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Biomedical subjects

F Raynaud

Publications and source records attributed to F Raynaud.

At least 73 records · Page 4Linked to original sources

High chemotactic response to platelet-derived growth factor of a teratocarcinoma differentiated mesodermal cell line.

Evidence is presented that a differentiated mesodermal line (MES-1) from P19 EC cells express a high chemotactic response to platelet-derived growth factor (PDGF) as assayed in a blind-well modified Boyden chamber. Compared to the NIH 3T3 fibroblasts the chemotactic response of MES-1 is increased by 10-fold at 0.3 ng/ml of PDGF, 4-fold at 1.25 ng/ml of PDGF, 2-fold at 2.5 ng/ml of PDGF. In contrast, PDGF induces the same increase in [3H]thymidine incorporation in both cell lines, made quiescent under reduced serum concentration. This high chemotactic response to PDGF seems specific for these mesodermal cells. Among the different teratocarcinoma cells tested, including stem cells (F9, PC 13, PCC4) and endodermal derivatives (PYS, F9 with retinoic acid, PSA 5E), only the visceral endodermlike cells (PSA5E) are slightly attracted by PDGF. This chemotactic response to PDGF is not related to the presence or characteristics of the type B PDGF receptors, which are less numerous in MES-1 cells (10(5) receptors/cell, KDa 1,2 mM) compared to NIH 3T3 cells (64 X 10(4) receptors per cell, KDa 1,8 nM). The MES-1 cell line might be of interest for studying the chemotactic effect of PDGF. These results also suggest a role for this soluble factor in cell migration during early embryogenesis.

Animals↗

Growth hormone secretion during sleep. II. Interrelationships between growth hormone secretion, insulin-like growth factor I and sex steroids.

The serum levels of insulin-like growth factor I (IGF I), dehydroepiandrosterone sulfate (DHAS), testosterone (T) and estradiol (E2) have been measured in 78 prepubertal and 57 early pubertal patients referred for short stature, at the same time when their secretion of GH was evaluated both during nocturnal sleep and by two conventional stimulation tests. According to the results of GH measurements they were considered as having a normal secretion of GH (group I), a complete GH deficiency (group II), a partial GH deficiency (group III), low responses to stimuli with normal secretion during sleep (group IV) or a nocturnal neurosecretory dysfunction (group V). Though widely scattered, the IGF I levels showed the following characteristics: a significant increase at puberty from 0.77 to 1.29 U/ml (p less than 0.001) in the so-called endocrinologically normal patients of group I, not in the other groups; in the prepubertal patients of group I, a correlation of IGF I with chronological age (r = 0.47, p less than 0.005) and bone age (r = 0.52, p less than 0.002); significantly reduced IGF I levels in patients of group II having complete GH deficiency (p less than 0.001); no significant differences between prepubertal patients with partial or atypical GH deficiency from groups III, IV, V and prepubertal patients from group I; lower pubertal levels in groups III, IV, V than in pubertal patients from group I (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Relation of the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the beginning of puberty in patients of short stature].

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGFI was slightly but highly significantly correlated to the growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated together.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

[The relation between the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the onset of puberty in patients of small stature].

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGF I was slightly but highly significantly correlated to growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

A cAMP binding abnormality in psoriasis.

In 34 psoriatic patients with various cutaneous manifestations (psoriasis vulgaris, erythroderma psoriaticum, guttate psoriasis), the ability of the RI regulatory subunit of cAMP-dependent protein kinase (PKA) to bind a cAMP analogue (8-azido [32P] cAMP) in erythrocyte membranes was significantly lower than that in 19 normal subjects (mean [SEM] 565 [35] vs 930 [35] fmol/mg protein). This enzyme defect was not found in patients with other forms of dermatitis that can be confused with psoriasis or with other inflammatory diseases. There was a significant negative correlation between the severity of the disease as expressed by the psoriatic area and severity index score and the binding of the cAMP analogue to PKA. A long-term study showed that oral retinoid treatment of psoriatic patients resulted in a correction of the binding defect. Unaffected members of psoriatic families had significantly lower than normal binding of cAMP to PKA (773 [60] fmol/mg protein). This study shows for the first time that in psoriasis a biochemical defect expressed in erythrocytes correlates with the severity of the disease as well as its clinical evolution. These results will be useful in clinical management of psoriatic disease for the choice and follow-up of retinoid therapy.

Administration, Oral↗

Serum thymic hormone thymulin activity is normal in children with asthma.

