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Biomedical subjects

A Petit

Publications and source records attributed to A Petit.

At least 19 recordsLinked to original sources

Microwave-assisted preparation of cyclic ketals from a cineole ketone as potential cosmetic ingredients: solvent-free synthesis, odour evaluation, in vitro cytotoxicity and antimicrobial assays.

Some cyclic ketals derived from (+)1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one were obtained in excellent yields by microwave activation under solvent-free conditions, as a 'green chemistry' procedure. The results obtained using acidic alumina containing 7% p-toluenesulfonic acid, as mineral support, are reported and compared with those obtained by classical methods. The new compounds were tested for their olfactive character and for a potential cosmetic use. In vitro skin cytotoxicity tests were carried out on the most promising compounds, by using NCTC 2544 human keratinocytes as target cells. They all displayed slight cytotoxic effects which were one order of magnitude lower than those found with sodium dodecylsulphate positive control. Two compounds that resulted interesting as toothpaste aromas, were submitted to antimicrobial assays and showed their activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus hominis, Propionibacterium acnes and Candida albicans.

Anti-Infective Agents↗

[Intracardial migration of a bullet: diagnosis and management].

Venous pellet embolism to the cardia after shotgun wound is a very rare occurrence. Number and size of pellets, at the impact make this migration easier; embolism is asymptomatic and may occur 15 years after the injury. Many problems must be mentioned: mechanics of entry into the heart (own velocity, venous flow), topographic diagnosis (chest X-ray, transthoracic, transoesophageal ultrasound and CT-scan), local outcomes of this projectile (local erosion, clot, endocarditis), destination of a new migration (pulmonary embolism, left heart), indications of extraction, supervision. Extraction musn't be systematic, but only in the event of a patent foramen ovale with a risk of systemic embolism, which clinical outcomes are most serious or in the event of complications. The authors report on a 22 years old patient observation whose treatment was abstention and supervision.

Adult↗

Seasonal fluctuations and long-term persistence of pathogenic populations of Agrobacterium spp. in soils.

Short- and long-term persistence of pathogenic (i.e., tumor forming) agrobacteria in soil was investigated in six nursery plots with a history of high crown gall incidence. No pathogenic Agrobacterium strains were isolated in soil samples taken in fall and winter in any plots, but such strains were isolated from both bulk soils and weed rhizospheres (over 0.5 x 10(5) pathogenic CFU/g of bulk soil or rhizosphere) in three out of six plots in spring and summer. PCR amplifications of a vir sequence from DNA extracted from soil confirmed the presence of Ti plasmids in summer and their absence in fall and winter. The results indicate that strains that harbor a Ti plasmid had an unforeseen positive fitness versus Ti plasmid-free strains in soil and rhizosphere in spring and summer in spite of the apparent absence of tumor, and hence of opines. The gain of fitness occurred during a bloom of all cultivable agrobacteria observed only in conducive soils. An evolution of the pathogenic population was recorded during a 4-year period in one particularly conducive soil. In 1990, the pathogenic population in this soil consisted of only biovar 1 strains harboring both octopine- and nopaline-type Ti plasmids. In 1994, it consisted of only nopaline-type Ti plasmids equally distributed among biovar 1 and 2 strains. These results suggest that nopaline-type Ti plasmids conferred a better survival ability than octopine-type Ti plasmids to biovar 2 agrobacteria under the present field conditions.

DNA, Bacterial↗

Astrocytes from cerebral cortex or striatum attract adult host serotoninergic axons into intrastriatal ventral mesencephalic co-grafts.

