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Biomedical subjects

D Leroy

Publications and source records attributed to D Leroy.

At least 55 records · Page 3Linked to original sources
PubMed1999

Hypersensitivity syndrome due to 2 anticonvulsant drugs.

Drug-induced hypersensitivity syndrome is a multiorgan-system reaction characterized by fever, pleomorphic eruption, lymphadenopathy, eosinophilia, lymphocytosis and hepatitis. We report a drug hypersensitivity syndrome in a 6-year-old Tunisian child treated for epileptic absences with sodium valproate and ethosuximide. Imputability of these 2 drugs is probable because of the chronological and clinical features. Positive rechallenge with ethosuximide confirmed the toxicity of this drug. Sodium valproate was also responsible because patch testing was positive and followed by a generalized eruption. Human herpesvirus 6 (HHV6) antibody titers increased significantly within 15 days. There was a favourable outcome after discontinuation of the drugs and corticosteroid therapy. Our case is interesting because this drug hypersensitivity syndrome occurred with non-aromatic anticonvulsant drugs. It is the 1st case with ethosuximide and the 2nd with sodium valproate. We also observed a reactivation of HHV6 infection that may contribute to the development of this hypersensitivity syndrome.

Antibodies, Viral↗
PubMed1999

Photo(chemo)therapy in private practice in Belgium, France and The Netherlands.

Photo(chemo)therapy is used widely, and ultraviolet (UV) sources, protocols and indications are numerous. A survey was carried out to examine how photo(chemo)therapy is employed in private practice and to determine whether safety guidelines are respected. A questionnaire survey sent to Belgian, French and Dutch dermatologists generated 593 useful responses. UV sources, doses of UV and 8-methoxypsoralen (8-MOP), as well as the frequency of the treatment, were all different in the three countries. UV starting doses were rarely chosen according to the minimal phototoxic dose (MPD) or to the minimal erythema dose (MED). Total cumulative UV doses were not always determined. Maintenance PUVA therapy for psoriasis was still performed by 15 to 40% of dermatologists in the respective countries. Another striking fact was that genital protection is not universal. On the other hand, the irradiance of tubes is checked regularly, and contraindications are respected. Despite the availability of guidelines, clinicians seem to be inconstant in their assessment of the carcinogenic risk of UV radiation.

Belgium↗
PubMed1999

Dissecting subdomains involved in multiple functions of the CK2beta subunit.

We have characterized several subdomains of the beta subunit of protein kinase CK2. The N-terminal half of the protein exhibits a pseudo-substrate segment in tandem with a polyamine binding domain responsible for the activation of the kinase by these polybasic compounds. Study of the chemical features of this polyamine binding site showed that polyamine analogs exhibiting the highest affinity for CK2 are the best CK2 activators. Mutational analysis disclosed that glutamic residues lying in the polyacidic region of the CK2beta subunit are involved in the interaction with polyamine molecules and allowed the delineation of an autonomous binding domain. Furthermore, this regulatory domain was shown to mediate the association of CK2 with plasma membrane. The C-terminal domain of the CK2beta subunit plays a role in the oligomerization of the kinase since it was observed that a truncated form of this subunit lacking its 33-last amino acids was incompetent for the assembly of polymeric forms of CK2. Altogether, our results support the notion that the beta subunit of CK2 is a modular protein made by the association of interdependent domains that are involved in its multiple functions.

Affinity Labels↗
PubMed1999

Mutations in the C-terminal domain of topoisomerase II affect meiotic function and interaction with the casein kinase 2 beta subunit.

Topoisomerase II is a major target of the protein kinase casein kinase 2 (PK CK2) in vivo. All major phosphorylation acceptor sites in the yeast enzyme are found in the C-terminal 350aa. The acceptor sites are generally clustered such that there is more than one modified Ser or Thr within a short peptide. Mutagenesis of the predicted acceptor sites have confirmed that five of the eight predicted sites are targeted in vitro and in vivo by PK CK2. Mutation to nonphosphorylatable, neutral residues provokes at most a 10% increase in mitotic doubling time. Truncation of the enzyme leaves the enzyme catalytically active, but slightly lengthens the doubling time during mitotic growth and impedes progress through meiosis. Since this could reflect the loss of interaction with an important ligand, we have examined whether the C-terminal domain of the yeast enzyme mediates interaction with the regulatory beta subunit of PK CK2, which was previously reported to bind topoisomerase II. We find that point mutation of the phospho-acceptor sites does not abrogate the interaction with a small region of PK CK2beta, while truncation at aa1276 or aa1236 does. The site of interaction within PK CK2beta does not coincide with the highly negatively charged spermine binding site.

Amino Acid Sequence↗
PubMed1998

The tight association of protein kinase CK2 with plasma membranes is mediated by a specific domain of its regulatory beta-subunit.

