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Biomedical subjects

F Besançon

Publications and source records attributed to F Besançon.

At least 19 recordsLinked to original sources

Post-transcriptional regulation of transferrin receptor mRNA by IFN gamma.

IFN gamma inhibits the rise in transferrin receptor mRNA level which is normally observed when stationary WISH cells are stimulated to proliferate. This effect is not attributable to a change in the transcription rate of the transferrin receptor gene or in the cytoplasmic stability of the mRNA. The IFN gamma-induced reduction of the transferrin receptor mRNA content is already present at the nuclear level to an extent comparable to that observed in whole cells. Thus, IFN gamma does not impair the passage of this mRNA from the nuclear to the cytoplasmic compartment but probably interferes with a nuclear post-transcriptional event during the processing of the immature transferrin receptor mRNA. Two different levels of regulation of transferrin receptor mRNA have been previously reported. Iron modulates the cytoplasmic stability of this mRNA through the binding of a specific cytoplasmic factor, whereas cell growth variation influences the transcription of this gene. Our results suggest the existence of another mechanism of regulation for transferrin receptor gene expression not so far considered. Furthermore, the distinction between the mechanism of regulation exerted by IFN gamma and that exerted by cell proliferation on transferrin receptor gene expression suggests that, in WISH cells, the IFN-induced transferrin receptor decay is not a consequence of cell growth arrest but rather one of the causes of the antiproliferative effect of IFN through iron deprivation.

Blotting, Northern

Direct induction of interferon-gamma- and interferon-alpha/beta-inducible genes by double-stranded RNA.

Using Northern analysis, we here show that the inducibility by double-stranded (ds) RNA of interferon-alpha/beta-inducible genes is not restricted to a few genes but extends to all the genes known to be stimulated by IFN type I in fibroblasts. Moreover, we show that some genes, preferentially regulated by IFN-gamma, are also activated by dsRNA. We present a series of arguments demonstrating that the induction by dsRNA is not mediated by IFN. In addition to the fact that this induction occurs in the presence of cycloheximide and/or anti-IFN-alpha/beta antibodies in fibroblasts, we observed that, in IFN-resistant Daudi cells, ISG15 and IP-10 genes which are not induced by IFN-beta, are still inducible by dsRNA. dsRNA is also still active on 2-5 AS and ISG15 genes in cells carrying homozygous deletions of IFN alpha/beta genes. Actinomycin D experiments and nuclear in vitro elongation assays reveal that the induction by dsRNA involves, as its early step, a transcriptional event. This induction was found not to require protein synthesis, suggesting that activation of preexisting cellular factors is involved. The opposite inducibility by dsRNA of IFN-beta and 2',5'-oligoadenylate (2-5A) synthetase genes in serum-deprived fibroblasts indicates that pathways of induction by dsRNA of these two genes are not identical. Inhibition by 2-aminopurine of the induction of IFN-inducible mRNAs by IFN-beta or dsRNA suggests the participation of a protein kinase in their mechanism of action.

2-Aminopurine

[Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis].

Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.

Adult

Tumour necrosis factor enhances induction by beta-interferon of a ubiquitin cross-reactive protein.

Tumour necrosis factor alpha (TNF-alpha) elicited an antiviral response in some cell lines (MG-63 and HEp-2) but not in others (MDBK). Cell lines that generated an antiviral response to TNF-alpha also showed induction of a 15K protein which shared sequence homology with ubiquitin and reacted with an antibody to ubiquitin. This ubiquitin cross-reactive protein (UCRP) had been demonstrated previously to be induced by interferon. The TNF-alpha induction of UCRP occurred at the level of transcription. TNF-alpha induction of both the antiviral state and the 15K protein was blocked by either monoclonal or polyclonal anti-beta-interferon (IFN-beta) antibody. However no measurable increase in the mRNA specific for IFN-beta was detected after TNF-alpha treatment. Nonetheless, in supernatants from cell cultures, the presence of an antiviral activity inhibitable by anti-IFN-beta antibody indicates that these cells are making IFN-beta already. We conclude that the TNF-alpha induction of antiviral activity and UCRP in cells is dependent upon the presence of constitutive low levels of IFN-beta in the responding cells. Furthermore TNF functions to enhance the existing IFN-beta activity.

