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C Briançon

Publications and source records attributed to C Briançon.

At least 19 recordsLinked to original sources

Intestinal fatty acid binding protein gene expression reveals the cephalocaudal patterning during zebrafish gut morphogenesis.

Intracellular fatty acid-binding proteins (FABPs) are small and highly conserved cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. We have examined, as a model for studying intestinal epithelial cell differentiation, the cell-specific and spatio-temporal expression of intestinal fatty acid-binding protein (i-fabp) gene during zebrafish larval development. After molecular cloning of zebrafish I-FABP cDNA, whole-mount in situ hybridization analysis revealed that i-fabp is expressed in the intestinal tube around day 3 postfertilization. By day 4, highest level of i-fabp transcript is encountered in the proximal columnar epithelium. From day 5 onwards, i-fabp is strongly expressed in the anterior intestine and its rostral expansion, slightly expressed in the esophagus mucosa and rectum, while no mRNA could be detected in the posterior intestine. Therefore, the regional differentiation of the intestine precedes first feeding and complete yolk resorption. I-fabp expression in the anterior intestine of the fed larvae is correlated with an intracellular storage of lipid droplets in the enterocytes and the massive synthesis of very low-density lipoprotein particles. In conclusion, the cephalocaudal expression pattern of i-fabp demarcates early during zebrafish gut morphogenesis the anterior fat absorbing to posterior cells of the intestine. This gene could be used as a marker for screening for mutations that affect the events of intestinal epithelial differentiation, cephalocaudal patterning, and asymmetric gut looping morphogenesis.

Amino Acid Sequence↗

Signal standardization of the secondary ion mass spectrometry (SIMS) microscope for quantification of halogens and calcium in biological applications.

The secondary ion mass spectrometry (SIMS) microscope is able to map chemical elements in tissue sections. Although absolute quantification of an element remains difficult, a relative quantitative approach is possible for soft tissue by using carbon (12C) as an internal reference present at large homogeneous and constant concentration in specimen and embedding resin. In this study, this approach is used to standardize the signal of an SIMS microscope for the quantification of halogens (9F-, 35Cl- and 79Br-) and calcium (40Ca+). Standard preparation was determined based on homogeneity and stability criteria by molecular incorporation (halogens) or mixing (calcium) in methacrylate resin. Standard measurements were performed by depth analysis on areas of 8 microns (halogens) and 150 microns (calcium) in diameter for 10-30 min, under Cs+ (halogens) or Ox+ (calcium) bombardment. Results obtained from 100-120 measurements for each standard dilution show that the relationship between the signal intensity measured and the elemental concentration (micrograms/mg of wet tissue or mM) is linear in the range of biological concentrations. This quantitative approach was applied firstly to bromine of the 5-bromo-2'-deoxyuridine (BrdU) used as nuclear marker of rat hepatocytes in proliferation. The second model concerns depletion of calcium concentration in cortical compartment in Paramecium tetraurelia during exocytosis. Then signal standardization in SIMS microscopy allows us to correlate quantitative results with those obtained from other methods.

Animals↗

Recent developments in medical applications of SIMS microscopy.

The purpose of this review is to present the recent developments in the medical applications of SIMS microscopy. This technique is one of the microanalytical mass spectrometry methods which allow in theory the detection of all the elements of the Mendeleiev table as well as the separation of stable and radioactive isotopes. It is based on a phenomenon whereby a biological sample surface is sputtered by bombardment with an energetic 'primary ion' beam. Part of the sputtered matter is ionized and the resulting 'secondary ions' are characteristic of the atomic composition of the analyzed area. These secondary positive or negative ions are collected and separated in a mass spectrometer at low or high mass resolution, which is dependent on both the element studied and its concentration. An analytic image which conserves the tissue distribution of the selected element is displayed on a fluorescent screen linked to an image processing system. Local elemental concentration can also be measured. Results are highly dependent on the techniques used for sample preparation which should preserve both the chemical and the structural integrity of the tissue. Further, the ionic images must be correlated with corresponding images of the same areas of the serial sections observed in a photonic microscope. With our SIMS microscope (lateral resolution approximately 0.5 microns, and mass resolution 300 to 12,000) we have demonstrated that this microscopic imaging technique is suitable for physiopathological studies. We revisited thyroid iodine metabolism by mapping chemical elements such as 32S and 127I, characteristic of hormonal physiology. Newly organified iodine (radioiodine) can be evaluated in relation to previously stored iodine (127I) in a given follicle, thus allowing an appraisal of glandular adaptation to aging and iodine overload. Another area in which SIMS can be used in medicine, is for the localization of drug markers in tumor tissue (e.g. fluorine-5-fluouracil, iodine in iododeoxyrubicin). This could facilitate the evaluation of the intratumor drug concentration at the onset of the treatment. Likewise, SIMS can be used to localize radiopharmaceuticals used in diagnosis (e.g. technetium) and therapy (131I of metaiodobenzylguanidine). This would permit a better evaluation of the radiation dose delivered to tissue. Further prospects are within reach with the imminent advent of higher lateral resolution (0.05 microns) SIMS microscopes.

