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Biomedical subjects

J Fournier

Publications and source records attributed to J Fournier.

At least 55 records · Page 3Linked to original sources

Absence of germline mutations of exons 5 to 8 of the P53 gene in 26 breast cancer families from the north of France.

We looked for germline mutations of exons 5 to 8 of the P53 gene in 27 female patients from 26 families originating from the north of France who had breast cancer and at least one first degree relative also affected with breast cancer. Detection of the mutations was made by single strand conformation polymorphism analysis. No mutation was found in any patient, confirming that germline mutations of the P53 gene are very rare in familial breast cancer (apart from Li Fraumeni families).

Adult↗

Radical oxidation reactions of the purine moiety of 2'-deoxyribonucleosides and DNA by iron-containing minerals.

The radical oxidation capability of several classes of iron minerals, including biotite, hematite, magnetite, minette, nemalite, pyrite, vivianite and two chrysotiles (asbestos), was investigated by using a double experimental approach. One involved the electron spin resonance spin-trapping measurement of organic radicals obtained by the reaction of activated oxygen species, released upon incubation of the minerals in phosphate buffered solutions with formate used as the target molecule. In addition, the formation of mineral-mediated oxidation purine decomposition products, including 7,8-dihydro-8-oxo-2'-deoxyguanosine and 7,8-dihydro-8-oxo-2'-deoxyadenosine, was searched within nucleosides and DNA by using specific and sensitive HPLC electrochemical assays. Emphasis was placed on the mechanistic aspects of the radical oxidation reactions involved in the formation of the two C(8) hydroxylated purine decomposition products.

Adenine↗

Mineral fibres: correlation between oxidising surface activity and DNA base hydroxylation.

In relation to their potential genotoxic properties, the ability of inorganic particles to induce activated species of oxygen with strong oxidative properties can be studied by various methods. In this study the oxidative surface properties of 10 different natural and synthetic mineral fibres were investigated by: (1) an electron paramagnetic resonance technique in which formate was used to trap oxidative species; and (2) a high performance liquid chromatography (HPLC) based method in which deoxyguanosine was used as a trapping agent and the formation of 8-hydroxy-deoxyguanosine (8 OHdG) was analysed. Ground iron-containing fibres such as crocidolite and amosite were the most reactive, whereas fibres without iron--for example, ceramic fibres, xonotlite, and Tismo L--were completely inactive. A good correlation was found when the results from the two methods were compared (r = 0.86).

Chromatography, High Pressure Liquid↗

Patient acceptance and differential perceptions of quality of life measures in a French oncology setting.

A three-part study evaluated French cancer patients' acceptance of self-rated quality of life measures, the predictive value of these measures, and the agreement between patient and health provider ratings of patient quality of life. In part one, 93% of 137 patients indicated a willingness to complete the Qualite de la Vie-Questionnaire (QOL-Q) and Analogues Lineaires pour la Mesure de la Qualite de vie (LA), and 63.6% indicated a willingness to be interviewed by a psychologist. Willingness to complete the scales was related to hospitalization status and treatment modality. In parts two and three, 100 patients were asked to complete the QOL-Q, LA, the Karnofsky Index (KI) and a side-effects checklist, and to undergo a psychological interview. Following interview, a psychologist rated the patients using the QOL-Q, and classified patient level of emotional distress. Oncologists rated the patient using the KI and the side-effects checklist. The results indicate that the patients' ratings of their quality of life were higher than the psychologist's ratings, and that the QOL-Q has predictive value in identifying severe emotional distress. Low level of patient and physician agreement on the KI was partially explained by patient age and cancer site. A moderate level of agreement was found between patient and physician perceptions of side effects. The study suggests that the QOL-Q, not the LA, may be useful as a screening tool to identify patients with impaired quality of life, and that self-rated measures should be included in quality of life assessments.

Adult↗

Enhancement of neurite outgrowth from central nervous system neurons in primary culture by thrombin inhibitors.