Previous immunocytochemical studies have shown that protein kinase CK2 is mostly detected both in the cytoplasm and the nucleus of most cells. In the present study, CK2 was detected in highly purified plasma membrane preparations from rat liver. The protein kinase could be released from the membranes by high salt extraction (>1 M NaCl). Plasma membranes prepared from SF9 insect cells expressing the alpha- and beta-subunits of CK2 also contained a significant amount of oligomeric CK2. Furthermore, it was demonstrated in this cell system as well as in rat liver plasma membranes, that the beta-subunit of the kinase is the targeting subunit which mediates the tight association of the enzyme to plasma membrane components. Binding studies using membranes and recombinant proteins corresponding to different regions of the beta-subunit suggest that a functional domain previously shown to be involved in the binding of polyamines may also participate to the binding of CK2 to membranes. Modification of membranes by trypsin and phospholipases indicated that the binding process may require both membrane protein(s) and phospholipids. Interestingly, it was observed that the amount of membrane-bound CK2 in liver of embryos and new born rats increases dramatically after birth and persists during the postnatal stages of development.

Animals↗
PubMed1998

Estrogen receptor and progesterone receptor-immunoreactive cells are not co-localized with gonadotropin-releasing hormone in the brain of the female mink (Mustela vison).

The distribution of gonadal steroid (estrogen, progesterone) receptors in the brain of the adult female mink was mapped by immunocytochemistry. Using a monoclonal rat antibody raised against human estrogen receptor (ER), the most dense collections of ER-immunoreactive (IR) cells were found in the preoptic/anterior hypothalamic area, the mediobasal hypothalamus (arcuate and ventromedial nuclei), and the limbic nuclei (amygdala, bed nucleus of the stria terminalis, lateral septum). Immunoreactivity was mainly observed in the cell nucleus and a marked heterogeneity of staining appeared from one region to another. A monoclonal mouse antibody raised against rabbit uterine progesterone receptor (PR) was used to identify the PR-IR cells in the preoptic/anterior hypothalamic area and the mediobasal hypothalamus (arcuate and ventromedial nuclei). This study also focused on the relationship between cells containing sex-steroid receptors and gonadotropin-releasing hormone (GnRH) neurons on the same sections of the mink brain using a sequential double-staining immunocytochemistry procedure. Although preoptic and hypothalamic GnRH neurons were frequently in close proximity to perikarya containing ER or PR, they did not themselves possess receptor immunoreactivity. The present study provides neuroanatomical evidence that GnRH cells are not the major direct targets for gonadal steroids and confirms for the first time in mustelids the results previously obtained in other mammalian species.

Animals↗
PubMed1998

[A new look at dyslexia-dysorthography. Plea for an early recognition of that handicap].

Dyslexia is a primary development disorder characterized by reading and writing disability. Although frequent, it remains underdetected at school and badly known by practitioners. As a consequence, many children remain severely handicapped in their school life, and later on in their adult social life, although being fairly intelligent. Pediatricians must be involved in its early detection and management. ERTL4 test is a useful test of detection to be applied in 5-7-year-old children.

Adult↗
PubMed1998

Morphological and functional integrity of precision-cut rat liver slices in rotating organ culture and multiwell plate culture: effects of oxygen tension.

We examined the maintenance of functional and morphological integrity of precision-cut rat liver slices cultured in various incubation systems and conditions for 72 h. Slices were incubated (37 degrees C) for 6, 24, 48, and 72 h in supplemented Williams E medium in 6-well plastic culture plates on a gyratory shaking platform (WPCS) or in a rotating organ culture system (ROCS) using 5% CO2--95% air (WPCS/air or ROCS/air) or 5% CO2--70% O2--25% N2 (WPCS/O2 or ROCS/O2). Biochemical and functional parameters of slices maintained in WPCS/air or WPCS/O2 were almost totally inhibited after 24 h, in keeping with the extensive and diffuse coalescing coagulative necrosis typical of post-ischemic injury affecting almost all the slice surface after 48 h. As compared to freshly isolated slices, slices maintained in ROCS/air for 72 h showed stable ATP and GSH content, increased protein synthesis, and a slight steady decrease in GST activity, while ATP and GST activity remained stable and protein synthesis and GSH content increased in slices incubated in ROCS/O2 for 72 h. The extent of coagulative necrosis was markedly lower in longitudinal sections from slices incubated for 72 h in ROCS/O2 than in ROCS/air. Transversal sections from slices kept in ROCS/air for 72 h showed a thick central band of necrotic cells edged by two peripheral layers of viable hepatocytes, whereas most of the slice was composed of viable hepatocytes lined by two thin layers of necrotic cells after 72 h in ROCS/O2. ROCS/O2 emerged as the system best preserving the histological and functional integrity of rat liver slices in long-term culture.

Adenosine Triphosphate↗
PubMed1997

Binding of polyamines to an autonomous domain of the regulatory subunit of protein kinase CK2 induces a conformational change in the holoenzyme. A proposed role for the kinase stimulation.