The identification of axon growth inhibitory molecules offers new hopes for repair of the injured CNS. However, the navigational ability of adult CNS axons and the guidance cues they can recognize are still essentially unknown. Astrocytes may express guidance molecules and are known to have different regional phenotypes. To evaluate their influence on the affinity of adult serotoninergic (5-HT) axons for a projection target, we co-implanted astrocytes from the neonatal striatum, cortex, or ventral mesencephalon together with fetal ventral mesencephalic tissue into the striatum of adult rats. Two months after surgery, quantification after in vitro 5-[1,2-(3)H]serotonin ([(3)H]5-HT) uptake and autoradiography showed that ventral mesencephalic grafts with co-grafted cortical or striatal astrocytes were four times and three times, respectively, more densely innervated by host 5-HT axons than control ventral mesencephalic grafts with or without co-grafted ventral mesencephalic astrocytes. Immunohistochemistry for glial fibrillary acidic protein, vimentin, or chondroitin-sulfate proteoglycans revealed no qualitative or quantitative differences in host astroglial scar or production of inhibitory molecules that could explain these differences in 5-HT innervation. These results demonstrate that astrocytes grown in culture from different brain regions have the potential to influence the growth and maintenance of adult 5-HT axons in a graft of neural tissue from another brain region. It should now be feasible to identify the molecules expressed by cultured cortical or striatal, but not by ventral mesencephalic, astrocytes that have these tropic actions on 5-HT axons of the neostriatum.

Animals↗

Effects of digestion protocols on the isolation and characterization of metal-metal wear particles. I. Analysis of particle size and shape.

Isolation of metal wear particles from hip simulator lubricants or tissues surrounding implants is a challenging problem because of small particle size, their tendency to agglomerate, and their potential for chemical degradation by digestion reagents. To provide realistic measurements of size, shape, and composition of metal wear particles, it is important to optimize particle isolation and minimize particle changes due to the effects of the reagents. In this study (Part I of II), transmission electron microscopy (TEM) was used to examine and compare the effects of different isolation protocols, using enzymes or alkaline solutions, on the size and shape of three different types of cobalt-based alloy particles produced from metal-metal bearings. The effect on particle composition was examined in a subsequent study (Part II). Large particles (<1200 nm) were generated by dry abrasion of CoCrMo alloy against itself and small particles (<300 nm) were generated by hip simulator testing of a metal-metal implant pair in the presence of either distilled-deionized water or a 95% bovine serum solution. The reagents changed particle size and to a lesser extent particle shape. For both large particles and small particles generated in water, the changes in size were more extensive after alkaline than after enzymatic protocols and increased with alkaline concentration and time in solution, up to twofold at 2 h and threefold at 48 h. However, when isolating particles from 95% serum, an initial protective effect of serum proteins and/or lipids was observed. Because of this protective effect, there was no significant difference in particle size and shape for both oval and needle-shaped particles after 2 h in 2N KOH and after enzymatic treatments. However, round particles were significantly smaller after 2 h in 2N KOH than after enzymatic treatments. Particle composition may also have been affected by the 2N KOH treatment, as suggested by a difference in particle contrast under TEM, an issue examined in detail in Part II.

Animals↗

Effects of digestion protocols on the isolation and characterization of metal-metal wear particles. II. Analysis of ion release and particle composition.

The isolation of metal wear particles from hip simulator lubricants is important for understanding wear mechanisms and the tissue response to particulate material. Part I of this study demonstrated that isolation protocols involving digestion reagents can chemically attack metal-metal wear particles, reducing their size and changing their shape. In part II of this study, Co and Cr ion concentrations in solution after each digestion protocol were measured by flame atomic absorption spectrometry, and wear particle composition was determined by X-ray analysis spectra. The exposure of wear particles in water to alkaline solutions caused an increasing release of Cr ions in solution with alkaline concentration and time, and a corresponding decrease in particle Cr peak intensity on X-ray spectra. As a result, particles exposed to 12N KOH for 48 h displayed Co peaks and no Cr. In contrast, enzymatic protocols caused a release of Co ions in solution and a corresponding decrease in particle Co peak intensity on X-ray spectra, especially with sodium phosphate as a buffer. However, when isolating particles from 95% serum, there was an initial protective effect of serum proteins, presumably because of their binding to Co and Cr. As a result, the extent of Cr ion release from metal wear particles in 95% serum after alkaline treatments was diminished, although still present, whereas both enzymatic protocols resulted in a negligible release of Co and Cr ions into solution. Particle composition analysis after enzymatic treatments revealed the presence of chromium oxide particles and CoCrMo particles with variable Co/Cr ratios. After alkaline treatments, the chromium oxide particles increasingly disappeared with time and alkaline concentration, demonstrating a change in particle composition after these treatments. This study demonstrated that digestion reagents can induce chemical changes that affect particle composition. Of all the protocols tested, the enzymatic protocols were the least damaging to the particles and appeared to be the best compromise for isolation and characterization of metal particles, especially in 95% serum. Special care on the choice of buffers should be taken when isolating particles from a lower concentration of serum.