Previous studies have shown that serine protease inhibitors promote neurite outgrowth from neuroblastoma cells, sympathetic neurons and sensory ganglia in culture. In the present study, a neurite promoting activity of thrombin inhibitors such as hirudin, D-Phe,Pro,Arg-CH2Cl, and paraamidinophenylalanine derivatives, was found in rat embryo (E17) septal neurons in primary culture. In contrast, no effect was shown on choline acetyltransferase activity of septal fragments in culture. These results suggest that thrombin inhibitors might interact with a thrombin-like protease involved in the control of neurite outgrowth.

Amidines↗

Differential regulation in tobacco cell suspensions of genes involved in plant-bacteria interactions by pathogen-related signals.

Six cDNA clones whose corresponding mRNAs accumulate early during the hypersensitive reaction in tobacco leaves have been classified into 2 groups according to their maximum levels of accumulation in an incompatible versus a compatible interaction with Pseudomonas solanacearum. We present evidence that, at least in the first stages of the interaction, tobacco cell suspensions retain the ability to respond differentially to compatible and incompatible isolates of P. solanacearum. In addition, studies on the effect of a fungal elicitor on the accumulation of the mRNAs corresponding to the cDNA clones in cell suspensions indicate that only one group of genes responds to this treatment.

Cells, Cultured↗

Feeding trials of Listeria monocytogenes with a nonhuman primate model.

One of the major unanswered questions regarding the presence of Listeria monocytogenes in foods is how many cells must be ingested in order to cause illness. To answer this question, studies were undertaken by using Macaca fascicularis (cynomolgus monkey) as an animal model. Healthy nonhuman primates were dosed with various concentrations of L. monocytogenes suspended in sterile whole milk. Final concentrations of 10(5), 10(7), and 10(9) total cells of the organism were used; a control was also included. Blood samples, as well as fecal and nasal specimens, were taken at various time intervals. Only animals that received 10(9) cells of L. monocytogenes became noticeably ill, with symptoms of septicemia, irritability, loss of appetite, and occasional diarrhea. Monkeys that received 10(7) and 10(9) cells shed L. monocytogenes in the feces for approximately 21 days. In monkeys that received the dose of 10(9) cells, severe lymphopenia and neutrophilia occurred within 48 h. In a separate trial, monkeys received Maalox to reduce the gastric acidity of the stomach. However, no substantial differences were observed between Maalox-treated and control monkeys.

Animals↗

[Various mechanic characteristics of bony structures of the temporo-mandibular joint in several classes of mammals studied by measurement of hardness and resistance to penetration].

Applying the principles of mechanics, the authors have studied and compared the bony structures of the temporo-mandibular joint. Using the means of investigation usually implemented in the metallurgical sector, they have tried to establish a link between the morphology and mechanical strength of the various components of this joint in some subjects belonging to the mammals classification and with various feeding modes. The results obtained by hardness micrometry tend to show that during masticatory movements, the temporo-mandibular joint works in a hanging rather than in a compressed mode.

Animals↗

[Mechanics of the characteristic geometry of the human spine undergoing vertical pressure].

Since MAGENDIE in 1816, it has been a common assertion in books of Anatomie that curves of the spine increase its strength. This increase in strength has been estimated by a formula attributed to EULER: R = nc2 + 1 in which R is the strength and nc2 stands for the square of the number of curves. Applying the actual law of Euler on the strength of beams submitted to a vertical effort, the authors conclude that strength is increased by about 30% and not multiplied by 10, 16 or even 17 as is often falsely written.

Biomechanical Phenomena↗

Induction of Proteinase Inhibitors in Tobacco Cell Suspension Culture by Elicitors of Phytophthora parasitica var. nicotianae.

An elicitor preparation obtained from Phytophthora parasitica var. nicotianae, a pathogen of tobacco, induced an accumulation of proteinase inhibitors and a stimulation of ethylene synthesis in a tobacco (Nicotiana tabacum) cell suspension culture. About 30 micrograms per milliliter of elicitor were necessary for maximal induction of proteinase inhibitor accumulation, and the response was detectable after 12 hours of incubation with elicitor. Accumulation of proteinase inhibitors required de novo protein synthesis, since cycloheximide completely inhibited its elicitation, and actinomycin D inhibited it partially. One of the inhibitors was purified by a procedure that included heating, (NH(4))(2)SO(4) precipitation, ion-exchange chromatography, and affinity chromatography. The purified inhibitor was shown to be a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of about 10,500. It inhibited trypsin but not chymotrypsin.

