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E Georges

Publications and source records attributed to E Georges.

53 records · Page 3Linked to original sources
PubMed1988

[Cleft lip and palate in Campeche Mayas].

It has been suggested that among American Indians, as in some genetically-related Asiatic ethnic groups, incidence of cleft lip and/or cleft palate is higher than among people of Caucasian extraction. Such hypothesis, plus growing demand for services observed at a center for the surgery of cleft lip and cleft palate in Campeche state, led the authors to undertake research among the Maya residents of that region. However, neither careful review of case histories nor field research performed in several Indian communities could confirm the hypothesis of a higher incidence among this ethnic community.

Cleft Lip↗
PubMed1987

Chemical modification of charged amino acid moieties alters the electrophoretic mobilities of neurofilament subunits on SDS/polyacrylamide gels.

The increase in the mobilities of neurofilament subunits on SDS-PAGE after dephosphorylation was reversed upon boiling in urea or trifluoroacetylation of lysine epsilon-amino groups. Trifluoroacetylation of native and dephosphorylated neurofilaments also resulted in an overall increase in the phosphorylation of the three subunits by the catalytic subunit of cyclic-AMP-dependent protein kinase. The gel-electrophoretic mobility of neurofilament subunits was also shown to be influenced by carboxylic amino acid residues, as neutralization of these moieties by glycinamidation increased the mobilities of all three subunits on SDS-PAGE. Neurofilament subunits that were both glycinamidated and dephosphorylated had apparent molecular masses of approximately 60 kDa, 112 kDa and 138 kDa. The major sites of these changes in the two largest subunits were shown to be the carboxy-terminal tail domains, which are known to contain high percentages of glutamate. Since interspecies differences in the apparent molecular masses of neurofilament subunits were shown to persist after glycinamidation and dephosphorylation, they appear to be due to differences in polypeptide chain length, rather than glutamate content.

Acetylation↗
PubMed1987

Hypophosphorylated neurofilament subunits in the cytoskeletal and soluble fractions of cultured bovine adrenal chromaffin cells.

The neurofilament proteins in cultured bovine adrenal chromaffin cells are in a hypophosphorylated state, as determined by the co-migration of the 160,000 and 210,000 molecular weight subunits with in vitro dephosphorylated bovine brain subunits on sodium dodecyl sulfate polyacrylamide gels. In addition, chromaffin cells were not stained by anti-heavy neurofilament subunit that binds only to phosphorylated epitopes. Pulse-labeling with 32Pi in the presence and absence of the protein synthesis inhibitor emetine indicated that some neurofilament protein phosphorylation occurred co-translationally and/or immediately after synthesis of the proteins. Pulse-chase experiments showed that the three neurofilament proteins rapidly attained their maximal phosphorylation levels, as multiple forms of either of the respective subunits were not seen after a one hour chase. We found that Triton X-100-soluble forms of high molecular weight neurofilament and middle molecular weight neurofilament subunits were present in chromaffin cells, and they also co-migrated with standard neurofilament proteins dephosphorylated in vitro. However, there were differences between the phosphopeptide maps of cytoskeleton-associated and soluble middle molecular weight neurofilament subunit, suggesting that the localization of phosphate moieties rather than extent of phosphorylation influences the association of the subunit with neurofilaments. Double immunofluorescence staining of cell cultures with antibody to the 70,000 molecular weight subunit and with anti-vimentin showed that chromaffin cells do not express vimentin.

Adrenal Glands↗
PubMed1986

Dephosphorylation of neurofilaments by exogenous phosphatases has no effect on reassembly of subunits.

Exhaustive in vitro dephosphorylation of porcine neurofilaments (NFs) by alkaline or acid phosphatase did not cause a dissociation of the 210-kD (NF-H), 160-kD (NF-M), or 70-kD (NF-L) subunits and had no effect on the reassembly of NFs from urea or guanidine solution. Electron microscopy revealed that the NFs reassembled from isolated or dephosphorylated subunits had similar morphologies. Phosphatase treatment caused significant increases in the mobilities of NF-M and NF-H on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the subunits underwent marked conformational changes after dephosphorylation. Chemical phosphate analysis showed that as isolated NF-H, NF-M, and NF-L contained about 22, 11, and 3 mol phosphate/mol polypeptide, respectively. The corresponding values for the three subunits from alkaline phosphatase-treated NFs were about 8, 6, and 2 mol phosphate/mol polypeptide, respectively. These results indicate the occurrence of a class of phosphate moieties that is not accessible to exogenous phosphatases.

