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Biomedical subjects

M H Jouvin

Publications and source records attributed to M H Jouvin.

At least 19 recordsLinked to original sources
PubMed1992

Significance of high levels of heparin cofactor II in the plasma and urine of adult patients with nephrotic syndrome.

Heparin cofactor II (HCII) is a thrombin inhibitor in human plasma which displays similarities with antithrombin III (ATIII). Hereditary HCII deficiency was recently reported to be associated with thrombophilia. Since thromboembolism constitutes one of the main complications of the nephrotic syndrome (NS), both activities and antigen concentrations of HCII and ATIII were measured in the plasma and urine of 33 adult patients with nephrotic syndrome. The mean HCII plasma level was significantly increased whereas the ATIII level was decreased. Plasma HCII was significantly correlated with proteinuria and with the fibrinogen level, suggesting that HCII could act as an acute phase reactant in patients with NS. HCII antigen was detectable in 16 of the 24 available urine samples, whereas ATIII antigen was present in all of them. In addition, functionally active HCII was detected in most of the urine samples containing HCII antigen, while ATIII was only present in the inactive form. In conclusion, these findings suggest that HCII is submitted to a metabolic pathway different from that of ATIII in patients with NS.

Adolescent↗
PubMed1991

Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement.

Triggering of mast cells and basophils by immunoglobulin E (IgE) and antigen induces various biochemical signals, including tyrosine kinase activation, which lead to cell degranulation and the release of mediators of the allergic reaction. The high-affinity receptor for IgE (Fc epsilon RI) responsible for initiating these events is a complex structure composed of an IgE-binding alpha-chain, a beta-chain and a homodimer of gamma-chains. It has been assumed that beta and gamma, which have extensive cytoplasmic domains, play an important but undefined role in coupling Fc epsilon RI to signal transduction mechanisms. Here we show that Fc epsilon RI engagement induces immediate in vivo phosphorylation on beta (tyrosine and serine) and gamma (tyrosine and threonine) by at least two different non-receptor kinases. We take advantage of unique features of this receptor system to demonstrate that the phosphorylation signal is restricted to activated receptors and is immediately reversible upon receptor disengagement by undefined phosphatases. Rapid phosphorylation and dephosphorylation may be a general mechanism to couple and uncouple activated receptors to other effector molecules. This could be particularly relevant to other multimeric receptors containing Fc epsilon RI gamma-chains or the related zeta and eta chains such as the T-cell antigen receptor (TCR) and the low-affinity receptor for immunoglobulin G (Fc gamma RIII, CD16).

Animals↗
PubMed1991

Mapping of the high affinity Fc epsilon receptor binding site to the third constant region domain of IgE.

Identification of the precise region(s) on the IgE molecule that take part in the binding of IgE to its high affinity receptor (Fc epsilon RI) may lead to the design of IgE analogues able to block the allergic response. To localize the Fc epsilon RI-binding domain of mouse IgE, we attempted to confer on human IgE, which normally does not bind to the rodent receptor, the ability to bind to the rat Fc epsilon RI. Employing exon shuffling, we have expressed chimeric epsilon-heavy chain genes composed of a mouse (4-hydroxy-3-nitrophenyl)acetic acid (NP)-binding VH domain, and human C epsilon in which various domains were replaced by their murine counterparts. This has enabled us to test the Fc epsilon RI-binding of each mouse IgE domain while maintaining the overall conformation of the molecule. All of the chimeric IgE molecules which contain the murine C epsilon 3, bound equally to both the rodent and human receptor, as well as to monoclonal antibodies recognizing a site on IgE which is identical or very close to the Fc epsilon RI binding site. Deletion of the second constant region domain did not impair either the binding capacity of the mutated IgE or its ability to mediate mast cell degradation. These results assign the third epsilon domain of IgE as the principal region involved in the interaction with the Fc epsilon RI.

Animals↗
PubMed1991

Recurrent acute glomerulonephritis.

