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F Raynaud

Publications and source records attributed to F Raynaud.

At least 55 records · Page 3Linked to original sources

[Preoperative localization of parathyroid adenomas. Role of cervical ultrasonography].

OBJECTIVES: We evaluated the sensitivity and specificity of cervical ultrasonography for the detection of primary parathyroid adenomas. METHODS: From January 1990 to May 1992, ultrasonography was performed before exploratory cervicotomy in 30 patients (10 males, 20 females, mean age 56.3 yr) whose diagnosis was primary hyperparathyroidism based on radioimmunoassay of parathyroid hormone. The same trained operator performed all the ultrasonographic examinations. RESULTS: Twenty-six parathyroid tumours were detected in 23 of the 30 patients examined by ultrasonography. The four standard localizations and one ectopic tumour were visualized. At surgery 37 tumours were found in 30 patients. Among the 11 false negatives, the operator had identified an abnormal tumour incorrectly as a cervical lymph node in 2. Most of the false negatives occurred early in the study. The sensitivity of ultrasonography was thus 70 % with a 100% specificity. CONCLUSIONS: Cervical ultrasonography is a reliable, non-invasive and relatively inexpensive examination which should be used as a first-line test for the aetiological assessment of hyperparathyroidism.

Adenoma↗

Folate deficiency and congenital malformations induced by pyrimethamine in the rat.

In order to establish a relationship between the appearance of congenital malformations and the decrease of folic acid in rat mothers and embryos, a folic acid antagonist, pyrimethamine (PY), was administered. On the 12th day of gestation/pregnant rats received an intraperitoneal injection of 12.5, 15.63, 18.75 or 25 mg/kg PY. On the 13th day of gestation folic acid was measured in different maternal and embryonic tissues obtained after surgical hysterectomy of 1 uterine horn. On the 21st day of gestation malformations were studied on live fetuses remaining in the opposite horn. The folate levels were identical in all maternal tissues. The concentration of folic acid significantly decreased (50%) within the embryonic tissues in all PY-treated groups. A decrease of fetal weight occurred in the 18.75 and 25 mg/kg PY groups. Malformations were observed in the same groups. A dysfunction of the placental transfer of folates is hypothesized.

Animals↗

High-performance liquid chromatographic assay for the measurement of the novel microtubule inhibitor 1069C85 in biological tissues and fluids.

1069C85 is a novel tubulin binder developed to circumvent the resistance associated with the Vinca alkaloids. Cytotoxic activity has been demonstrated in vitro against a variety of tumour cell lines, including a variant of the P388 leukaemia with acquired resistance to vincristine. A phase I clinical trial is planned and an assay suitable for preclinical and clinical pharmacokinetics has been developed. A high-performance liquid chromatographic (HPLC) assay is described which allows measurement of 1069C85 in plasma, urine, and tissue samples. The method uses reversed-phase chromatography with isocratic elution and detection by fluorescence at 406 nm following excitation at 340 nm. The assay is specific, sensitive (limit of sensitivity 0.25 ng/ml) and reproducible (coefficient of variation < 5%). The method has been used to study the pharmacokinetics of 1069C85 in Balb C mice following a single oral dose of 1 mg/kg. The maximum plasma concentration was reached 15 min after administration and subsequent elimination was slow with a half life of 6.5 +/- 2.2 h. The drug remained detectable in plasma, at 1 +/- 0.5 ng/ml, 24 h after this dose. This assay will be used to determine the pharmacokinetic profile of 1069C85 in mice and in a forthcoming phase I clinical trial.

Animals↗

Rapid effect of treatment of psoriatic erythrocytes with the synthetic retinoid acitretin to increase 8-azido cyclic AMP binding to the RI regulatory subunit.

