Survival in early-onset BRCA1 breast-cancer patients. Institut Curie Breast Cancer Group.
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Adult↗
Biomedical subjects
C Gautier
Publications and source records attributed to C Gautier.
Sensitivity of the relative-rate test to taxonomic sampling.
Relative-rate tests may be used to compare substitution rates between more than two sequences, which yields two main questions: What influence does the number of sequences have on relative-rate tests and what is the influence of the sampling strategy as characterized by the phylogenetic relationships between sequences? Using both simulations and analysis of real data from murids (APRT and LCAT nuclear genes), we show that comparing large numbers of species significantly improves the power of the test. This effect is stronger if species are more distantly related. On the other hand, it appears to be less rewarding to increase outgroup sampling than to use the single nearest outgroup sequence. Rates may be compared between paraphyletic ingroups and using paraphyletic outgroups, but unbalanced taxonomic sampling can bias the test. We present a simple phylogenetic weighting scheme which takes taxonomic sampling into account and significantly improves the relative-rate test in cases of unbalanced sampling. The answers are thus: (1) large taxonomic sampling of compared groups improves relative-rate tests, (2) sampling many outgroups does not bring significant improvement, (3) the only constraint on sampling strategy is that the outgroup be valid, and (4) results are more accurate when phylogenetic relationships between the investigated sequences are taken into account. Given current limitations of the maximum-likelihood and nonparametric approaches, the relative-rate test generalized to any number of species with phylogenetic weighting appears to be the most general test available to compare rates between lineages.
Adenine Phosphoribosyltransferase↗
Phylogenetic analysis of the Saccharomyces cerevisiae group based on polymorphisms of rDNA spacer sequences.
The phylogenetic relationships between species of yeasts assigned to the Saccharomyces sensu stricto group, which includes Saccharomyces cerevisiae and Saccharomyces bayanus, were studied together with Saccharomyces pastorianus and Saccharomyces paradoxus. The experimental approaches used were RFLP analysis of the PCR-amplified rDNA internal transcribed spacer (ITS) and intergenic spacer, and total ITS sequence analysis. Both RFLP and sequence analyses gave fairly similar results. The gene trees generated with either of the two data sets showed the distribution of the yeasts into two major, well-separated, phylogenetic clusters called 'cerevisiae' and 'bayanus'. The 'cerevisiae' cluster included the S. cerevisiae type strain, together with most of the species (16 out of 23), whereas the 'bayanus' cluster included the remaining seven type strains. Therefore, analysis of rDNA sequences confirmed S. cerevisiae and S. bayanus as two well-defined taxa. However, S. pastorianus and S. paradoxus, the two other usually accepted taxa of the now-defined Saccharomyces sensu stricto complex, could not be clearly separated from S. bayanus and S. cerevisiae, respectively. However, in both PCR-RFLP and ITS sequence analyses, S. paradoxus had the outermost position in the 'cerevisiae' cluster. PCR-RFLP analysis of the ribosomal spacer sequences was also carried out on 26 Saccharomyces strains isolated in various wine-growing regions of France in an attempt to clarify their positions in the Saccharomyces phylogenetic tree. Compared to the diversity of the Saccharomyces type strains, less genetic diversity was detected among these yeasts and several of them exhibited identical RFLP patterns. Most of the wine yeast strains (16 out of 26) were closely related to each other and were found within the 'cerevisiae' cluster. The remaining 10 wine yeast strains branched within the 'bayanus' cluster. PCR-RFLP analysis of ribosomal spacer sequences thus appears to be a useful and appropriate method for the correct characterization of Saccharomyces yeast strains used in food processing.
DNA, Fungal↗
Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves.