Biopsy-proven recurrent acute glomerulonephritis (AGN) is extremely rare and is usually seen in children with acute, well-defined streptococcal infections. We present here a patient with recurrent AGN in the absence of chronic bacterial infection. The subject, an 80-year-old man, had eight episodes of acute nephritic syndrome following upper respiratory tract infection. No abnormalities were detected during remissions. Renal biopsies during two of those episodes showed typical postinfectious acute exsudative endocapillary glomerulonephritis, while results of another biopsy performed during remission were normal.

Acute Disease↗
PubMed1991

The high-affinity receptor for immunoglobulin E: a target for therapy of allergic diseases.

The high-affinity receptor for IgE (Fc epsilon RI) on mast cells and basophils is a tetrameric complex, alpha beta gamma 2. Here we summarize the latest developments on the structure and function of this receptor. By genetic transfer, we have engineered a cell line secreting substantial amounts of a peptide containing exclusively the extracellular domain of the alpha-subunit. This domain by itself is sufficient to mediate high-affinity binding of IgE. Glycosylation and the presence of the other subunits are not necessary for the binding function. The gamma-subunit of Fc epsilon RI is part of other receptors such as Fc gamma RIII and the T cell receptor, and therefore is likely to play an important although still undefined functional role. A detailed knowledge of how the receptor interacts with IgE and induces cellular degranulation may lead to the design of new therapeutic approaches to allergic diseases. The potential strategies are discussed.

Animals↗
PubMed1989

Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16).

Granulocyte and natural killer (NK) cell Fc receptors for immunoglobulin G (CD16) differ in only a few amino acids, yet have phosphatidylinositol glycan (PIG) or polypeptide membrane anchors, respectively. Mutagenesis shows that anchoring is regulated by a serine residue near the PIG anchor attachment site in the extracellular domain. The NK cell isoform was not expressed on the surface of COS cells unless cotransfected with a subunit that was expressed in NK cells and that was identical to the gamma subunit of the high affinity IgE Fc receptor (Fc epsilon RI). However, the CD16 sequence and not expression of the gamma subunit is dominant in regulating PIG reanchoring.

Animals↗
PubMed1989

A macrophage Fc gamma receptor and the mast cell receptor for IgE share an identical subunit.

Fc receptors for immunoglobulins are found on many immune cells and trigger essential functions of the immune defence system. With the exception of the high-affinity receptor for immunoglobulin E (Fc epsilon RI), these receptors were thought to consist of single polypeptides. Fc epsilon RI is a tetrameric complex of one alpha-subunit, one beta-subunit and two gamma-subunits. Here we report the cloning of a polypeptide identical to the gamma-chains of Fc epsilon RI, from mouse macrophages that do not express this receptor. Biosynthetic labelling and gene transfer together show that these gamma-chains associate with one of the macrophage receptors (Fc gamma RIIa). The human homologue, Fc gamma RIII (CD16), from natural killer cells is also expected to associate with gamma-chains. It is possible that these gamma-chains and the homologous zeta-chains of the T-cell antigen receptor belong to a new family of related proteins which share a common role in the signal transducing pathway.

Animals↗
PubMed1989

Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells.

The high affinity receptor for IgE (Fc epsilon RI) found on mast cells and basophils is a tetrameric complex of a single alpha subunit, a single beta subunit, and two identical gamma subunits. The genes for the three subunits of mouse Fc epsilon RI have now been cloned from the mast cell line, PT18. When compared at the DNA level, the rat and mouse subunits are similarly conserved. However, at the protein level the homology between mouse and rat alpha is surprisingly low (71% identities) especially in the cytoplasmic regions (57% identities) which are of different length (25 and 20 residues, respectively). By contrast the beta and gamma are homogeneously conserved between mouse and rat (83 and 93% identities, respectively). The consensus amino acid sequence of the alpha subunit derived from three species (rat, mouse, and human) shows that the cytoplasmic tail diverges to the same extent as the leader peptide. Conversely, the transmembrane domain of the alpha is highly conserved and contains 10 consecutive residues that are identical. Comparisons between mouse Fc epsilon RI and other mouse proteins reveal regions of high homology between the alpha subunit and Fc gamma RIIa and between the gamma subunit and the zeta chain of the T cell receptor. Cells transfected with the alpha gene express the alpha subunit on their surface very inefficiently. Efficient expression is only achieved after co-transfection of the three rodent genes or of the human alpha gene together with the rodent gamma without apparent need for beta. The subunits are completely interchangeable upon transfection so that various chimeric mouse-rat-human receptors can be expressed.