3-Iodobenzylguanidine↗

SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier-free.

3-Iodobenzylguanidine↗

SIMS microscopy in the biomedical field.

We attempted to indicate the requirements for biomedical applications of SIMS microscopy. Sample preparation methodology should preserve both the structural and the chemical integrity of the tissue. Furthermore, it is often necessary to correlate ionic and light microscope images. This implies a common methodological approach to sample preparation for both microscopes. The use of low or high mass resolution depends on the elements studied and their concentrations. To improve the acquisition and processing of images, digital imaging systems have to be designed and require both ionic and optical image superimposition. However, the images do not accurately reflect element concentration; a relative quantitative approach is possible by measuring secondary ion beam intensity. Using an internal reference element (carbon) and standard curves the results are expressed in micrograms/mg of tissue. Despite their limited lateral resolution (0.5 microns) the actual SIMS microscopes are very suitable for the resolution of biomedical problems posed by action modes and drug localization in human pathology. SIMS microscopy should provide a new tool for metabolic radiotherapy by facilitating dose evaluation. The advent of high lateral resolution SIMS imaging (less than 0.1 microns) should open up new fields in biomedical investigation.

Animals↗

Significance of SIMS microscopy for the radioiodine detection in animal and human thyroid tissue.

We defined the SIMS conditions for radioiodine detection in animal and man thyroid follicles, in tissue sections (3 microns) chemically fixed and resin embedded. Two radioisotopes were tested: 125I and 129I, of high (14 mCi 125I micrograms-1) and low specific activity (1.07 10(-6) mCi 129I micrograms-1). In animal study, Wistar rats fed a normal iodine diet (10 micrograms 127I day-1) were injected ip 24 h before sacrifice either with 125I (7 10(-3) micrograms) or with 129I at a dose identical to iodine diet (10 micrograms) or 3 times higher (30 micrograms). No SIMS signal of 125I was obtained in vivo due to its too low concentration, while radioiodine distribution was evidenced with both doses of 129I. Local concentration of previously stored 127I in follicular lumen was not modified, when compared to control (4.14 +/- 0.03 micrograms/mg, m +/- SE), by 125I or 129I at a dose of 10 micrograms, but was nearly doubled with 129I at a dose of 30 micrograms, proof of a pharmacological effect on thyroid iodine regulation. In human study 129I was excluded due to its long half-life (1.6 10(7) years), and 125I was tested only in vitro on two surgical specimens of normal perinodular thyroid tissue maintained in mini-organ culture for 48 h in presence of 100 microCi/ml of 125I. The 125I was detectable, its concentration was 1,000-fold higher than that of 127I (1.5 +/- 0.004 micrograms/mg). For both in vivo and in vitro studies, a positive correlation exists between newly organified radioiodine (125I or 129I) and previously stored iodine (127I).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Macroscopic and microscopic imaging of stable iodine (127I) in the thyroid.