BACKGROUND AND PURPOSE: It has been shown previously that cerebral microemboli may occur frequently in patients with a normal mechanical heart valve (MHV) without prior history of stroke. Some arguments strongly suggest that these microemboli have a gaseous origin. In other circumstances such as extracorporeal circulation or decompression in divers, it has been demonstrated that cerebral microbubbles could lead to some deterioration in cognitive functions. Therefore, we have studied attention and memory, which are among the most impaired cognitive functions as demonstrated in previous studies, in patients with an MHV. METHODS: Three groups of 12 volunteers each were composed of patients with an MHV and embolic signals in the cerebral circulation (group 1), patients with biological prostheses (group 2), and healthy subjects (group 3). Groups were carefully matched for age and verbal intellectual abilities. For each group, a transcranial Doppler examination was performed and a set of cognitive tests assessing sustained and selective attention and episodic and working memory was administered. RESULTS: The mean embolic rate was 29 per hour in patients with an MHV. No embolus was detected in the other 2 groups. Episodic memory was significantly modified in both groups 1 and 2 compared with the control group for tasks that required high-processing resources. Working memory performance was significantly decreased in MHV patients. No between-groups differences were observed for the other parameters. CONCLUSIONS: Alteration of episodic memory can be attributed to a long-term effect of the surgical procedure. Deterioration of working memory can be related to the presence of cerebral microemboli in MHV patients.
Aged↗
Expression and effect of insulin-like growth factor I on rat fetal Leydig cell function and differentiation.
Insulin like growth factor I (IGF-I) is believed to be a potent para/autocrine stimulator of Leydig cell function in adult testis. We investigated whether IGF-I is also an intratesticular regulator of fetal Leydig cell function by measuring its production in the fetal testis and its ability to affect testicular steroidogenesis during fetal development. Northern blot analysis revealed one major IGF-I transcript of 7-7.5 kb and two minor transcripts of 3.8 and 1.8 kb in 20.5 day fetal testis. IGF-I was detected by RIA in 16.5 fetal day testes, and the amounts of IGF-I secreted by 16.5 and 20.5 fetal day testes in vitro were much greater than the amounts contained in the testes, indicating active synthesis in culture. The secretion of IGF-I by the fetal testis in vitro was increased with testicular age and time in culture. It was not modified by gonadotropins or (Bu)2cAMP. Testosterone secretion by fetal testes explanted 13.5, 16.5, 18.5, and 20.5 days after conception and cultured in the presence or absence of 100 ng/ml LH for 3 days was not affected by the addition of 50 ng/ml IGF-I to the medium. In contrast, the addition of IGF-I to dispersed fetal testicular cells cultured for 3 days in the presence or absence of LH increased the number of Leydig cells identified by a positive cytochemical reaction for 3beta-hydroxysteroid dehydrogenase (3betaHSD). This was more pronounced with cells from 16.5- day-old fetuses (stage when the fetal Leydig cells are differentiating in vivo) than with 20.5-day-old fetuses cells (stage when the number and the function of fetal Leydig cells are stable or decreasing). It results from both an increased differentiation of mesenchymal cells in fetal Leydig cells and an increase in the mitotic index of the fetal Leydig cells, as inferred from the small increase in the percentage of bromodeoxyuridine/3betaHSD-positive cells. Both LH and IGF-I increased significantly testosterone production by day 16.5 cells. In the presence of LH, a high amount of testosterone was produced per 3betaHSD-positive cell; IGF-I further increased this production. This effect was not observed with day 20.5 cells. The amounts of testosterone produced per 3betaHSD-positive cell cultured in the presence of both LH and IGF-I were more than additive. Like IGF-I, insulin (50 ng/ml) increased testosterone secretion per 3betaHSD-positive cells in cultures of day 16.5 cells, but not in those of day 20.5, cells. Lastly, IGF-I also increased the steroidogenic activity of each Leydig cell in cultures containing (Bu)2cAMP, but its effects were weaker than those observed in the presence of LH. This suggests that IGF-I has sites of action both upstream and downstream cAMP generation. These results suggest that IGF-I acts as paracrine/autocrine factor in the differentiation and activity of fetal Leydig cells.
Animals↗
[Infantile acne and isotretinoin].