We have recently demonstrated a deficiency in the cyclic adenosine monophosphate (cAMP)-dependent protein kinases (PKA), the intracellular mediator of AMP, in psoriasis. This enzyme defect is expressed in fibroblasts and in red blood cells isolated from psoriatic patients. In these cells, the abnormality noted in cAMP binding to PKA correlates well with the severity of the disease and is corrected by long-term treatment with etretinate. In this study, we determined the effect of oral administration of acitretin in four psoriatic patients on the altered cAMP binding observed with the RI regulatory subunit of PKA in erythrocytes prepared from these patients. Acitretin (30 mg/day) induced a rapid (within 1 h) increase in the ability of the RI regulatory subunit of erythrocytes to bind the 8-azido[32P]cAMP photoaffinity analogue of cAMP. The maximal plateau for this effect of acitretin was observed within 24 h of treatment and preceded the clinical improvement of the disease. The effect of acitretin was dose-dependent, with the maximal response observed at 40 mg acitretin/d. In addition, the rapid exposure (15 min) of erythrocytes isolated from untreated patients exhibiting severe psoriasis to acitretin also promoted an increase in binding of 8-azido[32P]cAMP to the RI cAMP binding protein. Retinoic acid and 13-cis-retinoic acid were as efficient as acitretin in inducing the increase in binding of 8-azido[32P]cAMP to the RI regulatory subunit, whereas arotinoid was without effect. These results suggest that acitretin may act to modify PKA (the RI regulatory subunit) at the post-transcriptional level, and this may reflect, in part, on the mechanism of action of this synthetic retinoid. Further, monitoring this biochemical event may be helpful in determining the choice of retinoid therapy and in the management of its pharmacology.

Acitretin↗

[Ovarian abscess. A case of a dermoid cyst with a secondary infection].

The authors report a case of an ovarian abscess presenting as acute sciatica with pyrexia in a 36-years-old woman with an intrauterine contraceptive device. Imaging (plain X-ray of abdomen and CT scan) was clear-cut, showing an air pocket as a result of abscess formation and dental calcifications which enabled a preoperative diagnosis of dermoid cyst. The outcome was successful following appropriate surgical treatment and unilateral tubo-oophorectomy.

Abscess↗

Calcitonin gene-related peptide: an autocrine growth factor with regulatory activity in vitro.

We show that an autocrine system for calcitonin gene-related peptide (CGRP) exists in F9 teratocarcinoma cells. Synthesis of CGRP by F9 cells was demonstrated by measuring the peptide concentration in cells and medium and by determining specific mRNA in cells. During six days of culture, CGRP secretion did not vary significantly in the medium, while intracellular CGRP and CGRP mRNA levels increased. F9 cells contained a CGRP-sensitive adenylate cyclase system and CGRP increases the accumulation of cAMP in the culture medium. Interestingly affinity purified antibodies against CGRP specifically inhibited growth of F9 cells by 50%. CGRP therefore stimulates F9 cell growth by an autocrine process, suggesting that CGRP may be a growth factor during early embryogenesis.

Animals↗

Characterization of specific proteases associated with the surface of human skin fibroblasts, and their modulation in pathology.

Human skin fibroblasts were probed for cell surface protease activity. One activity removing dipeptides from the NH2-terminal end of Gly-Pro-pNA was specifically inhibited by di-isopropyl-fluorophosphate (DFP), phenylmethanesulphony fluoride (PMSF), and diprotin A, and thus was identified as dipeptidyl peptidase IV (DPP IV). A group of bestatin-sensitive N-exoaminopeptidase activities was also characterized when Ala-, Leu-, and Arg-pNA were used as chromogenic substrates. Using human monoclonal antibodies anti-CD 13 and anti-CD 26 that recognized, respectively, an N-Ala-aminopeptidase and DPP IV, it was found that human dermal fibroblasts expressed the CD 13 and CD 26 antigen on their surface. In addition, both peptidases were specifically immunoprecipitated by monoclonal antibodies anti-CD 13 and anti-CD 26 from plasma membranes. Cell surface proteolytic activities were also investigated in human fibroblasts derived from dermatological and rheumatic diseases (i.e., psoriasis, rheumatoid arthritis, and lichen planus). It was found that these fibroblasts also expressed both types of proteinases initially identified on normal skin fibroblasts and that the levels of Ala-aminopeptidase activities were similar in all cases. In contrast, the levels of Arg-, Leu-exoaminopeptidase, and DPP IV activities were significantly higher (up to 6.6-fold) in the three pathological fibroblast populations than in their normal counterparts. These proteolytic enzymes, therefore, can potentially serve as markers in dermatological diseases. Taken together, our results suggest that skin fibroblast-derived proteinases associated with both serine and N-aminopeptidase activities may play an important role by participating in the extracellular events associated with fibroblast behaviour.

Antibodies, Monoclonal↗

Association of type II cAMP-dependent protein kinase with p34cdc2 protein kinase in human fibroblasts.

