Intravenous gammaglobulin, thrombocytopenia, and the acquired immunodeficiency syndrome.
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Biomedical subjects
Publications and source records attributed to M Dreyfus.
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Chorionic villus biopsies made during the first trimester of pregnancy offer the advantage of earlier antenatal diagnoses than usual methods. This technic was introduced about 15 years ago but recently improved thanks to innovations in equipment and the contribution of echography. 75 biopsies were made using aspiration technic by echographic-guided catheter. These biopsies were carried out before elective abortion, 18 in an ambulatory setting one to three weeks before the abortion in order to test the social acceptability and tolerance of this method, as well as the inherent risks involved. The biopsy technic is described as well as preliminary results of chromosomic analyses of biopsied chorionic tissues. Drawing from a perspicacious review of the literature, the respective advantages of various biopsy technics and their uses (i.e. sex determination and chromosome analyses by culture and especially direct methods, study of fetal DNA, and enzyme assay) are examined. Finally, the risks of biopsy technic in the immediate and near future are discussed, and the indications today for this new technic are described.
A review of current literature concerning developments of new parameters in fetal biometry is presented. To be sure, these parameters are very useful for detection of fetal malformations but outside of femoral length they do not contribute more valuable information than the already accepted parameters for determination of gestational age or detection of disorders of fetal growth.
The activity of Escherichia coli aspartate transcarbamylase (ATCase) is markedly influenced by the addition of organic solvents to the assay medium. The cosolvents tested, which include simple aliphatic alcohols, amides, and ureas, as well as acetone and dioxane, fall into two different classes: the most polar ones (formamide, acetamide, N-methylformamide, and urea) stimulate the enzyme activity for all concentrations tested. In contrast, solvents that are less polar than water inhibit the enzyme at low concentrations but stimulate it at higher concentrations. No comparable effects are observed in the case of the isolated catalytic subunits, a non-regulated form of ATCase. Extensive kinetic studies on ATCase and on two of its Michaelian derivatives, 2-thioU-ATCase and carbamylated ATCase, indicate that solvents modulate the same allosteric transition that is responsible for homotropic interactions between the catalytic sites. The stabilization of the R state of ATCase by comparatively high concentrations of cosolvents is reminiscent of similar findings made on hemoglobin and glycogen phosphorylase, suggesting a common underlying mechanism. Addition of organic cosolvents to water is known to reduce hydrophobic interactions, and we suggest that this effect may preferentially stabilize the more "relaxed" conformations of allosteric proteins, because they have a larger surface exposed to solvent [Chothia, C. (1974) Nature (London) 248, 338-339]. On the other hand, we suggest that the stabilization of the T state by low concentrations of all but the most polar cosolvents simply reflects stronger electrostatic interactions in this conformation.
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Genetic and biochemical evidence has strongly suggested that several introns located in yeast mitochondrial genes specifying apocytochrome b or cytochrome oxidase encode trans-acting proteins (termed mRNA-maturases) responsible for splicing the cognate intron and maturation of the mRNA. We have chemically synthesized three oligopeptides, predicted from the DNA sequence of the open reading frame (ORF) present in the second intron of the cob-box gene, and raised antibodies against them. These antibodies have allowed us to identify a protein of 42 kd as the product translated from the ORF of the wild-type intron. In two splicing-deficient mutants this protein is replaced by shorter polypeptides whose lengths and antigenic properties are in full agreement with the positions of TAA codons established by the DNA sequence of the intron's ORF.
Mutations that result in small decreases or increases in expression from the Escherichia coli galactose operon promoter region can be detected by using a plasmid in which the gal promoters were fused to the lac operon. We describe how the level of lac expression was adjusted so that the Lac phenotype of host cells was optimally sensitive to changes in the gal promoter sequence. We have investigated the properties of two new gal promoter mutations both in vivo and in vitro, and have determined their effects on the two overlapping gal promoters, P1 and P2. Although one mutation causes only a small reduction in overall expression in vivo, it completely suppresses transcription initiation at the P1 promoter. However, it also increases expression from the P2 promoter, which compensates for the change at P1. This mutation, a GC to AT transition, falls in a zone just upstream of the P1 Pribnow box, which is essential for P1 activity, whilst improving the homology between the P2 Pribnow box and the consensus sequence. The second mutation causes a small increase in P1 activity. This change, a GC to AT transition at -23, falls in the spacer region between the Pribnow box and the -35 region, a zone containing no known promoter consensus sequences. We suggest that this mutation, which creates a stretch of five AT base pairs, acts by increasing the twist angle of the sequences in the spacer region. We argue that the increase in promoter activity is due to this twist changing the relative orientation of the Pribnow box and -35 regions.