Acid Phosphatase↗
PubMed1985

Fine structure of the cottontail rabbit papillomavirus mRNAs expressed in the transplantable VX2 carcinoma.

We analyzed the polyadenylated mRNAs transcribed from the cottontail rabbit papillomavirus genomes present in the domestic rabbit transplantable carcinoma line VX2, employing a combination of S1 nuclease mapping and primer extension techniques with vector M13-based single-stranded DNA probes. Each of the two major mRNA species (1,860 and 1,110 bases long) contained two exons which corresponded to the E6-E7 and E2-E4 open reading frames. The splice donor site for these transcripts was located at position 1371 at the beginning of the E1 open reading frame. Consequently, the splicing event did not lead to the fusion of the E region proximal (E6 and E7) and distal (E2, E4, or E5) open reading frames. The translation of the polycistronic RNA could result in the production of E6 and E7 proteins alone or of an additional E1-E4 fusion product if translation reinitiation can occur after the E7 stop codon. A heterogeneity was detected in the 5' ends of the longer transcript; E6 transcripts could thus yield a full-length or a truncated E6 protein. We also detected a minor subset of mRNAs covering the E2-E4 coding region and including at least three species with estimated sizes of 4.2, 2.8, and 1.8 kilobases. All the viral transcripts detected in the VX2 tumor cells were polyadenylated at the same site (position 4367) 20 base pairs beyond the first AATAAA signal which borders the E region.

Animals↗
PubMed1985

Two Shope papillomavirus-associated VX2 carcinoma cell lines with different levels of keratinocyte differentiation and transplantability.

Two cell lines, named VX2T and VX2R, were isolated from the transplantable VX2 carcinoma, a wholly anaplastic tumor established from a carcinoma induced by the Shope cottontail rabbit papillomavirus (CRPV) (J.G. Kidd and P. Rous, J. Exp. Med. 71:813-838, 1940). The CRPV genome was found to be maintained and transcribed in both cell lines, as in the VX2 carcinoma. The VX2T cells retained the tumor-producing capacity in the rabbit and the low expression of epidermal keratinocyte differentiation of the VX2 tumor cells. The VX2R cells, although tumorigenic for nude mice, were no longer serially transplantable in the rabbit and expressed differentiated functions of keratinocytes. These data indicate that the anaplastic characteristic and the transplantability of VX2 carcinoma cells to immune competent allogenic hosts may be lost without any detectable modification of the physical state and transcription of the CRPV genome.

Animals↗
PubMed1984

Neurofilament proteins in cultured chromaffin cells.

Antibodies were raised against the 200-kd, 145-kd, and 68-kd subunits of a rat neurofilament preparation. Immunoblots showed that each antibody was specific for its antigen and that it did not cross-react with any of the two other neurofilament polypeptides. Use of the three antibody preparations to stain bovine chromaffin cells in culture by the indirect immunofluorescence technique indicated that the three neurofilament polypeptides are present in chromaffin cells maintained in culture for 3 or 7 days. The three anti-neurofilament antibodies labelled the cells in a similar pattern: very thin filaments specifically localized around the nucleus were observed whereas neurites and growth cones, developed by cultured chromaffin cells, were generally not stained. Some fibroblasts were present in our cultures but they were never stained by any of the neurofilament antibodies. This indicated that the antibodies used do not react with vimentin, the major intermediate filament protein found in fibroblasts. The three neurofilament antibodies were also used to immunoprecipitate specifically three proteins of molecular weights 210 kd, 160 kd, 70 kd from solubilized extracts of cultured chromaffin cells that were radiolabelled with [35S]methionine. These proteins correspond in molecular weight to the neurofilament triplet found in bovine brain. Finally, the presence of neurofilaments in freshly isolated chromaffin cells was tested by immunoblotting using the 68-kd antibody. A 70-kd protein was specifically stained by this antibody, suggesting that neurofilaments are not only present in cultured chromaffin cells but also in the adrenal gland in vivo. It is concluded from these results that chromaffin cells contain completely assembled neurofilaments. This additional neuronal property again illustrates that chromaffin cells are closely related to neurons and therefore represent an attractive model system for the study of functional aspects of adrenergic neurons.