Journal Article↗

Conjugates of elliptinium acetate with mouse monoclonal anti-alpha-fetoprotein antibodies or Fab fragments: in vitro cytotoxic effects upon human hepatoma cell lines.

Elliptinium acetate (EA) is a new anti-cancer compound displaying cytostatic activity against various malignancies including hepatoma. Using 3 hepatoma cell lines, we compared the in vitro activity of doxorubicin (reference drug), of EA and of conjugates made up with this latter drug and monoclonal antibodies (MAbs). The linkage was performed by a direct oxidation method. Specific immunoconjugates were prepared with an anti-alphafetoprotein (AFP) MAb (AF01) or its Fab fragment (Fab AF01). Non-specific conjugates were obtained with an anti-thyroglobulin MAb (TG01) or its Fab (Fab TG01). Direct membrane injury (51Cr-release), DNA and protein synthesis as well as AFP release were investigated for all compounds. Free EA displayed only weak activity on DNA and protein synthesis, at 10-fold higher molar concentration than doxorubicin. Conjugation of EA with whole AF01 allowed significant potentiation of protein synthesis inhibition without affecting the 3 other tests. In contrast, Fab AF01 x EA conjugates displayed a marked effect in the 4 tests; in particular, this conjugate was at least 100 times more efficient than any other compound when tested in the 51Cr-release test. Neither Fab AF01 nor free EA alone or in combination exhibited such an effect. Fab TG01 x EA conjugate was not directly cytotoxic but potentiated inhibition of DNA and protein synthesis between 2- and 10-fold. The mechanism of the direct cytotoxic effect of anti-AFP Fab x EA conjugate, which has never been described in any other immunodrug model, was investigated.

Alkaloids↗

[Assessment of the quality of life].

Increases in survival rates obtained in the years with cancer patients are offset by the aggressivity of the treatments and especially by those based on antitumor drugs. So far, oncologists have addressed themselves to the notions of survival (with or without evolution of the disease), and of indicators of tumor regression and toxicity. The global notion of quality of life may be an additional parameter for weighing the impact of anticancer therapies. The assessment of the quality of life of a patient is complicated by the issue of objective versus subjective judgements. The patient's self-appreciation of his status is of primary importance, but quality of life is only a relative assessment of the patient linked to the different stages of therapy. The quest for a suitable analytical tool endowed with sufficient sensitivity and reproducibility has not yet ended. Some authors regard to psychological contact as the only satisfactory means in terms of fruitfulness, although it raises questions of quantitative estimations. Others, especially anglo-saxon authors, have compiled questionnaires to be filled out by the patients and rated them using general or itemized scores. Similar to this type of questionnaires is the technique of the linear analogs which consists in asking the patient to express an appraisal of his state by indicated a position between two extreme situations on a linear scale graded in centimeters. Some authors have prepared general questionnaires suitable to all types of cancer. Others, instead, have perfected tools specific to certain types of tumors. Finally, methods of global assessment have also been proposed, notably by Bernheim. Thus, questions arise such as the evaluation (doctor's versus patient's judgement), and that of finding a tool for assessing the physical autonomy and the well-being (in the wide sense) of the patient. In addition, such a tool should be applicable to a large number of cancer patients in order to achieve an objective evaluation of the proposed treatments. Here we report preliminary results of a study aimed at answering these different questions. Our study intended to compare: the assessment of the general condition versus the toxicity of the therapy as evaluated by the patient and the doctor; the appreciation of quality of life as determined by questionnaires and linear analogues filled out by the patients and psychological interviews. Finally, a compliance study could be made on the assessment of the quality of life in a randomized chemotherapeutic trial concerning patients with metastatic breast cancers.

Female↗