Amino Acid Sequence↗
PubMed1989

The human C3b receptor (CR1).

The human complement system is comprised of 19 plasma components and regulatory proteins and of at least 9 distinct cellular receptors for these proteins or their activation fragments. The important role of complement in host defense against infection is related to its capacity to opsonize microorganisms, lyze target cells, and induce the release of inflammatory mediators from leukocytes. Complement participates in the processing and clearance of immune complexes and in regulation of the immune response. Most of the biologic effects derived from complement activation depend on ligand-receptor interactions between complement proteins or their cleavage fragments and specific receptors on cells. Two types of ligands are generated during complement activation: soluble low-molecular-weight ligands, such as the anaphylatoxins C3a and C5a, and so-called bifunctional ligands that attach both to the target of complement activation (opsonins) and to the appropriate receptor on effector cells. The most abundant complement protein in plasma is C3. Activation of the classic and alternative complement pathways generates C3 convertases that cleave C3 into an anaphylatoxic fragment, C3a, and a major fragment, C3b, which is capable of forming a covalent linkage with the targets of complement activation. Surface-bound C3b is the preferential ligand for the C3b receptor, CR1 (CD 35), which is expressed on most peripheral blood cells. The receptor plays an important role in the processing of immune complexes, the phagocytosis of C3b-bearing microorganisms, and regulation of the immune response. The cellular expression of the molecule is decreased in patients with systemic lupus erythematosus (SLE) and in patients infected with the human immunodeficiency virus (HIV).

Antigen-Antibody Complex↗
PubMed1988

A study of fibrinogen and fibrinolysis in 10 adults with nephrotic syndrome.

In 10 patients with nephrotic syndrome (NS), the coagulation inhibitors, the fibrinolytic system and several functions of the fibrinogen-fibrin molecule were studied. Among the coagulation inhibitors, only antithrombin III (AT III) was found decreased and correlated with serum-albumin levels. Venous occlusion test provoked a normal tissue plasminogen activator (tPA) release in all patients. The plasminogen activator inhibitor (PAI) had an increased activity in 5 out of the 10 patients. Thrombin and reptilase times were found abnormal in most patients. The thrombin time (TT) prolongation correlated with serum albumin levels and was corrected by adding purified albumin. The fibrinogen was purified from each of the 10 patients' plasma. Only 2 of them showed abnormal polymerization in purified system, suggesting dysfibrinogenaemia. Other functions (thrombin binding, tPA stimulating activity, lysis by purified plasmin) were found normal except in one of the 2 patients with dysfibrinogenaemia whose fibrinogen lysis by plasmin was delayed. It is concluded that an abnormal fibrinogen molecule is not the most frequent explanation for thrombin time prolongation in NS.

Adult↗
PubMed1988

[Decrease of erythrocyte receptors for the C3b fragment of complement in acquired immunodeficiency syndrome].

The number of C3b receptors (CR1) on erythrocytes (E) was measured, using a newly developed flow cytometry assay and a standard radioimmunoassay, in HIV-infected individuals and in a normal control population. The number of CR1/E was significantly decreased in symptomatic HIV-infected patients with ARC and acquired immunodeficiency syndrome and was normal in asymptomatic carriers of anti-HIV antibodies. Decreased numbers of CR1/E correlated with the clinical severity of the HIV-related disease. A close correlation was found between results obtained with flow cytometry and those obtained with the radioimmuno-assay. Flow cytometric assessment of CR1/E may be of interest in large scale prospective clinical studies of HIV-infected subjects.

AIDS-Related Complex↗
PubMed1987

Enumeration of CR1 complement receptors on erythrocytes using a new method for detecting low density cell surface antigens by flow cytometry.