The means by which the cell regulates protein kinase CK2 remain obscure. However, natural polyamines, cellular compounds required for cell proliferation, have been reported to strongly stimulate CK2-mediated phosphorylation of a number of substrates. Using spermine analogs, we have shown that polyamines directly interact with the CK2 beta subunit, and the chemical features of the highly acidic binding site (Asp51-Tyr80) have been determined. In the present study, we show that the isolated beta subunit region extending from residue Asp51 to Pro110 exhibits a specific and efficient polyamine binding activity similar to that of the entire beta subunit. Moreover, the replacement of Glu60, Glu61, and Glu63 of the beta subunit by 3 alanine residues leads to a loss of the spermine-induced stimulation of CK2 activity which correlates with a decrease in spermine binding affinity. Thermal stability studies indicate that the binding of spermine induces a 4 degrees C decrease of the Tm value for the holoenzyme. This was confirmed by circular dichroism analyses, which show that the 6 degrees C negative shift of the CK2 Tm value provoked by spermine binding, reflects a conformational change in the kinase. Together, these observations strongly suggest that this newly defined polyamine-binding domain is involved in the intrasteric regulation of CK2 activity.

Animals↗
PubMed1997

Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha.

Timely deactivation of kinase cascades is crucial to the normal control of cell signaling and is partly accomplished by protein phosphatase 2A (PP2A). The catalytic (alpha) subunit of the serine-threonine kinase casein kinase 2 (CK2) bound to PP2A in vitro and in mitogen-starved cells; binding required the integrity of a sequence motif common to CK2alpha and SV40 small t antigen. Overexpression of CK2alpha resulted in deactivation of mitogen-activated protein kinase kinase (MEK) and suppression of cell growth. Moreover, CK2alpha inhibited the transforming activity of oncogenic Ras, but not that of constitutively activated MEK. Thus, CK2alpha may regulate the deactivation of the mitogen-activated protein kinase pathway.

3T3 Cells↗
PubMed1997

Chemical features of the protein kinase CK2 polyamine binding site.

Protein kinase CK2 is a ubiquitous eukaryotic Ser/Thr kinase whose catalytic activity is enhanced several times by polyamines. We have shown previously that the regulatory beta-subunit of CK2 bears a polyamine binding site located in the region Asp51-Tyr110. In the present study, we have used spermine analogs to investigate the structural requirements of the CK2 polyamine binding site. We have observed a strong correlation between the stimulations of CK2 activity by all tested polyamines and their binding efficiencies to the enzyme. As a result, spermine was found to be the most efficient stimulator of the kinase activity and the best CK2 ligand. The effect of the pH on the stimulation of CK2 activity by spermine strongly suggests the involvement of ionic interactions between the positive charges of spermine and the negative charges of acidic amino acids of the beta-subunit. Using a fusion protein made of MBP and the beta-subunit region encompassing amino acid residues Asp51-Pro110, we have studied the binding of spermine as a function of the ionic strength. We show that this region delineates a functional and autonomous domain containing a binding site involved in the interaction with the four positive charges of spermine. Altogether, these results led to the elaboration of the first model defining the crucial structural parameters of a polyamine-protein interaction at the molecular level.

Animals↗
PubMed1997

Skin reactions to hydroxyzine.

Sensitivity to histamine H1-antagonists has mainly been observed with phenothiazine and ethylenediamine, and is very rare with hydroxyzine. We report 3 cases of sensitization to hydroxyzine, which was prescribed to treat urticaria and atopic dermatitis. A generalized maculopapular eruption appeared shortly after taking the drug. Patch tests with Atarax tablet were positive +3, and +2 or +3 with different dilutions of hydroxyzine. Patch tests with ethylenediamine, piperazine and other antihistamines were negative; therefore, there is no cross-allergy. We believe these rapid systemic reactions to hydroxyzine after the initial dose may have been due to prior systemic sensitivity to this drug, which cannot be used topically. Allergy to antihistamines must be considered when cutaneous lesions worsen on such therapy.

Adult↗
PubMed1997

Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones.

The aim of this study was to evaluate the possibility of cross-reactivity between ketoprofen, fenofibrate and benzophenones because of their structural similarities. Seven patients presenting photodermatitis from ketoprofen underwent patch and photopatch tests. Ketoprofen, fenofibrate, benzophenone 3, benzophenone 10, benzophenone 4, personal medications and topical creams were tested. All patients had positive patch or photopatch tests to ketoprofen and fenofibrate, four patients had positive UVA photopatch tests to benzophenone 3, and two to benzophenone 10. Patients presenting photosensitization to ketoprofen may also have cross-reactivity to fenofibrate and some benzophenones.

Adult↗
PubMed1997

Factors influencing the photo-reproduction of hydroa vacciniforme lesions.

Hydroa vacciniforme vesicles can be reproduced experimentally with repetitive UVA irradiations, but this photo-reproduction is not constant. The aim of this study was to search for the factors that influence photo-reproduction. To reproduce hydroa vacciniforme lesions six patients underwent repetitive UVA and polychromatic irradiations on the back. In four patients out of six, UVA irradiation with high doses induced papulo-vesicular lesions. Photo-induced lesions were very close to those induced by sunlight. Photo-reproduction failed when phototesting was done after or shortly before remission. Therefore, the absence of photo-reproduction appears to be a good prognostic factor.

Adolescent↗