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Biomedical subjects

F Dubois

Publications and source records attributed to F Dubois.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mechanisms of severe, immediate reactions to iodinated contrast material.

PURPOSE: To measure and elucidate the mechanisms of presumed mediators of unexpected severe, immediate reactions to iodinated contrast materials. MATERIALS AND METHODS: In a multicenter study, 20 patients with mild to severe reactions to iodinated contrast material and 20 control subjects without reactions were evaluated. Ionic contrast material was associated with 18 (90%) of 20 reactions. Concentrations of plasma histamine, tryptase, urinary methylhistamine, specific immunoglobulin E (IgE) against ioxitalamate or ioxaglate, and the anaphylatoxins C3a and C4a were measured with radioimmunoassays; complement C3 and C4 levels were measured with nephelometry. RESULTS: Histamine levels were increased in 14 patients; tryptase levels, in 16; and methylhistamine levels, in six. Histamine and tryptase values correlated with the severity of the reaction (P < .02 and P < .004, respectively). Significantly higher levels of specific IgE against ioxaglate (P < .005) and ioxitalamate (P = .045) were found in patients. No differences were found for complement fractions. Skin test results in two patients with life-threatening reactions were positive for the administered contrast material. CONCLUSION: Histamine release and mast cell triggering are related to severe reactions. An IgE-related mechanism is strongly suspected. Radiologists should be trained to identify and treat anaphylactic shock in patients who react to iodinated contrast material.

Adult↗
PubMed1998

Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95).

Long-term spaceflights induce bone loss as a result of profound modifications of bone remodeling, the modalities of which remain unknown in humans. We measured intact parathyroid hormone (PTH) and serum calcium; for bone formation, serum concentrations of bone alkaline phosphatase (BAP), intact osteocalcin (iBGP), and type 1 procollagen propeptide (PICP); for resorption, urinary concentrations (normalized by creatinine) of procollagen C-telopeptide (CTX), free and bound deoxypyridinoline (F and B D-Pyr), and Pyr in a 36-year-old cosmonaut (RTO), before (days -180, -60, and -15), during (from days 10 to 178, n = 12), and after (days +7, +15, +25, and +90) a 180-day spaceflight, in another cosmonaut (ASW) before and after the flight. Flight PTH tended to decrease by 48% and postflight PTH increased by 98%. During the flight, BAP, iBGP, and PICP decreased by 27%, 38%, and 28% respectively in CM1, and increased by 54%, 35%, and 78% after the flight. F D-Pyr and CTX increased by 54% and 78% during the flight and decreased by 29% and 40% after the flight, respectively. We showed for the first time in humans that microgravity induced an uncoupling of bone remodeling between formation and resorption that could account for bone loss.

Adult↗
PubMed1997

Supramolecular assemblies from lysosomal matrix proteins and complex lipids.

Most lysosomal hydrolases are soluble enzymes. Lamp-II (lysosome-associated membrane protein-II) is a major constituent of the lysosomal membrane. We studied the aggregation of a series of lysosomal molecules. The aggregation-sensitive lysosomal marker enzymes were optimally aggregated at intralysosomal pH. A similar pH dependence was recorded for aggregation of Lamp-II. The pH-dependent loss of solubility of isolated Lamp-II required components of the lysosome extract. Conditions of mild acid pH promoting aggregation triggered the formation of complexes with lipids of lysosomal origin. We fractionated a membrane-free lysosome extract by gel-filtration chromatography and could reconstitute assemblies in vitro from separated fractions. We found some selectivity in the lysosomal proteins binding to complex lipids, phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine being most effective. We propose that the formation at pH 5.0 of such supramolecular assemblies between lysosomal proteins and lipids occurs within the intralysosomal environment. Some possible consequences of such an intralysosomal matrix formation on organelle function are discussed.

Animals↗
PubMed1997

Hepatitis C in a French population-based survey, 1994: seroprevalence, frequency of viremia, genotype distribution, and risk factors. The Collaborative Study Group.