UNLABELLED: We report a case of severe infantile cystic acne, which required a treatment with oral isotretinoin. CASE REPORT: The patient, a 22-month-old boy, presented cystic acne since 6 months of age. The child was otherwise healthy and endocrine evaluation was normal. Previous treatments had no effect, oral isotretinoine led to cure without secondary effects. COMMENTS: The etiology of infantile acne is not clearly defined, but may result from a persisting androgen-driven stimulation of sebaceous glands. Oral isotretinoin is safe and effective in case of recalcitrant infantile acne, but close monitoring is necessary because of the well-known side effects of oral retinoids.
Acne Vulgaris↗
[Cutaneous manifestations of erysipeloid septicemia].
BACKGROUND: Rouget du porc, or swine erysipelas, usually occurs in man as Rosenbach's erysipeloid. Septicemic forms are more uncommon and can be associated with dermal involvement far from the site of inoculation. We report a case in a patient given corticosteroid therapy for systematic lupus. CASE REPORT: A 50-year-old farmer was seen with fever, infiltrative erythema of the long finger and dorsal lesions on the ring finger which developed after a skin lesions caused by a duck. The diagnosis of septicemic rouget du porc was made after isolating the germ from blood cultures. There was no associated endocarditis. Fever and skin lesions totally regressed after treatment with ceftriaxone. DISCUSSION: The diagnosis of erysipeloid was supported by epidemiologic arguments and characteristic clinical features. The corticosteroid therapy was probably a favoring factor for development of septicemia. Positive diagnosis is usually obtained from blood culture but the germ can be isolated from skin biopsies at the site of inoculation. Our patient was free of endocarditis which should always be suspected. Endocarditis is frequent and often fatal. Intravenous high-dose penicillin G is recommanded treatment.
Animals↗
[Dermatitis caused by estrogens].
BACKGROUND: We report a case of sensitization to estrogen. CASE REPORT: A 40-year-old woman consulted for skin disorders which followed a cyclic pattern. At each menses, the patient developed pruritus and erythematous papulovesicular lesions over the members and trunk. Estraderm patch contact dermatitis was evident. Prick and patch tests with alcoholic solutions of estrone alone were positive. Serum tests were positive for anti-ethinyl-estradiol antibodies and anti-progesterone antibodies. DISCUSSION: Autoimmune dermatitis can be caused by sensitization to endogenous or exogenous sex hormones. Clinical manifestations and histological findings are variable and non-specific. The cyclic nature of the manifestations is however quite suggestive. Positive prick and patch tests performed with alcohol solutions of the hormones may give the diagnosis and serum tests may be positive for specific anti-steroid antibodies. These complementary explorations are however difficult to perform and interpret and definitive diagnosis is based on an association of clinical findings, skin tests, laboratory tests and the clinical course. In case of progesterone sensitization, the treatment of choice is estrogen inhibition of ovulation. For estrogen sensitization, anti-estrogen treatment appears to be more effective. Finally, bilateral ovariectomy may be required in difficult cases.
Administration, Cutaneous↗
Impact of changes in GC content on the silent molecular clock in murids.
Murid nuclear genomes are more homogeneous in GC content than those of most mammals, which leads to the question of how such important compositional changes have accumulated. This paper reports on relationships between frequencies of synonymous differences and GC change, in the lineages leading to human and murids. For this, we used the four-species approach: GC changes between human and murids were compared to the frequencies of synonymous differences, measured between two independent species without GC change (bovine and pig), by using orthologous genes common to all four species. We report three conclusions: (1) Among genes with little GC change, 60% of the variability of synonymous substitution frequencies is explained by the gene-specific rate component. (2) GC changes in murid genomes are independent of the gene-specific rate component. Slowly evolving genes in pig bovine comparison can show strong GC change in murids. (3) By using a GC-independent estimate of the substitution rate, we show that GC changes in murid genomes increase synonymous substitution frequencies. The GC homogenization considerably weakens the gene-specific conservation of substitution rates in murids, and could explain part of the increase of evolutionary rates observed in this group. We present a mechanism that can account for the evolution of the GC homogenization in murids.
