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Biomedical subjects

G Brun

Publications and source records attributed to G Brun.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Does axillary liposuction modify histologic study of excised lymph nodes?].

OBJECTIVE: To determine the pathological features of lymph nodes removed by axillary liposuction. METHODS: A prospective study of 34 axillary dissections performed from July 1995 to September 1996 in patients with breast cancer N0. After lipolysis, the fat was drained from the axillary cavity by means of liposuction (Karman nozzle ch.8; suction pressure of 1 Bar). The remaining nodes were removed by an endoscopic dissection in conservative treatments. The remaining nodes were removed during modified radical mastectomy in non-conservative treatments. Lymph nodes were fixed in formol and examined by the pathologist. RESULTS: An average of 15 lymph nodes (8-35) were removed. 502 lymph nodes were examined: 458 (91%) were not involved and 44 (9%) were involved, including 21 (4%) with rupture of the capsule. No pathological traumatism was seen. CONCLUSION: Axillary liposuction did not alter the pathological features of lymph nodes in our study.

Adult↗
PubMed1996

The product of the v-src-inducible gene nr-13 is a potent anti-apoptotic factor.

Tumorigenesis can be induced either by activating cell proliferation or by inhibiting metabolic pathways regulating programmed cell death (apoptosis). There is evidence suggesting that p60(v-src) and other tyrosine kinases protect cells against apoptosis. This effect could contribute to cell transformation by the Rous sarcoma virus. Mechanism of cell death inhibition by p60(v-src) remains largely unknown. We have recently reported that in avian cells p60(v-src) activates the expression of nr-13, a bcl-2-related gene. In this paper, we demonstrate, using the bone marrow derived cell line Baf-3 as an experimental model, that the product of this avian gene (nr-13) is a potent anti-apoptotic factor. In addition, we report that, in quail neuroretinal cells, nr-13 expression is activated upon infection by the Rous sarcoma virus (RSV) but not by other oncogenic retroviruses like FSV or MH2, suggesting that nr-13 is a specific target of v-src. Activation of nr-13 expression may be a key step in cellular transformation by v-src.

Animals↗
PubMed1996

Viral inhibition of apoptosis.

Viral propagation is limited both by the host immune response and by apoptosis of infected cells. Viruses circumvent apoptosis by different mechanisms: direct inhibition of particular proteases involved in cell death, stimulation of anti-death pathways or regulation of the activity of transcription factors monitoring cell survival.

Animals↗
PubMed1996

Two distinct regulatory elements control quail cdc2 transcription: possible involvement in the control of retinoblast differentiation.

It is a characteristic of the central nervous system of higher eukaryotes that neurons, after an initial proliferation phase, remain postmitotic for their whole life span. In the developing quail neuroretina, most retinoblasts become postmitotic after 7-8 days of incubation. They also cease to express cdc2, which is presumably necessary to allow retinoblasts to definitively leave the cell cycle. The molecular mechanisms monitoring cdc2 expression during differentiation remain partly understood. To further study the control of cdc2 transcription in avian cells, we have cloned the quail cdc2 promoter. Two functional regulatory elements have been characterized. One of them contains an E2F-binding site. Human E2F-1 was found to transactivate the quail cdc2 promoter very efficiently in avian and human cells. Gel retardation experiments are presented, suggesting that E2F, in association with different partners, is a major regulatory of cdc2 transcription during the development of the neuroretina. Our data also indicate that another transcription factor binds to the octamer CAGGTGGC located 115 nucleotides above the main transcription start site. This motif is thus another important regulatory element participating in the control of cdc2 expression.

Amino Acid Sequence↗
PubMed1995

Isolation and characterization of a chicken homolog of the E2F-1 transcription factor.

In higher eukaryotes, the E2F-1 transcription factor is an essential and limiting component of cell cycle progression in late G1. E2F-1 heterodimerizes with members of the DP gene family and the resulting heterodimer regulates the expression of several proto-oncogenes and the genetic machinery of DNA replication. Cell cycle regulation of E2F activity is mediated through its association with the tumor suppressor Rb gene product. To examine the evolutionary conservation of the E2F-1 protein sequence and its developmental expression pattern we have isolated and sequenced the chick E2F-1 gene (chE2F-1) cDNA. The chicken protein is 34 amino acids (a.a) shorter than its human counterpart (403/437 a.a.) but has extremely well conserved bHLH and pRb binding domains, with respectively 94% and 83% identity. The position of the leucine zipper is also strictly conserved thereby accounting for ability of E2F-1 to form heterodimers with human and chicken DP-1. E2F-1 expression was analysed in synchronized cells as well as in embryonic or newborn chick tissues and appears to be closely correlated to the cell proliferation rate. In situ hybridization studies have shown very high expression levels in the neuroretina during the early stages of embryonic development when active neuroblast division occurs. In contrast, a sharp down-regulation is observed when cells become postmitotic. Overexpression of the chE2F-1 protein leads to oncogenic transformation only when a truncated version of the transgene lacking the pRb binding domain is used; the full length protein either has no effect or may be deleterious for cell survival.

