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Biomedical subjects

P Arnaud

Publications and source records attributed to P Arnaud.

At least 19 recordsLinked to original sources

The human hepatoma Hep3B cell line as an experimental model in the study of the long-term regulation of acute-phase proteins by cytokines.

The regulation of the synthesis by the cytokines interleukin-1 (IL-1) and IL-6 of the positive acute-phase protein alpha 1-acid glycoprotein (AGP) and of the negative acute-phase protein alpha 2-HS glycoprotein (AHSG) has been studied in a long-term culture system of the human hepatoma cell line Hep3B. The culture system contained 30 nM-sodium selenite as the only supplement. This allowed maintenance of the synthesis of the proteins under study at a near steady state for over 3 months. An increase in AGP mRNA and a decrease in AHSG mRNA were observed when cells were treated for two successive 48 h-periods with monocyte-conditioned medium. A return to basal levels was obtained after cessation of the cytokine addition. Two further additions of cytokines led to alterations in mRNA levels similar to those observed following the first cytokine treatment. The amounts of AGP and AHSG secreted were altered in accordance with the mRNA modifications. These results suggest that new cytokine receptors were being constantly synthesized during cell culture. When cytokines were present in the culture medium for 10 days, maximum alterations in AGP and AHSG synthesis were obtained following 2 and 4 days of treatment respectively, but further alterations in protein levels could not be observed afterwards. Expression of IL-6 receptor mRNA was not up-regulated by cytokines, but only by 1 microM-dexamethasone. Our results show that, in this long-term culture system, cytokines induce a response in hepatoma cells similar to that observed in vivo during human inflammatory states. This model could be used to evaluate the effects of agonists or antagonists of cytokines responsible for the hepatic acute-phase protein response.

Acute-Phase Proteins

Molecular cloning and sequence analysis of the cDNA encoding human apolipoprotein H (beta 2-glycoprotein I).

Apolipoprotein H, also known as beta-2-glycoprotein I, was purified from human serum, and antiserum produced to denatured apolipoprotein H detected a cDNA clone from a lambda gt11 library derived from human liver. This cDNA coded for the complete sequence of the mature protein. The cDNA insert, along with a polymerase chain reaction product which extended the 5' end of the message, were subcloned and both strands were sequenced. The apolipoprotein H precursor was found to code for 345 amino acids, 326 of which appear in the mature protein. The deduced amino acid sequence of human apolipoprotein H differs from its rat homologue by the presence of a 48-amino acid stretch which is absent from the rat protein. The remainder of the proteins share a greater than 80% similarity. The amino acid sequence of apolipoprotein H consists largely of repeated units approximately 60 amino acids in length. These repeats are comparable to "sushi structures" found in a large number of diverse proteins, including complement components, receptors and regulators of complement activation, serum proteins, membrane-associated adhesion proteins, and other structural and catalytic proteins. Apolipoprotein H was shown to be transcribed by human hepatoma cell lines Hep 3B and Hep G2, and rat liver by detection of mRNA using northern blot analysis.

Amino Acid Sequence

Magnesium, total calcium, phosphorus, copper, and zinc in plasma and erythrocytes of venous cord blood from infants of diabetic mothers: comparison with a reference group by logistic discriminant analysis.

Concentrations of magnesium (Mg), total calcium (Ca), phosphorus (P), copper (Cu), and zinc (Zn) were investigated in plasma (Pl) and erythrocytes (Erc) of venous cord blood of 44 infants of diabetic mothers (IDMs). These same concentrations plus total glycohemoglobin and fructosamine were determined at delivery in a subset of 15 mothers of these infants. Mineral results for IDMs were compared with those for 66 apparently healthy newborns. The duration of gestation in the two groups was significantly different (P < 0.001). After adjustment for gestational age, the mean (+/- SD) differences between groups were significant for birth weight, head circumference, Erc-Mg (1.71 +/- 0.17 for IDMs vs 1.76 +/- 0.15 mmol/L for control subjects), Pl-Ca (1.96 +/- 0.32 vs 2.48 +/- 0.22 mmol/L), Pl-P (1.99 +/- 0.40 vs 1.57 +/- 0.25 mmol/L), and Erc-Cu (10.9 +/- 2.41 vs 12.9 +/- 3.00 mumol/L), but not for Erc-Zn (33.0 +/- 18.3 vs 40.4 +/- 13.6 mumol/L). The variable that best discriminated between the two infant groups after adjustment for gestational age was Pl-Ca. In the 15 mothers, Pl-Mg (0.67 +/- 0.07 mmol/L) and Pl-Ca (1.66 +/- 0.21 mmol/L) concentrations were low, Pl-Zn (9.81 +/- 3.40 mumol/L) was normal, and Pl-Cu (33.5 +/- 10.7 mumol/L) was above normal. Correlations between total glycohemoglobin and mineral values of the mothers or paired IDM mineral values were not significant. The concentration of Pl-Ca was positively correlated with Erc-Cu (P < 0.001) and Pl-Cu (P < 0.05) in the comparison group newborns but not in the IDMs.

