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Biomedical subjects

E André

Publications and source records attributed to E André.

At least 19 recordsLinked to original sources

Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily.

Nuclear orpan receptors are members of the superfamily of structurally related, ligand-inducible transcription factors for which no ligand has yet been identified. Over the past few years many nuclear orphan receptors have been cloned, but only for the retinoid X receptor (RXR) has a natural ligand (9-cis-retinoic acid) been found. Here we report the identification of melatonin as a ligand for the recently cloned orphan receptor retinoid Z receptor beta (RZR beta). We found RZR beta expression in the rat brain nearly coincident with binding sites for the pineal gland hormone melatonin (5-methoxy-N-acetyltryptamine). We show here binding and activation of RZR beta by melatonin with Kd and EC50 values in the low nanomolar range. A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effects of this hormone, for example, in the context of circadian rhythmicity.

Animals

Hemorheological and hemostatic parameters in children with nephrotic syndrome undergoing steroid therapy.

Disturbances in hemostatic and hemorheological parameters have been investigated in a group of 29 children with nephrotic syndrome: 23 children classified as steroid-sensitive and 6 as steroid-resistant. Studies were performed before prednisone treatment and 3 weeks later, after initiation of steroid therapy. Before treatment, the alterations in hemostatic system involved moderate thrombocytosis with spontaneous aggregation in 19 patients. High levels of fibrinogen, factor VIII, Willebrand factor, protein C, protein S and alpha 2-macroglobulin (alpha 2M) were observed. Factor XII and alpha 1-antitrypsin (alpha 1AT) were lower than normal. Antithrombin III (ATIII) level was normal in the majority of patients. A plasma and blood hyperviscosity syndrome was also observed as well as an increase in erythrocyte aggregation. During treatment, an improvement in the hemostatic parameters was observed in the patients who responded to prednisone. The expected increase in factor VIII (frequently described in the literature) was not observed, while there was a significant increase in protein C. In the steroid-resistant patients, the only significant changes observed were decreased fibrinogen and increased protein C. The hemorheological parameters showed a tendency towards normality regardless of whether or not the treatment provided remission of NS. The relationship between hemorheological and hemostatic factors changes are discussed.

Adolescent

Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences.

Highly degenerate PCR primers were designed based on the amino acid sequence of the zinc finger motifs of known nuclear receptor members. Reverse transcription (RT)-PCR was performed using these degenerate primers starting with total RNA isolated from human umbilical vein endothelial cells (HUVEC). We identified 13 nuclear receptors of which three were novel. Of the novel orphans two-RZR alpha and PHR-1-were further characterised. Cloning of their cDNAs and sequence comparisons revealed that RZR alpha is related to Drosophila DHR3, RAR and RXR. PHR-1 turned out to be the human homologue of the recently published murine LRH-1. By Northern blot analyses we found RZR alpha mRNA expressed in a variety of organs, whereas a high amount of PHR-1 mRNA was found in pancreas and less in liver. This technique not only aides in the identification of additional members of the nuclear receptor superfamily but also measures relative changes in the expression of nuclear receptors between two different biological states, for example, normal and disease states.

Amino Acid Sequence

Cap100, a novel phosphatidylinositol 4,5-bisphosphate-regulated protein that caps actin filaments but does not nucleate actin assembly.

The fast and transient polymerization of actin in nonmuscle cells after stimulation with chemoattractants requires strong nucleation activities but also components that inhibit this process in resting cells. In this paper, we describe the purification and characterization of a new actin-binding protein from Dictyostelium discoideum that exhibited strong F-actin capping activity but did not nucleate actin assembly independently of the Ca2+ concentration. These properties led at physiological salt conditions to an inhibition of actin polymerization at a molar ratio of capping protein to actin below 1:1,000. The protein is a monomer, with a molecular mass of approximately 100 kDa, and is present in growing and in developing amoebae. Based on its F-actin capping function and its apparent molecular weight, we designated this monomeric protein cap100. As shown by dilution-induced depolymerization and by elongation assays, cap100 capped the barbed ends of actin filaments and did not sever F-actin. In agreement with its capping activity, cap100 increased the critical concentration for actin polymerization. In excitation or emission scans of pyrene-labeled G-actin, the fluorescence was increased in the presence of cap100. This suggests a G-actin binding activity for cap100. The capping activity could be completely inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2), and bound cap100 could be removed by PIP2. The inhibition by phosphatidylinositol and the Ca(2+)-independent down-regulation of spontaneous actin polymerization indicate that cap100 plays a role in balancing the G- and F-actin pools of a resting cell. In the cytoplasm, the equilibrium would be shifted towards G-actin, but, below the membrane where F-actin is required, this activity would be inhibited by PIP2.

Actin Cytoskeleton

[Passive smoking respiratory risk. A quantitative synthesis of the literature].