In asthma, it has been hypothesized that suppressor T-lymphocytes play a protective role and have been reported to be functionally abnormal. Thymic hormone thymulin plays a role in the differentiation of T-lymphocytes and plasmatic thymulin concentration and is related to the functional state of the thymus. To assess the participation of the thymus in the impairment of T-lymphocyte function, we measured plasma thymulin activity in children with allergic asthma (N = 40). The plasma thymulin activity was compared with plasma thymulin activity of children with nonallergic asthma (N = 6), children with atopic dermatitis (N = 9) or allergic rhinitis (N = 7), and in age-matched healthy control children (N = 18) (age range of children studied, 2 to 19 years). Thymulin activity was found within the normal range (1/16 to 1/64) in all control children and in all children with allergic asthma and allergic rhinitis, as well as in all children with intrinsic asthma and atopic dermatitis. Our findings are at variance with the low thymulin activity previously reported in allergic asthma, and we could not explain these discrepancies. (Both studies used the same bioassay, and the population studied did not appear to be different.) T-lymphocyte abnormalities in subjects with asthma must be assessed by other means than measurement of thymic function.

Adolescent↗

Food-induced alterations of intestinal permeability in children with cow's milk-sensitive enteropathy and atopic dermatitis.

Intestinal permeability was evaluated by measuring the excretion of two orally absorbed (0.1 g/kg of weight) nonmetabolizable markers, mannitol and lactulose. In 39 controls, the lactulose/mannitol urinary ratio (L/M ratio) was 2.45 +/- 1.01% during fasting and remained stable after food ingestion. In 12 children with cow's milk-sensitive enteropathy under an exclusion diet, the L/M ratio was comparable with that of controls during fasting and exhibited a threefold rise during a provocation intestinal permeability test (IPT) with milk. In 28 children with atopic dermatitis (AD), the fasting IPT L/M ratio was significantly higher than in controls (3.60 +/- 3.31%). This rise was related to an increase of lactulose urinary clearance. A provocation IPT with food induced significant L/M ratio changes only in the group in which the food was proved to be responsible for the exacerbation of skin lesions. We concluded that in cow's milk-sensitive enteropathy, an IPT allows a good evaluation of mucosal reactivity to milk, and in AD, permeability changes are present in at least some cases with cutaneous lesions clearly related to food ingestion.

Adolescent↗

The effect of 5-methoxytryptamine on golden hamster gonads is not a consequence of its acetylation into melatonin.

Radioimmunoassay and high performance liquid chromatography were used to determine if the gonadal atrophy induced by late afternoon injections of 5-methoxytryptamine (5-MT) in golden hamsters kept under long photoperiod could be due to the acetylation of this compound into melatonin. An increase in plasma concentrations of melatonin (10-13 nmol/l) was detected 15 min after injection of 130 nmol 5-MT. An injection of 4.3 nmol melatonin generated a similar plasma concentration of melatonin. 5-MT (130 nmol) and melatonin (4.3 nmol) were then injected daily in the late afternoon to golden hamsters kept under long photoperiod. After 8 weeks, 5-MT induced total testicular regression, while melatonin induced partial atrophy only. Thus under these experimental conditions, 5-MT had a physiological activity independent of that of melatonin.

5-Methoxytryptamine↗

Radioimmunoassay of 5-methoxytryptophol in plasma.

5-Methoxytryptophol (ML) is synthesized by the pineal gland, but no radioimmunoassay has been described for its routine measurement in human plasma. We have developed and validated such an RIA. The assay is sensitive (detecting as little as 8 ng/L) and specific, and requires no extraction stage. A preliminary study of healthy volunteers showed an intra-individual variation in plasma ML that was independent of the sex of the subject and the time of daytime collection. Investigation of the 24-h pattern of ML in seven men revealed a low-amplitude daily rhythm (P less than 0.03). Mean concentrations of ML between noon and midnight significantly exceeded those between 0030 and 1130 hours in each individual (P less than 0.05). This assay is practical and convenient, and it should greatly assist in investigation of factors affecting concentrations of ML in human plasma.

Adult↗

Effect of retinoic acid on cAMP dependent protein phosphorylation in psoriatic fibroblasts.

Retinoic acid treatment of psoriatic fibroblasts increases the activity of cyclic AMP dependent protein kinase. In this study we report that retinoic acid treatment of cultured psoriatic fibroblasts modifies their subsequent cAMP dependent protein phosphorylation. In the soluble fraction of normal fibroblasts cAMP clearly enhances the in vitro phosphorylation of proteins of MW 37,49,54,56,68,83 kD while retinoic acid treatment of the same cells results in a decrease of the cAMP dependent phosphorylation of the first five of the same proteins. In contrast, in psoriatic fibroblasts from psoriatic patients retinoic acid either has no effect or increases the cAMP dependent phosphorylation of some of these proteins. Moreover the phosphorylation of a protein of MW 54 kD, undetectable in untreated psoriatic cells, is more phosphorylated in the presence of cAMP after retinoic acid treatment. The appearance of this phosphorylated proteins is time dependent and dose dependent upon the addition of retinoic acid. These in vitro phosphorylation results suggest that retinoic acid treatment of psoriatic fibroblasts change the level of cAMP dependent phosphorylation of some cytosolic proteins. These specific phosphorylations could be implicated in a variation of cell functions.

