Nucleotide sequence of the quail c-jun protooncogene.
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Animals↗
Biomedical subjects
G Brun
Publications and source records attributed to G Brun.
Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer.
Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.
Cotinine↗
[Another case of Sertoli-Leydig cell ovarian tumor (arrhenoblastoma). Review of the literature].
In reporting another case of Sertoli-Leydig cell tumor (SLCT) treated by conservative management, the principal characteristics of these tumors are reviewed and a general review is made: SLCT (arrhenoblastomas) are rare endocrine tumors (1 p. cent of tumors of the ovary). They most frequently occur in young women, are unilateral in 98 p cent of cases, and are manifest after a long period by endocrine signs (75 p. cent of cases) whose most frequent combination is: amenorrhea-hirsutism-hoarse voice. They are classified in four histological types which have different prognoses. Their potential development varies and is variously assessed: these are tumors with a low incidence of malignancy (mean 18 p. cent). Under certain conditions, this permits the institution of conservative therapy conserving future fertility. Malignant types of tumors are treated in the same way as other malignant ovarian tumors: surgery is the main tool; radiotherapy is often insufficient and chemotherapy often provides remission more frequently than cure (80 p. cent 5 year survival).
Adult↗
Expression of a novel gene encoding a 51.5 kD precursor protein is induced by different retroviral oncogenes in quail neuroretinal cells.
A cDNA clone, named T64, was isolated from a library of quail neuroretinal cells transformed by a thermosensitive v-src mutant of Rous sarcoma virus. it corresponds to the most abundant mRNA with thermodependent expression in these cells. T64 accumulation also correlated with pp60v-src activity in other cell types transformed by RSV, such as fibroblasts and myoblasts, but was independent of the proliferative state of the cells, indicating that T64 is rather implicated in the process of morphological transformation. Nuclear run on experiments showed that the accumulation of T64 mRNA in transformed neuroretinal cells is the consequence of an increased transcription rate. Enhancement of T64 expression on QNR cells was also achieved by infection with avian retroviruses harboring other oncogenes with protein kinase activity such as v-fps and v-mil. The 1.6 kb T64 mRNA was detected in vivo in a few quail tissues at levels 50-200-fold lower than in RSV-infected cells. DNA sequencing of the T64 cDNA revealed an open reading frame encoding a 449 amino acids protein with a typical N-terminal signal peptide and with significant amino acid sequence homology with a rat-secreted protein.
Amino Acid Sequence↗
[Stress urinary incontinence associated with an ectopic ureteral junction. Apropos of 1 case].
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Female↗
[Uterine rupture after tubal reimplantation].
The authors report a case of rupture of the right cornu of the uterus in the ninth month of pregnancy in a woman who had had her right tube implanted into her uterus. This complication is considered, in the discussion, to be rare. It is very difficult to prevent it happening during pregnancy. It would seem that a prophylactic caesarean operation should be carried out if the insertion of the placenta is in the area of the implantation.
Adult↗
DNA synthesis in a mitochondrial lysate of Xenopus laevis oocytes. H strand replication in vitro.
Conditions for efficient replication in vitro of mitochondrial DNA L strand into H strand products have been established. Gel electrophoresis and hybridization analyses of the products show that neosynthesized H strands are progressively elongated from the D-loop region, and some of them are synthesized as full-length molecules. Evidence for initiation of these H strands de novo is presented. In contrast, there is no detectable L strand synthesis in vitro in this system. This may prove useful for analyzing the distinct molecular mechanisms operating at OH and OL. Use of specific inhibitors indicates that DNA synthesis in the mitochondrial lysate in vitro requires DNA polymerase gamma. These observations support the conclusion that replication in vitro in this system closely resembles the first steps of mitochondrial DNA replication in vivo.
Animals↗
A DNA binding protein showing sequence specificity for a region containing the replication origin of Xenopus laevis mitochondrial DNA.