Animals↗

[Anti-digoxin antibodies in severe digitalis poisoning in an 11-day old infant. Review of the literature].

Acute digitalis intoxication bringing into play the prognosis for survival is a rare complication in children, particularly in the neonatal period. We describe the case of an accidental massive digitalis intoxication in a newborn aged 11 days, which caused a complete atrioventricular block and a state of cardiogenic shock. The outcome was favorable four hours after administration of the first dose of anti-digoxin antibodies, with a complete reversal of clinical and electrocardiographic signs. The onset of first-degree atrioventicular block 48 hours afterward made us consider the possibility of the tissular salting-out effect of the digoxin and led us to administer a second dose of specific antibodies. The originality of this case has to do with the severity of the initial clinical picture, its total reversal with antibodies and the salting-out phenomena that followed. The case reminds us, along with the data in the literature, the criteria of wrong prognoses in massive digitalis intoxication in the child and the indications for anti-digoxin antibodies.

Antibodies↗

Structure and characterization of the crown gall opines heliopine, vitopine and ridéopine.

The crown gall opines heliopine from tumors induced by octopine type Agrobacterium tumefaciens strains A6, A136(pTiB6-806), E9, A652 and 1590-1 and vitopine from tumor induced by grapevine strains S4 and T2 are identical to synthetic N2-(1'R-carboxyethyl)-L-glutamine. Tumors produced by strains S4 and T2 do not contain octopine or lysopine, but they do contain heliopine and the new opine ridéopine identified as N-(4'-aminobutyl)-D-glutamic acid. Grapevine strains S4 and T2 grow normally on tumor heliopine or synthetic heliopine and on tumor and synthetic ridéopine as well as on ridéopine lactam as sole carbon source. While octopine strains A6 and A136(pTiB6-806) do not grow on heliopine, mutant colonies do appear after a few weeks. Heliopine catabolism by octopine strains is not induced by octopine.

Agrobacterium tumefaciens↗

New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage.

We have designed new non-peptidic potential inhibitors of gamma-secretase and examined their ability to prevent production of amyloid-beta 40 (Abeta40) and Abeta42 by human cells expressing wild-type and Swedish-mutant beta-amyloid precursor protein (betaAPP). Here we identify three such agents that markedly reduce recovery of both Abeta40 and Abeta42 produced by both cell lines, and increase that of C99 and C83, the carboxy-terminal fragments of betaAPP that are derived from beta-and alpha-secretase, respectively. Furthermore, we show that these inhibitors do not affect endoproteolysis of endogenous or overexpressed presenilins. These inhibitors are totally unable to affect the mDeltaEnotch-1 cleavage that leads to generation of the Notch intracellular domain (NICD). These represent the first non-peptidic inhibitors that are able to prevent gamma-secretase cleavage of betaAPP without affecting processing of mDeltaEnotch-1 or endoproteolysis of presenilins. The distinction between these two proteolytic events, which are both prevented by disruption of presenilin genes, indicates that although they are intimately linked with betaAPP and Notch maturation, presenilins are probably involved in the control of maturation processes upstream of enzymes that cleave gamma-secretase and Notch.