Cross Reactions

Relationship between inhibition of cell growth and of transferrin receptor expression by interferon (IFN) alpha: studies in IFN-sensitive and IFN-resistant Daudi cells.

We previously showed that treatment of different cell lines with interferon-alpha (IFN-alpha) concurrently inhibited both cell growth and the rise observed in 125I-labelled transferrin binding when cells are exposed to culture conditions that stimulate proliferation. To gain insight into the relationship between these two IFN-induced inhibitory processes, we investigated the effect of IFN-alpha on the binding of 125I-labelled transferrin to Daudi cells sensitive or resistant to its antiproliferative action. We found a close correlation between the ability of IFN-alpha to inhibit cell growth and to inhibit transferrin receptor expression. Since growth inhibition induced by other agents is not always accompanied by an inhibition of transferrin receptor expression, the previous and present observations suggest that the inhibitory effect of IFN on this expression is at least one of the mechanisms by which IFN inhibits cell proliferation. We also observed that IFN-alpha did not modify transferrin receptor biosynthesis in IFN-sensitive Daudi cells, suggesting that IFN-alpha may change the processing of the transferrin receptor molecules, making them unable to bind transferrin.

Cell Cycle

[Compensatory growth of the kidney. Effects of 3 antihistaminic drugs].

The compensatory growth of the kidney (C. G. K.) in the rat, is accompanied by a lowering of the renal concentration of histamine (507 micrograms/kg 48 hours after the beginning of the C. G. K. against 1,070 micrograms/kg in the normal kidney). Three antihistamines were injected i.p. during the first 48 hours of the C. G. K.: dexchlorpheniramine (H1 antagonist), cimetidine (H2 antagonist) and doxepin (both H1 and H2 antagonist). The C. G. K. was significantly lowered only in the rats that had been treated with doxepin in doses of 0.3 and 1 mg/kg/24 h. None of these treatments altered the histamine concentration in the kidney 48 hours after the beginning of the C. G. K. The action of doxepin might pass through mechanisms other than its anti-histaminic activity.

Animals

[Prediction of new outbreaks of myocardial infarction, based on a multivariate meteorological analysis].

In a previous paper, meteorological circumstances of myocardial infarctions, cerebrovascular attacks, and suicidal attempts were studied by a univariate method. The present work used the same clinical reports, collected by the Medical Emergency Assistance System (SAMU) in the Paris area from 1975 to 1977, but with multivariate calculations. 150 potential predictive indicators were submitted to "progressive ascending selection". Selected indicators were then combined into a composite index by "linear canonic discrimination". This index was tested in terms of successful prediction. The 150 indicators were: 1) meteorological variables, recorded at ground level, such as wind and temperature (expressed respectively in 28 and 24 ways), airpressure, moisture; 2) variables computed from data recorded in altitude; 3) pollutants; 4) non-meteorological indicators, such as day of the week, season, solar activity; 5) the "past of the predictand", i.e. the frequency of infarctions during the previous days; 6) types of weather, defined after confronting meteorological maps with clinical data. The coding of qualitative data required a new procedure. The event to be predicted, which occurred only one day a week, was an incidence of infarctions of at least twice the average. The percentage of successful prediction was 78.7%. The type of weather was by far the best indicator. Detrimental circumstances were changing weathers, with in the order of decreasing correlations, atmosphere fluxes coming from S-SE, E, SW, and NW. These results complete those of univariate analysis. They validate a simple and efficient predictive method, similar in its principle to that used in Germany.

Epidemiologic Methods

[The internal medicine patient at the general hospital].

Patients are defined as internal medicine patients when more than one system is involved. Such patients are lacking in the clinical and epidemiological literature. Among 330 patients discharged from a unit of internal medicine, 212 (64%) were prospectively classified in that category. As compared to the "specialty patients", the "internal medicine patients" were almost the same age (56 vs 53 years) and sex, but more diagnoses were recorded for each: 4.16 vs 2.9 p less than 0.001; their death rate was apparently higher: 12.7% vs 7.6% (NS). Therapeutic results were poor. Psychic disturbances were prevailing, with classical mental diseases, but also major somatic consequences of seemingly minor behavioral deviations. This morbidity is largely avoidable. The discussion addresses the validity of results and their confrontation with data collated in the literature; a few specific characteristics of care; the widely variable psychological reactions of nurses, students, residents and physicians; risks of rejection from the general hospital, for technical and economic reasons; and lastly, risks of rejection by public opinion. Who is prepared to be involved with major morbidity which is time-consuming, largely refractory to management, preventable, unchallenging for some though instructive for others, unsaleable and useless as a vote-catcher?

