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)

A monoclonal antibody to the double-stranded polyribonucleotide complex poly(A) . poly(U) was derived from the fusion of spleen cells from immunized DBA/2 mice and the P3 X X63-Ag8 plasma cytoma. Specificity studies using radioimmunoassays showed that the anti-poly(A) . poly(U) does not cross-react with single-stranded polyribonucleotides. RNA X DNA hybrids or DNAs. In addition to RNA duplexes associating adenine and uracil, it recognizes synthetic poly(I) . poly(C) and naturally occurring reovirus RNA. It is thus directed against a conformational epitope with an absolute requirement for two polyribose phosphate chains. However, the antibody does not cross-react with poly(G) . poly(C) and is therefore able to distinguish between RNA double helices.
Mol Immunol 1984 Oct
PMID:A monoclonal antibody to the double-stranded polyribonucleotide complex poly(A) X poly(U). 650 52

DBA/2 mice were made tolerant to and dependent on ethanol by administration of an ethanol-containing liquid diet for 7 days. Fluorescent probe molecules were used to estimate the fluidity and ethanol sensitivity of brain synaptic membranes from these mice. The fluorescence polarization of cis- parinarate , trans- parinarate , and 1,6-diphenyl-1,3,5-hexatriene (probes of the membrane core) and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the membrane surface) was higher in membranes from ethanol tolerant-dependent mice than in membranes from control mice. The decrease in fluorescence polarization produced by in vitro exposure to ethanol was attenuated in membranes from ethanol tolerant-dependent mice when 1,6-diphenyl-1,3,5-hexatriene was used as the probe, but not when 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene was used. These results indicate that chronic ingestion of ethanol decreased the fluidity and the ethanol sensitivity of the synaptic membranes. In contrast to the alterations observed with intact membranes, liposomes of lipids extracted from synaptic membranes of control and ethanol tolerant-dependent mice did not differ in their physical properties. Analysis of membrane lipids demonstrated that chronic ethanol treatment selectively decreased the unsaturated acyl groups of phosphatidylserine without altering the acyl composition of other phospholipids or sphingolipids. The amount of each phospholipid was not changed, but membrane cholesterol was decreased by chronic ethanol ingestion. Use of 2-dimensional thin-layer chromatography allowed the quantitation of 10 different gangliosides. The concentrations of these lipids were unchanged in synaptic membranes from ethanol tolerant-dependent mice. Thus, the changes in membrane physical properties produced by chronic ingestion of ethanol may be due, at least in part, to altered acyl composition of phosphatidylserine. The differences observed between intact membranes and extracted lipids suggest, however, that chronic ethanol treatment also produced changes in the lipid arrangement or lipid-protein interactions of the intact membranes.
Mol Pharmacol 1984 May
PMID:Physical properties and lipid composition of brain membranes from ethanol tolerant-dependent mice. 653 18

Single-step mutants were isolated from the murine metastatic MDAY-D2 cell line after selection in toxic concentrations of wheat-germ agglutinin. They were partially characterized by measuring their relative level of resistance to WGA, PHA, Con A, RIC, and LCA (Lec phenotype), and by comparing their karyotype and their ability to produce metastases upon transplantation into syngeneic DBA/2 mice. Based on their Lec phenotype, a total of 19 independent isolates were ranked into 10 distinct classes. Among them, two EMS-induced mutants were nontumorigenic (Lec II, Lec III), one nonmetastatic (Lec IV), and one spontaneous mutant (Lec I) failed to produce blood-borne metastases. Other spontaneous mutants belonging to Lec I, Lec II, and other classes were as metastatic as their parents. The Lec IV phenotype was found to segregate independently from metastatic potential in somatic hybrids. Metastatic ability was recovered in mutants expressing the Lec IV phenotype, after further selection for resistance to RIC. Our results strongly suggest that the loss or reduction of the invasive property of tumor cells is associated with only few Lecr1 phenotypes and, therefore, that a restricted number of cell surface glyconjugates are essential for this particular function.
Somat Cell Mol Genet 1984 Sep
PMID:Metastatic properties of distinct phenotypic classes of lectin-resistant mutants isolated from murine MDAY-D2 cell line. 659 45

Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGAr) mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAs) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4 (WGAr) tumor cells and normal host cells, at least some of which are of bone marrow origin. Thus, growth of the H-2d MDW4 tumor cells in (C3H X DBA/2)F1 (H-2k X H-2d) or (C57BL/6 X DBA/2)F1 (H-2b X H-2d) mice led to the appearance of WGAs revertants bearing the H-2k or H-2b major histocompatibility complex antigens associated with the C3H or C57BL/6 parental strains, respectively. Similarly, WGAs revertants of MDW4 were found to express H-2k antigens after growth in CBA/HT6T6 (H-2k) leads to DBA/2 bone marrow radiation chimeras. Attempts to mimic the in vivo hybridization process were successful in that in vitro somatic cell fusion between an ouabain-resistant (OuaR), 6-thioguanine-resistant (Thgr) derivative of the MDW4 mutant and either normal bone marrow or spleen cells resulted in loss of the WGAr phenotype in the hybrids (thus showing its recessive character) and increased malignant properties in vivo. An analysis of spontaneous frequencies of re-expression of various drug resistance genetic markers in several hybrid metastatic cells was also consistent with chromosome segregation of the sensitive alleles. The results show that tumor progression and the emergence of metastatic cell variants could arise as a consequence of tumor X host cell fusion followed by chromosome segregation. We also discuss the possibility that this type of event may normally be a very rare one during the growth of tumors, the frequency of which can be artificially amplified by the use of certain classes of lectin-resistant mutants carrying particular cell surface alterations.
Mol Cell Biol 1983 Apr
PMID:Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor. 668 20

Mouse liver cytochromes P1-450 and P3-450 represent those forms of polycylic hydrocarbon-induced P-450 most closely associated with induced aryl hydrocarbon (benzo[a] pyrene) hydroxylase and acetanilide 4-hydroxylase activity, respectively. These two proteins are controlled by the Ah receptor: C57BL/6N mice possess the high-affinity receptor; DBA/2N mice, the poor-affinity receptor. 3-Methylcholanthrene at the highest dose technically possible induces both proteins in C57BL/6N but not DBA/2N mice, whereas sufficiently high doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce both proteins in both inbred mouse strains. Plasmids containing DNA complementary to P1-450 and P3-450 mRNA, respectively, were used in an in vitro nuclear transcription assay to determine the mechanism of the induction response. In C57BL/6N mice, transcriptional rates of the P1-450 and P3-450 genes increase dramatically as early as 3 hr after 3-methylcholanthrene treatment and at 12 hr reach maximal levels of 20- and 15-fold, respectively, above control values. In contrast, no increase in either gene is found in 3-methylcholanthrene-treated DBA/2N mice. Following TCDD administration, both P1-450 and P3-450 gene transcription rates are elevated in DBA/2N mice. There is a 3- to 6-hr lag period between the early onset of enhanced transcription rates and the later rise in P1-450 and P3-450 mRNA. Basal and induced levels of P3-450 mRNA are about 5-fold greater than those of P1-450 mRNA. These data confirm that the 3-methylcholanthrene and TCDD induction responses, governed by the Ah receptor, are mediated principally through an increase in specific gene transcription.
Mol Pharmacol 1984 Jul
PMID:Structural gene products of the Ah locus. Transcriptional regulation of cytochrome P1-450 and P3-450 mRNA levels by 3-methylcholanthrene. 674 29

A simple and unique procedure was developed to purify phosphoglucose isomerase variants from the whole mouse body extracts and Drosophila homogenate. It involved the use of an 8-(6-aminohexyl)-amino-ATP-Sepharose column followed by a preparative isoelectric focusing. In each case, the enzyme in the homogenate was adsorbed by ionic interaction on the ATP-Sepharose column. Substantial purification was achieved by the affinity elution with the substrate-glucose-6-phosphate. Mouse and Drosophila phosphoglucose isomerase as well as the corresponding variants were shown to be dimers of similar molecular weight and to exhibit similar kinetic properties. The isoelectric points for the variants from DBA/2J and C57BL/6J mice were determined to be 8.4 and 8.7 respectively, while they were 6.8 and 6.3 respectively for Drosophila and 4/4 variants. Differential thermal stability was observed for the two mouse variants but not for the Drosophila ones. Amino acid composition analysis was performed for both mouse and Drosophila enzymes. Rabbit antisera for mouse (DBA/2J) and Drosophila (2/2) enzymes were raised. Within each species, complete immunological identity was observed between the variants. The antisera were used to characterize the null mutants of phosphoglucose isomerase identified in the mouse and Drosophila populations. By rocket immunoelectrophoresis, the null allele of the naturally occurring heterozygous null variant of Drosophila was shown to express no cross-reacting materials (CRM).
Mol Cell Biochem 1980 Jan 16
PMID:Biochemical characterization of phosphoglucose isomerase and genetic variants from mouse and Drosophila melanogaster. 676 7