The aims of this study were the following: 1) to estimate the prevalence of hepatitis C virus (HCV) antibody (anti-HCV) in a population-based survey of French residents not selected for risk factors; 2) to investigate the association between anti-HCV seropositivity, viremia, the infecting HCV genotype, and the alanine transaminase (ALT) level; and 3) to identify risk factors for HCV infection by a nested case control study within this survey sample. The anti-HCV seroprevalence survey was performed in 6,283 volunteers (20- to 59-years-old) randomly selected from 45,377 consecutive individuals undergoing routine medical checkup in social security medical centers covering 4 of the 22 "regions" of France. Seventy-two volunteers were anti-HCV positive, a crude prevalence of 1.15%. Fifty percent of these positive volunteers also had an abnormal ALT level and 81% were HCV-RNA positive by polymerase chain reaction (PCR). The prevalence weighted for age, sex, and place of residence was 1.05% (95% CI: 0.75-1.34). The weighted prevalence was lower among men > 40-years-old (0.5%; 95% CI: 0.1-1.0) and was close to 1% in all other age and sex groups. Prevalence was inversely correlated with socioprofessional status with the highest rate being found among those with no paid employment (2.2%; 95% CI: 1.3-3.0). The HCV prevalence (1.7%; 95% CI: 1.0-2.3) was highest in southeastern France. Seventy-eight percent of positive intervenous (I.V.) drug abusers were infected with HCV genotypes 1a or 3, whereas 80% of the transfusion-associated cases were infected by HCV genotypes 1b or 2a. Only three variables were significantly associated with HCV seropositivity in multivariate analysis: I.V. drug abuse (21 cases, 14 men all < 40-years-old), previous transfusion (22 cases, 18 women), and not having paid employment. Although routes of transmission other than I.V. drug abuse and transfusion may not be formally excluded they were not found to be statistically significant. Hepatitis C appears to be a major public health concern in France. A more active screening policy may be required because only 17 of 72 cases (24%) were aware of their HCV seropositivity before enrollment in the study.

Adult↗
PubMed1997

Intrahepatic cholestasis of pregnancy: a French prospective study.

The aim of this prospective study was to analyze the characteristics of intrahepatic cholestasis of pregnancy (ICP) in a French population. From 1989 to 1995 we studied 50 consecutive pregnant women with ICP (41 single, 7 twin, and 2 triplet pregnancies) referred for hepatologic consultation. All patients suffered from pruritus and/or jaundice associated with elevated fasting serum levels of total bile acids (mean 49 micromol/L, range 7-290). No patients had concomitant liver disease and all recovered normal liver function after delivery. Overall prematurity rate was 60%: 100% in multiple pregnancies and 41% in single pregnancies. Three of 61 babies died. Systematic clinical interviews revealed that 34 patients had been treated with oral micronized natural progesterone (200-1,000 mg/d) during the current pregnancy for risk of premature delivery, including at least 32 (64%) before the onset of pruritus. Onset of pruritus was statistically earlier in patients previously receiving progesterone than in patients not receiving progesterone (217 +/- 21 vs. 240 +/- 26 days, P < .01). This was also found in the single pregnancy subgroup of patients (222 +/- 19 vs. 240 +/- 26 days, P < .05). Pruritus disappeared before delivery in 10 of 50 patients, i.e., after withdrawal of progesterone in 7 patients (only one concurrently treated with cholestyramine), after decrease in dose of progesterone in 1 patient, and spontaneously in 2 patients. During the same period, the percentage of pregnant women without ICP who had been treated with progesterone during pregnancy was statistically lower than the percentage of patients treated with progesterone before the onset of pruritus in our group of patients with ICP (36% vs. 64%, P < .01, odds ratio 3.16, 95% CI:1.29-7.80). These results suggest that orally administered progesterone might be an exogenous factor which triggers ICP in predisposed women.

Adolescent↗
PubMed1997

Imaging of pyelonephritis.

OBJECTIVE: Accurate diagnosis of pyelonephritis using clinical and laboratory parameters is often difficult, especially in children. The main aims of this prospective study were to compare the value of different imaging techniques [renal sonography, cortical scintigraphy with technetium-99m dimercaptosuccinic acid (99mTc DMSA) and computed tomography (CT)] in detecting renal involvement in acute urinary tract infections and to determine the sensitivity of DMSA scans for permanent renal scars 6 months later. MATERIALS AND METHODS: Between February 1992 and January 1993, 55 children admitted to our pediatric unit with febrile symptomatic urinary tract infections were eligible for analysis. Ultrasonography (US), DMSA scanning and micturating cystourethrography were performed in every case. Only 18 children underwent CT. A second DMSA scan was performed in 48 children a mean of 7.5 months after the first. RESULTS: US abnormalities were found in 25 children (45 %). The first DMSA scan showed a parenchymal aspect suggestive of pyelonephritis in 51 patients (93 %). Among the 18 patients studied by CT, 14 had abnormalities. Normal US findings did not rule out renal parenchymal involvement. Scintigraphy appeared to be more sensitive than CT for renal involvement. The frequency and degree of initial renal parenchymal damage seemed to correlate with vesicoureteral reflux, but the most severe initial parenchymal defects were not associated with marked clinical or laboratory manifestations. Repeat DMSA scans, performed on 45 kidneys with abnormalities at the first examination, showed resolution in 19, improvement in 16, persistence in 8 and deterioration in 2. The prevalence of vesicoureteral reflux was not higher in patients with renal scarring on the second DMSA scan than in patients whose scans showed an improvement. CONCLUSION: DMSA scans should be considered as a reference in the detection and follow-up of renal scarring associated with acute urinary tract infection as this technique is more sensitive than US and CT, the latter being unsuitable because it entails radiation exposure and sedation of patients.