Fifty nine scientific papers had been published in english or french literature, by 1988, on the matter of respiratory health effects of environmental tobacco smoke exposure (ETS). Fifteen dealt with lung cancer. An original meta-analytical approach was used in order to assess the consistency of these results, where the quality of the papers contributes to the weighing scheme, along with the traditional precision parameters. Lung cancer studies converge towards a point estimate of the relative risk (RR) near 1.5, contrasting non smokers exposed during a long time to ETS (mostly at home) and non exposed non smokers (95% confidence interval = 1.3-1.6). Important methodological difficulties did not allow, to date, to show consistent dose-effect relationship with duration or intensity of exposure. Chronic infections of lower respiratory tract related to ETS have been frequently observed (RR = 1.3; 1.2-1.4) as well among adults as among children. Wheezing and asthma are likewise more frequent among children exposed to ETS at home (RR = 1.2; 1.1-1.4). A modest, although statistically significant decrease of Forced Expiratory Volume at One Second is associated with passive smoking among children (mean effect = -0.5%). Health risk related to passive smoking are much lower than those caused by active smoking. However, this hazard should not be underlooked, since ETS is universally present in everyday life and since anyone may be exposed, including children, the elderly and those who suffer from chronic respiratory diseases. Many research needs are underscored by this meta-analysis. It remains that the current state of knowledge on health risks associated with passive smoking warrants that strong preventive action, educative or statutory, be promoted.

Adolescent

[Accidents caused by poisons in children in Guadeloupe. A 3-1/2 year study in Pointe-à-Pitre CHRU].

We report the results of a study on poisoning by ingestion of toxic products in children performed in the Pointe-à-Pitre hospital from January 1986 to June 1989. We found a high frequency of domestic poisoning, a balanced sex ratio, a prevalence among the 1-5 years old children and a high annual cost of hospitalization. This underlines the need for intensified preventive measures.

Academic Medical Centers

A Dictyostelium mutant deficient in severin, an F-actin fragmenting protein, shows normal motility and chemotaxis.

A severin deficient mutant of Dictyostelium discoideum has been isolated by the use of colony immunoblotting after chemical mutagenesis. In homogenates of wild-type cells, severin is easily detected as a very active F-actin fragmenting protein. Tests for severin in the mutant, HG1132, included viscometry for the assay of F-actin fragmentation in fractions from DEAE-cellulose columns, labeling of blots with monoclonal and polyclonal antibodies, and immunofluorescent-labeling of cryosections. Severin could not be detected in the mutant using these methods. The mutation in HG1132 is recessive and has been mapped to linkage group VII. The mutant failed to produce the normal severin mRNA, but small amounts of a transcript that was approximately 100 bases larger than the wild-type mRNA were detected in the mutant throughout all stages of development. On the DNA level a new Mbo II restriction site was found in the mutant within the coding region of the severin gene. The severin deficient mutant cells grew at an approximately normal rate, aggregated and formed fruiting bodies with viable spores. By the use of an image processing system, speed of cell movement, turning rates, and precision of chemotactic orientation in a stable gradient of cyclic AMP were quantitated, and no significant differences between wild-type and mutant cells were found. Thus, under the culture conditions used, severin proved to be neither essential for growth of D. discoideum nor for any cell function that is important for aggregation or later development.

Actins

Severin, gelsolin, and villin share a homologous sequence in regions presumed to contain F-actin severing domains.

cDNA clones encoding the actin filament severing protein severin from Dictyostelium discoideum were isolated from a cDNA library in lambda gt 11 using monoclonal antibodies. Comparison of the deduced amino acid sequence with the sequence of a severin peptide indicated that the complete coding region of severin is contained in the isolated clones. Severin, a 39.9-kDa protein, is encoded by one gene in D. discoideum. An mRNA of approximately 1.4 kilobases is present throughout the developmental cycle of D. discoideum. The amino acid sequence of severin contains a region highly homologous to a conserved sequence in villin and gelsolin, two proteins of similar function isolated from vertebrates. This homologous region is believed to participate in the actin filament severing activity of these proteins. Comparison of the severin sequence to the entire gelsolin sequence shows remarkable homologies pointing to a common origin from an ancestral gene from which gelsolin has been derived by a duplication.

Actins

Actin-binding proteins are conserved from slime molds to man.

DNA clones encoding the actin-binding proteins alpha-actinin and severin from Dictyostelium discoideum were isolated and sequenced. Comparisons of the deduced amino acid sequences with proteins from other species showed striking similarities at distinct regions. The F-actin cross-linking molecule alpha-actinin carries two characteristic EF-hand structures highly homologous to the Ca2+-binding loops of proteins from the calmodulin superfamily. An N-terminal region that is conserved in alpha-actinin from D. discoideum and vertebrates is also related to parts of the dystrophin sequence and might represent the F-actin binding site. Severin, gelsolin, villin, and fragmin share homologous sequences that are believed to participate in the severing activity of these proteins.

Amino Acid Sequence

[Pollution and smoking in pregnant women].

