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Biomedical subjects

D Georges

Publications and source records attributed to D Georges.

At least 19 recordsLinked to original sources
PubMed1999

Immunohistochemical evidence for the presence, localization and partial coexistence of insulin, insulin-like growth factor I and relaxin in the protochordate Ciona intestinalis.

The occurrence and coexistence of peptides of the insulin-like growth factor (IGF)/insulin superfamily were investigated in the ovary and gastro-intestinal tract of the protochordate Ciona intestinalis. Antisera specific for mammalian IGF-I, insulin and relaxin were used in a double-immunofluorescence method on paraffin sections and with an immunogold technique on consecutive semi-thin sections. IGF-I and relaxin immunoreactions but no insulin immunoreactions occurred in the ovary and were confined to medium-sized and mature follicle cells. Two subpopulations of reacting follicular cells were present: those containing only IGF-I immunoreactivity (5%) and those containing IGF-I and relaxin immunoreactivities (95%). In the gastro-intestinal tract, IGF-I and insulin immunoreactions coexisted, whereas no relaxin immunoreactions were obtained. Gel chromatography and radioimmunoassay in Ciona ovary revealed IGF-I immunoreactivity in two peaks with apparent molecular masses of approximately 16 kDa and 3 kDa. The present results indicate that (1) the same IGF-I-related peptide probably occurs in gastro-intestinal tract and ovary, (2) three different members of the insulin/IGF family of peptides are probably present in protochordates, (3) different types of coexistence of these peptides seem to exist in protochordates, i.e. an IGF-I-related peptide and an insulin-related peptide in the digestive tract and, as shown previously, in central nervous system, and the IGF-I-related peptide and relaxin in the ovary, (4) an IGF-I-related peptide and relaxin may be involved in oocyte maturation in the protochordate ovary.

Animals↗
PubMed1999

Porcine relaxin, a 500 million-year-old hormone? the tunicate Ciona intestinalis has porcine relaxin.

The fossil record of tunicates reaches back to the upper Cambrian period. Ascidians have mobile, tadpole-like juvenile forms with a notochord, which inspired the classification of tunicates as Urochordata, i.e., predecessors of vertebrates. The genome of the tunicate Ciona intestinalis contains a relaxin coding region that is organized like a mammalian gene, i.e., signal peptide, B-chain domain, connecting peptide domain, followed by the A-chain domain with a stop codon after cysteine A-22. RNA-derived cDNA encodes a relaxin that is identical to the circulating form of the porcine hormone. In contrast to the porcine gene, the ascidian gene has no intron in the C-peptide domain, and in that respect is similar to the bombyxin gene of the silkworm. During the spawning period, only enough relaxin could be extracted and isolated from gonads of C. intestinalis for a partial sequence analysis. Remarkable as it may be, these findings suggest that relaxin is identical in pigs, whales, and the tunicate C. intestinalis.

Amino Acid Sequence↗
PubMed1998

Energy cost and running mechanics during a treadmill run to voluntary exhaustion in humans.

The aim of the present study was to examine the physiological and mechanical factors which may be concerned in the increase in energy cost during running in a fatigued state. A group of 15 trained triathletes ran on a treadmill at velocities corresponding to their personal records over 3000m [mean 4.53 (SD 0.28) m x s(-1)] until they felt exhausted. The energy cost of running (CR) was quantified from the net O2 uptake and the elevation of blood lactate concentration. Gas exchange was measured over 1 min firstly during the 3rd-4th min and secondly during the last minute of the run. Blood samples were collected before and after the completion of the run. Mechanical changes of the centre of mass were quantified using a kinematic arm. A significant mean increase [6.9 (SD 3.5)%, P < 0.001] in CR from a mean of 4.4 (SD 0.4) J x kg(-1) x m(-1) to a mean of 4.7 (SD 0.4) J x kg(-1) x m(-1) was observed. The increase in the O2 demand of the respiratory muscles estimated from the increase in ventilation accounted for a considerable proportion [mean 25.2 (SD 10.4)%] of the increase in CR. A mean increase [17.0 (SD 26.0)%, P < 0.05] in the mechanical cost (CM) from a mean of 2.36 (SD 0.23) J x kg m(-1) to a mean of 2.74 (SD 0.55) J x kg(-1) x m(-1) was also noted. A significant correlation was found between CR and CM in the non-fatigued state (r=0.68, P < 0.01), but not in the fatigued state (r=0.25, NS). Furthermore, no correlations were found between the changes (from non-fatigued to fatigued state) in CR and the changes in CM suggesting that the increase in CR is not solely dependent on the external work done per unit of distance. Since step frequency decreased slightly in the fatigued state, the internal work would have tended to decrease slightly which would not be compatible with an increase in CR. A stepwise regressions showed that the changes in CR were linked (r=0.77, P < 0.01) to the changes in the variability of step frequency and in the variability of potential cost suggesting that a large proportion of the increase in CR was due to an increase in the step variability. The underlying mechanisms of the relationship between CR and step variability remains unclear.

