Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The expression of the gene codifying for CD4, the most important human immunodeficiency virus type 1 (HIV-1) receptor molecule, was analyzed in 11 fetal brains at various gestational ages and in 9 human neuroblastoma (NB) cell lines. CD4 gene expression in fetal and malignant neural cells was then compared with that observed in a hematopoietic cell line and adult hippocampus. 2. In addition, CD4 mRNA was evaluated in two NB cell lines induced to differentiate in vitro with retinoic acid (RA) or 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H7), a protein kinase C inhibitor. 3. All fetal brains and NB cell lines express a 1.8-kb signal when hybridized with pT4BcDNA probe, while a 3.0-kb signal such as observed in hematopoietic human cells was found in 1 of 11 fetal brains and in 0 of 9 NB cell lines. The 1.8-kb signal was lost in all analyzed poly(A)+ mRNA samples. 4. Moreover, CD4 gene expression was not induced in either RA- or H7-treated NB cells at any tested time and dose. The analysis of NB cells by polymerase chain reaction failed to demonstrate CD4 expression in either poly(A)+ or poly(A)- RNA. 5. In conclusion, the results show that the 1.8-kb signal observed in RNA extracted from fetal or transformed human neural cells is probably due to an aspecific hybridization. However, the gene codifying for CD4 can rarely be expressed by fetal brain cells early during gestation, in still unclear circumstances.
Cell Mol Neurobiol 1992 Apr
PMID:Analysis of CD4 gene expression in human fetal brain and neuroblasts. 135 Sep 44

In cultured, undifferentiated normal human bronchial epithelial (HBE) cells, transglutaminase activity was localized predominantly in the cytosolic fraction of cell lysates. Upon squamous differentiation, this cytosolic activity declined and was replaced by a 40-fold increase in the activity of particulate (membrane-associated) transglutaminase. Immunoblot analysis demonstrated that the cytosolic transglutaminase was Type II (tissue) transglutaminase and that squamous differentiation shifted gene expression to the Type I (epidermal) transglutaminase. Retinoic acid, an inhibitor of squamous cell differentiation, suppressed the increase in Type I transglutaminase. The decrease in Type II transglutaminase activity was unaffected by retinoic acid. Transforming growth factor-beta 1 (TGF-beta 1) enhanced Type II transglutaminase activity about 10-fold in the undifferentiated cells but did not increase Type I transglutaminase or cholesterol sulfate, two early markers of squamous differentiation. TGF-beta 2 was equivalent to TGF-beta 1 in inducing Type II transglutaminase and in inhibiting the growth of HBE cells. The differentiation-related and TGF-beta-induced changes in transglutaminase activity were reflected in the level of transglutaminase Type I and Type II protein and mRNA. Expression of transglutaminases in lung carcinoma cell lines was variable. No correlation was observed between the expression of Type I transglutaminase and the classification of the cells as squamous cell carcinoma. Several lung carcinoma cell lines exhibited high levels of Type II transglutaminase activity that were increased several-fold by TGF-beta 1 treatment. Retinoic acid was ineffective in altering transglutaminase expression in most cell lines but induced Type II transglutaminase in a time- and dose-dependent manner in NCI-HUT-460 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jul
PMID:Regulation of type I and type II transglutaminase in normal human bronchial epithelial and lung carcinoma cells. 135 92

We report results from a study of Hox-7 expression during mouse embryonic and fetal development and compare the localization of Hox-7 transcripts with those of the retinoic acid receptors. Transcripts were detected by in situ hybridization. Hox-7 expression occurs in (1) cephalic neural crest and its derivatives, (2) sites of ectomesodermal interaction, (3) extraembryonic tissues, and (4) endocardial cells. Hox-7 does not seem to be involved in defining rostrocaudal boundaries, but instead appears to be expressed along the proximodistal axes at these sites. We further investigated the active sites of morphogenesis, which involve an ectomesodermal interaction (e.g., limb buds, visceral arches), including genital tubercle and tail ridge. These are regions highly positive for Hox-7 transcripts, and many are known to be sites for the expression of gamma-retinoic acid receptors (RARs) and cellular retinoic acid binding proteins. Most regions that express Hox-7 are subregions of gamma-RAR expression. In the developing limb bud, expression of Hox-7 takes place in the interdigital region, where it overlaps areas of beta-RAR expression.
Mol Reprod Dev 1992 Aug
PMID:Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with retinoic acid receptor mRNA localization. 135 71

A new human cell line, termed Muraoka, has been established from the recurrent tumor of a case of congenital primitive neuroectodermal tumor (PNET) arising at the temporofacial region of a male infant. The microscopic findings of this cell line were epithelioid, and the xenografted tumor in a nude mouse consisted of the malignant epithelioid cells. Immunohistochemically, the cells were positive for neuron-specific enolase, S-100 protein, carcinoembryonic antigen, cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein. These findings were quite similar to those of the epithelioid cells in the original tumor and of the xenografted tumor cells. Neither chromosomal abnormalities nor N-myc amplification were observed. Morphological differentiation after treatment with N6-2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP), all-trans-retinoic acid (RA), prostaglandin E1 (PGE1), and 5-bromo-2'-deoxyuridine (BrdU) showed two different results. Bt2-cAMP and PGE1 induced neuronal differentiation with the extension of neurites, whereas RA and BrdU predominantly induced Schwannian differentiation (flat cells). In these respects, the cell line Muraoka seems to be useful for studying characteristics of PNET as well as for developing the new treatments against such tumors.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Establishment and characterization of a cell line of congenital primitive neuroectodermal tumor of soft tissue. 135 16

