod 1998 Mar
PMID:The proliferation of spermatogonia in normal and pathological human seminiferous epithelium: an immunohistochemical study using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen. 957 Feb 68

Inflammatory pseudotumour of the lung is a lesion mainly composed of histiocytes. Histiocyte accumulation may arise from local proliferation of migratory cells, from cytokine induced recruitment of monocytes from the systemic circulation, or both. Cell proliferation was investigated with Ki-67 immunostaining and cytokine production with reverse transcriptase-polymerase chain reaction in two cases of inflammatory pseudotumour of the lung. It was found that the two lesions were composed mainly of non-proliferating (Ki-67 non-binding) macrophages that stained positive for CD68, CD14, CD4, and mannose receptor. Both cases contained mRNA transcripts for monocyte chemotactic protein-1 (MCP-1), a monocyte chemoattractant, and for interleukin 6 (IL-6), an inducer of plasma cell differentiation. One of the two cases also contained mRNA transcripts for IL-8, a neutrophil chemoattractant. These findings are consistent with the possibility that accumulation of non-proliferating histiocytes induced by MCP-1 is one of the pathogenic events occurring in inflammatory pseudotumour of the lung.
Mol Pathol 1998 Feb
PMID:Monocyte chemotactic protein-1 in the inflammatory pseudotumour of the lung. 962 22

A cyclin-dependent kinase (cdk) inhibitor, p27Kip1 (p27), binds to the cyclin E-cdk2 complex and functions as a suppressor of cell cycle promotion. Here, the involvement of p27 in the growth of normal human endometrium was immunohistochemically studied, and the findings were compared with those of Ki-67, cyclin E and cdk2. In addition, to elucidate the effect of progesterone on the expression of p27, tissues from patients with endometrial hyperplasia were examined before and after the administration of medroxyprogesterone acetate (MPA) for the treatment of this disease. In the glandular cells of the normal endometrium, p27 was negligible during the proliferative phase, whereas it was markedly increased in the secretory phase. The staining pattern of Ki-67 was the reverse. Cyclin E/cdk2-positive cells were observed throughout the menstrual cycle. In the secretory phase, the cyclin E/cdk2-positive cells were also positive for p27, suggesting an interaction between these molecules. Stromal cells, especially in the basalis, showed a consistent expression of p27 throughout the menstrual cycle. The expression of p27 in hyperplastic epithelia before the MPA treatment was negligible, whereas it was greatly increased after the treatment. The Ki-67 positivity decreased after the treatment. These findings suggest that p27 is involved in the progesterone-induced growth suppression of normal and hyperplastic endometria.
Mol Hum Reprod 1998 Sep
PMID:Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone. 978 52

The major regulators of endometrial function are oestrogen and progesterone, which act through binding their nuclear receptors and by activating transcription of their target genes. Interactions between steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate steroid action at the transcriptional level. The 19-nortestosterone-derived progestin, levonorgestrel, is used for contraception, treatment of menorrhagia and for endometrial protection during hormone replacement therapy, but the signalling pathways of its action are totally undefined. We examined the effect of an intrauterine system, releasing 20 microg of levonorgestrel per 24 h (LNG-IUS), on immunoreactive oestrogen receptor, progesterone receptor, c-JUN and Ki-67 expression in 29 endometrial specimens, obtained from fertile women using the LNG-IUS for contraception. Moderate to strong immunostaining for oestrogen receptors was observed in the stromal cells in all specimens, in glandular epithelial cells in 26 cases and in flattened luminal epithelial cells in 17 specimens. Decidualized stromal cells showed no progesterone receptor immunoreactivity in 19 of the 29 specimens, and weak to moderate immunostaining in 10 cases. Luminal epithelial cells were negative for progesterone receptor in all samples. Intense nuclear staining for C-JUN was observed in epithelial cells in 26 and in decidualized stromal cells in all 29 of the samples. In 16 samples, Ki-67 immunoreactivity was evaluated as weak to moderate in decidualized stroma, and in 13 samples absent. Our data demonstrate that intrauterine release of LNG maintains constant expression of C-JUN and exerts progestational effects in the endometrium in the absence of progesterone receptors. In contrast, LNG-IUS inhibits several cellular responses to oestrogen despite the presence of endogenous oestrogen and oestrogen receptors. These data suggest that the progestational effects induced by progesterone and levonorgestrel are mediated through different signalling pathways.
Mol Hum Reprod 1998 Dec
PMID:The effect of intrauterine levonorgestrel use on the expression of c-JUN, oestrogen receptors, progesterone receptors and Ki-67 in human endometrium. 987 60