Cells, Cultured↗

Increased chemotactic and mitogenic response of psoriatic fibroblasts to platelet-derived growth factor.

The effect of increasing doses from 1.25 to 10 ng/ml of PDGF was tested for chemotactic and mitogenic activity on psoriatic fibroblasts cultured from involved and uninvolved skin of five patients compared to normal fibroblasts from five matched control subjects. The chemotactic response of psoriatic fibroblasts from involved skin (p less than 0.05) and uninvolved skin (p less than 0.005) is significantly enhanced compared to normal fibroblasts. Similarly, PDGF in the presence of platelet poor human plasma is a more potent mitogenic agent in psoriatic fibroblasts than in normal fibroblasts. This increased sensitivity of psoriatic fibroblasts to PDGF may be related to the inflammatory and vascularization processes involved in psoriatic dermis.

Adult↗

Growth hormone secretion during sleep. I. Comparison with GH responses to conventional pharmacologic stimuli in pubertal and early pubertal short subjects. Effects of treatment with human GH in patients with discrepant measurements of GH secretion.

Growth hormone (GH) was measured in 215 short children (147 males and 68 females, 123 prepubertal, 92 at early pubertal stages), comparing GH responses to classical pharmacologic stimulation tests and spontaneous GH secretion during sleep. GH secretion during sleep, but not GH responses to stimuli, was higher in early pubertal than in prepubertal subjects. The patients were classified into five groups, according to the agreement between GH responses to stimuli and GH secretion during sleep: group I, normal GH-secreting children; group II, completely GH-deficient; group III, partially GH-deficient; group IV, with normal secretion during sleep and low responses to stimuli; group V, with the reverse situation. 30% of the patients were in groups IV and V, both at prepubertal and early pubertal stages. 46 patients of groups II-V were treated with extracted human GH(hGH). The growth rate was enhanced in groups IV and V, to the same extent as in groups II and III. Four points can be concluded: (1) the rise of GH secretion during sleep is an early event at the onset of puberty; (2) the discrepancy between the GH responses to classical stimuli and GH secretion during sleep are of pathological significance; (3) disturbances of GH secretion might be diagnosed by measuring GH secretion during sleep rather than by using conventional stimulation tests; (4) a trial course of hGH treatment could be proposed in patients with both kinds of discrepancies between GH responses to stimuli and GH secretion during sleep.

Adolescent↗

Retinoid treatment of human psoriatic fibroblasts induces an increase in cyclic AMP-dependent protein kinase activity.

We recently showed a deficiency of cyclic AMP (cAMP)-dependent protein kinases in psoriatic cells. In this work the effects of retinoids on cAMP-dependent protein kinases of fibroblasts from 7 normal subjects and 7 psoriatic patients were studied. The levels of RI and RII (two forms of the cAMP-dependent protein kinases) present in control and retinoic acid-treated cells were quantitated by photoaffinity labeling with [8-azido-32P]cAMP. In psoriatic fibroblasts the levels of RII are decreased or undetectable compared with those of normal fibroblasts both in the cytosolic and membrane fractions. The amount of RI was normal in the cytosol of fibroblasts of 5 out of 7 patients and decreased in 2 patients. Membrane-associated levels of RI were decreased in 5 patients and normal in 2 patients. Retinoic acid treatment induces an increase in the amount of RI and RII regulatory subunits when they are deficient in the cytosolic and membrane fractions of psoriatic fibroblasts. Retinoic acid had no effect on RI and RII in normal fibroblasts. In addition, with in vitro retinoic acid treatment the cAMP-dependent protein kinase activity, measured in the fibroblasts of 4 psoriatic patients, was increased in the cytosol in 2 patients and in the membranes in all 4 patients. In these studies, comparable results were obtained with fibroblasts cultured from involved and uninvolved skin. This in vitro effect of retinoids on cAMP-dependent protein kinases in psoriatic fibroblasts may help to explain some of the in vivo therapeutic effects of retinoids.

Fibroblasts↗

Comparison of growth hormone response to growth hormone-releasing factor 1-44 according to the combined study of sleep secretion with the responses to pharmacologic stimuli.

The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.