Adult↗
PubMed1998

Measurement of induced cytokines in AIDS clinical trials using whole blood: a preliminary report. ACTG Inducible Cytokines Focus Group. AIDS Clinical Trials Group.

Measures of immune function have become increasingly important as endpoints in AIDS clinical trials, with respect to both modulation and reconstitution of immunity by experimental therapies. Measurement of immune function in this setting requires the development of robust analytic approaches suitable for the clinical laboratory. Experiments were performed to evaluate the suitability of using cultured heparinized ("whole") blood for induction of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), two cytokines critical in AIDS pathogenesis. TNF-alpha expression ranged from 229 to 769 pg/ml in lipopolysaccharide (LPS)-stimulated cultures and was not detected in unstimulated cultures. IFN-gamma expression ranged from 0 to 112,000 pg/ml in phytohemagglutinin A (PHA)-stimulated cultures and from 0 to 789 pg/ml in antigen-stimulated cultures. The mean coefficient of variation observed in three weekly determinations was 0.47 for TNF-alpha and ranged from 0.12 to 1.73 for IFN-gamma. These values indicate that sample sizes of 8, 24, and 29 subjects would be sufficient to detect twofold changes in LPS-induced TNF-alpha and in PHA- and antigen-induced IFN-gamma respectively, if two baseline and two treatment determinations were obtained, and if the interpatient variability of changes in true levels from baseline to follow-up is negligible compared to the variability in the three weekly measurements. Measurement of LPS-induced TNF-alpha and mitogen- or antigen-induced IFN-gamma can be performed simply and reproducibly in human immunodeficiency virus-infected persons by the whole-blood culture method. Further studies are warranted to determine the effect of overnight shipping on assay reproducibility and to determine the extent to which responses can be reliably detected in subjects with low CD4 cell numbers.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Human immunodeficiency virus type 1 activation after blood transfusion.

BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/- 5.1 (mean +/- SE) pg per mL at Week 2 after transfusion and 18 +/- 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/- 40 percent (SE) at Week 1, 70 +/- 27 percent at Week 2, and 67 +/- 38 percent at Week 4 (p = 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion.

Anemia↗
PubMed1995

L-2-oxothiazolidine-4-carboxylic acid (procysteine) inhibits expression of the human immunodeficiency virus and expression of the interleukin-2 receptor alpha chain.

These studies were undertaken to examine the in vitro effects of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (Procysteine) on human immunodeficiency virus expression. Procysteine inhibited HIV expression in human peripheral blood mononuclear cells as detected by measurement of supernatant core antigen. In transient transfection assays, Procysteine inhibited gene expression controlled by the HIV-1 promoter in activated Jurkat cells but not in resting Jurkat cells. Gel-shift assays showed that Procysteine inhibited NF-kappa B DNA binding activity in nuclear extracts. Procysteine did not affect the production of interleukin-2 by peripheral blood mononuclear cells of healthy HIV-seronegative subjects, as measured by bioassay but it decreased the density of cell-surface interleukin-2 receptors detected by flow cytometry after stimulation with phytohemagglutinin (PHA). Thus, Procysteine inhibits HIV expression, HIV promoter activity, and NF-kappa B binding activity in vitro. Procysteine does not affect interleukin-2 production but inhibits interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells.

Cells, Cultured↗
PubMed1994

Cell cycle-related fluctuations in oocyte surface area of the ascidian Ciona intestinalis after meiosis resumption.