We have studied the idiotypic specificities expressed by 22 anti-GAT hybridoma products (HP). These antibodies, although derived from cells of mice with three distinct heavy-chain linkage groups (BALB/c, Igh-1a, DBA/2, Igh-1c and C57BL/6, Igh-1b) all express the same public idiotypic specificity, p. GAT, defined by the heterologous binding of anti-idiotypic serum 715 to C57BL/6 anti-GAT antibodies. None of these antibodies expressed the strain-restricted idiotypic specificity, s.r. GAT-1, defined by the binding of anti-idiotypic serum JL 122 to BALB/c anti-GAT antibodies. BALB/c anti-GAT HP could be shown to fall into three subsets with respect to their fine antigenic specificity for GAT, GT and GA. An individual idiotypic specificity, i1-GAT (defined by syngeneic anti-idiotypic sera raised against one of the BALB/c HP), was also found on a group of BALB/c HP which all shared a similar fine antigenic specificity pattern. Taken together, these observations suggest that the expressed mouse anti-GAT repertoire derives from a very few V-germ-line genes (VH-GAT and VK-GAT) which are highly conserved in the species, and which determine the structure resulting in the p. GAT idiotypic specificity. The variations in fine specificity and individual idiotype are likely therefore to reflect somatic variations affecting these germ-line genes.
Mol Immunol 1982 Aug
PMID:Monoclonal anti-GAT antibodies with different fine specificities express the same public idiotype. 713 68

One prominent symptom of acute toxicity from 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) is a loss of adipose tissue and body weight, a phenomenon known as the wasting syndrome. In the current study, we examined the effect of TCDD on glucose transport in mice. A single intraperitoneal dose of TCDD (116 micrograms/kg) resulted in a time-dependent decrease in transport activity in adipose tissue and brains of C57BL/6 mice. Reduction of transport occurred within 24 hr in both tissues. In adipose tissue a slight recovery was observed by 30 days, but in the brains of treated animals glucose transport was significantly decreased even at the latest time. A comparison of dose-response relationships for several tissues between C57BL/6 (TCDD-responsive) and DBA/2J (TCDD-nonresponsive) mice showed parallel curves, with the C57BL/6 animals showing a 10-20-fold greater sensitivity. The estimated ED50 values for reduction of transport in adipose tissue were 50 micrograms/kg and 800 micrograms/kg for the C57BL/6 and DBA/2J strains, respectively. Treatment of isolated adipose tissue in culture with TCDD and two biphenyl congeners produced a decrease in transport activity that matched the rank order of aryl hydrocarbon receptor affinity for the compounds. Immunoblotting for the adipose-type (type 4) glucose transporter (GLUT) showed a 40% decrease in the membrane fraction of adipose tissue from C57BL/6 mice treated with 116 micrograms/kg TCDD for 40 hr. A similar decrease in the brain-type GLUT1 was observed in the plasma membrane fraction of brain tissues isolated from the same animals. Analysis of RNA for the corresponding GLUT4 and GLUT1 genes showed a dramatic decrease in GLUT4 mRNA as early as 24 hr after treatment. In contrast, the level of GLUT1 mRNA increased slightly in the brains of treated mice. We conclude that regulation by TCDD of glucose transport activity in mice is an aryl, hydrocarbon receptor-dependent process and that the adipose-type GLUT4 appears to be regulated at the mRNA level, whereas the brain-type GLUT1 is affected mainly at the protein level.
Mol Pharmacol 1995 Jan
PMID:Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the "adipose- type" and "brain-type" glucose transporters in mice. 753 Aug 7

Erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are often used as indices of vitamin B-6 nutritional status; however, results using a mixed population of erythrocytes can be quite variable. Erythrocytes from two strains of mice (Mus domesticus), A/Ibg and DBA/Ibg, were separated according to age by centrifugation through discontinuous Percoll density gradients into three fractions: top (least dense, youngest), middle and bottom (most dense, oldest). A sufficient yield of age-fractionated erythrocytes was obtained from a single mouse for all of the enzyme measurements. The activities of AST, ALT and three age-marker enzymes, pyruvate kinase, acetylcholinesterase and hexokinase, were found to be significantly higher in the youngest cell fractions, and declined in the older, more dense fractions. A mice had significantly lower AST and ALT activities in the age separated fractions than did DBA mice. The measurement of enzyme activities in low density, young cells may be especially useful in studies involving conditions in which the proportion of young erythrocytes may be elevated with respect to the entire erythrocyte mass.
Comp Biochem Physiol B Biochem Mol Biol
PMID:Aminotransferase activities in mouse, Mus domesticus, erythrocytes separated according to age. 755 57

Many natural environments are contaminated with carcinogenic polycyclic aromatic hydrocarbons (PAHs) and N-heterocyclic aromatic hydrocarbons (NHAs) as complex mixtures of coal tar, petroleum, and shale oil. These potentially hazardous substances are prevalent at many former tar production and coal gasification sites. Three polycyclic [benzo(a)pyrene (BaP), benz(a)anthracene (BAA), and 7,12-dimethylbenz(a)anthracene (DMBA)] and two N-heterocyclic [7H-dibenzo(c,g)carbazole (DBC), and dibenz(a,j)acridine (DBA)] aromatic hydrocarbons were analyzed for cytotoxic and genotoxic effects on human lymphocytes. All of these polyaromatic compounds are normally present in the environment, except for DMBA. Lymphocytes from healthy donors were isolated from whole blood. The 5-ring polycyclic aromatic BaP consistently induced micronuclei in a linear dose-dependent manner with doses from 0.1-10.0 micrograms/ml, whereas the 4-ring compounds (BAA and DMBA) had no effect on the induction of micronuclei above controls except at 5 and 10 micrograms/ml. Of the two N-heterocyclic compounds, DBC produced a significant increase in micronuclei in lymphocytes, but the dose response tended to plateau above 0.1 microgram/ml. DBA showed an effect on the frequency of micronuclei above controls only at high doses of 5 and 10 micrograms/ml. The average background frequency of micronuclei for 7 lymphocyte donors averaged 3.1 per 1,000 stimulated cells, whereas the average frequency of micronuclei at 10 micrograms/ml BaP was 36.8 per 1,000 stimulated cells. The lowest effective dose in 2 donors for BaP occurred at 0.1 microgram/ml. At a challenge dose of 1 microgram/ml (4 microM) of BaP, considerable variation in micronuclei induction between 7 individuals was observed, ranging from 2-6-fold increases above spontaneous frequency. Over a dose range of 1-10.0 micrograms/ml (4-40 microM), BaP also induced sister chromatid exchanges (SCEs) in lymphocytes, whereas BAA had no effect above controls. Parallel studies of both cytogenetic endpoints showed that the micronucleus assay is a more sensitive indicator of BaP exposure at equivalent doses. Mitotic and replication indices of BaP-exposed lymphocytes showed that cell proliferation is only moderately inhibited even at the highest dose; this shows that bulky DNA-adducts are generally compatible with cell survival. The cytogenetic data are consistent, first-off, with reports that individuals in the population vary widely with respect to the inducibility of the CYP1A1 gene, which is known to be involved in polycyclic aromatic hydrocarbon metabolism, in particular, in BaP. Secondly, the data support the fact that polyaromatic compounds differ with regard to micronucleus induction within the same sample(s) of human lymphocytes, indicating selective metabolism of polyaromatic compounds that may reflect carcinogen sensitivity of the individual.(ABSTRACT TRUNCATED AT 400 WORDS)
Environ Mol Mutagen 1995
PMID:Induction of micronuclei and sister chromatid exchanges by polycyclic and N-heterocyclic aromatic hydrocarbons in cultured human lymphocytes. 755 7


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