Animals↗
Expression and regulation of transforming growth factor beta1 mRNA and protein in rat fetal testis in vitro.
The expression and secretion of Transforming Growth Factor beta1 (TGFbeta1) by cultured testes of day 20.5 rat fetuses were investigated. The testes were found to express two TGFbeta1 mRNA transcripts of 2.5 and 1.8 kb. By using mink lung epithelial cell bioassay based on the measurement of the inhibition of tritiated thymidine incorporation in response to TGFbeta1 immunoreactive material, the fetal testes were shown to secrete TGFbeta1 protein in organ culture. This secretion was positively regulated by dibutyryl cyclic AMP or by LH and FSH together, but not by LH alone and very slightly by FSH alone, which suggests interactions between Leydig and Sertoli cells for the control of TGFbeta1 production. These regulations probably take place at a posttranscriptional step since no concomitant increase of TGFbeta1 mRNA levels was observed. Such a positive regulation of TGFbeta1 secretion by gonadotropins could be a characteristic of the rat fetal testis.
Animals↗
Transforming growth factor beta1 inhibits steroidogenesis in dispersed fetal testicular cells in culture.
TGF beta1 has been detected by immunohistochemistry in the rat fetal testis. Therefore, we attempted to determine whether this factor can act as a local regulator of Leydig cell function during fetal development. An inhibitory effect of TGF beta1 on basal and luteinizing hormone (LH)-stimulated testosterone secretion by fetal testes in vitro was observed only with testes from 13.5 day-old fetuses and not with testes from older stages. The lack of effect of exogenous TGF beta1 in organ culture after day 13.5 might be related to an elevated intratesticular concentration that would already exert maximal biological effect. On the contrary, in a model of dispersed testicular cells in culture, TGF beta1 was able to inhibit LH-stimulated testosterone production by fetal Leydig cells from 16.5 and 20.5 day-old fetuses. This inhibition of LH-stimulated testosterone production was dose- and time-dependent and was maximal after 48 h of treatment with 1 ng/ml TGF beta1, with testosterone secretion being reduced to 25% of control values. Inhibition of testosterone secretion was also observed in basal and dbcAMP-stimulated conditions, suggesting that one site of action of TGF beta1 is located after the production of cAMP. However, TGF beta1 was also able to inhibit LH-induced cAMP production. As demonstrated by the transformation of steroidogenic precursors into testosterone, TGF beta1 did not significantly alter 3beta-hydroxysteroid dehydrogenase (3beta HSD) activity but induced a strong inhibition of cytochrome P450 17alpha-hydroxylase/C17-20 lyase (P450C17) activity which was associated with a marked diminution of cytochrome P450C17 mRNA levels (26% of control values) but not of cytochrome P450scc mRNA. In addition to its effect on steroidogenesis, TGF beta1 exhibited morphogenic actions on the fetal testicular cells, inducing spreading when the cells were adherent and aggregation when the cells were cultured in conditions of lesser adherence and without any significant effect on either total cell number or 3beta HSD positive cells. Taken together these results suggest that TGF beta1 likely plays a morphogenic and physiological role very early in the fetal testis via paracrine/autocrine mechanisms.
Animals↗
The immunohistochemical localization of transforming growth factor-beta 2 in the fetal and neonatal rat testis.
The localization of transforming growth factor beta-2 (TGF beta 2) in the fetal and neonatal testis (from day 13.5 of fetal life to postnatal day 9) was investigated by an immunohistochemical staining method employing a specific polyclonal antibody. Immunostaining appeared on fetal day 13.5 in primitive Sertoli cells as they begin to come in contact with each other and surround the germ cells to form the seminiferous cords. Staining in Sertoli cells was still clearly observed until fetal day 16.5 and became faint or undetectable from fetal day 18.5 onwards. In fetal-type Leydig cells, a positive reaction for TGF beta 2 appeared on day 16.5 and became very intense from day 18.5 onwards. In the germ cells, immunoreactivity for TGF beta 2 appeared on fetal day 20.5, rose to a maximum on postnatal day 4 and decreased thereafter. On postnatal day 9, staining was still present in type A spermatogonia and absent in type B spermatogonia. No immunoreactivity was detected in peritubular cells on any day studied. In conclusion, our results are in favour of an autocrine/paracrine role of TGF beta 2 in the differentiation of the testis during the perinatal period. It may be involved in the organization of the seminiferous cords, the regulation of testosterone production and the regulation of the number of germ cells. When compared with the immunolocalization of TGF beta 1 that we have previously reported [1], the present study suggests that the roles of TGF beta 2 in the developing rat testis can be specific but also overlap from those of TGF beta 1.