Calcium

Study of the gastrointestinal diffusion system (GDS): influence of acacia gum on mechanical and chemical properties in free cellulose acetate films.

In this work a study of free cellulose acetate films was carried out in the presence and absence of acacia gum at high concentrations (50 and 75%). The mechanical toughness and the aspect were influenced by operatory conditions and by the relative air humidity. The increase of relative humidity from about 0% to 75% decreased the mechanical toughness and the color film changed from a clear to opaque white. The presence of acacia gum decreased the mechanical toughness and the water vapour transmission rate and increased the film water solubility.

Cellulose

The diagnostic performance of computer programs for the interpretation of electrocardiograms.

BACKGROUND: Computer programs for the interpretation of electrocardiograms (ECGs) are now widely used. However, a systematic assessment of various computer programs for the interpretation of ECGs has not been performed. METHODS: We undertook a large international study to compare the performance of nine electrocardiographic computer programs with that of eight cardiologists in interpreting ECGs in 1220 clinically validated cases of various cardiac disorders. ECGs from the following groups were included in the sample: control patients (n = 382); patients with left ventricular hypertrophy (n = 183), right ventricular hypertrophy (n = 55), or biventricular hypertrophy (n = 53); patients with anterior myocardial infarction (n = 170), inferior myocardial infarction (n = 273), or combined myocardial infarction (n = 73); and patients with combined infarction and hypertrophy (n = 31). The interpretations of the computer programs and the cardiologists were compared with the clinical diagnoses made independently of the ECGs, and the computer interpretations were compared with those of the cardiologists. RESULTS: The percentage of ECGs correctly classified by the computer programs (median, 91.3 percent) was lower than that of the cardiologists (median, 96.0 percent; P less than 0.01). The median sensitivity of the computer programs was also significantly lower than that of the cardiologists in diagnosing left ventricular hypertrophy (56.6 percent vs. 63.9 percent, P less than 0.02), right ventricular hypertrophy (31.8 percent vs. 46.6 percent, P less than 0.01), anterior myocardial infarction (77.1 percent vs. 84.9 percent, P less than 0.001), and inferior myocardial infarction (58.8 percent vs. 71.7 percent, P less than 0.0001). The median total accuracy level (the percentage of correct classifications) was 6.6 percent lower for the computer programs (69.7 percent) than for the cardiologists (76.3 percent; P less than 0.001). However, the performance of the best programs nearly matched that of the most accurate cardiologists. CONCLUSIONS: Our study shows that some but not all computer programs for the interpretation of ECGs perform almost as well as cardiologists in identifying seven major cardiac disorders.

Cardiology

Identification of Thy-1 homologue in rabbit brain by immunoblot, immunohistochemistry and DNA/DNA hybridization.

A membrane glycoprotein with an apparent molecular weight of approximately 26,000 reacted on immunoblot with a monoclonal antibody (HB-3S-17) directed toward human Thy-1. At cellular level, HB-3S-17 reacted with both rabbit and human cerebral cortexes in a similar manner as demonstrated by immunohistochemical staining. Screening of a rabbit brain expression cDNA library with HB-3S-17 resulted in the isolation of a clone designated RBT-2A-1. The rabbit cDNA insert of RBT-2A-1 hybridized in Southern blot with an oligonucleotide probe derived from the mouse Thy-1.2 gene. These data strongly indicate the existence of a glycoprotein in rabbit brain which is the counterpart of human and mouse Thy-1.