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
Cell Mol Neurobiol 1992 Jun
PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

We have used single cell imaging of [Ca2+]i and single channel cell-attached patch clamp recording to characterise the Ca2+ channels present on the plasma membrane of retinoic acid-differentiated human neuroblastoma (SH-SY5Y) cells. Exposure to raised K+ (45 or 60 mM) for 1 min resulted in a transient rise in [Ca2+]i which was abolished by cadmium (100 microM). The amplitude of the evoked rise varied from cell to cell. Both omega-Conus toxin (500 nM) and nifedipine (10 microM) reduced, but did not abolish, the rise in [Ca2+]i whereas Bay K 8644 (3 microM) potentiated it. In single channel records both L- and N-type Ca2+ channel openings were observed during membrane depolarisations from a holding potential of -90 mV. L-type channel openings (unitary conductance 22.5 pS) were prolonged by S(+)-PN 202-791 (500 nM) and could still be evoked from a depolarised holding potential (-40 mV). N-type channel openings (unitary conductance 12.5 pS) were unaffected by the dihydropyridine agonist but were inactivated at a holding potential of -40 mV. These results indicate that, in contrast to previous observations using whole cell recording, retinoic acid-differentiated SH-SY5Y cells express both L- and N-type Ca2+ channels.
Brain Res Mol Brain Res 1992 Mar
PMID:Characterisation of the L- and N-type calcium channels in differentiated SH-SY5Y neuroblastoma cells: calcium imaging and single channel recording. 137 5

In order to elucidate the complex mechanism(s) of action of steroid hormones, thyroid hormone and retinoic acid in pituitary mammotrophs, a clonal cell line (G3) was isolated from the rat pituitary tumor MtT/F84. G3 cells were found to secrete prolactin constitutively and to contain receptors for estrogen, glucocorticoid, progesterone and thyroid hormone. Stimulation of G3 cells with thyroid hormone resulted in a modest but significant increase in estrogen and progesterone receptor levels, however, retinoic acid treatment had no effect. Simultaneous addition of thyroid hormone and estrogen showed an additive effect on progesterone receptor levels in G3 cells. Thyroid hormone as well as estrogen enhanced the growth of G3 cells. Interestingly, retinoic acid was also found to enhance their growth but its enhancement was less potent than thyroid hormone and estrogen. Low concentrations of estradiol and thyroid hormone showed additive effects, but G3 cells stimulated with high concentrations of thyroid hormone failed to elicit an additive effect with estrogen, suggesting the presence of a common pathway in the growth-stimulatory actions of these hormones. In addition, exposure of G3 cells to retinoic acid completely abolished the effects of estrogen or thyroid hormone in terms of cell growth. These results suggest that there are complex interactions in the signalling pathways for estrogen, thyroid hormone and retinoic acid action in G3 cells.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Effects of retinoic acid on estrogen- and thyroid hormone-induced growth in a newly established rat pituitary tumor cell line. 139 Feb 78

The retinoic acid-induced differentiation of F9 cells into parietal endoderm-like cells activates transcription of the endogenous mouse retrovirus, the intracisternal A-particle (IAP). To investigate the elements that control IAP gene differentiation-specific expression, we used methylation interference, Southwestern (DNA-protein), and transient-transfection assays and identified the IAP-proximal enhancer (IPE) element that directs differentiation-specific expression. We find that the IPE is inactive in undifferentiated F9 cells and active in differentiated parietal endoderm-like PYS-2 cells. Three proteins of 40, 60, and 68 kDa bind to the sequence GAGTAGAC located between nucleotides -53 and -47 within the IPE. The 40- and 68-kDa proteins from both the undifferentiated and differentiated cells exhibit similar DNA-binding activities. However, the 60-kDa protein from differentiated cells has greater binding activity than that from undifferentiated cells, suggesting a role for this protein in F9 differentiation-specific expression of the IAP gene. The IAP gene is negatively regulated by the adenovirus E1A proteins, and the E1A sequence responsible for repression is located at the N terminus, between amino acids 2 and 67. The DNA sequence that is the target of E1A repression also maps to the IPE element. Colocalization of the differentiation-specific and E1A-sensitive elements to the same protein-binding site within the IPE suggests that the E1A-like activity functions in F9 cells to repress IAP gene expression. Activation of the IAP gene may result when the E1A-like activity is lost or inactivated during F9 cell differentiation, followed by binding of the 60-kDa positive regulatory protein to the enhancer element.
Mol Cell Biol 1992 Nov
PMID:A DNA element that regulates expression of an endogenous retrovirus during F9 cell differentiation is E1A dependent. 140 64

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Neurobiol 1992
PMID:Vitamin neurotoxicity. 146 88

A cDNA clone, Vgr-2, with homology to certain members of the transforming growth factor-beta superfamily has been isolated from a mouse embryo cDNA library. The encoded protein shows significant similarity to members of the Vg-1/decapentaplegic/bone morphogenetic protein subgroup of the transforming growth factor-beta family. Within this group, Vgr-2 is more similar to Xenopus Vg-1 than to any other member so far isolated. The gene is expressed at highest levels during midgestation mouse development, and transcripts are localized by in situ hybridization to the osteogenic zone of developing bone. Vgr-2 is expressed in F9 teratocarcinoma cells, and its RNA levels are down-regulated within 24 h after differentiation with retinoic acid. The genomic organization of Vgr-2 and its location on mouse chromosome 6 are reported.
Mol Endocrinol 1992 Nov
PMID:Isolation of Vgr-2, a novel member of the transforming growth factor-beta-related gene family. 148 Jan 82


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