Search PubMed⌕ Search

Biomedical subjects

D Jullien

Publications and source records attributed to D Jullien.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effected of insulin and insulin-like growth factor-I on glucose transport and its transporters in soleus muscle of lean and obese mice.

The mechanisms underlying insulin and insulin-like growth factor-I (IGF-I) action on glucose transport share similar processes leading to Glut 4 translocation after respective receptor activation. Among these steps are phosphorylation of insulin receptor substrate-1 (IRS-1) and activation of phosphatidylinositol-3-kinase (P13-kinase). This enzyme could be involved in stimulated glucose transport in muscle, since its inhibitor, wortmannin, blocks the hormonal effect in muscle. P13-kinase is activated by insulin and IGF-I in a rapid and transient manner in incubated soleus muscles. When P13-kinase activation was studied in muscle of obese insulin-resistant mice, there was a marked alteration in the response to insulin both in vivo and in vitro. P13-kinase activation by IGF-I was also altered in obese mice, although to a lesser degree.

Animals↗
PubMed1995

Evolutionarily conserved positive and negative cis-acting elements control the blastoderm-specific expression of the Drosophila serendipity alpha cellularisation gene.

The serendipity alpha (sry alpha) cellularisation gene is only transcribed at the blastoderm stage, when this morphogenetic event takes place. We show that a 95 bp sry alpha upstream region is sufficient for blastoderm-specific expression of a lacZ reporter gene. This region encompasses four nucleotide motifs (I-IV, 5' to 3') conserved at similar relative positions in several Drosophila species. Removal of motif I leads to ectopic expression of lacZ in precursor cells of the PNS. Deletion of motif IV decreases the level of lacZ transcripts and modifies their banded pattern of accumulation late in cycle 14, whereas deletion of motifs II and III abolishes the sry alpha promoter activity. Motif III includes a consensus recognition site for b-HLH proteins. A point mutation in this E-box both severely reduces lacZ expression at blastoderm and prevents its ectopic expression in the PNS upon deleting motif I. These two effects depend upon da+ activity, suggesting that daughterless may positively control sry alpha transcription.

Animals↗
PubMed1995

[Eruptive nevus in the course of Lyell syndrome].

INTRODUCTION: Eruptive nevus have been described after severe bullous cutaneous adverse drug reactions. We report herein a berloque-like nevus extension after toxic epidermal necrolysis. CASE REPORT: A 23 year-old woman was hospitalized for toxic epidermal necrolysis. A blister was in contact with a nevus. Four months after healing, extension of the nevus was seen on the blister area. DISCUSSION: During toxic epidermal necrolysis and healing: 1) cytokines and growth factors are produced favouring nevocytes proliferation; 2) macromolecules are exposed on the wound bed; 3) adhesion molecules are expressed on nevocytes, restricting cell migration on exposed macromolecules. Interaction between matrix macromolecules and adhesion molecules could explain the limitation of nevus extension.

Adult↗
PubMed1993

Differential effects of okadaic acid on insulin-stimulated glucose and amino acid uptake and phosphatidylinositol 3-kinase activity.

The effect of okadaic acid, a serine/threonine phosphatase inhibitor, was analyzed in two insulin-responsive systems, the isolated mouse soleus muscle and 3T3-L1 adipocytes. While okadaic acid alone was a potent stimulator of glucose transport in both systems, it prevented transport stimulation by insulin. To gain insight into this inhibitory action, the activation of phosphatidylinositol 3-kinase (PI3-kinase), one of the earliest postreceptor steps identified so far, was studied. In 3T3-L1 adipocytes and muscle, insulin increased PI3-kinase activity in immunoprecipitates obtained with antibodies to phosphotyrosine. Okadaic acid alone had no effect but strongly inhibited this hormonal action. Okadaic acid treatment did not interfere with insulin-induced receptor autophosphorylation or with its tyrosine kinase activity toward artificial substrates. In contrast, in the presence of the phosphatase inhibitor, we did not observe tyrosine phosphorylation of the insulin receptor cellular substrate p185 (IRS-1) or immunoprecipitation of PI3-kinase by antibodies to phosphotyrosine. These results suggest that okadaic acid interferes with insulin's stimulation of glucose transport by inhibiting IRS-1 phosphorylation and its association with PI3-kinase and/or other signaling molecules. However, okadaic acid did not block the insulin stimulation of aminoisobutyric acid uptake in muscle. This would indicate that IRS-1 phosphorylation and PI3-kinase activation are not required for all the effects of insulin and that the serine/threonine phosphorylation events implicated in the translocation of glucose transporters are not controlling amino acid transport in muscle.