Amyloid Precursor Protein Secretases↗

Endogenous beta-amyloid production in presenilin-deficient embryonic mouse fibroblasts.

Genetic and biochemical evidence have led to the suggestion that presenilins could be the long-searched-for gamma-secretase, the proteolytic activity that generates the carboxy terminus of amyloid beta-peptides. This activity is also thought to be responsible for the release of the Notch intracellular domain (NICD) from Notch. Here, we report the production of endogenous secreted and intracellular 40- and 42-amino-acid Abeta peptides in mouse fibroblasts deficient in presenilin 1, presenilin 2 or both. We show that the endogenous production of Abeta40 and Abeta42 was not altered by presenilin deficiency. By contrast, inactivating presenilin genes fully abolished NICD production. These data indicate that Abeta and NICD production are distinct catabolic events. Also, even though NICD formation is indeed presenilin dependent, endogenous secreted and intracellular beta-amyloid peptides are still generated in absence of presenilins, indicating that there is a gamma-secretase activity distinct from presenilins, at least in murine fibroblasts.

Amyloid beta-Peptides↗

[Magnetic resonance imaging of dilatation of the ascending aorta after repair of coarctation of the aorta].

The authors studied the risk factors for dilatation of the ascending aorta in patients operated for coarctation of the aorta. A prospective study of the diameters of the ascending aorta by magnetic resonance imaging was undertaken in 46 patients with an average age of 30 months (range 6 days to 11 years) at surgery, and 10 years of age (6 months to 31 years) at the time of the investigation. The diameters were measured at the level of the sinus of Valsalva, at the sino-tubular junction, and compared with reference tables with respect to body surface area. Twenty six per cent of patients had dilatation of the ascending aorta. The predisposing factors were investigated. Age, type of surgery, postoperative hypertension. Doppler gradient in the isthmic region, anatomical appearances of the repair observed by MRI were not predictive of this complication. On the other hand, age of patients at MRI and bicuspid aortic valves (present in 66% of cases) (p < 0.05) were significant risk factors. These results indicate that regular follow-up by echocardiography or MRI of the diameter of the ascending aorta is necessary in patients operated for coarctation of the aorta and with bicuspid aortic valves.

Age Factors↗

Lupine leghemoglobin I: expression in transgenic Lotus and tobacco tissues.

The proximal parts of the promoters of the genes for symbiotic-type hemoglobins are generally conserved, but the promoter of the lbI gene of lupine (LulbI) shows some unusual structural features. It lacks typical organ-specific elements characteristic of all the leghemoglobin gene promoters described thus far. We have analysed its functional activity in transgenic Lotus corniculatus. A fusion construct between the lbI promoter and the GUS reporter gene was expressed mainly in the central zone of the root nodule, but the product was also detected in the non-nodule root zone and in roots in tissue culture. In roots of transgenic tobacco, the activity of the promoter was only 24% lower than in Lotus nodules. LulbI promoter activity was also detected in tobacco leaves. Lupine hemoglobin I has a higher sequence identity to symbiotic-type hemoglobins and thus it groups within the "Class II" hemoglobins.

Base Sequence↗

Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy.

