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Biomedical subjects

Y Gauthier

Publications and source records attributed to Y Gauthier.

At least 19 recordsLinked to original sources

Ptx1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene.

The pituitary gland contains six distinct hormone-producing cell types that arise sequentially during organogenesis. The first cells to differentiate are those that express the pro-opiomelanocortin (POMC) gene in the anterior pituitary lobe. The other lineages, which appear later, include cells that are dependent on the POU factor Pit-1 and another POMC-expressing lineage in the intermediate pituitary lobe. Using AtT-20 cells as a model for early expression of POMC in the anterior pituitary, we have defined a regulatory element conferring cell specificity of transcription and cloned a cognate transcription factor. This factor, Ptx1 (pituitary homeo box 1), contains a homeo box related to those of the anterior-specific genes bicoid and orthodenticle in Drosophila, and Otx-1 and Otx-2 in mammals. Ptx1 activates transcription upon binding a sequence related to the Drosophila bicoid target sites. Ptx1 is the only nuclear factor of this DNA-binding specificity that is detected in AtT-20 cells, and it is expressed at high levels in a subset of adult anterior pituitary cells that express POMC. However, Ptx1 is expressed in most cells of Rathke's pouch at an early time during pituitary development and before final differentiation of hormone-producing cells. Thus, Ptx1 may have a role in differentiation of pituitary cells, and its early expression pattern suggests that it may have a role in pituitary formation. In the adult pituitary gland, Ptx1 appears to be recruited for cell-specific transcription of the POMC gene.

Amino Acid Sequence

Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene.

Previous studies defined a DNA element necessary for glucocorticoid repression of the pro-opiomelanocortin (POMC) gene. The glucocorticoid receptor (GR) binds this negative glucocorticoid response element (nGRE) with an in vitro affinity similar to that of GR for positive GREs. However, whereas GR binds GREs as homodimers, a novel GR complex which forms with nGRE appears to contain three GR molecules. Biochemical characterization of this complex as well as equilibrium binding studies suggest that it is formed by sequential binding of a GR homodimer followed by binding of a GR monomer on the opposite side of the double helix. The DNA-binding domain (DBD) of GR is sufficient for differential binding of GRE and nGRE, as bacterially-expressed DBD formed unique nGRE complexes that contain three GR polypeptides. Thus, the POMC nGRE provides the first example of an interaction between GR and DNA in which GR binds otherwise than as a homodimer. Despite its high affinity for GR, the nGRE differs significantly from GREs in that it does not activate transcription in any context. As the nGRE appears insufficient on its own to confer hormone responsiveness, other POMC promoter elements are likely to be required to mediate glucocorticoid repression.

Animals

[Child development: primary influences, primary stages and foundations of psychotherapy].

Recent research on child development and on infant-mother psychotherapy is reviewed. The problem of continuity or discontinuity of early patterns is thus brought out, as well as the possibility of change under the influence of environmental modifications or in psychotherapy. After briefly presenting the most often proposed mechanisms to explain change, the possibility is suggested that such change could be better conceptualized by using fundamental modes of development that can be particularly observed in mother-infant or parent-young child interaction.

Child

Autologous grafting with noncultured melanocytes: a simplified method for treatment of depigmented lesions.

BACKGROUND: Achromic lesions on the trunk and the extremities often do not respond to treatment and little improvement is obtained in cases of segmental vitiligo. OBJECTIVE: Transplantation of autologous noncultured melanocytes was performed to obtain a successful repigmentation. METHODS: The grafting method is carried out in two steps: production of blisters on the depigmented lesions by freezing with liquid nitrogen and injection in each blister of a suspension of epidermal cells (mainly keratinocytes and melanocytes). The cellular suspension was obtained from samples of skin of the hair scalp after trypsinization. RESULTS: Repigmentation was evident within 25 to 30 days. Coalescence of the pigmented areas was spontaneously observed or obtained after UVA stimulation. Patients with two types of leukoderma-vitiligo or nevus depigmentosus had successful repigmentation after transplantation of autologous noncultured melanocytes. CONCLUSION: This technique appears to be an effective and simple method for treating patients with achromic areas lacking melanocytes.

Adult

Child and adult psychiatry: comparison and contrast.

Since its development from general psychiatry, child psychiatry has been influenced by its close involvements with the child guidance movement and pediatrics and by the age of its patient population. This has led it to evolve in ways quite distinct from adult psychiatry, so much so that at times the understanding and relationship between the two disciplines has been somewhat strained. This paper relates the development of child psychiatry to its history, its tasks and its patient population, highlighting some of the major differences between child and adult psychiatry. It then looks at why research in child psychiatry has lagged behind research in adult psychiatry. It concludes by discussing tensions between the two disciplines, and why it serves the interests of both professions as well as those of our patients, that a better understanding and collaboration between them be established.

Age Factors

[Use of a disposable peroperative autotransfusion device in uncomplicated vascular surgery].