3T3 Cells↗
PubMed1993

Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.

Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. Insulin did not affect total PI3K activity. Both the antiPTyr-PI3K stimulation and activation of insulin receptor tyrosine kinase were dependent on hormone concentration. In muscles from obese, insulin-resistant mice, there was a 40-60% decrease in antiPTyr-PI3K activity after 2 min of insulin that was present equally in the cytosolic and membrane fractions. A significant reduction in insulin sensitivity was also observed. The defect appears to result from alterations in both insulin receptor and postreceptor signaling. Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. The results demonstrate that: (a) antiPTyr-PI3K activity is responsive to insulin in mouse skeletal muscle, (b) both the insulin responsiveness and sensitivity of this activity are blunted in insulin-resistant muscles from obese mice, (c) these alterations result from a combination of insulin receptor and postreceptor defects, and (d) starvation restores normal insulin responses.

Animals↗
PubMed1993

Alpha interferon treatment in atopic dermatitis.

Eight patients suffering from atopic dermatitis were treated with interferon alpha 2b. They received low or intermediate doses (9-15 x 10(6) U/week) for a short period of time (4-8 weeks), with a moderate improvement of skin lesions in 4 of them and no change or an exacerbation of the disease in the other 4. Among the 4 patients who slightly improved at 4 weeks, 3 did not show any beneficial effect of interferon after 8 weeks. Serum IgE levels, which were increased in all patients before treatment, were not reduced under interferon therapy. This study shows that intermediate doses of interferon alpha 2b are not effective in the short-term treatment of atopic dermatitis.

Adult↗
PubMed1992

[Insulin receptors: structure and physiology].

Insulin receptor is a transmembrane glycoprotein. It is synthetized, in endoplasmic reticulum, as a proreceptor which is processed (glycosylation, proteolytic cleavage) and transported to the cell surface. The receptor is a hetero-tetramer comprising 4 subunits: the two alpha-subunits are extracellular; they are held, through disulfide bonds, to the beta-subunits. These are located across the membrane; their intracellular domain possesses a tyrosine-kinase activity. Insulin receptor gene has been located on chromosome 19 and its nucleotide sequence is known. The first functional property of the receptor is to recognize the hormone. Specific and high affinity binding site is supported by the alpha subunit. Shortly after insulin binding, the tyrosine-kinase is activated, resulting in autophosphorylation and phosphorylation of various substrates. Current research focuses on these nature of there substrates which activate intracellular putative mediators of insulin action. Insulin-resistant states are associated with functional alteration of the receptor. But only a few cases are directly related to nucleotide mutations at the level of the gene resulting in structurally abnormal receptor.

Receptor, Insulin↗
PubMed1992

Keratinocyte migration is partially supported by the cell-binding domain of fibronectin and is RGDS-dependent.

Fibronectin (FN) plays a key role in cell attachment, embryonic development, and wound healing. In this respect, it is known that FN promotes keratinocyte migration. The aim of this study was to examine specific FN domains (120-kD cell-binding fragment, 45-kD collagen fragment, and 40-kD heparin fragment) and a biologically active peptide within the molecule (RGDS) for their ability to influence human keratinocyte (HK) locomotion. HKs were plated on gold salts coated with different substrates (type IV collagen, FN with or without the RGDS peptide, and the three FN fragments). After 20 h, locomotion tracks were quantified by computer-assisted image analysis that determines the area of each microscopic field occupied by migration tracks, a so-called migration index (MI). MIs on type IV collagen and FN were 39.14 +/- 2.8% and 30 +/- 0.4%, respectively. The maximal MIs on the collagen-binding domain and heparin-binding domain of FN were similar to our negative controls (plastic and albumin): 3 +/- 1%. In contrast, the maximal MI on the cell-binding fragment of FN was 18.45 +/- 2.1%. The effect of the cell-binding domain on keratinocyte motility was found to be dose dependent. Moreover, we could specifically inhibit the FN-driven locomotion using the RGDS sequence contained in the cell-binding fragment. We did not observe a synergistic effect (i.e., a higher MI) when we added the three fragments in a same dish. These results suggest i) that the cell-binding fragment of FN partially supports HK locomotion, ii) that other untested FN domain(s) should act in synergy with the cell-binding fragment to promote keratinocyte locomotion, or alternatively iii) that the FN function of promoting cell migration resides within the FN cell-binding domain, but the proper presentation of this domain to the cell requires an intact, native FN molecule, and iv) that the RGDS sequence is essential for HK movement.