Female

[Value of the health questionnaire in family medicine and hospital consultation].

Questionnaires calling for answers of yes or no were tested in the field of family medicine (125 questions) and in a hospital outpatient clinic (164 questions). In the hospital, results were not given to physicians before evaluation of the patient. In family medicine, 3 328 positive answers were given by 200 patients (average 17), against 3 439 and 115 (average 30) respectively in the hospital. As compared with questionnaires, conventional case-reports missed two out of three symptoms or antecedents, many of which were important. Examples are given. Such omissions were more frequent in males, and in some, specialties. They were not less frequent in common diseases. Unexpectedly, omissions were all the more numerous that patients already had more diagnoses. Filling the questionnaire took an average of 3.5 seconds per question. The opinion of patients was usually favorable. The duration of consultations was slightly increased when using the questionnaires. Questionnaires were useful: to patients, by reducing risks of omissions, fatigue of physicians and disparities between physicians; to physicians, by reducing risks of lawsuits. Economic results are complex. Acceptability is discussed. The initial reluctance of physicians can be overcome. From this experience, the number of questions can be brought down to 89.

Evaluation Studies as Topic

[Epidemiology, an accessory application of health questionnaires].

Positive answers to health questionnaires, including 3 328 answers by 200 family physician patients and 3 439 answers by 115 hospital outpatients disclosed numerous symptoms, antecedents, and side effects of therapy. Several correlations between findings were detected. Data confirmed previous publications, and may be of use for teaching programs, care organization, and preventive medicine. However, these applications appear as accessory and the main utility of health questionnaires is to help diagnosis in individuals. Should the purpose be epidemiology, questionnaires would become longer as the result of the influence of psychosociologists and experts in data processing. They would only be suitable for polls. In everyday practice, questionnaires will be accepted only if they are kept short.

Epidemiologic Methods

[Is computed interpretation of electrocardiograms suitable for a general medicine department?].

Computed interpretation of electrocardiograms may be needed as French hospitals are divided into units in which physicians belonging to other specialities than cardiology may be in charge of internal medicine patients. We experimented two rival systems: SADE and CARDIONICS. Recordings were taken in the wards, on paper and magnetic tape. The computer, called by telephone, read the tape, interpreted the data, and printed conclusions and measurements. No useful information was provided in any of the 32 first patients studied (mean age: 71). The machine made our situation worse, as we were repeatedly prompted to call in a cardiologist without sufficient reason. A rejection reaction was observed. Telephone problems in French hospitals, losses of time, errors of manipulation, sometimes unintelligible language, and inappropriate material are discussed from the point of view of the internist. We did not consider the problems of cardiologists, screeners and archivists. In non-universitary hospitals, the needs may be greater, calling for improvements in software and hardware.

Aged

[Oscillating algorithm in medical diagnosis : alternation of flow-charts and diary programs].

26 programs of paraclinical tests for inpatients were written in diary form. Conditions of use were clearly defined with emphasis on optimal utilization of the first two or three days of the stay. Nine diaries are presented as examples. In order to reconcile various clinical, logical and economic requirements, the algorithm should oscillate between the flow-chart and the diary. For clinical evaluation, the flow-chart, completed by a health questionnaire, is satisfactory. But, for prescription of the first paraclinical tests, the diary appears more efficient under the specified conditions of use. The next step should then be a flow-chart, and so on. Flow-charts and diaries may be provided separately, each clinician having the possibility of alternating from one to the other, according to findings and local conditions.

Diagnosis

[Contraindications to health education in hospitalized patients in general medicine departments].