Previous independent studies suggested that type II cAMP-dependent protein kinase and the p34cdc2 protein kinase cell cycle regulator co-localize at centrosomes. In order to investigate whether there is an association of type II cAMP-dependent protein kinase with p34cdc2 in human fibroblasts, we used three different approaches. First, the regulatory subunits RI and RII were photoaffinity-labeled with 8-N3-[32P]cAMP, and anti-p34cdc2 immunoprecipitates were screened for the presence of either RI or RII regulatory subunits by one- or two-dimensional gel electrophoresis. Second, anti-RII alpha immunoprecipitates were screened for the presence of p34cdc2 by Western blot using three different affinity-purified antibodies recognizing different domains of human p34cdc2. Conversely, anti-p34cdc2 immunoprecipitates (three different antibodies), as well as the material retained on p13suc1-Sepharose Bio-Beads, which binds specifically p34cdc2, were screened for the presence of RII alpha. Finally, we have looked for cAMP-dependent protein kinase activity specifically inhibited by PKI in immunoprecipitates obtained from extracts treated with different anti-p34cdc2 antibodies. All these experiments gave concordant results and demonstrate that at least at G0/G1, human fibroblasts contain a complex of active type II cAMP-dependent protein kinase associated through its RII alpha subunit with p34cdc2.

Adult↗

Determination of 5-methoxyindoles in pineal gland and plasma samples by high-performance liquid chromatography with electrochemical detection.

A liquid chromatographic analysis with electrochemical detection of 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxyindoleacetic acid and melatonin is described. Optimal elution conditions were determined by studying several variables: pH, buffer salt, counter ion and organic modifier. Measurement of 5-methoxyindoles in the pineal gland and plasma of hamsters has been performed after extraction. This method is specific and sensitive, and enables detection of 5-methoxyindoles in a pool of two hamster pineal glands. This is also the first time that these three 5-methoxyindoles have been measured simultaneously in plasma.

5-Methoxytryptamine↗

5-Methoxytryptamine is metabolized by monoamine oxidase A in the pineal gland and plasma of golden hamsters.

Pineal concentrations of 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxyindole acetic acid and melatonin were determined using high performance liquid chromatography following administration of different monoamine oxidase (MAO) inhibitors (clorgyline, pargyline and deprenyl) to golden hamsters. Plasma concentrations of 5-methoxytryptamine, 5-methoxytryptophol and melatonin were also measured following 5-methoxytryptamine administration to hamsters pretreated with MAO inhibitors. A significant increase in pineal and plasma 5-methoxytryptamine together with a decrease in 5-methoxytryptophol concentrations was observed after clorgyline or pargyline. In contrast, following deprenyl administration, no change in pineal and plasma 5-methoxyindoles was observed. These results indicate that monoamine oxidase A is responsible for oxidative deamination of 5-methoxytryptamine.

5-Methoxytryptamine↗

Plasma concentrations of 5-methoxytryptamine, 5-methoxytryptophol and melatonin after 5-methoxytryptamine administration of golden hamsters: physiological implications.

5-Methoxytryptamine (5-MT), 5-methoxytryptophol (5-ML) and melatonin (Mel) were measured in the plasma after 2, 5, and 8 weeks administration of 25 micrograms 5-MT to golden hamsters kept under long photoperiod. 5-MT showed a one compartment kinetic profile in the plasma with half lives of 14.8 min after 2 weeks, 15 min after 5 weeks and 19.1 min after 8 weeks. A rapid metabolism of 5-MT was shown, Mel and 5-ML being detected in the plasma following 5-MT administration. However it was also shown that the gonadal atrophy observed after 5-MT administration cannot be due to its metabolism into these 2 compounds. Indeed when exogenously administered at a dose generating the same plasma concentration as that observed after 5-MT, the gonadal regression observed after the association of 5-ML and Mel is much less than that observed after 5-MT. 5-MT is thus a compound of great physiological interest.

5-Methoxytryptamine↗

Effect of different photoperiods on the diurnal rhythm of 5-methoxytryptamine in the pineal gland of golden hamsters (Mesocricetus auratus).