Animals

Partial hepatectomy and mediators of inflammation decrease the expression of liver alpha 2-HS glycoprotein gene in rats.

Liver mRNA levels of two acute phase reactant (APR) proteins, alpha 2-HS glycoprotein (a major negative APR) and alpha 1-acid glycoprotein (a major positive APR) were measured in male rats at different times after the administration of turpentine, of tumor necrosis factor, or following partial hepatectomy. In every case, a marked decrease in mRNA levels of alpha 2-HS glycoprotein was observed which reached a maximum at 24 h. A concomitant increase of alpha 1-acid glycoprotein mRNA levels was observed under the same conditions. These results indicate that the decreased levels of alpha 2-HS glycoprotein induced by the acute-phase response following inflammatory mediators and partial hepatectomy are due to a down-regulation of the gene expression of this protein in rat liver.

Animals

Stability of computer ECG amplitude measurements in the presence of noise. The CSE Working Party.

An important feature of an ECG analysis program is its ability to provide reliable measurements under various operating conditions, e.g., on noise-free and noisy ECGs. Therefore, within the European cooperative project "Common Standards For Quantitative Electrocardiography" (CSE), the accuracy and stability of ECG measurements obtained by several computer programs has been compared. To investigate the stability of measurements two sets of 10 ECGs with and without seven different high- and low-frequency types of noise--altogether 160 electrocardiograms and 160 vectorcardiograms--have been analyzed by eight electrocardiographic and five vectorcardiographic computer programs. The stability of measurement was tested with respect to results obtained for the noise-free recordings. In a previous paper, the influence of noise on wave boundary recognition has been reported. In the present paper, the effect of noise on amplitude measurements and on problems of waveform definitions within the QRS complex are described. The results indicate that programs analyzing an averaged beat exhibit less variability than programs which measure every complex or a selected beat. Comparability and stability of measurements could be improved if a standardized procedure for amplitude references were to be introduced. In addition, the stability of QRS waveform labelling could be improved if waveforms' minimum amplitude and duration were to be validated against the noise level which itself should be determined by a standardized procedure.

Analog-Digital Conversion

[Right ventricular diastolic overloading in left bundle-branch block].

The combination of left bundle-branch block with right ventricular hypertrophy is said to be exceptional. Faced with this possibility, many authors consider a diagnosis of right ventricular hypertrophy as impossible. The two cases reported were found in a total of approximately 10,000 vectorcardiograms. Starting in 1950, Laham drew attention to the special morphology of precordial left bundle-branch block when there is right ventricular hypertrophy. In 1971, Chou and Helm suggested vectorcardiographic criteria for right ventricular hypertrophy in the case of left bundle-branch block--right posterior shift of the QRS loop and clockwise rotation on the horizontal plane. These criteria are satisfied in the first case, i.e. partial atrioventricular canal, but not in the second, i.e. ostium secundum defect. In both cases, the appearance of the left bundle-branch block is very atypical.

Adult

[False tendons of the left ventricle associated with vectorcardiographic changes. Preliminary study].

False tendons are not simply a curiosity discovered on echocardiographic examination or at autopsy. These fibromuscular structures might be connective bundles which contribute to intraventricular activation. They have been implicated in the genesis of arrhythmia (extrasystole or even ventricular fibrillation) by certain authors. 26 subjects with a strictly normal vectorcardiogram (VCG) were chosen at random and 71 subjects with an abnormal VCG were selected from a large population of young, healthy subjects. Using echocardiography, a false tendon was discovered in one subject from the first group and in eight subjects in the second group. Such disproportion (1/26 versus 8/71) was quite unexpected and lends weight to the idea that the false tendon is frequently active and is capable of altering the process of intraventricular activation. The modifications might result in vectorcardiographic traces such as those occasionally observed in healthy subjects.

Adult

Common standards for quantitative electrocardiography: goals and main results. CSE Working Party.