A sensitive enhancing system was developed for detecting low density cell surface antigen by flow cytometry. The system termed the 'super avidin-biotin system' (SABS) uses biotinylated antibody, phycoerythrin-streptavidin (StreptA-PE), biotinylated goat anti-streptavidin antibody, and StreptA-PE. CR1 complement receptor antigenic sites were quantified on erythrocytes from healthy individuals and patients with antibodies against human immunodeficiency virus (HIV) using SABS and a conventional radioimmunoassay (RIA) with monoclonal anti-CR1 antibody. As little as 50 sites/cell were detected using either SABS or RIA. Accurate quantification of CR1 antigenic sites was achieved within the range of 100-1300 sites/cell. Similar results were obtained using either of the two methods. Intra-assay and day-to-day reproducibilities using SABS were 2% and 12% respectively, comparable to those of conventional RIA measurements. In addition to enumeration of CR1 on erythrocytes for clinical purposes, the use of SABS may probably be extended to a wide number of situations where a sensitive detection of low density cell surface antigen is needed.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human diseases associated with C3 receptor deficiencies.

Genetic deficiencies of complement receptors have recently been described. CR1 expression is reduced on erythrocytes, leucocytes and podocytes of many patients with systemic lupus erythematosus because of both genetic and acquired mechanisms. CR1 deficiency is also found in AIDS and AIDS-related syndromes and correlates with clinical subpopulations of HIV-infected patients. The pathogenic significance of CR1 deficiency relates to the functions of CR1 in clearance of immune complexes, phagocytosis and immune regulation. CR3 deficiency occurs as an autosomal recessive inherited disease characterized by the lack of or severe reduction in expression of the leucocyte antigens CR3, LFA1, p150,95 and their common chain. The disease is associated with severe defects in neutrophil and lymphocyte functions and recurrent bacterial infections. The in vivo effects of C3 receptor deficiencies emphasize the critical role of these membrane molecules in immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Fluoride-induced chronic renal failure.

Renal fluoride toxicity in human beings is difficult to assess in the literature. Although experimental studies and research on methoxyflurane toxicity have shown frank renal damage, observations of renal insufficiency related to chronic fluoride exposure are scarce. We report a case of fluoride intoxication related to potomania of Vichy water, a highly mineralized water containing 8.5 mg/L of fluoride. Features of fluoride osteosclerosis were prominent and end-stage renal failure was present. The young age of the patient, the long duration of high fluoride intake, and the absence of other cause of renal insufficiency suggest a causal relationship between fluoride intoxication and renal failure.

Adult↗
PubMed1987

Decreased expression of the C3b/C4b complement receptor (CR1) in AIDS and AIDS-related syndromes correlates with clinical subpopulations of patients with HIV infection.

Expression of the C3b/C4b receptor (CR1) was studied on erythrocytes of 153 individuals infected with HIV and 104 age-matched normal individuals by measuring the uptake of 125I-labelled monoclonal anti-CR1 antibody. The mean number of CR1 sites on erythrocytes of asymptomatic seropositive individuals (822 +/- 270; mean +/- s.d.) and of patients with persistent generalized lymphadenopathy (PGL; 775 +/- 320) did not differ significantly from that of normal subjects. The number was significantly lower in patients with AIDS-related complex (ARC; 543 +/- 233; P less than 5 x 10(-3)) and further decreased in patients with AIDS (442 +/- 271; P less than 1 x 10(-4)), whether they presented with Kaposi's sarcoma (KS) or opportunistic infections. An additional finding was that of decreased expression of antigenic and functional CR1 in neutrophils from patients with AIDS, as assessed by radioimmunoassay of CR1 in detergent-solubilized cells and the capacity of intact cells to form rosettes with C3b-coated erythrocytes. Low numbers of CR1 on cells from patients with AIDS were not due to occupation of the receptor by C3 fragments on immune complexes. The correlation that was observed between decreased numbers of CR1 on erythrocytes and clinical subpopulations of symptomatic HIV-infected patients suggests that CR1 expression on erythrocytes may represent a valuable marker of the severity and natural history of HIV-associated disease.

AIDS-Related Complex↗
PubMed1986

Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis.

Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