Animals↗
Evolution of isochores in rodents.
The most deviant isochore pattern within mammals was found in rat and mouse; most other mammals possess a different kind of isochore organization called the "general pattern." However, isochore patterns remain largely unknown in rodents other than mouse and rat. To investigate the taxonomic distribution of isochore patterns in rodents, we sequenced the nuclear gene LCAT (lecithin:cholesterol acyltransferase) from 17 rodents species (bringing the total of LCAT sequences in rodent to 19) and compared their GC contents at third codon positions and in introns. We also analyzed an extensive sequence database from rodents other than rat and mouse. All murid LCAT sequences are much poorer in GC than all nonrodent LCAT sequences, and the hamster sequence database shows exactly the same isochore pattern as rat and mouse. Thus, all murids share the same special isochore pattern--GC homogenization. LCAT sequences are GC-poor in hystricomorphs too, but the guinea pig sequence database indicates that large changes in GC content occur without an overall modification of the isochore pattern. This novel mode of isochore evolution is called GC reordering. LCAT sequences also show that the evolution of isochores in sciurids and glirids is nonconservative in comparison with that in nonrodents. Thus, at least two novel patterns of isochore evolution were found. No rodent investigated to date shared the general mammalian pattern.
Animals↗
[Estimation of the treatment cost of cervical cancer].
BACKGROUND: The goal of this study was to estimate direct costs induced by the first year of treatment of cervix cancers according to the stage at diagnosis. METHODS: Fifteen patients of the Gynaecology Department of the Besançon hospital (Doubs, France) were involved in a prospective study to estimate the real cost of treatment of carcinomas in situ (CIS) by conization and of microinvasive carcinomas (MIC) by simple hysterectomy. Costs of invasive cancers were obtained from a retrospective analysis of 24 hospital records in the Radiotherapy Department. RESULTS: The average real cost of treatment for the CIS was 5023 FF (1995 French Francs). Real treatment cost of the MIC was 15,867 FF. The average cost of treatment for the IB and IIA cancers stage (FIGO classification) was 61,540 FF and 145,314 FF for the IIB to IV stage cancers. CONCLUSIONS: Cost-estimation of cervix cancer treatment according to the stage of diagnosis has to be done before starting a cost-effectiveness analysis of mass screening for cervix cancers. This study will allow us to take into account changes in the stages distribution following on a screening campaign.
Carcinoma in Situ↗
[Isolated mucosal ulcers disclosing idiopathic hypereosinophilic syndrome].
INTRODUCTION: Idiopathic hypereosinophilic syndrome is an uncommon disease often associated with diverse non-specific skin manifestations. Mucosal ulcerations suggest a myeloproliferative from with poor prognosis due to possible progression to malignant hemopathy or visceral complications. CASE REPORT: A 28-year-old man presented idiopathic hypereosinophilia with isolated mucosal ulcerations involving the buccal and genital areas. Laboratory results (hematology, CD25) suggested a myeloproliferative form. Treatment with alpha interferon (18 months) led to regression of the mucosal lesions and a decrease in the markers of eosinophil toxicity. There was no visceral involvement. DISCUSSION: Immunosuppression with/without high-dose alpha interferon is usually used for the treatment of hypereosinophilic syndrome. In our case favorable outcome was obtained with lower doses of alpha interferon than those reported in the literature. There was objective decrease in eosinophil toxicity (regular counts of hypodense eosinophils, CD25 or interleukin 2 soluble receptor) and no progression (malignant hemopathy, mortal visceral involvement).