Adrenal Glands↗
PubMed1984

Physical state and transcription of the cottontail rabbit papillomavirus genome in warts and transplantable VX2 and VX7 carcinomas of domestic rabbits.

The physical state and the transcription of the genome of cottontail rabbit papillomavirus (CRPV) in non-virus-producing warts and in the VX2 and VX7 transplantable carcinomas of domestic rabbits were compared. The CRPV DNA present in VX2 and VX7 carcinomas (10 to 20 and 100 to 200 genome equivalents per diploid cell, respectively) was found to be entirely integrated into the cellular DNA, most probably as head-to-tail tandem repeats, in contrast to warts, in which viral DNA (10 to 100 copies per diploid cell) was found only as free, mainly monomeric, molecules. In the VX7 tumor, ca. 50% of the viral DNA molecules were found to be longer than one genome length, indicating that viral DNA rearrangements had occurred. A major viral transcript of 1,250 bases was detected in warts and in VX2 and VX7 carcinomas. Complementary sequences were localized within the E region, the putative transforming region inferred from the nucleotide sequence of the CRPV genome (I. Giri, O. Danos, and M. Yaniv, manuscript in preparation). Analysis of heteroduplexes formed between single-stranded CRPV DNA and polyadenylated RNAs from the VX2 tumor showed that the 1,250-base RNA resulted from the splicing of the sequences corresponding to the open reading frame E6 to those corresponding to the 3' third of E2. A second viral transcript, measuring 2,000 bases, was detected in warts and, in lesser amounts than the 1,250-base species, in VX2 carcinoma, and a 2,100-base RNA was found in VX7 carcinoma. Complementary sequences to these messengers were localized to the same part of the genome as the 1,250-base species and to a contiguous fragment situated upstream. Heteroduplex analysis showed that the 2,000-base species from VX2 carcinoma resulted from the splicing of the sequences corresponding to E6 and E7 to those corresponding to the 3' third of E2. The sequences spliced out upon the maturation of the two messengers of VX2 carcinoma correspond to E1, the two-thirds of E2, and most of E4. Additional transcripts were found in VX7 carcinoma, a major 3,100-base species transcribed from the E region, and several minor species, measuring from 2,400 bases, which all hybridize with a subgenomic fragment contained in the L region encoding the viral capsid polypeptides. This could account for the antiviral antibodies found in animals bearing the VX7 carcinoma.

Animals↗
PubMed1982

Polyoma virus mutants as probes of variety among mouse embryonal carcinoma cell lines.

Embryonal carcinoma (EC) cells are resistant to infection with polyoma virus and become permissive when allowed to differentiate. Polyoma host-range (PyEC) mutants have been selected on two embryonal carcinoma cell lines, PCC4 and F9, which differ in their differentiation potential, both in vitro and in vivo. Since PyEC mutants selected on one line failed to develop, or developed only poorly on the other, we used these two classes of mutants as probes towards several EC lines which differed in their origin and differentiation properties. From their susceptibility to either mutant, and from the effect of temperature upon the efficiency of infection, we inferred a classification of these teratocarcinoma cell lines, which is an agreement with a previous one based upon metabolic coupling. We also discussed results indicating that different EC cell lines might present steps in the process of cell determination at the embryonic level.

Animals↗
PubMedDate not supplied

Body fat distribution in men and women of the Hispanic health and nutrition examination survey of the United States: associations with behavioural variables.

