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Biomedical subjects

S Michel

Publications and source records attributed to S Michel.

At least 73 records · Page 4Linked to original sources
PubMed1998

Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes.

The expression of mRNA encoding peroxisome proliferator-activated receptor (PPAR) subtypes in human keratinocytes was determined by semiquantitative reverse transcriptase-polymerase chain reaction. When normal human keratinocytes were induced to differentiate by shifting the culture medium to high Ca2+ concentration, the expression of PPAR-alpha and -gamma mRNA was increased, whereas that of PPAR-delta remained unchanged. At the protein level, the expression of PPAR in cultured human keratinocytes was demonstrated by a DNA mobility shift assay and the functionality of the receptor subtypes was assessed by transactivation experiments. In epidermis reconstructed in vitro, the level of PPAR-alpha and -gamma mRNA was also associated with keratinocyte differentiation. In lesional compared with nonlesional psoriatic epidermis, the expression of PPAR-alpha and -gamma mRNA was reduced, indicating that these two subtypes are tightly linked to the epidermal differentiation process.

Cell Differentiation↗
PubMed1998

A new concept of drug delivery for acne.

Adapalene is a stable naphthoic acid derivative that displays a strong retinoid agonist pharmacology. This drug controls cell proliferation and differentiation, and possesses significant anti-inflammatory action. The retinoid action of adapalene are mediated by the ligand-activated gene transcription factors retinoic acid receptors RAR beta and RAR gamma. We describe here how an aqueous gel containing adapalene was selected for the topical treatment of acne.

Acne Vulgaris↗
PubMed1998

Doxorubicin prodrugs with reduced cytotoxicity suited for tumour-specific activation.

The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.

Antibiotics, Antineoplastic↗
PubMed1998

[Insulin-dependent diabetes in Senegal: HLA-DR combinations according to age of onset and sex].

In insulin-dependent diabetes mellitus, HLA-DR markers are involved, namely DR3, DR4 and DR9 alleles, among black senegalese populations. Studying the different associations of these alleles showed a strong predisposition to insulin-dependent diabetes mellitus with DR3/4 (p > 10(-2); OR = 13.6); DR4/9 (p < 10(-2); OR = 8.32) and DR9/9 (p < 0.05; OR = 7.78). And then it was observed a tendency to an inverse relationship of DR3/4 frequency with age of onset in male patients.

Adolescent↗
PubMed1997

Differential effects of synthetic nuclear retinoid receptor-selective retinoids on the growth of human non-small cell lung carcinoma cells.

Retinoids are promising agents for cancer chemoprevention and therapy. Nuclear retinoic acid receptors (RARs; RARalpha, -beta, and -gamma) and retinoid X receptors (RXRs; RXRalpha, -beta, and -gamma) are thought to mediate most of retinoids' effects on cell growth and differentiation. Because the majority of human non-small cell lung carcinoma (NSCLC) cell lines are resistant to all-trans-retinoic acid, we searched for more potent retinoids. Therefore, we examined the effects of 37 natural and synthetic retinoids that exhibit specific binding to and transactivation of individual RARs or RXRs on the proliferation of eight human NSCLC cell lines. All of these cells expressed mRNAs of the three RXRs; however, they expressed varying levels of RARalpha and RARgamma, and only three of the eight cell lines expressed RARbeta mRNA. Cellular retinoic acid-binding proteins (CRABPs) I and II were detected in one and three of the eight cell lines, respectively. Only 8 of the 37 retinoids exhibited growth-inhibitory activity (IC50, < 10 microM) against at least two of the eight NSCLC cell lines. The active retinoids included one (TD550) of five RARalpha-selective, one (Ch55) of three RARbeta-selective, three (CD437, CD2325, and SR11364) of six RARgamma-selective, and one (CD271) of four RARbeta/gamma-selective retinoids. The potency of these retinoids was low (IC50, > 1 microM), except for CD437, which was very potent (IC50, 0.1-0.5 microM). The six RXR-selective retinoids were mostly inactive even at 10 microM. However, combinations of RAR-selective and RXR-selective retinoids exhibited additive effects. There appeared to be no simple correlation among the histological type of the NSCLC (adeno- or squamous), the levels of nuclear receptors or CRABPs, and the response of the cells to the growth-inhibitory effects of retinoids. Nevertheless, in contrast with former studies with natural retinoids, these results suggest that several synthetic retinoids do exhibit inhibitory activity against NSCLC cells, and some of them may be useful clinically.

Antineoplastic Agents↗
PubMed1997

Activity of retinoic acid receptor-gamma selectively binding retinoids alone and in combination with interferon-gamma in breast cancer cell lines.