Adenovirus E2 Proteins↗
PubMed1995

A Bcl-2-related gene is activated in avian cells transformed by the Rous sarcoma virus.

The oncoprotein p60v-src encoded by the Rous sarcoma virus (RSV) genome is the prototype of non-receptor tyrosine kinases. More than 50 targets of p60v-src have been described to date. However, the precise mechanisms of RSV transformation remain to be elucidated. Here, we present the study of a new v-src-activated gene, NR-13, which encodes a protein identified as a new member of the Bcl-2 family. This protein is localized in the membrane with a pattern already observed with Bcl-2. In quail embryos, this gene is mainly expressed in neural and muscular tissues. Its expression is dramatically down-regulated after embryonic day 7 (E7) in the optic tectum. To evaluate a possible role for NR-13 in the control of apoptotic processes in this particular brain area, in situ hybridization and DNA ladder fractionation studies were performed to correlate NR-13 expression with typical situations of apoptosis during brain development. Our results support the idea that RSV could activate anti-apoptotic functions of the host cell resulting in an increase of their lifespan, which could be particularly relevant to tumour formation.

Amino Acid Sequence↗
PubMed1995

The expression of the avian clusterin gene can be driven by two alternative promoters with distinct regulatory elements.

Clusterin cDNA has been isolated as a copy of a mRNA overexpressed in a wide variety of biological disorders, including tissue regression, brain injuries and oncogenic cell transformation. While the molecular cloning of the rat and the human clusterin genes has revealed a high degree of conservation of the genomic organization between mammals, the avian locus described here illustrates several divergent features. The avian gene has the particularity to be transcribed from at least two different promoters, both of which are active in transient expression assays using the quail QT6 transformed cell line. The detection of the two clusterin mRNA species by reverse-transcription-mediated PCR reveals a coordinated initiation of transcription from both promoters in all organs tested. In possible relation to the bipartite organization of the avian regulatory region, the putative cis-elements described in the unique mammalian promoters appear divided among the two avian promoters. In addition, the sequence comparison of avian and mammalian regulatory sequences has allowed the identification of a conserved putative cis-element which appears to be the target for specific DNA-binding factors.

Amino Acid Sequence↗
PubMed1995

The relationship of Piry virus to other vesiculoviruses: a re-evaluation based on the glycoprotein gene sequence.

By sequencing the 3 half of the Piry virus genome, we show that Piry virus, like the other vesiculoviruses, contains the genes for nucleoprotein N, phosphoprotein P, matrix protein M, glycoprotein G and polymerase protein L, in that order. Our analysis of the Piry G protein sequence suggests that Piry and Chandipura are related to each other as closely as the Indiana and New Jersey vesicular stomatitis virus serotypes are to each other. A re-examination of amino acid sequences in the nucleocapsid protein shows that this relationship is also true of the more conserved central region of this protein and that the greatest divergence between Piry and Chandipura has occurred in two other regions of the nucleocapsid protein.

Amino Acid Sequence↗
PubMed1995

RNA-dependent DNA binding activity of the Pur factor, potentially involved in DNA replication and gene transcription.

The PUR element is a polypurine polypyrimidine motif that can stimulate transcription, encountered in the 5' regions of various genes and in the vicinity of several DNA replication initiation zones. We demonstrate that the PUR complex formation between the purine-rich strand of PUR and nuclear extracts can be prevented by pretreatment of nuclear extracts with RNA-damaging agents such as UV light or RNase A. A biochemical affinity method reveals that small RNA molecules copurify with the Pur factor. Moreover, the PUR binding activity of RNA-depleted nuclear extracts can be restored by addition of phenol-extracted RNAs. This work adds a new member in the emerging class of ribonucleoprotein particles as regulatory factors of the genetic expression.

Animals↗
PubMed1994

Induction of apoptosis in mouse [correction of rat] olfactory neuroepithelium by synaptic target ablation.

The olfactory system provides a useful in vivo model for studying the influence of synaptic targets on the survival of relay neurones. The bipolar sensory neurones located in the olfactory mucosa project synaptically onto the ipsilateral olfactory bulb, and their survival depends on the integrity of this connection. We demonstrate here that the retrograde neuronal degeneration induced by olfactory bulb removal involves apoptosis. As revealed by typical nucleosome-sized fragmentations of the genomic DNA, the apoptosis rate reaches a maximum 32 h after bulbectomy. A transient c-fos mRNA accumulation was detected, peaking 16 h after bulbectomy, suggesting that c-fos is involved in the early steps of programmed cell death.