Amino Acid Sequence↗
PubMed1990

[Treatment of borderline lesions and non-infiltrating carcinoma].

As mammography is increasingly prescribed systematically and mammography films are of better quality, diagnostic biopsies are performed in growing numbers, leading to the discovery of "borderline" histological lesions which were relatively rare a few years ago. The authors have studied the frequency and clinical presentation of these lesions. In patients with atypical hyperplasia simple monitoring is the rule since the short- and long-term effects of medical treatments are too uncertain for these to be recommended routinely. The finding at histology of lobular carcinoma in situ is regarded as indicating a high risk of cancer infiltrating both breasts, and in all but some special cases close supervision with 6-monthly clinical examination and annual mammography is advocated. Whether or not endocrine treatments reduce the incidence of infiltrating carcinoma is unknown. In patients with intraductal carcinoma mastectomy gives excellent results at the cost of a considerable loss of tissue. In view of the N.S.A.B.P. and Curie Institute experience, tumorectomy alone is not recommended because of the high risk of recurrence, but a conservative treatment (limited surgery followed by radiation) is permitted. Conservative treatment may also be attempted in Paget's disease without palpable tumour.

Breast Neoplasms↗
PubMed1989

Presentation of axillary lymphadenopathy without detectable breast primary (T0 N1b breast cancer): experience at Institut Curie.

Between 1960 and 1985, 31 patients presented to Institut Curie with isolated axillary lymphadenopathy, of probable metastatic origin from the breast, but without clinical or radiological evidence of a breast tumor and no other primary tumor. The mean age was 54.6 years (range 39-79 years). Histological diagnosis was obtained by axillary surgery (22 cases), drill biopsy (6 cases), and cytology (3 cases). All slides were reviewed for the present study. Treatment consisted of axillary surgery followed by radiotherapy in 22 patients, radiotherapy followed by axillary surgery in 6 patients, radiotherapy followed by modified radical mastectomy in one patient, and radiotherapy alone in 2 patients. Systemic adjuvant treatment was given to 11/31 patients. The median follow-up was 9 years (range 2-26 years). Eight recurrences have appeared. Four patients recurred in the breast only (mean time to relapse: 112 months, range 63-162 months). The four other patients recurred both in breast and/or axilla (mean time to relapse: 23 months, range 7-46 months). Nine patients have developed distant metastases, of whom three also had locoregional recurrence. Among the 11 patients who had had systemic treatment, 5/11 had recurrence or metastases. The overall 5 and 10 year actuarial survival rates were 76 and 71%, respectively. The metastasis-free 5 and 10 year actuarial survival rates were 73 and 71%, respectively. Axillary metastases without clinical or radiological evidence of a primary breast tumor represents a discrete clinical entity, the prognosis of which appears to be better than that of clinical invasive breast cancer with associated lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Axilla↗
PubMed1987

Paget's disease of the nipple without detectable breast tumor: conservative management with radiation therapy.

Between 1960 and 1984, 20 selected patients with Paget's disease of the breast confined to the nipple were treated conservatively with radiotherapy alone (17/20 pts) or limited surgery and radiotherapy (3/20 pts). Median follow-up was 7.5 years. No patients died of breast disease. Three patients had recurrence in the treated breast, and were treated by mastectomy. All recurrences were located in the nipple or areola and were all Paget's disease, without associated intraductal or invasive carcinoma. No axillary node recurrences occurred. The actuarial 7-year probability of living free of disease with breast preserved was 81%. Among the 15 patients who had a minimum follow-up of 3 years, without recurrence, 12 (80%) had a good cosmetic result. These results suggest that radiation therapy could be an effective alternative to radical surgery in the treatment of patients with Paget's disease of the nipple without concomitant breast tumor.

Adult↗
PubMed1987

Medullary breast carcinoma: the role of radiotherapy as primary treatment.

The results are reported of a selected series of 41 patients with medullary carcinoma of the breast, treated with primary radiotherapy with (24 patients) or without (17 patients) adjuvant chemotherapy. Complete responses to radiotherapy occurred with moderate doses (67% of the patients had a complete response after a dose of 55-60 Gy) and were increased by the addition of an irradiation boost. The 6-year actuarial free of local recurrence survival, metastase-free survival and survival rates were 86, 83, and 83%, respectively. The 6-year actuarial probability of living with breast preserved was 72%. Recurrences and survivals were not influenced by the tumor size or clinical axillary node status. Adjuvant chemotherapy had no effect on the rate of recurrence or survival.

Adult↗