In Xenopus laevis mitochondria up to 14 different polypeptides with affinity for the DNA, have been identified by the protein blotting technique. Under stringent binding conditions only one polypeptide displayed specific affinity for a restriction fragment containing the H strand origin of replication of the Xenopus laevis mt chromosome. The proteins were fractionated by double stranded DNA cellulose chromatography. Under conditions which favor high affinity interactions between proteins and DNA, a protein of the 2M NaCl step shows specific binding to the DNA fragments containing the D-loop region. Some physical properties of the protein have been studied. It has a MW of 21.5 Kd and a globular shape as can be inferred from the relationship between MW and sedimentation coefficient (2.7 S). It binds non cooperatively to DNA and forms relatively stable complexes as demonstrated by DNA competition experiments.
Animals↗
Evaluation of the genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO), a broad-spectrum pesticide, in multiple in vivo and in vitro short-term tests.
The genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO) were evaluated in multiple in vivo and in vitro short-term tests preparatory to its potential wide use as a molluscicide in control of schistosomiasis. When tested in the rec assay in Bacillus subtilis, TBTO was not mutagenic and it did not induce reverse mutations in Klebsiella pneumoniae. Neither in the presence nor in the absecne of rat liver activation system did TBTO produce point mutations in Salmonella typhimurium strains TA1530, TA1535, TA1538, TA97, TA98 or TA100. TBTO was matagenic in strain TA100 in a fluctuation test, but only in the presence of rat liver S9 (Aroclor-induced). TBTO did not induce gene mutations in the yeast Schizosaccharomyces pombe, mitotic gene conversions in the yeast Saccharomyces cerevisiae, nor sister-chromatid exchange in Chinese hamster ovary cells in the presence or absence of rat or mouse liver S9. In the latter cells, structural chromosomal aberrations, endoreduplicated and polyploid cells were induced. TBTO did not induce gene mutations in V79 Chinese hamster cells (to 8-azaguanine-, ouabain- or 6-thioguanine-resistance) in the presence of a rat liver postmitochondrial fraction or in cell (hamster embryo cells and human and mouse epidermal keratinocyte)-mediated assays. In mouse lymphoma cells, TBTO did not induce 6-thioguanine- or BUdR-resistant mutations. As many tumour promoters inhibit metabolic cooperation between V79 Chinese hamster 6-thioguanine-resistant/-sensitive cells, TBTO was tested but showed no such activity. TBTO was examined for the induction of recessive lethal mutations in adult Berlin K male Drosophila melanogaster, either by feeding or by injection. Doses of 0.37 or 0.74 mM did not increase the number of X-linked recessive lethal mutations. An increased number of micronuclei was observed in the polychromatic erythrocytes of male BALB/c mice 48 h after a single oral dose of TBTO (60 mg/kg bw), while a lower dose (30 mg/kg bw) was ineffective. Neither of the two doses had induced micronuclei 30 h after treatment. The reproductive toxicity of TBTO was studied in NMRI mice. In a 10-day toxicity study, the LD50 and LD10 were 74 and 34 mg/kg bw, respectively. An increased frequency of cleft palates was seen in the fetuses of mice (compared with controls, 0.7%) treated orally during pregnancy with 11.7 mg/kg TBTO (7%), 23.4 mg/kg (24%) or 35 mg/kg (48%).(ABSTRACT TRUNCATED AT 400 WORDS)
Abnormalities, Drug-Induced↗
A monoclonal antibody against cytochrome P-450 enhances mutagen activation of N-nitrosodimethylamine by mouse liver S9: studies on the mode of action.