Adult↗
[Melanoma of soft tissues].
INTRODUCTION: Soft tissue melanoma was described in 1965 by Enzinger who used the term clear-cell sarcoma. In 1983, Chung and Enzinger coined the term soft tissue melanoma due to the immunohistochemical similarity with melanoma. We report a case of this rare type of melanoma. CASE REPORT: A 59-year-old woman had pain between the first two toes for 3 years. A subcutaneous tumor was found at examination. Histologically, the tumor was composed of weakly eosinophilic cell proliferation. Protein S100 and HMB45 were positive. The cells were organized in theques. Pathology diagnosis was soft tissue melanoma. Complete remission was obtained for 3 years when several local recurrences required surgery and chemotherapy then surgery and radiotherapy. Complete remission has been achieved for 9 months. DISCUSSION: This case presented the main characteristics of soft tissue melanoma as described in a review of 209 analyzable cases reported in the literature. This tumor occurs in young subjects with no sex or race predominance. It is an ubiquitous tumor which develops in close relation with tendons and aponevroses, usually in limbs (especially feet). Pain is sometimes the revealing manifestation, but the tumor is often asymptomatic, so the volume is often important at diagnosis. Pathology examination shows rather monomorphic proliferation of cells with a clear or weakly eosinophilic cytoplasm grouped in clusters or theques separated by fibrous septa. Intracytoplasmic melanin is sometimes observed, indicating interest of protein S100 and HMB45 immunohistochemistry which is almost always positive. The principle differential diagnoses are metastasic melanoma and epithelioid sarcoma. Prognosis of soft tissue melanoma is similar to that in sarcomas with a high rate of local recurrence and metastases (lymph nodes, lungs). Mortality reaches 56 p. 100. Treatment is wide surgical exeresis. CONCLUSION: Soft tissue melanoma is a rare tumor of the melanocyte. It differs from melanoma by the population involved, its clinical expression and its prognosis which is similar to that in sarcoma.
Combined Modality Therapy↗
[True popliteal venous aneurysm. 2 cases].
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Adolescent↗
Immunohistochemical localization of transforming growth factor beta 1 and beta 2 in the fetal and neonatal rat ovary.
The localization of transforming growth factor beta (TGF beta) in the differentiating ovary (from fetal day 13.5 to postnatal day 14) was investigated immunohistochemically using polyclonal antibodies for TGF beta 1 and TGF beta 2. Immunostaining was undetectable in the gonadal primordium on fetal day 13.5. From fetal day 14.5 and throughout fetal life, there was intense immunostaining for TGF beta 1 and faint staining for TGF beta 2 in some ovarian somatic cells which were identified as epithelial cells at the end of fetal life. This pattern of staining was also found in the presumptive granulosa cells present between the oocytes on postnatal day 1. The staining for TGF beta 2 persisted while the staining for TGF beta 1 decreased in the granulosa cells of primordial and primary follicles of older rats. In the subsequent stages of follicular development, the staining for TGF beta 1 disappeared while faint staining for TGF beta 2 persisted in the granulosa cells of secondary and small antral (postnatal day 14) follicles. On day 14, the newly functional thecal/interstitial cells were moderately stained for TGF beta 2 and intensely stained for TGF beta 1. These results plus our previous immunolocalization of TGF beta 1 in the fetal testis [13] show that, in both sexes: (1) TGF beta 1 is detectable in the gonads on the same fetal age (day 14.5); (2) TGF beta 1 is present in the somatic cells which are the precursors of Sertoli and granulosa cells, at the time of their organization in seminiferous tubules or in primordial follicles; and (3) TGF beta 1 is largely present in cells synthesizing androgens, from the onset of their steroidogenic capacity (fetal day 16.5 for Leydig cells and postnatal day 14 for thecal/interstitial cells.
Animals↗