Acute Disease↗
PubMed1997

The role of technetium-99m sestamibi single photon emission tomography in the follow-up of malignant melanoma and the detection of lymph node metastases.

In the follow-up of patients with malignant melanoma treated by surgical resection of the cutaneous tumour, it is important to achieve early detection of possible lymph node metastasis. In many cases, clinical examination alone will not be sufficient. In our study, single-photon emission tomography (SPET) with technetium-99m sestamibi (MIBI) was used in the assessment of 30 patients with previously resected malignant melanoma when the clinical examination raised the suspicion of lymph node metastasis. Using MIBI, 16 out of 17 lymph node metastases were detected and confirmed by histology. No false-positive results were obtained during this prospective study. It is concluded that MIBI scintigraphy may be useful in the early detection of lymph node metastases of malignant melanomas. If our preliminary results are confirmed, early detection of lymph node metastasis of previously resected malignant melanoma by 99mTc-MIBI scintigraphy may have a significant impact on the management of these patients.

Evaluation Studies as Topic↗
PubMed1997

Efficacy of low doses of radioiodine in the treatment of autonomous thyroid nodules: importance of dose/area ratio.

Radioiodine (131I) represents an interesting alternative to surgery in the treatment of autonomously functioning thyroid nodules (AFTN), but leads to a significant incidence of hypothyroidism when high doses are used. Over 4 years, we have treated 40 patients (hyperthyroid [Plummer's disease]: 6, single hot nodules with undetectable thyrotropin [TSH] and normal serum free thyroxine [FT4]: 34), 34 single hot nodules with undetectable thyrotropin TSH and normal serum free thyroxine [FT4] with 131I. The dose level was neither related to the concentration of FT4 nor to the iodine uptake on thyroid scintigram. Retrospectively we measured the nodule's area on the scan and calculated the dose/area ratio (DAR). Three months after treatment, 30 patients were euthyroid, 9 were still hyperthyroid, and 1 was hypothyroid. The mean DAR of the euthyroid patients was twofold higher than for the hyperthyroid subjects (1.4 +/- 0.8 vs. 0.7 +/- 0.3 mCi/cm2; p = .003) and one-half the DAR for the hypothyroid patient (2.82 mCi/cm2). Twenty of the 30 euthyroid patients had received a dose higher than 1 mCi/cm2 and 7 of 9 hyperthyroid patients had received a dose lower than 1 mCi/cm2. (chi2 = 12.9; p = .02). The initial values of T4, TSH, and dose level of patients who were euthyroid or hyperthyroid at 3 months were not different. These data suggest that the efficacy of 131I for treating AFTN depends on the DAR, rather than the initial T4 value or the 131I uptake. A DAR between 1 and 1.5 mCi/cm2 seems to be optimal and avoids hypothyroidism.

Aged↗
PubMed1997

Effects of indapamide on Ca2+ entry into vascular smooth muscle cells.

Part of the antihypertensive action of indapamide has been attributed to a direct inhibitory action on Ca2+ entry into vascular smooth muscle cells. The present study has been performed to identify the possible mechanisms involved. To this end the effect of indapamide on intracellular Ca2+ activity - [Ca2+]i - has been tested under control conditions and under conditions known to increase [Ca2+]i such as osmotic cell swelling (mimicking mechanical stress), depolarization (increase of extracellular K+ concentration) and oxidative stress (H2O2). Indapamide (10 micromol/l) was without effect on control [Ca2+]i, but significantly blunted the increase of [Ca2+]i following potassium-induced depolarization or following osmotic cell swelling. It did not significantly modify the increase of [Ca2+]i induced by H2O2. The effects on cell membrane potential induced by increased [K+], osmotic cell swelling, or H2O2 were not significantly modified by indapamide (10 micromol/l). Voltage-gated Ca2+ currents were not significantly modified by 10 micromol/l indapamide, but were significantly reduced by 100 micromol/l and blunted by 1 mmol/l. In conclusion, indapamide at high concentrations (100 micromol/l) inhibits voltage-gated Ca2+ channels, an effect which blunts the increase of [Ca2+]i during depolarization of the cell membrane at increased extracellular [K+] or osmotic stress. Whether these effects at high concentrations of indapamide are relevant to the antihypertensive action, however, cannot be established from these in vitro studies.

Animals↗
PubMed1996

Cationic lipids delay the transfer of plasmid DNA to lysosomes.