Retinoids modulate several cell functions and especially inhibit the growth of a wide variety of cells including breast cancer. Retinoic acid receptor-gamma (RAR-gamma) has been shown to mediate the antiproliferative activity of retinoids. To further test this hypothesis we examined the effects of different RAR-gamma selectively binding retinoids (CD2325, CD2247, CD666 and CD437) on breast cancer cell lines. With exception of CD2247, all retinoids inhibited proliferation of MCF-7, SKBR-3, T47D and ZR-75-1 breast cancer cell lines, similar to the natural compound all-trans retinoic acid (ATRA). In addition, all 4 compounds were able to act synergistically with interferon-gamma (IFN-gamma) in all breast cancer cell lines including the retinoid-resistant BT-20 and 734-B lines. In functional transactivation assays we demonstrated that only in the MCF-7 cell line, TPA-mediated AP-1 activity was suppressed only by ATRA and CD2325, whereas in SKBR-3, another RA-sensitive breast cancer cell line, it was not. The synergistic antiproliferative activity involving retinoids and IFN-gamma could not be explained by an enhanced anti-AP-1 activity. No correlation was found between expression of RARs and cellular retinoic acid binding proteins (CRABPs) and antiproliferative effects of the retinoids. RAR-gamma selectively binding retinoids are potent inhibitors of breast cancer cell proliferation, alone and in combination with IFN-gamma. For this reason and because of a possible low toxicity, as compared with retinoic acid, we speculate that these RAR-gamma selective binding retinoids might be of clinical importance.

Binding, Competitive↗
PubMed1997

[Q-switched ruby laser in dermatologic therapy. Use and indications].

The Q-switched ruby laser (QSRL) with its wavelength of 694 nm and a pulse duration of around 40 nsec is an effective modality for the removal of tattoos and cutaneous pigmented lesions. Based on the principle of selective photothermolysis, selective damage to cutaneous pigment or pigmented cells is possible, allowing the scar-free elimination of endogenous or exogenous pigment in the skin. Main indications for the treatment with the QSRL are tattoos (amateur, professional, accidental, or cosmetic) and lentigines but the QSRL can also be used for lightening or even removing other pigmented lesions such as nevus spilus or café au lait macules. Furthermore, pigmented lesions of mucous membranes can be removed easily. Since treatment results in postinflammatory hyperpigmentation, myoplasma, and Becker' nevus have proven to be inconsistent, the QSRL cannot be routinely recommended for these lesions. Melanocytic lesions are generally not treated, with the exception of nevus of Ota and nevus of ito where there exacts a lack of therapeutic alternatives. Non-pigmented cells, which exist in nearly all melanocytic lesions, do not absorb the light of the QSRL and, therefore, do not react to this particular treatment. No information is available on the risk of partially damaged cells to become malignant after QSRL treatment. The QSRL is an excellent therapy for the removal of endogenous and exogenous pigment because of both the excellent treatment results and the lack of side effects, which are limited to transient hypo- and hyperpigmentation. The QSRL has occurred a wide range of applications within the field of dermatology.

Humans↗
PubMed1997

Determination of the origin of single nucleated cells in maternal circulation by means of random PCR and a set of length polymorphisms.

Non-invasive prenatal diagnosis on fetal nucleated erythrocytes from the maternal circulation is hampered by the small number of nucleated erythrocytes and the uncertainty as to whether they are of fetal or maternal origin. To overcome the latter limitation, single nucleated erythrocytes were separated and enriched from maternal blood by a triple density gradient and a monoclonal antibody (CD71) in combination with a magnetic activated cell sorter. Single nucleated cells were microscopically examined, individually collected with extended Pasteur pipettes, and each transferred into separate caps for the polymerase chain reaction (PCR). The DNA of the single nucleated erythrocytes was amplified at least 50-fold with a random PCR technique, viz., primer extension preamplification. Precise differentiation between maternal and fetal nucleated erythrocytes was achieved via PCR by using primers flanking highly polymorphic nucleotide repeats (DIS53, ACTBP2 and D21S11) and with a XY-specific primer pair (amelogenin). A total of 134 putative nucleated erythrocytes were analyzed from blood samples of 19 pregnant women. With the help of the polymorphic repeats, 25% were assigned as being of maternal origin, 26% of fetal origin, and 48% were uninformative. In cases with male fetuses, the amelogenin primers revealed 30% of cells to be fetal nucleated erythrocytes, the remaining 70% being of maternal origin. The results indicate that the combination of random PCR and PCR-mediated polymorphism analysis on the DNA of single nucleated erythrocytes is a useful technique for non-invasive prenatal diagnosis.