The purpose of this review is to describe the two imaging methods which allow direct estimation of stable iodine (127I) within thyroid gland either in vivo by X-ray fluorescence or in vitro by secondary ion mass spectrometry (SISM) microscopy. X-ray fluorescence of thyroid is mainly used for the estimation of thyroid iodine content (TIC) in human pathophysiology. Although its measurement has little revelance for routine explorations of thyroid function, this is a valuable method for understanding complex pathophysiological conditions such as hyperthyroidism without radioactive uptake, the fate of irradiated glands or the thyroid adaptation to iodine overload. On the other hand, SIMS microscopy which combines the phenomena of secondary ion emission and mass spectrometry, makes possible the quantitative mapping of 127I on tissue section. This technique is able to characterize the functional activity of thyroid tissue without prior administration of radioiodine by measuring 127I concentration within the thyroid follicles. Furthermore, SIMS microscopy can be used to determine the extent to which exogeneous iodine affects the regulation of iodine within the thyroid follicles. Both methods were used to evaluate the quantitative changes in thyroid 127I induced by amiodarone overload. TIC measurements shows that hyperthyroidism occurred only in patients who increased their iodine stores, while the patients who developed hypothyroidism had low iodine stores. These data demonstrate that the mechanisms by which subjects who become hypothyroid under amiodarone iodine overload differ from those of subjects who remain euthyroid or become hyperthyroid: iodine organification is blocked in hypothyroid patients and increased in the euthyroid and hyperthyroid patients. The SIMS microscopy data obtained in mice demonstrated that the thyroid response to amiodarone is related to dietary iodine intake leading to an increase in iodine stores in iodine deficient mice and a decrease in iodine supplemented mice. These results could explain that hyperthyroidism with high thyroid iodine content occurred in areas with low thyroid iodine intake and hypothyroidism with low thyroid iodine content in areas with a supplemented iodine diet.

Animals↗

[Direct evaluation of thyroid I-127 in an iodine overload situation: in vivo study by X-ray fluorescence and in vitro by analytical ion microscopy].

This review describes the two methods which allow direct estimation of stable iodine (127I) within thyroid gland either in vivo by X-ray fluorescence or in vitro by secondary ion mass spectrometry (SIMS) microscopy on tissue section. Although the measurement of thyroid iodine content (TIC) by X-ray fluorescence has little relevance for routine explorations of thyroid function, this is a valuable method for understanding complex pathophysiological conditions such as the thyroid adaptation to iodine overload. On the other hand, SIMS microscopy which is able to characterize the functional activity of thyroid tissue by measuring 127I concentration within the thyroid follicles, can be used to determine the extent to which exogenous iodine affects the regulation of iodine within the thyroid follicles. Both methods were used to evaluate the quantitative changes in thyroid 127I induced by amiodarone iodine overload. TIC measurements shows that hyperthyroidism occurred only in patients who increased their iodine stores, while the patients who developed hypothyroidism had low iodine stores. The SIMS microscopy data obtained in mice demonstrated that the thyroid response to amiodarone is related to dietary iodine intake leading to an increase in local iodine concentration in iodine deficient mice and to a decrease in iodine supplemented mice. This response is specific and different from that induced by an iodide overload. These results could explain that hyperthyroidism with high thyroid iodine content occurred in areas with low thyroid iodine intake and hypothyroidism with low thyroid iodine content in areas with a supplemented iodine diet.

Amiodarone↗

[Functional microscopic imaging of the thyroid gland with the help of analytical ion microscopy].

Secondary ion mass spectrometry (SIMS) microscopy provides a direct mapping of 127I in thyroid follicles. Thyroid tissue should be fixed and embedded in methacrylate resin, then cut in 3 microns-thick sections which are placed on a gold coverslip. The histological structure of the tissue is determined by the phosphorus ion (31P) which is present in large amounts in nuclei and phosphorylated molecules in the cytoplasm. An image processing system is used to superimpose images of 127I and 31P: this system allows measurement of local concentration of 127I in the follicular cell and follicular lumen compartments. A study in 8 subjects with normal thyroid glands showed that the level of 127I within follicular cells (430 +/- 250 micrograms/g; m +/- SE) was 6 to 7 times lower than the level in the follicular lumen (2.780 +/- 230 micrograms/g). In simple goiter (9 patients with macrofollicular adenomas), follicular lumen (346 +/- 17 micrograms/g) and cellular (68 +/- 6 micrograms/g) concentrations of 127I were decreased fivefold but the ratio of concentrations remained similar to that seen in normal tissue. In hyperfunctioning nodules (2 microfollicular and 3 macrofollicular adenomas), follicular cell and follicular lumen 127I levels varied widely and showed considerable overlap (2 to 16,000 micrograms/g and 1-21,000 micrograms/g, respectively). In benign cold nodules (1 microfollicular adenoma and 2 macrofollicular adenomas), follicular cell and follicular lumen 127I levels were barely detectable (3 +/- 0.6 micrograms/g and 6 +/- 0.7 micrograms/g respectively). In the 9 malignant nodules studied, no difference in 127I level profile was found with benign nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Goiter, Nodular↗

Correlated autoradiographic and ion-microscopic study of the role of iodine in the formation of "cold" follicles in young and old mice.