Plasmid 35S DNA, naked or associated with different cationic lipid preparations was injected to rats. Subcellular distribution of radioactivity in the liver one hour after injection, was established by centrifugation methods. Results show that at that time, 35S DNA has reached lysosomes. On the contrary, when 35S DNA was complexed with lipids, radioactivity remains located in organelles whose distribution after differential and isopycnic centrifugation, is clearly distinct from that of arylsulfatase, lysosome marker enzyme. Injection of Triton WR 1339, a specific density perturbant of lysosomes, four days before 35S DNA injection causes a density decrease of radioactivity bearing structures, apparent one hour after naked 35S DNA injection but visible only after more than five hours, when 35S DNA associated with a cationic lipid is injected. These observations show that cationic lipids delay the transfer to lysosomes, of plasmid DNA taken up by the liver.

Animals↗
PubMed1996

Soluble form of Lamp II in purified rat liver lysosomes.

Lamp II (for lysosomal associated membrane protein II) is an integral type I glycoprotein. It consists of a very large and heavily glycosylated luminal domain, a single transmembrane segment, and a short cytoplasmic tail. We show that in highly purified lysosomes from rat liver, Lamp II, immunodetected with a monoclonal antibody on Western blots, it surprisingly distributed between a membrane bound form and a "soluble" form. The partition of the protein between the membrane and the content of lysosomes is strongly pH dependent. The soluble Lamp II population is sensitive to pH dependent aggregation as it is for many lysosomal content enzymes.

Animals↗
PubMed1996

Phagocytosis by rat liver: relationships between phagosomes and lysosomes.

To study the transfer of phagocytosed components from phagosomes to lysosomes, we have investigated phagocytosis by rat liver of killed Staphylococcus aureus labelled with (125)I tyramine cellobiose. Lysosomes were identified by injecting the animals with Triton WR1339, a non ionic detergent that is endocytosed by the liver and accumulates in lysosomes, causing a marked decrease of their density; that allows these organelles to be well separated from other particles in a density gradient. Bacteria were quickly taken up by the liver; their uptake is followed by a slow degradation as ascertained by the increase of acid-soluble radioactivity in the homogenates with time. Triton WR1339 injection does not affect the uptake and the degradation of the particles. Differential centrifugation of homogenates shows that at any time after injection, most of the radioactivity is recovered in the mitochondrial fractions. Distributions of acid precipitable and acid soluble radioactivities amongst subcellular structures present in mitochondrial fractions were studied by isopycnic centrifugation in sucrose gradients, at increasing times after bacteria injection. Results show that: 1) acid-precipitable radioactivity is quasi-exclusively present in gradient fractions of high density, well separated from the fractions where there are recovered lysosomes; 2) with time, acid-soluble radioactivity is more and more associated with lysosomes, however, a significant proportion can be detected for many hours after injection, in gradient fractions where acid-precipitable radioactivity is located. The most plausible explanation of our observations is that phagocytosed particles are degraded in phagosomes and that the degradation products are delivered to lysosomes, probably by a vesicular process.

Animals↗
PubMed1996

Localization of tobacco cytosolic glutamine synthetase enzymes and the corresponding transcripts shows organ- and cell-specific patterns of protein synthesis and gene expression.

The subcellular localization of glutamine synthetase in tobacco and the differential expression of two genes encoding cytosolic enzyme was investigated using both immunocytochemistry and in situ hybridization. Two full length cDNA clones each encoding cytosolic GS (Gln 1-3 and Gln 1-5) were isolated from a tobacco seeding cDNA library. A strong homology was found in the coding region of the two clones whereas the 3'- and 5'-untranslated sequences were dissimilar. In order to determine the levels of transcription, specific sequences from Gln1-3 and Gln1-5 were used in an RNAse protection assay. This experiment clearly showed that the gene encoding Gln1-3 is expressed in roots and flowers whereas the gene encoding Gln1-5 is transcribed at a high level in stems and at a lower level in roots and flowers. Immunogold labelling was used to examine the subcellular and cellular distribution of glutamine synthetase in vegetative and reproductive organs of tobacco plants. In mature leaf tissue or petals and sepals, plastidic GS was visualised only in the stroma matrix of chloroplasts and plastids. Cytosolic GS was detected in a number of vegetative or reproductive organs including leaves and flowers. In leaves cytosolic GS was preferentially located in the vascular tissue. In situ hybridization was performed using sections of tobacco organs and specific antisense RNA probes to the genes encoding Gln1-3 and Gln1-5. Gln1-5 transcripts were localised in the vascular tissues of stems and roots whereas Gln1-3 transcripts were detected in all root cells and floral organs including petals, sepals and anthers.

Antisense Elements (Genetics)↗