Amelogenin↗
PubMed1997

Pharmacology and chemistry of adapalene.

BACKGROUND: Retinoid research in the field of dermatology has been influenced by the clinical success of topical tretinoin and oral isotretinoin in the treatment of acne, and by the discovery of high-affinity binding proteins for retinoic acid mediating its action and interaction with other vitamins and hormones. OBJECTIVE: We sought molecules with an optimal balance between stability, efficacy, and local tolerance for topical acne therapy. METHODS: In vitro and in vivo bioassay systems were used to test the ability of retinoids to modulate cell proliferation and differentiation. In addition, antiinflammatory properties were assessed. Binding and transactivation assays were used to compare affinities and transcriptional activities of adapalene and tretinoin for the nuclear transcription factors, retinoic acid receptors (RARs). RESULTS AND CONCLUSION: Adapalene is a stable naphthoic acid derivative with potent retinoid pharmacology, controlling cell proliferation and differentiation. In addition it has significant antiinflammatory action. The nuclear gene transcription factors RAR beta and RAR gamma mediate the retinoid activity of adapalene.

Adapalene↗
PubMed1997

Blood pressure response to sodium in children and adolescents.

The predisposition to primary hypertension is composed of genetic factors, and aberrant mechanisms leading to the clinical expression of hypertension may be operational in children and adolescents. Dietary composition may play a role in the expression of hypertension. The effects of diet on blood pressure in the young may be indirect, reflecting the relation of diet with growth and body composition. Alternatively, there may be a direct effect of a specific dietary factor, such as sodium, on mechanisms regulating blood pressure. The average daily sodium intake by children and adolescents exceeds recommended amounts. Despite the high sodium intake among children, there are few data showing that decreasing sodium intake lowers blood pressure. Children who do express blood pressure sensitivity to sodium intake also have related risk factors for cardiovascular disease such as a positive family history or obesity. Prospective data are needed in children with characteristic risk factors to determine whether sodium intake contributes to the pathogenesis of hypertension and whether this course can be modified by alterations in diet.

Adolescent↗
PubMed1997

Induction of apoptosis by retinoids and retinoic acid receptor gamma-selective compounds in mouse thymocytes through a novel apoptosis pathway.

Retinoic acids are morphogenic signaling molecules that are derived from vitamin A and involved in a variety of tissue functions. Two groups of their nuclear receptors have been identified: retinoic acid receptors (RARs) and retinoic acid X receptors (RXRs). All-trans retinoic acid is the high affinity ligand for RARs, and 9-cis retinoic acid also binds to RXRs with high affinity. In cells at high concentrations, all-trans retinoic acid can be converted to 9-cis retinoic acid via unknown mechanisms. It was previously shown that retinoic acids prevents activation-induced death of thymocytes. Here, we report that both all-trans and 9-cis retinoic acid induce apoptosis of mouse thymocytes and purified CD4+CD8+ cells in ex vivo cultures, with 9-cis retinoic acid being 50 times more effective. The induction of apoptosis by retinoic acids is mediated by RARgamma because (a) the phenomenon can be reproduced only by RARgamma-selective retinoic acid analogs, (b) the cell death induced by either retinoic acids or RARgamma analogs can be inhibited by RARgamma-specific antagonists, and (c) CD4+CD8+ thymocytes express RARgamma. In vivo administration of an RARgamma analog resulted in thymus involution with the concomitant activation of the apoptosis-related endonuclease and induction of tissue transglutaminase. The RARgamma pathway of apoptosis is RNA and protein synthesis dependent, affects the CD4+CD8+ double positive thymocytes, and can be inhibited by the addition of either Ca2+ chelators or protease inhibitors. Using various RAR- and RXR-specific analogs and antagonists, it was demonstrated that stimulation of RAR alpha inhibits the RARgamma-specific death pathway (which explains the lack of apoptosis stimulatory effects of all-trans retinoic acid at physiological concentrations) and that costimulation of the RXR receptors (in the case of 9-cis retinoic acid) can neutralize this inhibitory effect. It is suggested that formation of 9-cis retinoic acid may be a critical element in regulating both the positive selection and the "default cell death pathway" of thymocytes.

Animals↗
PubMed1997

Susceptibility to type 1 diabetes in the Senegalese population is linked to HLA-DQ and not TAP and LMP genes.