The genomic DNAs that specify the renin mRNAs found in the submaxillary gland and in the kidney of Swiss mice have been isolated by molecular cloning in phage lambda. The Ren1 and Ren2 genes, encoding the kidney and submaxillary renins, respectively, span about 9.5 kilobases each. Restriction maps of both renin genes and their flanking sequences are presented. To correlate the differential expression of the renin genes with their structures, a sequence analysis of the putative 5' regulatory sequences of both genes was conducted. The results show that the leader sequences and promoter regions of both genes are highly homologous to a point located 179 nucleotides upstream from the transcription start point; the sequences diverge beyond this position.
To evaluate hemodynamic, angiographic, and biological effects of a single bolus of urokinase, an open descriptive trial was conducted in a homogeneous group of 14 patients with acute life-threatening pulmonary emboli and without prior cardiopulmonary disease. For every patient the efficacy of the treatment was evaluated by comparing control and posttherapeutic values after the bolus injection of 15,000 IU/kg body weight urokinase (urinary source) administered in 10 min in the right atrium, followed by continuous intravenous full-dose heparin therapy. In two patients clinical status, hemodynamics, vascular obstruction, and biological (fibrinogen and plasminogen levels) parameters remained unchanged. One of these two patients died, making the mortality rate for the whole group 7%. Twelve of 14 patients showed rapid clinical improvement. Evaluation at 12 hr demonstrated significant decreases in pulmonary vascular obstruction (Miller index, 34%), total pulmonary vascular resistances (37%), and fibrinogen and plasminogen levels (41% and 40%, respectively), without any significant change in cardiac index. The hemodynamic sequential measurements performed (1,3, 6, and 12 hr) in seven of the 12 improved patients showed that the greatest percentage of the total hemodynamic improvement occurred within the first 3 hr after bolus administration of urokinase. No severe hemorrhagic complications were observed. Because of its rapid efficacy and its low cost, the bolus technique appeared particularly useful in the treatment of patients with acute life-threatening pulmonary emboli.
In many cases of neonatal thrombocytopenia, etiology does not fit with usually known causes. Analyzing, in an intensive care unit, 64 cases of severe neonatal thrombocytopenia (platelets less than 50 x 10(9)/l before hour 72), the authors attempted to determine other possible causes of the disorder. In this study, classical etiologies were present in 33% of cases. In the other 67%, hypotrophy and/or hypoxia were significantly more frequent (p less than 0.01) than in the first group. With reference to clinical and experimental data in the literature, the possible role of acute or chronic hypoxia as a cause of thrombocytopenia is discussed.
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We have previously reported the physicochemical and kinetic properties of glycogen phosphorylase modified by arginine-specific reagent under different conditions [Dreyfus, M., Vandenbunder, B., & Buc, H. (1980) Biochemistry 19, 3634-3642]. The properties of the modified enzyme depend upon the conformation adopted by the enzyme during the modification reaction. In this paper, we report the localization of the crucial modified arginine residues on the primary structure. The chymotryptic peptide extending from residue Asp-563 to residue Tyr-572 was shown to contain one arginine residue (Arg-568) which is chemically modified by phenylglyoxal in phosphorylase a and in activated phosphorlase b. Inclusion of glucose 1-phosphate in the modification medium protects this residue from modification, with a concomitant protection of the enzyme activity. Furthermore, this residue is not reactive toward phenylglyoxal in phosphorylase b in the absence of any effector. Addition of the AMP analogue 2'dAMP, which is not an activator of the enzyme, does not increase Arg-568 reactivity but protects from modification several arginine residues located between Arg-242 and Leu-348. The location and the role of Arg-568 in phosphorylase are discussed with reference to recent data from X-ray crystallography.
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Arginine residues have been shown to be present in the binding sites of both phosphorylated substrates and nucleotide activators of glycogen phosphorylase. The former residue can only be modified by arginine-directed reagents when the enzyme is activated, i. e. in phosphorylase a, or in phosphorylase b in the presence of activators. Conversely, after this residue has been modified, phosphorylase b is irreversibly blocked in an active conformation.
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Five full term neonates presented with haematemeses on one of the first three days of life. All but one had been given vitamin K at birth. Two out of five had clotting abnormalities that suggested vitamin K deficiency. All had evidence of hiatus hernia and, on oesophagoscopy, had evidence of peptic oesophagitis. Bleeding is another complication of neonatal peptic oesophagitis.
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