Computer processing of electrocardiograms (ECGs) has over the last 15 years increased rapidly. Still, there are at present no standards for computer ECG interpretation. Different techniques are used not only for measurement and interpretation, but also for transmission and storage of data. In order to fill these gaps, a large international project, sponsored by the European Commission, was launched in 1980 to develop "Common Standards for Quantitative Electrocardiography (CSE)". The main objective of the first CSE study was to reduce the wide variation in wave measurements currently obtained by ECG computer programs. The second study was started in 1985 and aimed at the assessment and improvement of diagnostic classification of ECG interpretation programs. To this end reference libraries of well documented ECGs have been developed and comprehensive reviewing schemes devised for the visual and computer analysis of ECGs. This task was performed by a board of cardiologists in a Delphi review process, and by 9 VCG and 10 standard 12-lead programs developed by university research groups and by industry. A third action was started in June 1989 to harmonize acquisition, encoding, interchange and storing of digital ECG data. The action thus performed have become internationally recognized milestones for the standardization of quantitative electrocardiography.

Algorithms

Evaluation of ECG interpretation results obtained by computer and cardiologists.

In an international project investigators from 25 institutes are trying to establish a common reference library and evaluation methods for testing the diagnostic performance of various ECG computer programs and of cardiologists, based on ECG-independent clinical information. A first set of 500 validated ECGs was collected and analyzed by fifteen different computer programs and nine cardiologists, seven of who analysed the ECG and five the VCG. A coding scheme was used to map individual diagnostic statements onto a common set. Combined program and referee results were obtained by weighted averaging. Preliminary results indicate that the classification accuracy of several programs can still be improved. However, it was also apparent that the results of the best 12-lead ECG computer programs proved to be almost as accurate as the best of seven cardiologists in classifying seven main disease categories, i.e., normal, left, right and biventricular hypertrophy, anterior, inferior and combined myocardial infarction. Evaluation of rhythm statements and conduction disturbances was not included in the study. The data collection is still being pursued in order to reach over 1,000 cases. In this way a common diagnostic database is being established for comparative testing of diagnostic computer programs. This should lead to consumer protection and improve the accuracy and reliability of computerized electrocardiography.

Cardiovascular Diseases

Methodology of ECG interpretation in the Lyon program.

To provide an in-depth interpretation of the spatial QRS-T contour, we established a set of vectorcardiographic parameters computed octant by octant. For each statement the criteria constitute a model which is closely related to pathophysiological patterns. The diagnostic strategy is of the heuristic type. For each diagnosis a table lists several criteria providing both specific and differential diagnostic information. Inter-table competition is handled by specific logic. The program classifies diagnoses according to the number of non-satisfied criteria. Three versions are available including 124, 51 and 7 diagnoses, respectively. The first, intended for interpretation of complex situations, has given satisfactory results in such situations. Rhythm analysis is performed from 8-second recordings. All functions--acquisition, quality control, choice of a dominant complex, wave recognition, parameter extraction, interpretation, editing, storage--are integrated into a mobile cart. A complementary program performs serial analysis of successive tracings. It highlights with great precision morphological changes in the spatial loops and interval variations.

Diagnosis, Computer-Assisted

[Early vectorcardiographic diagnosis of rejection in long-term follow-up of heart transplantation].

A series of 194 transplant subjects was followed-up by over 2,600 vectorcardiograms. Several cases of rejection were chosen among the most patent and best documented cases (eight cases of acute rejection and seven cases of chronic rejection) and 15 control cases where all tests, including the vectorcardiogram, had always remained negative. Two criteria of rejection were used, i.e. the amplitude of the left maximum QRS vector less than 1.10 mV and relative right spatial area greater than 35 per cent. By accumulating all traces for each patient, recorded during and outside the rejection phase, it was found that the mean of the individual means was 0.96 mV for the left amplitude in cases of rejection versus 1.74 mV in the control group, and 44 versus 22 per cent for the right area. The first trace which, on the curves showing the progress of each patient, was likely to signal acute or chronic rejection always had a left amplitude less than 1 mV (mean 0.89 mV) and a right area greater than 33 per cent (mean 45%). The first suspicious trace always preceded the detection of signs by echography or biopsy (except in one case where it occurred at the same time). The interval varied from 16 to 112 days in five cases of rejection assessed as acute, and from 63 to 600 days in seven cases of chronic rejection. There was no echographic control in two other cases, but death occurred 45 and 63 days after the first vectorcardiographic signs. The vectorcardiogram improves after recovery from acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies

Planarity of the spatial QRS loop. Comparative analysis in normals, infarcts, ventricular hypertrophies, and intraventricular conduction defects.