The role of iodine in the formation of "cold" follicles (not labeled on autoradiograms after radioiodine administration) was analysed in ICR female mice during aging and involution of thyroid hyperplasia, by use of light and electron microscopy and by comparing autoradiographic and analytical ion-microscopic images for the same follicle in serial sections. The proportion of "cold" and "partly cold" (displaying a patchy or ring labeling pattern on autoradiograms) follicles increased significantly during aging. This increase was more pronounced in old mice fed an iodine-rich diet as compared to mice fed a moderate iodine diet. Similarly, during goiter involution produced by refeeding iodine, the follicular heterogeneity of iodine metabolism was more accentuated with a high dose of iodine, regardless of the age of the mice. The follicular lumina of "hot" and "cold" follicles had the same concentration of stable iodine, as shown by analytical ion microscopy, and the cells of both types of follicles formed colloid droplets in response to TSH. Furthermore, when a goitrogenic treatment was induced in aged mice, some "cold" follicles persisted after 8 days, but all follicles resumed "hot" after 16 days. By analytical ion microscopy, 127iodine was also found inside thyroid cells of old mice, but the cytoplasmic patches of 127iodine were not labeled with 125iodine. They corresponded to lipofuscin pigments and secondary lysosomes, as observed in serial sections at the electron-microscopic level. This intracellular stable iodine could constitute a slow turnover compartment not used for hormone synthesis.

Aging↗

Secondary ion mass spectrometry analysis of the copper distribution in Drosophila melanogaster chronically intoxicated with Bordeaux mixture.

The fungicides used intensively in agriculture may affect non-target organisms. The concentrations of copper sulfate-based fungicide, Bordeaux mixture, normally used in agriculture, can significantly reduce both the life span and breeding rate of Drosophila melanogaster. The present study examines the distribution of copper in organ sections of fruit flies intoxicated with Bordeaux mixture, by secondary ion mass spectrometry. The organs of most control flies contained no copper. In contrast, copper accumulated in the cytoplasm of all the mesenteron and Malpighian tubule epithelial cells of the treated flies. There were also copper deposits in the fat body and the epithelia of the seminal receptacle and accessory glands of some flies, but there was little or no copper in the ovaries. The mesenteron and Malpighian tubules are generally responsible for detoxification by accumulation of ingested metal salts in insects. The high concentration of Bordeaux mixture used saturated these organs and resulted in excess copper being deposited in other sites, such as the fat body and the reproductive system.

Animals↗

Changes in 127I mice thyroid follicle studied by analytical ion microscopy: a key for the comprehension of amiodarone-induced thyroid diseases.

Analytical ion microscopy was used to evaluate the quantitative changes in thyroid 127I mapping induced by amiodarone in relation to the iodine intake. Mice were maintained on a normal diet (NID), on a low iodine diet (LID) or on a high iodine diet (HID) during 3 months. They received daily ip injections of amiodarone or NaI during the last 10 days. Microanalysis of iodine was performed on thyroid sections. In NID mice, the cellular 127I concentration (mean +/- SE: 0.90 +/- 0.06 micrograms/mg) was lower than that of follicular lumina (6.99 +/- 0.17). Amiodarone increased cellular concentration (2-fold) and decreased follicular concentration; NaI induced the same results. In LID mice, both concentrations, which were decreased 60- to 70-fold in comparison with NID, were restored by amiodarone, while NaI enhanced follicular concentration more than amiodarone. In HID mice, the follicular concentration (1.5-fold higher than normal) returned to a normal range with amiodarone, but cellular concentration (2.5-fold lower than normal) remained low, while NaI increased the cellular concentration 3-fold. These data show that iodine released by amiodarone has a bioavailability different from that of NaI. They indicate that thyroid response to amiodarone is related to dietary iodine intake, which, in turn, determines autoregulatory mechanisms. They also raise the question of the possible existence of an intrinsic property of amiodarone which would explain the specificity of its activity on thyroid iodine organification and the development of amiodarone-induced human thyroid diseases.

Amiodarone↗