The effect of the monoclonal antibody MAb 2-66-3, directed against the major rat liver phenobarbital (PB)-induced cytochrome P-450 (P-450), on the S9-mediated mutagenicity of N-nitrosodimethylamine (DMN) in Salmonella typhimurium strain TA1530 was studied using liver S9 from PB-treated mice. This MAb enhanced approximately 2-fold S9-mediated mutagenicity of DMN but inhibited both its N-demethylation and N-denitrosation by 50%. Thus MAb-mediated enhancement of DMN mutagenesis does not result from altered activation/inactivation pathways, both known to involve P-450 isozymes. DMSO, a hydroxyl radical (HO.) scavenger and desferrioxamine, an inhibitor of HO.-dependent reactions, quenched the MAb-mediated enhancement of DMN mutagenesis, implicating the HO.-dependent activation of DMN to mutagenic species. As a mechanism, we propose that the binding of this MAb to P-450 isozyme implicated in DMN metabolism decreases the functional coupling between the reductase and the P-450 complex, leading to an increased electron flow from the reductase towards molecular oxygen to form reduced oxygen species (HO.) at the expense of the monooxygenase functions.
Animals↗
[Functional tubal obstructions: a great deceiver].
The authors report 40 cases of proximal tubal obstructions++ identified during conventional hysterography practised within a primary or secondary infertility investigation. The functional aspect of these tubal obstruction is easily proved in the great majority of cases by a coeloscopy with permeability test. The most difficult clinical situations are those where coeloscopy does not allow any conclusions concerning the hindrance nature.
Anesthesia, General↗
[Current treatment of endometrial cancer].
The elements of the poor prognosis of endometrial cancer are well known: grade, degree of infiltration of the myometrium, isthmal localization, pelvic and lumboaortic node invasion. But the ways of improving the results are less known: extension of the surgical procedure and the combination surgery-radiotherapy do not improve survival, except in case of grade 3 tumors invading more than half of the myometrium. However, vaginal curietherapy decreases the number of vaginal recurrences. Additional progesterone therapy is the subject of conflicting results. Preventive therapy consists in avoiding exogenous hyper-estrogenias by an adequate prescription of hormone therapy, in an early diagnosis of hyperplasias in risk patients (obesity, dys-ovulation) by a test with progesterone-like substances and endo-uterine smears, and in treating these hyperplasias with a medical treatment, curettage or hysterectomy, according to the circumstances.
Combined Modality Therapy↗
[Management in the case of an echo-free pelvic image].
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Female↗
The secondary structures of the Xenopus laevis and human mitochondrial small ribosomal subunit RNA are similar.
Extensive corrections of the nucleotide sequence of the Xenopus laevis mitochondrial small ribosomal subunit RNA gene [Roe et al. (1985) J. Biol. Chem. 260, 9759-9774] are reported. We found an additional fragment of 142 nucleotides and describe 25 nucleotide differences scattered in the gene. The nucleotide sequence the same gene of bovine mitochondrion. We propose a new secondary structure for the product of the X. laevis gene. Contrary to the finding of Roe et al., we observed the same general organization of stems and loops as for the human mitochondrial 12 S rRNA gene product. On the other hand, the structural homology observed between the mitochondrial and cytoplasmic small subunit rRNAs of X. laevis appears much lower. These results strongly suggest that animal vertebrate mitochondrial DNAs have followed the same evolutionary pathway.
Animals↗
Monoclonal antibody-directed analysis of cytochrome P-450-dependent monooxygenases and mutagen activation in the livers of DBA/2 and C57BL/6 mice.