The aim of the present study was to gain a better understanding of the localization of apoptotic cells within the human endometrium during the menstrual cycle and to elucidate the relationships among the following for the human endometrium: apoptosis, p21 expression, and cell proliferation. Apoptosis and p21 expression were identified mainly in the glandular cells of the basal layer in the late secretory phase. In contrast, cells positive for Ki-67 were observed predominantly in the functional layer (in the proliferative phase in glandular cells and in the secretory phase in stromal cells). A very strong positive correlation (r = 0.81; P < 0.001) was demonstrated between the number of apoptotic cells and the number of p21-positive cells present among the glandular cells but, topographically, individual apoptotic cells were not coincident with p21-positive cells in serial sections. The results of this study suggest that the proliferation of the glandular cells of the basal layer is regulated by both apoptosis and p21 expression, particularly in the late secretory phase. Such regulation may be necessary to maintain a healthy population of glandular cells in the basal layer of the endometrium.
Mol Hum Reprod 1998 Dec
PMID:Localization of apoptotic cells within the human endometrium and correlation between apoptosis and p21 expression. 987 67

The cellular mechanism of growth of coronary collateral vessels (adaptive arteriogenesis) is still poorly understood. To define a possible role of an altered expression pattern of cellular and matrix proteins in this process we implanted a constricting device around the left circumflex artery in 25 canine hearts and sacrificed the animals at the time of initiation (3 weeks), high activity (6 weeks) and discontinuation (8 weeks) of vessel growth. Methods were electron microscopy, labeling with Ki-67, the TUNEL method and immunofluorescence with confocal laser microscopy. As described earlier, the collateral vessels increased in wall thickness by the formation of a neointima without luminal narrowing. We report here for the first time that extensive vascular remodeling including migration, proliferation and apoptosis in all cell types takes place during the growth phase but not in more mature vessels. The most obvious difference with normal vessels is the reiteration of an embryonal expression pattern in smooth muscle cells of the neointima which includes a significant reduction of desmin and alpha-smooth muscle actin, calponin and vinculin. Fibronectin as a promoter of migration and adhesion was abundant, its antagonist tenascin and chondroitin sulfate showed patchy localization. A completely new finding in arteriogenesis is the involvement of mast cells releasing histamine and serotonin and probably cytokines. Vascular protein expression returned to almost normal at 8 weeks indicating cessation of remodeling. We conclude that in collateral vessel development an altered cellular and matrix protein expression is involved in a drastic case of positive vascular remodeling finally resulting in mature vessels 20-fold increased in size which are capable of maintaining the functional and structural integrity of the myocardium at risk.
J Mol Cell Cardiol 1998 Nov
PMID:Vascular remodeling and altered protein expression during growth of coronary collateral arteries. 992 66