BACKGROUND: The topoisomerase II-targeted drugs, epipodophyllotoxins and anthracyclines, have been shown to induce therapy-related AML (t-AML) characterized by a short latency period after chemotherapy, the absence of prior myelodysplastic syndrome and stereotyped chromosome aberrations. Few reports have been published on patients treated with the anthracenedione mitoxantrone which also targets topoisomerase II. We observed 10 cases of such t-AML over a 7-year-period in breast cancer patients treated with mitoxantrone combined with fluorouracil, cyclophosphamide and regional radiotherapy, and in three cases with vindesine. PATIENTS AND METHODS: We retrospectively analyzed patients referred to our hospital for AML with a past history of polychemotherapy for breast cancer, including mitoxantrone, either as adjuvant (8 patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1 patient). We studied the probability of developing t-AML in a prospective series of 350 patients treated with an adjuvant FNC regimen (mitoxantrone, fluorouracil, cyclophosphamide) and radiation therapy. RESULTS: The median age was 45 years (range 35-67). t-AML developed 13-36 months (median 16) after beginning chemotherapy for breast cancer, and 4-28 months (median 10.5) after ending treatment. As described in t-AML following treatment with epipodophyllotoxins or anthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10), and characteristic karyotype abnormalities that also can be found in de novo AML: breakpoint on chromosome 11q23 (3 patients), inv(16)(p13q22) (2 patients), t(15;17)(q22;q11) (1 patient), t(8;21)(q22;q22) (1 patient) and del(20q)(q11) (1 patient). The prognosis was poor. All patients died of AML shortly after diagnosis. Since two patients had been enrolled in a prospective trial for the treatment of breast cancer which included 350 patients, the probability of developing t-AML was calculated to be 0.7% from 25-40 months, using the Kaplan-Meier method (95%, confidence interval (95% CI): 0.1-4.5). CONCLUSIONS: The combination of mitoxantrone with cyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, as with other topoisomerase II-targeted drugs. Despite a low incidence, the prognosis appears to be poor.

Adult↗

Novel proline endopeptidase inhibitors do not modify Abeta40/42 formation and degradation by human cells expressing wild-type and swedish mutated beta-amyloid precursor protein.

Previous studies have suggested that proline endopeptidase (PE) could participate to the catabolism of the beta-amyloid peptide (Abeta) or to the physiopathological maturation of the beta-amyloid protein precursor (betaAPP). We have examined the putative ability of human purified PE to catabolize Abeta40 and Abeta42 and the possible contribution of this enzyme to the generation of Abeta40 and Abeta42 in human HEK293 cells. We show first that purified human PE does not degrade synthetic Abeta40 and Abeta42, in vitro. We establish that HEK293 cell homogenates exhibit a Z-Gly-Pro-7AMC-cleaving enzyme, the activity of which is inhibited by Z-Pro-Prolinal and S17092 and S19825, two novel PE inhibitors, with affinities similar to those displayed on the purified human PE. These inhibitors also penetrate cells and achieve a full inhibition of endogenous proline endopeptidase in human cells. By means of selective antibodies directed towards the C-terminal of Abeta40 and Abeta42, we assessed the effect of PE inhibitors on the recovery of both Abeta species. This was examined in HEK293 cells stably overexpressing the wild-type and the familial Alzheimer's disease-related Swedish mutated beta-APP. We establish that none of these inhibitors affected Abeta40 or Abeta42 production in these transfected cells. Overall, our study indicates that human PE does not degrade Abeta40 and Abeta42. Furthermore, PE does not contribute to Abeta40 and Abeta42 formation in HEK293 cells. Therefore, PE does not appear to contribute to the Abeta-related aetiology of Alzheimer's disease.

Amyloid beta-Peptides↗

Characterization of plasmid-borne and chromosome-encoded traits of Agrobacterium biovar 1, 2, and 3 strains from France.

We collected 111 Agrobacterium isolates from galls of various origins (most of them from France) and analyzed both their plasmid-borne and chromosome-encoded traits. Phenotypic analysis of these strains allowed their classification in three phena which exactly matched the delineation of biovars 1, 2, and 3. A fourth phenon was identified which comprises three atypical strains. The phenotypic analysis has also allowed us to identify 12 additional characteristics which could be used to identify the three biovars of Agrobacterium. Our results also suggest that biovar 1 and 2 represent distinct species. Analysis of plasmid-borne traits confirmed that tartrate utilization is a common feature of biovar 3 strains (now named Agrobacterium vitis) and of Agrobacterium grapevine strains in general. Among pathogenic strains of Agrobacterium, several exhibited unusual opine synthesis and degradation patterns, and one strain of biovar 3 induced tumors containing vitopine and a novel opine-like molecule derived from putrescine. We have named this compound ridéopine.

Chromosome Mapping↗