OBJECTIVE: To investigate the frequency of the transporter associated with antigen processing (TAP) and large multifunctional protease (LMP) alleles and their role in the susceptibility to type 1 diabetes, in comparison with the well-known HLA-DQ alleles susceptibility, in Senegalese subjects. RESEARCH DESIGN AND METHODS: Three loci in the TAP/LMP region were analyzed in 92 type 1 diabetic subjects and 117 nondiabetic control subjects by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No association was found between the studied polymorphisms of TAP1, TAP2, and LMP2 and type 1 diabetes in the Senegalese population, in contrast to the HLA-DQA1 and DQB1 genes, which were associated with type 1 diabetes. CONCLUSIONS: Diabetogenic genes in the class II HLA region are located near the DQA1 and DQB1 loci rather than the TAP and LMP loci.

ATP-Binding Cassette Transporters↗
PubMed1997

The role of extracellular sodium in the mechanism of a neuronal in vitro circadian pacemaker.

In evaluation of whether extracellular ion concentrations or fluxes are involved in the mechanism of the circadian pacemaker in Bulla retinal neurons, previous studies have ruled out obligatory requirements for extracellular calcium and chloride. In this study, it is demonstrated that extracellular sodium and magnesium are also not requirements for and do not contribute to the circadian pacemaker mechanism. Since sodium-free solutions inhibit the output rhythm of compound action potential activity, pacemaker motion during long pulse treatments was evaluated retrospectively from the phase of the circadian rhythm subsequent to the treatment. Although some pulses of sodium-free solutions were capable of affecting pacemaker phase in a manner consistent with the stopping of pacemaker motion, these effects were reversed by elevating extracellular pH, suggesting that sodium-free solutions can only affect pacemaker motion indirectly through a previously demonstrated effect of low pH on pacemaker motion.

Action Potentials↗
PubMed1996

Synthesis and cytotoxic and antitumor activity of esters in the 1,2-dihydroxy-1,2-dihydroacronycine series.

Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17,19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.

Acridines↗
PubMed1996

[Treatment of pediatric hemangiomas with the flashlamp-pumped pulsed dye laser].

We treated 166 infants and children with 177 hemangiomas with the flashlamp-pumped pulsed dye laser (FPDL, 585 nm, 450 microseconds, 5 mm phi). The hemangiomas were classified as initial, superficial, cutaneous-nodular, and compound (cutaneous-subcutaneous) lesions according to the clinical involvement. After one treatment (n = 124), good results ( > 75% clearance) were obtained in 56% of initial and in 36% of the nodular lesions. With repeated treatment sessions (n = 82), good results were achieved in 63% of the initial, in 67% of the superficial and in 70% of the nodular angiomas. Complete resolution requiring one or more treatment sessions was reached in 44% of the initial, in 42% of the superficial and in 16% of the nodular lesions. In compound lesions, only the cutaneous part responds to treatment owing to the limited penetration depth of the laser light. In our opinion, early FPDL therapy of most initial and/or rapidly growing hemangiomas should be recommended especially since this therapy is fast, has few side effects and can even be used in newborns.

Child↗
PubMed1996

Circadian rhythm generation, expression and entrainment in a molluscan model system.

The Bulla ocular pacemaker provides remarkable opportunities for cellular study of circadian pacemaker systems. The demonstration of circadian oscillations within individual neurons maintained in culture provides us with a first occasion to study the biophysical and biochemical properties of bona fide neuronal circadian pacemakers. The ocular clock is robust and shares formal similarity with other circadian systems. The development of molecular techniques that can be applied to single neurons should allow research on the Bulla retina to continue to progress towards a molecular analysis of circadian timekeeping.

Animals↗
PubMed1996

Distribution of HLA-DQA1 and -DQB1 alleles and DQA1-DQB1 genotypes among Senegalese patients with insulin-dependent diabetes mellitus.

Transracial analysis is one method for distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA II alleles from those related to linkage disequilibrium. Black people have different DR-DQ relationships from other races and are a useful group to investigate HLA-D regions associated with IDDM. In this study, we compared the frequencies of HLA-DQA1 and DQB1 alleles in Senegalese IDDM and control subjects. DQA1*0301 was positively associated with insulin-dependent diabetes mellitus (p < 10(-9), OR 5.21), as were DQB1*0201 and *0302 (p < 10(-7) OR = 3.55, p < 10(-3) OR = 3.20, respectively). The positive associations with DQA1*0301, DQB1*0201 and DQB1*0302 are consistent with all racial groups investigated. However, taken together, the data in Senegalese population show that susceptibility and resistance to IDDM are associated both with particular haplotypes and DQA1-DQB1 heterodimers.

Adolescent↗