The molecular genetic hallmark of mantle cell lymphomas (MCL) is the reciprocal translocation t(11;14)(q13;q32) which juxtaposes the bcl-1 proto-oncogene to one of the joining segments of the immunoglobulin heavy chain gene. This translocation is very common in MCL and occurs in up to 70% of these malignancies. Due to the aggressive nature of MCL, markers identifying tumor progression and clinical outcomes are necessary. In this study we examined whether a corroborative relation exists between p53 mutations, bcl-1 translocation, and the proliferative fraction in MCL. We evaluated the proliferative fraction, p53 gene status, and bcl-1 translocation in 21 patients with confirmed MCL. Controls consisted of normal DNA and 7 B-cell lymphomas. Immunohistochemical detection of Ki-67 was used to assess proliferative activity while molecular techniques were used to detect p53 mutations and the bcl-1 gene translocation. Reactivity to the monoclonal antibody Ki-67 on neoplastic cells ranged from 5% to 40% in typical MCL cases. The bcl-1 gene translocation was detected by PCR in 48% (10/21) of MCLs while no rearrangements were detected by PCR in case control DNA. Screening exons 5-8 of the p53 gene for mutations did not identify a single mutation in any of the MCL cases. No correlation was found between p53 mutations, the presence of a bcl-1 translocation, and the proliferative activity of neoplastic MCL cells. We conclude that these markers may demonstrate independent events which occur during the pathogenesis of MCL.
Int J Mol Med 1999 Apr
PMID:Proliferative fraction, bcl-1 gene translocation, and p53 mutation status as markers in mantle cell lymphoma. 1008 8

Growth differentiation factor-9 (GDF-9), a secreted member of the transforming growth factor-beta superfamily, is expressed at high levels in the mammalian oocyte beginning at the type 3a primary follicle stage. We have previously demonstrated that GDF-9-deficient female mice are infertile because of an early block in folliculogenesis at the type 3b primary follicle stage. To address the molecular defects that result from the absence of GDF-9, we have analyzed the expression of several important ovarian marker genes. The major findings of our studies are as follows: 1) There are no detectable signals around GDF-9-deficient follicles for several theca cell layer markers [i.e. 17alpha-hydroxylase, LH receptor (LHR), and c-kit, the receptor for kit ligand]. This demonstrates that in the absence of GDF-9, the follicles are incompetent to emit a signal that recruits theca cell precursors to surround the follicle; 2) The primary follicles of GDF-9-deficient mice demonstrate an up-regulation of kit ligand and inhibin-alpha. This suggests that these two important secreted growth factors, expressed in the granulosa cells, may be directly regulated in a paracrine fashion by GDF-9. Up-regulation of kit ligand, via signaling through c-kit on the oocyte, may be directly involved in the increased size of GDF-9-deficient oocytes and the eventual demise of the oocyte; 3) After loss of the oocyte, the cells of the GDF-9-deficient follicles remain in a steroidogenic cluster that histologically resembles small corpora lutea. However, at the molecular level, these cells are positive for both luteal markers (e.g. LHR and P-450 side chain cleavage) and nonluteal markers (e.g. inhibin alpha and P-450 aromatase). This demonstrates that initially the presence of the oocyte prevents the expression of luteinized markers, but that the absence of GDF-9 at an early timepoint alters the differentiation program of the granulosa cells; and 4) As demonstrated by staining with either proliferating cell nuclear antigen (PCNA) or Ki-67 and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) labeling, the granulosa cells of GDF-9-deficient type 3b primary follicles fail to proliferate but also fail to undergo cell death. This suggests that granulosa cells of type 3b follicles require GDF-9 for continued growth and also to become competent to undergo apoptosis, possibly through a differentiation event Thus, these studies have enlightened us as to the paracrine roles of GDF-9 as well as the normal steps of granulosa cell and theca cell growth and differentiation within ovarian follicles.
Mol Endocrinol 1999 Jun
PMID:Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. 1037 99

The occurrence of radiation-induced apoptosis in normal brain was investigated using an animal model of radiosurgery. Adult male Fischer rats aged 3 to 4 months were subjected to single dose convergent beam irradiation (10 Gy). Apoptotic cell death was determined by in situ labeling of DNA nick ends (TUNEL) and light microscopic evaluation of cell morphology. Five hours after irradiation, a highly significant increase of apoptotic cells in the subgranular zone of the dentate gyrus was paralleled by a corresponding significant decrease of cells immunoreactive for the proliferation marker Ki-67. Morphology, location and distribution of cells affected by radiation-induced apoptosis in the dentate gyrus subgranular zone, together with NeuN-immunohistochemistry, support the contention that these cells belong to the immature progenitor population responsible for neurogenesis in the adult rat hippocampus.
Brain Res Mol Brain Res 1999 Jul 23
PMID:Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus. 1040 87


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