Variations in capacitance or cell surface area were recorded on patch-clamped eggs of the ascidian Ciona intestinalis between the resumption of meiosis and the first mitotic cleavages. The membrane surface area increased within the first minutes after fertilization and then oscillated in phase with the cell cycles of the two meiotic divisions and first mitotic cleavage. With drugs, we generated two opposite situations (removal and insertion) or artificial variation in capacitance. In unfertilized eggs, cytochalasin induced a drop in capacitance linked to a decrease in calcium current intensity and specifically disturbed membrane removal linked to the first meiotic division cycle. It left unaffected the following cycles, in agreement with previous results that only the first meiosis cycle is microfilament dependent. In fertilized eggs, membrane removal at each cycle was hindered by emetine, an inhibitor of protein synthesis. The resulting membrane extrusion was observed in sections by electron microscopy and was linked to an increase in calcium current intensity. These fluctuations in surface area never involved the microtubule network, since nocodazole had no effect on any cycle. The fluctuations of membrane surface area after meiosis resumption in phase with cell cycles in Ciona oocytes paralleled the pattern previously described in the ascidian Boltenia villosa. This may reflect the mechanism by which the oocyte regulates, with possibly different mediators at each cycle, the connection between cell surface and internal membrane networks. This interrelation includes the insertion and removal of ion channels necessary to developmental control.

Animals↗
PubMed1994

Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial. French Multicenter Study Group.

The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 micrograms twice daily) with slow-release (SR) terbutaline (5 mg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (+/- SD) was significantly higher in the salmeterol group: 5.3 +/- 2.4 vs 4.6 +/- 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 +/- 109 l/min-1 vs 332 +/- 105 l/min-1, P = 0.04), PEF diurnal variation 6 +/- 10% vs 11 +/- 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes (P = 0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Usefulness of salmeterol in nocturnal asthma: a comparative study with theophylline-ketotifen association. A French multicenter group].

Ninety-six patients with nocturnal asthma (FEV1 = 60-90% pred, reversibility greater than or equal to 15%, at least 2 awakenings in the week preceding the trial) were included in a double-blind, randomized, crossover, multicenter study which compared the efficacy and side effects of inhaled salmeterol (50 micrograms morning and evening) to the association theophylline-ketotifen (300 mg and 1 mg morning and evening, respectively). The trial included a run-in period of 14 days and 2 periods of successive treatment of 28 days each. The efficacy was expressed in terms of therapeutic success, defined by the total disappearance of nocturnal symptoms during the treatment week. A statistically significant difference (p less than 0.01) was found between salmeterol and the association for this criteria: during the first period, 46% of subjects treated by salmeterol did not present nocturnal awakenings during the last treatment week by comparison with 15% of subjects taking the association; during the second period, corresponding figures were 39% for salmeterol by comparison with 26% for the association. Differences were also significant, favoring salmeterol, for other criteria (lung function tests, extra-need for salbutamol). Side effects were 5 times more frequent for the association (p less than 0.004). Salmeterol is clearly superior to the association theophylline-ketotifen in the treatment of nocturnal asthma.

Adolescent↗
PubMed1992

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

Administration, Inhalation↗
PubMed1991

Killing kinetics of cefuroxime axetil against Haemophilus influenzae in an in-vitro model simulating serum concentration profiles after oral administration.

We have used a dynamic in-vitro model to determine the killing kinetics of two formulations of cefuroxime axetil against 18 clinical strains of Haemophilus influenzae. The concentration of cefuroxime axetil was adjusted dynamically to simulate the mean serum profile in healthy volunteers following the administration of a single 250 mg dose in oral suspension or tablet form. Bacterial numbers were reduced by 3 log10 cfu/mL during the eight-hour experimental period with both dosage form simulations. Our results suggest that cefuroxime axetil, 250 mg in oral suspension or tablet form, may protect against the dissemination of H. influenzae during episodes of bacteraemia.

Administration, Oral↗
PubMed1991

High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.

Administration, Inhalation↗
PubMed1990

Relaxin-like peptide in ascidians. I. Identification of the peptide and its mRNA in ovary of Herdmania momus.