Animals↗
PubMed1994

Structure-activity studies in E. coli strains on ochratoxin A (OTA) and its analogues implicate a genotoxic free radical and a cytotoxic thiol derivative as reactive metabolites.

Ochratoxin A (OTA), its major metabolite in rodents, ochratoxin alpha, and seven structurally related substances were assayed for SOS DNA repair inducing activity in Escherichia coli strain PQ37. At concentrations of 0.1-4 mM, OTA, chloroxine, 5-chloro-8-quinolinol, 4-chloro-meta-cresol and chloroxylenol induced SOS DNA repair in the absence of an exogenous metabolic activation system. Ochratoxin B, ochratoxin alpha, 5-chlorosalicylic acid and citrinin were inactive, but all except ochratoxin alpha were cytotoxic. Thus, the presence of chlorine at C-5 appears to be one determinant of genotoxicity in these substances. Amino oxyacetic acid, an inhibitor of the cysteine conjugate beta-lyase, decreased the cytotoxicity of OTA but did not alter its genotoxic activity, suggesting the formation of a cytotoxic thiol-containing derivative. The mechanisms by which OTA and some of its active analogues induce SOS DNA repair activity was further investigated in E. coli PQ37 and in three derived strains (PQ300, OG100 and OG400), containing deletions within the oxy R regulon. The response in strain PQ37 was measured in the absence and presence of Trolox C, a water-soluble form of vitamin E. Trolox C completely quenched the genotoxicity of OTA, and the effect was similar in the mutant and wild-type strains. These results implicate an OTA-derived free radical rather than reduced oxygen species as genotoxic intermediate(s) in bacteria.

Escherichia coli↗
PubMed1994

Familial hemolytic-uremic syndrome and homozygous factor H deficiency.

Inherited hemolytic-uremic syndrome (HUS) is unusual. We report the occurrence of HUS in two siblings; one died at an early age while the other (the proband) has presented with three episodes of HUS since the age of 19 years. The finding of a persistently low serum C3 level in this patient led to a thorough evaluation of her complement cascade and a family investigation. The proband and her asymptomatic younger sister were found to have very low serum levels (5% of normal) of factor H, a regulatory protein of the alternative complement pathway. Both patients had low levels of serum C3, factor B, CH50 and VAH50, reflecting persistent alternative pathway activation. The father and mother both had half-normal serum factor H levels but an otherwise normal complement profile. Other members of the extended pedigree were also found to have half-normal serum factor H levels. In conclusion, in this family, factor H deficiency appears to be associated with HUS and is transmitted as an autosomal recessive trait. Persistent C3 hypocomplementemia in the setting of familial and/or recurrent HUS should be a clue to a possible inherited complement deficiency.

Adult↗
PubMed1993

The PUR element stimulates transcription and is a target for single strand-specific binding factors conserved among vertebrate classes.

The PUR element has originally been defined in human, as a purine-rich motif present in a DNA replication initiation zone, whose purine strand is capable of binding a single strand-specific factor termed Pur, present in HeLa cell nuclear extracts. We have identified a related DNA element, in the 5' region of the quail clusterin gene, for its positive influence on the transcription of this gene. In the present work, we show that this element does correspond to a novel cis-element of transcription, still active when placed in an heterologous promoter. We also present a series of evidences showing that the avian PUR-specific binding factors are closely related to those previously identified in human. The human Pur alpha protein is capable of binding the quail clusterin PUR element as well as the human c-myc gene-derived PUR element. UV-crosslinking and Southwestern analyses reveal that the Pur factors present in HeLa and avian cells are closely related. The physical interactions with the PUR motif of Pur alpha and of the avian Pur factor are identical, as shown by PUR mobility-shift assay and methylation interference. Our results suggest that, in addition to their possible involvement in the initiation of DNA replication, these Pur factors are likely to act as transcription trans-activators.

Animals↗
PubMed1993

Transforming growth factor beta 1-mediated growth inhibition in chick embryo fibroblasts: reversion by virally-expressed nuclear oncogenes.

Transforming growth factor beta 1 (TGF-beta 1) inhibits growth of primary cultures of chick embryo fibroblasts by affecting G1 and strongly increasing the generation time. This inhibition is reversed by the nuclear oncogenes v-jun, v-fos, v-myc, but not v-erbA and v-ets. It is also reversed by v-myb from either avian myeloblastosis virus or avian E26 retrovirus. Taken together, these results strongly suggest that independent, functional interferences may take place between the TGF-beta 1-induced growth inhibitory pathway and the oncogen-driven stimulatory pathway(s) at the level of the AP-1, Myc, and Myb transcription factors.

Animals↗