Adolescent↗

[Dowling-Meara dominant epidermolysis bullosa. An intraepidermal epidermolysis bullosa which hides its prognosis well].

The epidermolysis bullosa simplex (intraepidermal) disorders represent a heterogeneous group of bullous diseases all inherited in an autosomal dominant mode. The prognosis is usually good and the bullous lesions heal without scarring. We present here three patients affected with intraepidermal epidermolysis bullosa of the Dowling-Meara type with varying prognoses. Case n. 1. This 4-year-old girl was first seen at the age of 15 months for numerous bullous lesions distributed over her entire skin surface and on her oral mucosa. The blisters, first noted shortly after birth, showed an herpetiform distribution and a thick and hyperkeratotic roof. A yellowish palmoplantar keratoderma was also present. At the age of four the bullous eruption remained extremely severe. The family history revealed no similar cutaneous disorders. Histology showed focal intraepidermal separation and ultrastructural examination revealed that the split occurred above the dermoepidermal junction within the basal cell cytoplasm. Tonofilament clumping was observed. The dermoepidermal junction was normal with hemidesmosomes and anchoring fibrils showing no significant abnormalities. Case n. 2. This 8-year-old boy presented at the age of 5 with numerous bullous lesions involving most of the skin surface and mucosa. The family history was unremarkable. The blisters, present since birth, were numerous and were often circinate with central healing. Palmoplantar keratoderma was noted. Electron microscopy showed intraepidermal separation occurring in the basal cell layer with tonofilament clumping.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Deficiency of cyclic AMP-dependent protein kinases in human psoriasis.

To determine possible differences in the cyclic AMP-dependent protein kinases of normal and psoriatic human fibroblasts, the levels of the regulatory subunits (RI and RII, respectively) of protein kinase I and protein kinase II were quantitated by photoaffinity labeling with 8-azido[32P]cAMP. The level of RII was significantly decreased, or was undetectable, in cytosol prepared from fibroblasts from five psoriatic subjects when compared to RII levels found with normal human fibroblasts. The level of cytosolic RI was decreased in fibroblasts from four psoriatic patients and was within the normal range for one diseased patient when compared to RI levels in normal human fibroblasts. The elution profile from a DEAE-cellulose column of protein kinase activity in the soluble fraction from two psoriatic patients also showed a decrease in type I kinase activity and the complete absence of type II kinase activity. Other results indicate that the level of RI in erythrocyte membranes from psoriatic subjects is significantly decreased when compared to that of erythrocyte membranes from eight normal subjects. A significant correlation (P less than 0.001) was observed between the severity of the cutaneous manifestation of the disease and the level of RI in psoriatic erythrocyte membranes. The changes noted in the levels of RI and RII in cell types other than those thought to be specifically involved in the proliferative epidermis disorder of the disease suggest a general protein kinase deficiency.

Affinity Labels↗

Forward motility protein (FMP): localization in hamster epididymal spermatozoa.

The presence of FMP was investigated by immunocytochemistry in spermatozoa from the hamster caput and cauda epididymis. Spermatozoa from the caput showed no staining whereas spermatozoa pre-incubated with FMP were stained on the acrosome. Pre-treatment of the same sperm with epididymal plasma induced staining on the principal piece of the flagellum. Spermatozoa from the cauda were stained without previous incubation both on the acrosome and on the principal piece of the flagellum. These results suggest that the action of FMP, which prevents head-to-head agglutination of motile spermatozoa and allows acquisition of forward motility, may be due to at least two proteins. The first localizes to the acrosome during epididymal transit (anti-sticking factor), whilst the second localizes to the principal piece of the flagellum (forward motility initiation factor).

Acrosome↗

[Comparison of the secretion of growth hormone during sleep and after pharmacologic stimulation. Results of treatment with hGH in cases of dissociated secretions].

Maximal response (peak) of growth hormone (GH) after conventional pharmacologic stimuli have been compared to maximal level reached during sleep in 215 children (123 prepubertal, 92 early pubertal) (group A). A weak correlation (r = 0.37, p less than 0.001) was observed. Five sub-groups of patients could be distinguished according to their GH pharmacologic or sleep peaks: 115 with normal secretion in both cases (I), 10 with complete deficiency (II), 27 with partial deficiency (III), 34 with normal GH sleep secretion and low responses to stimuli (IV) and 29 with the inverse situation (V). A second group (B) of 30 very short children (17 prepubertal and 13 early pubertal) had borderline or variable responses after several pharmacologic stimuli. hGH therapy was done to every patients of sub-group A II, 12 of sub-group A III, 9 of subgroup A IV, 5 of sub-group A V and every one of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. hGH effect in the three last kinds of patients, with atypical GH secretion, was better in those who were in early puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