We used a simple single process to recover total blood during surgery. All the process stands on a low burdensome jib and does not require additional staff in theater. Its cost is low. The indications concern all surgical operations enduring low or mean bleeding, except in septic and cancer surgery. It may be used in emergencies, even in war surgery with an incorporated source of depression.

Animals

[Progressive and confluent hypomelanosis of the melanodermic metis].

Melanodermic half-castes may develop a progressive and extensive hypomelanosis presenting as an original skin condition. The course of the disease is characteristic: it occurs mainly in females from 18 to 25 years of age with a progressive development of hypochromic and coalescent macules on the back and abdomen. This disease may regress spontaneously within 5 years and healing seems to be facilitated by UV exposure. Decreased epidermal melanin is the only histological feature. Ultrastructural examination has led to characterize this bizarre disease by a switch from stage IV single melanosomes negroid type to small type I-III aggregated melanosomes (caucasoid phenotype of melanogenesis). Although the pathogenesis of the disorder remains obscure, it may be stated that the variation in skin coloration in these patients is due to a variation in melanosome size and distribution. It is possible that this variation is due to a decrease in production of type IV melanosomes and that this apparent change of ultrastructural phenotype represent the consequence of a simple imbalance in melanosomes production favoring small I to III melanosomes. This disease is not restricted to a limited geographic group: it is present in melanodermic half-castes of different areas and therefore deserves to be known and recognized.

Adult

[Developmental psychopathology and psychoanalysis].

In face of the apparent contradiction between psychoanalysis and observational-experimental methods, the author briefly summarizes the input of direct observation to the knowledge of child development and suggests that the reservations of many psychoanalysts to these methods may be explained by the greater importance given to external events in such research, as if the causal role of fantasy was thus being questioned. The author further reviews most recent experimental works, particularly those around the concepts of "competence of the infant", "self", "attachment and security", and suggests that the main object of these research endeavors more and more concerns the foundations and origins of the child's fantasy life. Other recent experimental works bring out the continuity between the observations made during the first year of the child's life and those made of these children now up to the age of six. The author comes to the conclusion that the whole of these observational and experimental works, far from contradicting psychoanalytic hypotheses based on reconstruction, confirms institutions and hypotheses which have become essential to psychoanalysis, particularly concerning the importance of the child's first year of life and of mother-child interaction.

Child

Developmental regulation of murine mammary-gland 90 kDa heat-shock proteins.

We have examined the regulation of murine mammary-gland 90 kDa heat-shock protein (hsp-90) as a function of normal development and differentiation. We find that both hsp-90 and amounts of its mRNA are modulated during development and differentiation, with the highest concentrations of mRNA and protein being present in tissues from pregnant and lactating animals respectively. Metabolic labelling experiments with [35S]methionine reveal that the rate of synthesis of hsp-90 also varies among tissues from various developmental states and correlates with the relative hsp-90 mRNA content. These data also suggest that the highest concentration of hsp-90 found in lactating mammary tissues may be due to a greater stability of this protein in this developmental state. The possible significance of the developmental modulation of mammary hsp-90 to mammary steroid-receptor properties is discussed.

Animals

Transferrin receptor and ferritin levels during murine mammary gland development.

Various types of proliferating cell are known to express transferrin receptors which are necessary for transferrin-mediated cellular iron uptake. Neither the mechanism nor the physiological role of transferrin receptor induction has been established with certainty; although it may reflect an increased cellular requirement for iron which is essential for ribonucleotide reductase, a key enzyme of DNA synthesis. The aim of this study was to examine murine mammary gland transferrin-receptor levels during gland development. As compared to virgin controls, total mammary gland transferrin receptors expressed on the basis of DNA, increase during pregnancy and lactation by 29- and 45-fold, respectively. However, on the basis of DNA, mammary gland ferritin, measured by radioimmunoassay, decreased by about 75% and 85% during pregnancy and lactation, respectively, indicating that the increased transferrin receptor levels probably do not lead to intracellular iron accumulation. When epithelial cells from mammary glands of pregnant mice were cultured in vitro transferrin receptor expression correlated with cell proliferation. These results suggest that normal mammary growth which occurs mainly in mammary epithelial cells is associated with a significant increase in transferrin receptor. Since transferrin receptor levels remain high during lactation they are not associated solely with tissue growth, but may also function in transporting iron during milk production.

Animals

Estrogenic regulation of murine uterine 90-kilodalton heat shock protein gene expression.

Murine uterine steady-state protein levels of the 90-kilodalton heat shock protein (HSP90) have been demonstrated recently to be increased by estrogen in a target tissue- and steroid-specific manner (C. Ramachandran, M.G. Catelli, W. Schneider, and G. Shyamala, Endocrinology 123:956-961, 1988). We now report that this regulation occurred with both the HSP86 and HSP84 forms of HSP90 as well as with the 94-kilodalton glucose-regulated protein. At the mRNA level, this response was greatest for HSP86 (15-fold). In contrast, estradiol had no significant effect on HSP70.