The ovaries of the ascidian Herdmania momus were extracted for relaxin. Relaxin immunoactivity was eluted from Sephadex G-50 in the position of authentic porcine ovarian relaxin and these fractions were parallel to porcine relaxin in an homologous porcine relaxin radioimmunoassay. Poly(A)+ RNA from ascidian ovaries hybridized to a 32P-labeled porcine relaxin B-chain 48 mer oligonucleotide probe. There was no hybridization with 32P-labeled probes of equal length but was rather directed to the B-chain of human relaxin or to two different regions of the C-peptide of porcine relaxin. We conclude that the ascidian ovary produces a relaxin-like molecule, possibly with greater homology in the B-chain to mammalian relaxins than in the C-peptide region.

Animals↗
PubMed1990

Relaxin-like peptide in ascidians. II. Bioassay and immunolocalization with anti-porcine relaxin in three species.

A substance related to vertebrate relaxin, previously identified by radioimmunoassay and Northern hybridization in the ascidian Herdmania momus, was also purified and tested in bioassay in another species, Ciona intestinalis. In addition, immunocytochemistry with anti-porcine relaxin was performed, at the light and electron microscopic levels, on sections of ovary from three different species, living in various environmental conditions. A positive immunoreaction was located specifically in follicle cells surrounding mature oocytes. The role of this relaxin-like substance in ascidian reproduction is unknown.

Animals↗
PubMed1990

[Digital bone densitometry. A routine method for evaluating and monitoring bone mineralization].

Digitalized bone densitometry is a simple technique for studying bone mineralization which can be performed during the radiological examination. Digitalized bone densitometry was used to estimate the bone mineral content of the third lumbar vertebra in 30 women and 16 men, the neck of the femur in 27 women and 20 men and the second metacarpal in 27 women and 17 men. The results were compared to the data provided by conventional methods. The appearance of the curves, the index of accuracy and reproducibility of the method suggest that it can be used to detect and monitor bone mineralization of patients for a moderate cost.

Absorptiometry, Photon↗
PubMed1990

[Intermittent treatment or preventive treatment of recurrence in duodenal ulcer disease? A controlled, double-blind study with 150 mg ranitidine daily for one year].

This 1-year study compared two pragmatic strategies in long-term management of duodenal ulcer: continuous treatment with ranitidine 150 mg after dinner and treatment of duodenal ulcer attacks with ranitidine 300 mg and placebo in the interval. A multicentric, randomized double-blind study was conducted in 399 patients, 197 in the ranitidine group and 202 in the placebo group. Efficacy was judged by the prevalence of ulcer-pain recurrences; secondary criteria were the prevalence of endoscopic recurrences, complications and the number of facultative visits, hospitalizations and days off work related to duodenal ulcer disease. Both groups were similar with regard to main epidemiologic features and number of drop-outs (10.5 percent). Fifty-two patients were withdrawn for symptomatic or endoscopic relapses: 6 in the ranitidine group, 46 in the placebo group (p less than 0.05). Sixty-six percent of the patients remained asymptomatic at one year in the ranitidine group versus 33 percent in the placebo group (p less than 0.001). Seventeen patients with ranitidine (8.6 percent) and 59 with placebo (29.2 percent) experienced at least one endoscopic recurrence (p less than 0.05). In the placebo group, 8 complications were observed (bleeding = 5, duodenal stenosis = 3), and none in the ranitidine group (p less than 0.005). Patients with ranitidine had significantly less facultative visits and endoscopies, number of days off work, and hospitalizations (p less than 0.05). Tolerance was good (5 percent side-effects, all minor) and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Calcium blocker lacidipine and carotid arteriolar vasodilation in healthy volunteers.

Systemic and carotid hemodynamics were studied in 10 healthy male volunteers before and after short-term administration of a 4 mg dose of the calcium entry-blocker lacidipine in a placebo-controlled, double-blind, crossover study. Hemodynamic parameters of the right common carotid artery were measured before and at 1 1/2 and 3 hours after dose administration by means of pulsed Doppler flowmetry. In addition, systemic hemodynamic parameters were calculated from cardiac impedance measurements at the same time. In comparison with placebo, lacidipine produced a significant decrease in blood pressure, together with systemic and carotid arteriolar dilatation. Heart rate increased sharply, whereas carotid arterial diameter and tangential tension did not change. The study provided evidence that the calcium entry-blocker lacidipine produces systemic and carotid arteriolar vasodilation and that the heart rate baroreflex response after administration of calcium inhibitor is not associated with a significant modification of the geometry of carotid arterial wall.

Administration, Oral↗