Monoclonal antibodies (MAb 1-7-1 and Mab 2-66-3) specific for cytochrome P-450 (cyt. P-450) isozymes inhibited the metabolism of carcinogens, other xenobiotics, and endogenous compounds in two strains of mice. Postmitochondrial liver supernatant (S9) was prepared from untreated, 3-methylcholanthrene-treated, phenobarbital-treated, and pregnenolone 16 alpha-carbonitrile-treated C57BL/6 (B6) and DBA/2 (D2) mice. The modifying effect of two types of MAb to a 3-methylcholanthrene-induced cyt. P-450 and a phenobarbital-induced cyt. P-450 was investigated for: (a) S9-mediated mutagenicity of aflatoxin B1, benzo(a)pyrene 7,8-dihydrodiol, 2-acetylaminofluorene, and N-nitrosomorpholine in Salmonella typhimurium strains; and (b) the activity of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, aminopyrine N-demethylase, and testosterone 6 beta-, 7 alpha-, and 16 beta-hydroxylases. With certain S9s, MAb-1-7-1 inhibited only those cytochrome P-450 isozymes involved predominantly in activity of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase, and ethoxycoumarin O-deethylase and mutagenicity of 2-acetylaminofluorene and benzo(a)pyrene 7,8-dihydrodiol; MAb 2-66-3 inhibited only those involved in aminopyrine N-demethylase and testosterone 6 beta-, 7 alpha, and 16 beta-hydroxylase activity and aflatoxin B1 mutagenicity. Both Mab 1-7-1 and MAb 2-66-3 inhibited cytochrome P-450 isozyme(s) implicated predominantly in testosterone 7 alpha-hydroxylation in S9 from pregnenolone 16 alpha-carbonitrile-treated B6 mice. MAb 1-7-1 did not inhibit N-nitrosomorpholine mutagenicity and MAb 2-66-3 increased it by 2- to 6-fold depending on the source of S9. Using these MAbs, it is thus possible to identify the contribution of the epitope-defined single or class of cyt. P-450 to specific metabolic reactions in S9 from untreated and inducer-treated mice.
Animals↗
[Gonadoblastoma. Review of the literature. Apropos of a case].
Gonadoblastoma, which was described for the first time by Scully in 1953, is a rare tumour of the gonads. Only about 150 cases have been reported. Anatomo-pathologically it shows itself by a combination of large primitive germinal cells, small cells which resemble the immature cells found in the granulosa and in the Sertoli and sometimes Leydig-theco interstitial cells. Calcification is suggestive. Gonadoblastomas usually develop in a dysgenetic gonad. Pure gonadic dysgenesis is more commonly found. The subjects usually are of feminine phenotype and can demonstrate somatic or sexual abnormalities. The caryotypes most frequently found are 46 XY or 45 XO/46 XY. It is rare for the Y chromosome to be absent. All patients with gonadoblastomas should be HY antigen positive. The tumour is benign but the germinal epithelium can change towards a seminoma type. Because of this it is wise to carry out laparotomy with removal of both adnexae if there is a gonadoblastoma present. The case we have studied illustrates the typical profile of a gonadoblastoma. It occurred in a young woman who had pure gonadic dysgenesis with a caryotype 46 XY (Swyer's syndrome). It was bilateral associated on the left side with a seminoma, and for this reason we carried out bilateral extirpation of the adnexae followed up by therapy with cobalt.
Adult↗
Nucleotide sequence of a Xenopus laevis mitochondrial DNA fragment containing the D-loop, flanking tRNA genes and the apocytochrome b gene.
Extensive corrections of the nucleotide sequence of the Xenopus laevis mitochondrial (mt) displacement (D) loop and surrounding genes [Wong et al., Nucl. Acids Res. 11 (1983) 4977-4995] are reported, including addition of two stretches of nucleotides and 60 scattered modifications. The additional sequences presented here correspond to the apocytochrome b gene, the tRNAGlu gene and part of URF6. This allows us to propose a conformational model for the X. laevis apocytochrome b protein and also permits comparisons with mammalian mtDNA. The D-loop sequence is poorly conserved except for sequences involved in the regulation of the mt genome (conserved sequence blocks and the DNA polymerase stop sequences). On the other hand, all genes show marked conservation both of their nucleotide sequence and their respective location on the mt genome. Organization of the genetic information described for mammalian mtDNA also holds for the X. laevis mtDNA. This result strongly suggests that all animal vertebrate mtDNAs have followed the same evolutionary pathway.
Amino Acid Sequence↗
[C1 esterase inhibitor acquired deficiency: apropos of 4 cases].
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Aged↗