Body fat distribution is a biological risk factor for cardiovascular disease and diabetes. There are known genetic factors influencing body fat distribution, but variation in this characteristic is also attributable to human behavioural and socioeconomic variables such as social class. Björntorp has proposed that these associations may be due to a series of physiological responses to psychosocial stress, most prominently chronic stimulation of the adrenal-cortical system. This system is known to affect body fat distribution. Elsewhere we have shown that general socioeconomic status is related to body fat distribution in men and women of the Hispanic Health and Nutrition Examination Survey (HHANES) of the United States. In this paper we explore the relationship with those behavioural variables available from the HHANES which could hypothetically serve as indicators of psychosocial stress: smoking, drinking and depression. For both sexes in all Hispanic ethnic groups except Puerto Rican men, as socioeconomic status declined, subcutaneous fat became more centrally distributed. This relationship continued to be significant after controlling for the behavioural variables. A positive relationship was also found between smoking and central body fat distribution which was independent of socioeconomic status. This relationship was statistically significant for all subsamples except Cuban-American women. No consistent relationships were found between body fat distribution, drinking and depression. The data support the hypothesis that body fat distribution may be linked to the social stress of low socioeconomic status, independent of the behavioural factors tested.

Adipose Tissue↗
PubMedDate not supplied

Toremifene resistance in a rat mammary tumour model.

The effect of Toremifene on cell growth in vitro was tested on the R3230AC rat mammary adenocarcinoma as model. Toremifene differed from Tamoxifen in that it did not induce resistance; some cross-resistance was observed in Tamoxifen tolerant tumour cell lines. Toremifene does not influence P-glycoprotein expression in this model and at the levels studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

R-verapamil decreases anti-estrogen resistance in a breast cancer model.

Drug resistance eventually limits the effectiveness of antiestrogens in breast cancer treatment. Pharmacological reversal of this refractoriness has been attempted with R-Verapamil, a well tolerated calcium channel blocker. This drug significantly decreased the incidence of lung foci after intravenous seeding of the R3230AC rat adenocarcinoma; this effect was correlated with reduction in the expression of P-glycoprotein. The simultaneous administration of antiestrogens with a non-toxic enantiomer of Verapamil was beneficial in the tumour model investigated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

N-ethylmaleimide increases P-glycoprotein photoaffinity labeling with iodoaryl-azidoprazosin in multidrug resistant cells.

P-glycoprotein (P-gp) mediates a multidrug resistance (MDR) phenotype in tumor cell lines selected with lipophilic cytotoxic drugs. Transport studies using purified P-glycoprotein reconstituted into defined liposomes have shown energy-dependent drug efflux of structurally dissimilar drugs. In this report, we have examined the effects of N-ethylmaleimide, a potent inhibitor of the P-gp ATPase, on P-gp drug binding in intact MDR cells and in plasma membranes. Our results show that short term treatment of MDR cells with 1-50 microM N-ethylmaleimide led to a concentration dependent increase in P-gp photoaffinity labeling with iodoaryl-azidoparazosin (IAAP). In addition, N-ethylmaleimide increases [3H] vinblastine accumu-lation in drug-resistant but not in sensitive cells. Comparison of IAAP photolabeled P-gp from intact cells with or without N-ethylmaleimide treatment did not show differences in the pattern of IAAP photolabeled peptides. Thus, the observed increase in P-gp photolabeling with IAAP in N-ethylmaleimide treated cells is not due to photolabeling at different sites. Incubation of MDR cells with [14C] N-ethylmaleimide showed that P-gp is directly modified at several Cysteine residues, as found from a complete proteolytic digestion of [14C] Nethylmaleimide labeled P-gp. The comparison of V8 staphylococcus aureas peptides from [14C] Nethylmaleimide or IAAP modified P-gp showed some peptides to co-migrate on SDS PAGE. However, modification of plasma membranes from drug resistant cells treated with N-ethylmaleimide did not show a dose-dependent increase in P-gp photolabeling with IAAP as seen with intact MDR cells. Interestingly, N-ethylmaleimide increases P-gp phosphorylation by inhibiting the turnover of Pgp phosphates. However, inhibition of P-gp phosphorylation with calyculin A did not show an increase in P-gp photolabeling in MDR cells. Taken together, the results of this study suggest that N-ethylmaleimide potentiates P-gp photolabeling with IAAP by inhibiting P-gp ATPase thereby increasing the local concentration of IAAP in intact MDR cells. Furthermore, inhibition of P-gp ATPase by N-ethylmaleimide does not lead to conformational changes that affects P-gp drug binding.

ATP Binding Cassette Transporter, Subfamily B, Mem↗