This study tested the photo-dependency of the rhythmic synthesis of 5-methoxytryptamine (5-MT) in the pineal gland of golden hamsters. After pargyline administration, pineal 5-methoxytryptamine and melatonin were measured by HPLC in male golden hamsters kept under short and long photoperiod. In both photoperiodic regimes, a clear 5-MT rhythm was observed which fitted a sinusoidal function with high values occurring during the daytime and low values occurring during the night-time. The duration of the low night-time levels was clearly proportional to the length of the dark phase. A marked rhythm of melatonin synthesis was also seen with low daytime levels and high night-time values. An inverse relationship between 5-MT and melatonin levels was observed. Thus, after pargyline administration, the rhythms of 5-MT and melatonin in the pineal gland of golden hamsters are photoperiod-dependent and show a reciprocal relationship.

5-Methoxytryptamine↗

Effect of retinoic acid on platelet-derived growth factor (PDGF) bioactivity and type-B PDGF receptors in normal and psoriatic human fibroblasts.

Psoriasis is a common skin disease in which retinoids have beneficial effects. It offers a model for the study of benign hyperproliferation with abnormal differentiation. The dermis has a prominent role in the appearance of epidermal lesions. It is therefore of interest to study the factors that modulate dermal cell proliferation. In this study, the role of retinoids in modulating platelet-derived growth factor (PDGF) bioactivity was studied in normal (six subjects) and psoriatic fibroblasts from involved and uninvolved tissues (six patients). Retinoic acid treatment (for 4 d at 10(-6) M) of psoriatic fibroblasts significantly increased the chemotactic effect of PDGF in these cells (p less than 0.01 and p less than 0.05, respectively, in involved and uninvolved skin at 20 ng/ml of platelet-derived growth factor as measured in a modified Boyden Chamber Assay). In the same way, retinoic acid treatment of psoriatic fibroblasts increased the mitogenicity of platelet-derived growth factor in these cells. Retinoic acid treatment has no significant effect on the mitogenic and chemotactic activity of PDGF in normal fibroblasts. The binding of the homodimer BB PDGF to its type-B receptor, which mediates the mitogenic and chemotactic effect of PDGF, was not modified by retinoic acid treatment either in psoriatic and/or normal fibroblasts. These results suggest that retinoic acid may modulate the PDGF bioactivity in psoriatic fibroblasts not by affecting the binding of this ligand to these cells but by influencing a post-receptor event.

Adult↗

Protein kinase C activity in normal and psoriatic cells: cultures of fibroblasts and lymphocytes.

Protein kinase C (PKC) activity was measured in cultures of fibroblasts from biopsies of the involved and uninvolved skin of seven patients with psoriasis and from the skin biopsies of nine normal controls. PKC activity was significantly increased (P less than 0.005) in the particulate fraction of fibroblasts obtained from the involved areas of skin (450 +/- SEM 89 pmol/mg protein/3 min) and the uninvolved skin (394 +/- 94 pmol/mg protein/3 min) in psoriasis as compared to that of controls (103 +/- 24 pmol/mg protein/3 min). The soluble fraction of PKC activity was comparable in controls and in the fibroblasts obtained from involved areas and not significantly different from the values in fibroblasts from uninvolved skin. PKC activity was also measured in the soluble and particulate fractions of lymphocytes from 13 patients with psoriasis and from 14 normal controls. The PKC activity did not differ in the lymphocytes of patients with psoriasis from the controls in either the cytosolic or the membrane fractions. The increase in PKC activity as expressed at the membrane level of psoriatic fibroblasts may be related to an increase in sensitivity of these cells to hormones or growth factors involved in the regulation of their growth.

Adult↗

Low ambient temperature does not affect the pineal concentrations of either 5-methoxytryptamine or melatonin in golden hamsters kept under short photoperiod.

This work investigates the rhythmic synthesis of pineal 5-methoxytryptamine and related indoles in golden hamsters as a function of ambient temperature. 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxyindole acetic acid, and melatonin were measured by high pressure liquid chromatography (HPLC) in the pineal gland of golden hamsters after inhibition of monoamine oxidase. In our experimental conditions, the pineal 5-methoxyindole concentrations of hamsters kept at 5 degrees C were similar to those observed at 20 degrees C. These results suggest that low temperature, which is known to accelerate the short photoperiod-induced gonadal regression, acts at a level different to that of the pineal gland or affects another compound in the pineal gland.

5-Methoxytryptamine↗

[Neonatal lupus].

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Age Factors↗