Animals

Effects of progesterone, promegestone and RU 486 on glucocorticoid receptor levels in primary cultures of mouse mammary epithelial cells.

Mammary epithelial cells isolated from midpregnant mice and cultured on collagen gels contain glucocorticoid receptors whose levels are modulated by a variety of steroids. In the absence of any added steroid to the cell culture medium, the levels of glucocorticoid receptors in the cells decline during culture, which is counteracted by the addition of a variety of glucocorticoid agonists. The effectiveness of the glucocorticoid in preventing the loss of glucocorticoid receptors is in turn counteracted by the addition of the synthetic progestin promegestone and the synthetic antiglucocorticoid RU 486. Of the two, RU 486 is the most potent in antagonizing the effect of cortisol on the GR levels. Promegestone antagonizes the effect of cortisol, too, although higher concentrations are necessary. Progesterone was without a clear effect either as a glucocorticoid agonist or an antagonist. Progesterone, however, was extensively metabolized by mammary epithelial cells in culture. Based on these observations we conclude that in mammary epithelial cells glucocorticoids positively regulate the metabolism of their own receptors and that antiglucocorticoids, such as RU 486 and progestins, can antagonize that effect.

Animals

Progressive macular hypomelanosis of the trunk: primary acquired hypopigmentation.

Dermatological practice in Martinique frequently encounters a bizarre skin condition presenting as a progressive and extensive hypomelanosis on the back. The course of this disorder is highly characteristic: it occurs mainly in females from 18-25 years of age, with a progressive development of round, pale, coalescent macules on the back and sometimes on the abdomen. This disease, which does not respond to therapy, spontaneously regresses within 3 to 4 years. Decreased epidermal melanin is the only histological feature. Ultrastructural examination of two cases found that the macular lesions were characterized by a switch from Stage IV single melanosomes (negroid) to small Type I-III aggregated melanosomes (caucasoid). It may thus be stated that the variation in skin coloration in these patients was due to a variation in melanosome size and distribution.

Adolescent

[Quantitative approach of melanin in human cultured melanocytes].

The purpose of the study was to establish an in vitro model for the quantification of the melanin produced in human melanocytes in culture. Melanin content in these cultured human melanocytes is determined by spectrofluorimetric assay. Fluorescence intensity is quantitatively related to the melanin content present in cultured melanocytes.

Cell Count

[Intraoperative autotransfusion of traumatic hemoperitoneum in emergency surgery].

The système à lavage globulaire was used for intraoperative auto-transfusion of adult patients with traumatic hemoperitoneum. This method provides a rapid supply of blood of large amount and of quality superior to that supplied by a blood-bank: a massive autologous transfusion carries less risk of complications than a homologous transfusion. Although this procedure is without risk to patients it is essential to comply with its contraindications (rupture of a hollow organ for the septic risk and existence of a neoplasm for the dissemination risk) and also its precautions in use, mainly the combined use of frozen fresh plasma beyond a certain autotransfused quantity of blood (about 1,200 cc). This latter problem of supplementary supply of coagulation factor is identical to that raised by massive homologous transfusion.

Abdominal Injuries

Linear cutaneous neuromas (dermatoneurie en stries): a limited phakomatosis with striated pigmentation corresponding to cutaneous hyperneury (featuring multiple endocrine neoplasia syndrome?).

A 60-year-old woman developed a progressive linear pigmentation on the trunk. Skin biopsy demonstrated an increase in the number and size of neural fibers in the dermis. Clinical and paraclinical investigations of this unusual disease showed findings similar to the hereditary type of Sipple syndrome (multiple endocrine neoplasia syndrome, Type 2b). Such findings as Marfanoid habitus, abnormal electromyography and hypertrophy of the corneal nerves suggest that our patient's disease and Sipple syndrome are identical. However, such other symptoms of Sipple syndrome as presence of endocrine tumors are absent. Questions of long-term prognosis and physiopathogenicity are raised, since no nerve growth factor was detected in this patient. The name of linear cutaneous neuromas is suggested for the patient's lesions, and a possible association with the pigmentation and cutaneous neuromas of the MEN 2b syndrome.

Biopsy

Solitary Langerhans cell histiocytoma.

Biopsy of a solitary tumor of the buttock in a 3-month-old girl was diagnosed as a histiocytic proliferation suggestive of histiocytosis X. Electron microscopy showed Birbeck granules and dense myelinlike bodies within the cytoplasm of the tumor cells. An immunoperoxidase study, using a panel of monoclonal antibodies (OKT6, OKT4, and OKM1) and a polyclonal anti-S100 protein antibody, showed positive staining for OKT6 and OM1 and moderately positive staining for OKT4 and S100. After surgery to remove the tumor, visceral involvement could not be demonstrated during a 20-month follow-up.

Buttocks