An almost perfect planarity of the spatial QRS loop is known as a characteristic of normal hearts. The Lyon VCG program routinely computes an original planarity index based on the relative magnitude of a so-called geometrical area vector (GAV%). It provides an indirect assessment of any kind of loop distortion (distorted segments lying outside the preferential plane, concavities, figures of eight, narrow configuration). Mean intraindividual variations of GAV%, studied in three different conditions, showed its relatively good stability. Eleven groups totaling 1,435 subjects were investigated. The highest GAV% values (mean, 88%) and the smallest scatter (sigma = 7) were found in normal tracings. GAV% was lower in right (mean, 82%) and left (76-82%) ventricular hypertrophies, in inferior (82%) and anterior (61%) myocardial infarctions, and in right (55%) and left (49%) bundle branch blocks. The diagnostic value of this index was tested for the normal-abnormal discrimination. Using a threshold of 80%, specificity was 89.6%, sensitivity was 78.6% for anterior myocardial infarction, right BBB was 86.6%, left BBB was 91.0% and other groups had unsatisfactory sensitivity. Poor correlations were observed with six other structural parameters, demonstrating that GAV% is relatively independent and may provide new diagnostic information.

Adolescent

Comparative affinity of the major genetic variants of human group-specific component (vitamin D-binding protein) for 25-(OH) vitamin D.

Binding studies with [3H] 25-(OH) D3 were performed under a variety of conditions using Gc (Vitamin D-binding protein) purified from individuals displaying different phenotypes. No significant differences in affinity of binding were found between Gc1f, Gc1s and Gc2 allelle products in either homozygous or heterozygous individuals, nor between Gc1 anodal and Gc1 cathodal isotypes. Affinity was not significantly affected by different reaction temperatures (4, 22 or 37 degrees C), the presence or absence of Ca2+ ions, and binary and ternary interactions with G-actin and G-actin-DNase complexes respectively. However, reduction of pH caused a progressive decrease in binding with virtual abolition at pH less than or equal to 5.0. The latter might promote dissociation of D3 metabolites from Gc carrier protein in acidic compartments of cells.

Calcifediol

Correlations between magnesium and heavy metals in blood and sixteen tissues of rabbits.

Spearman correlations between magnesium and heavy metals (lead and cadmium) were investigated in blood and 16 tissues of four groups of rabbits receiving different diets: I (controls), II (water with 9.66 mumols/litre of lead), III (atherogenic), and IV (atherogenic + 9.66 mumols/litre of lead). On days 1, 42 and 172 of the experiment there were no significant correlations between magnesium and lead in rabbit blood. After 25 weeks, among the 16 tissues studied only liver presented a significant positive correlation (P less than 0.01) between magnesium and lead. Correlations between magnesium and cadmium were significantly positive (P less than 0.01) in lung, liver, adrenal gland and spleen. It is thus possible that a rise in magnesium in tissues with high metabolic activity serve to combat the harmful effects of an increase in these heavy metals.

Adrenal Glands

Statistical interpretation of concentrations of magnesium, zinc, calcium, potassium, cholesterols, and creatine kinase isoenzymes in men at different stages of ischemic heart disease.

We present a statistical interpretation of plasma (Pl) and (or) erythrocyte (Erc) concentrations of magnesium, zinc, calcium, potassium, and total high-density lipoprotein (HDL) cholesterol, as well as of the activity of total creatine kinase (CK) and its CK-MB isoenzyme, in 26 men with pre-infarction syndrome (PIS) and 34 men with acute myocardial infarction (MI). Discriminant analysis allowed overall comparison of both groups and determination of the most significant variables: CK and Pl-Zn. By non-hierarchical cluster analysis we defined three homogeneous subgroups among MI men, with CK, CK-MB, and Pl-Zn differing significantly between the groups. In PIS men, Pl-Zn was correlated with Pl-Ca, whereas in MI men Pl-Zn was correlated with Pl-Mg. Stepwise regression indicated that Pl-Zn was the most significant regressor of CK in PIS men and of CK-MB in MI men. All these statistical interpretations support a special role of Pl-Zn in diagnosis and perhaps prognosis. After MI, interleukin-1 release may possibly mediate observed hypozincemia via formation of a heart Zn-metallothionein.

Aged