Among 408 patients discharged from a hospital unit of internal medicine (as defined in France), education appeared desirable and possible in 28%, but contraindicated in 72%. Personal care was satisfactory in 7%; stay was too short in 7%; short-term prognosis was fatal in 13%; psychic contraindications were found in 45%. This last group included impenitent alcoholics, drug addicts and tramps; other non-complaint patients; patients with learning disabilities or various mental diseases. In subjects classified as "internal medicine patients", results were identical. Other obstacles were intervals between admissions, duration of stays, heterogeneity of patients, and patients' age. Patients admitted into units of internal medicine should not be given priority for educational programs, in Paris hospitals.

France

[Health education for about 100 children (aged 6 to 14) in heat therapy at La Bourboule, compared to controls].

99 children, aged 6 to 14, received health education and were compared to 93 controls, living in another "children house" at the same resort. The two groups were similar, and completely separated. All children had respiratory and cutaneous infections or allergies, none of them being disabled. The health education consisted in five sessions held over three weeks. Topics were the excesses of what people put into their glasses, ash-trays, plates and medicine chests. The teaching method was mainly based on creative games. Evaluations were presented as games, with colored blocks. The answers given to ten questions, before the educational sessions, were similar in both groups. The final answers did not show any progress in the control group, whereas the rate of correct answers increased by 30% in the educated group. Differences were highly significant, in all age groups. Progresses concerned especially the excesses of sugar, tobacco and meat. The educational needs seemed different according to age, with the main excesses being sugar and other food in children under ten, and tobacco and alcoholic drinks in older children. Spa resorts, and La Bourboule in particular, are suitable for brief controlled health education actions.

Adolescent

[The department budget, in the context of the hospital global budget. Initial results in general medicine].

In a general hospital (Hôtel-Dieu, in the center of Paris), run with a global budget, budgets determined for each unit were introduced as an experiment in 1980. Physicians were in charge of certain expenses, mainly: linen, drugs, transportation of patients to and from other hospitals within Paris, and blood fractions. The whole does not exceed 4% of the turnover (FF 20 millions in 1980) of a 67 bed internal medicine unit. Other accounts deal with the stays, admissions, prescriptions of technical acts, laboratory analyses, and X-rays. In 1980, expenses were 11% more than budgeted, but the increase in stays and particularly in admissions was significantly greater. The resulting savings were 8.8% and 18.7% for stays and admissions respectively. Psychic reactions were variable. The subsequent budgets followed the fluctuations of recorded expenses, which were fairly important in both directions. The unit budget may be an advance or a regression, in a restrictive and past-perpetuating context. The coherence between the unit budget and the global hospital budget is questionable. Physicians were willing to take part in accounting and saving. They have good reason for not enlarging their financial responsibilities. Conversely, they may give more attention to diseases of public opinion.

Budgets

Induction of 2',5'-oligoadenylate synthetase by retinoic acid in two transformed human cell lines.

2',5'-Oligoadenylate (2-5A) synthetase, which polymerizes adenosine triphosphate into 2-5A, is induced upon treatment of cells with interferon (IFN) and is thought to be involved in its antiviral and anticellular action. We report here that retinoic acid (RA) enhanced the level of this enzyme in two human transformed cell lines, WISH and Namalva. Like IFN, RA induced 2-5A synthetase activity in a time- and dose-dependent manner. Addition of anti IFN-alpha, -IFN-beta, or -IFN-gamma antibodies to the medium concomitantly with RA did not prevent such induction; therefore, the effect of RA is clearly not mediated through the induction and externalization of IFN. Pretreatment of cells with actinomycin D inhibited 2-5A synthetase induction by RA, suggesting that RA increased the transcription of the 2-5A synthetase gene. In WISH cells, the growth of encephalomyocarditis virus was inhibited by RA treatment, which is consistent with the hypothesis that 2-5A synthetase plays an important role in the antiviral action of IFN, at least in encephalomyocarditis virus replication. When the anticellular effects of IFN and RA were compared to their ability to induce 2-5A synthetase activity in four human cell lines, there was no strict correlation between the amplitude of the enzyme activity induced and the extent of the antiproliferative effect. It is concluded that the 2-5A system is probably not the only pathway responsible for the antiproliferative effect of both substances. We further suggest that the induction of 2-5A synthetase by IFN and RA might be connected with at least some of the similarities observed between other biological effects of both compounds.

2',5'-Oligoadenylate Synthetase