For nine months the pregnant woman, and indirectly her fetus, is exposed to an aerosol composed of different pollutants. With some of these, as for smoking, it has been possible to define objectively and statistically an alteration of the health status and of the satisfactory outcome of pregnancy; with others it has not been possible at present to define a dose relation effect or a threshold of risk. In this study, known connections were studied between pregnancy and smoking (specific risks, perinatal mortality, childhood cancer and breastfeeding), industrial pollution and particularly those related to lead, fertilisers and pesticides, opiates and cannabis derivatives (in particular their effect on reproductive function), radioactivity and its correlation with the genetic code and the risk of cancer and pollution by micro-organisms. If these risks exist, even it they are not all assessable objectively, the short term action of the most benefit is certainly a change in individual behaviour, for example with tobacco consumption.

Air Pollutants

[Is enoxaparine (PK 10169) a good anticoagulant in chronic hemodialysis?].

Tolerance and efficacy of single i. v. injections of PK 10169 (1 mg/kg) during installation were evaluated in 10 patients with stable chronic renal insufficiency treated with 3 sessions of hemodialysis weekly (sessions of 4 and 5 hours). Tolerance was good in all cases. Efficacy was globally satisfactory (no complete coagulation) but by the 4th hour in 7 out of 30 sessions coagulation was apparent in the bubble trap with elevation of residual blood volume, recurring in the same patient but not affecting result of dialysis. In these cases anti-Xa activity was reduced from the 2nd hour and at end of dialysis, with a markedly elevated FPA level. For most patients it is possible to envisage 5-hour sessions, but in those few susceptible to develop coagulation repeated clinical surveillance of all circuit elements is necessary.

Adult

Structural genes of coagulation factors VII and X located on 13q34.

From 7 cases of abnormalities involving chromosome 13, the structural gene(s) coding for coagulation factors VII and X were located in the region 13q34-13qter. Gene-dosage effects for these coagulation factors seem to act in both directions, causing a decrease when there is monosomy of segment 13q34, but also, as has not been demonstrated before, an increase when there is trisomy of this same segment.

Adolescent

[Immunological status of hemophiliacs: study of blood T-lymphocyte populations, serum immunoglobulins, and the prevalence of anti-LAV antibodies].

Blood T-lymphocyte subsets and serum immunoglobulin levels were studied in a group of 52 haemophiliacs (44 patients with haemophilia A and 8 patients with haemophilia B). None of the patients had AIDS or belonged to any AIDS high-risk group. Patients were exclusively treated with clotting fractions obtained from healthy volunteers in metropolitan France. As compared to a group of 52 normal donors, haemophiliacs had increased numbers of suppressor lymphocytes, which resulted in depressed helper/suppressor (H/S) ratios, and increased levels of serum IgG and IgA. 21 haemophiliacs (40,3%) had a H/S ratio less than 1.4. Among patients with haemophilia A a higher mean IgG level was found in patients presenting lymphadenopathy. Decreased mean H/S ratio and increased mean serum IgG level were found in patients receiving more than 50 000 U of factor VIII during the 2 years preceding the study. No striking difference in mean serum IgG, IgA and IgM levels was found in patients with haemophilia A when H/S ratios were higher and lower than 1.4 respectively. As AIDS and immunological abnormalities among haemophiliacs probably share a common viral origin, this study emphasize the need to discourage blood donation from donors who belong to any AIDS high-risk group, and to screen sera from the blood donor population for antibodies to LAV/HTLV III.

Acquired Immunodeficiency Syndrome

[Practical value of the determination of urinary fibrin degradation products in the early management of renal transplants].

We studied daily urinary excretion of fibrin degradation products (UFDP) during the first month following renal transplantation in 31 patients using the Merskey technique. After the 48 first hours a rise of UFDP was observed in 3 circumstances: 1) acute rejection: twenty-four acute rejections were observed in twenty-two patients. The increase of UFDP was constant. It preceeded the clinical diagnosis of rejection in 63 p. 100 of the patients. It has a predictive value in all cases. 2) Severe urinary infection. In 5 patients with urologic complications UFDP rose markedly. 3) Macroscopic hematuria. In 2 patients with gross hematuria very high rates of excretion were observed.

Female

[Practical interest of the determination of urinary fibrin degradation products in the early monitoring of kidney transplants].

We studied daily urinary excretion of fibrin degradation products (UFDP) during the first month following renal transplantation in 31 patients using the Merskey technique. Passed the 48 first hours a rise of UFDP was observed in 3 circumstances: 1) acute rejection: twenty four acute rejections were observed in twenty two patients. The increase of UFDP was constant. It preceded the clinical diagnosis of rejection in 63 p. 100 of the patients. It has a predictive value in all cases. 2) Severe urinary infection. In 5 patients with urologic complications UFDP rose markedly. 3) Macroscopic hematuria. In 2 patients with gross hematuria very high rates of excretion were observed.

Circadian Rhythm

[Centric relation].

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Dental Occlusion, Centric

[Acquired coagulation inhibitors. 10 cases (author's transl)].

A circulating anticoagulant with antiprothrombinase activity was detected in 10 patients, 4 of whom had systemic lupus erythematosus. Clinically, haemorrhages occurred only in patients with associated thrombopenia; some developed thrombosis. Recalcification time and activated partial thromboplastin time were prolonged in the patients' plasma and in mixed patients' and control plasma. In 5 cases the anticoagulant was isolated by chromatography as IgG or IgM.

Adolescent