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Biomedical subjects

G Touchard

Publications and source records attributed to G Touchard.

At least 55 records · Page 3Linked to original sources
PubMed1993

Monoclonal Ig L chain and L chain V domain fragment crystallization in myeloma-associated Fanconi's syndrome.

Monoclonal free L chains secreted in immunoproliferative disorders are frequently involved in renal complications, including a specific proximal tubule impairment, the Fanconi's syndrome, which is generally featured by intracellular crystallization of L chain-related material. In a patient with myeloma-associated Fanconi's syndrome, hexagonal crystals (most surrounded by smooth membranes) were found in kidney proximal tubular cells and bone marrow plasma cells and phagocytes. The sequence of the patient's monoclonal kappa-chain was deduced from that of identical kappa-cDNA clones from the tumoral plasma cells. Small protein-enriched gel filtration fractions from urine yielded crystals morphologically similar and with the same 60 A periodicity on electron micrographs as those found in the cells. N-terminal sequencing and mass spectrometry studies showed that the crystals contained a 107-amino acid fragment (with a C-terminal lysine) corresponding to the V domain together with a low proportion of the entire kappa-chain. In vitro trypsin and pepsin treatment of the native entire kappa-chain yielded a homogeneous V domain fragment which, contrary to other monoclonal kappa-chains, was completely resistant to further proteolytic attack. The patient's kappa-chain also displayed an unusual self-reactivity, as demonstrated by a Western blot technique. The peculiar proneness of the V domain to resist proteolysis and to form crystals might prevent the normal cell catabolism of the L chain and lead to crystallization and renal impairment.

Adult↗
PubMed1992

Complementary DNA sequence of human amyloidogenic immunoglobulin light-chain precursors.

The primary structure of three amyloid precursor light chains was deduced from the sequence of complementary DNA (cDNA) from bone marrow cells from patients affected with classical lambda (patient Air) or kappa (patient Arn) amyloidosis and from a patient (Aub) in whom lambda amyloid deposits were unusual by their perimembranous location in the kidney glomerulus. All three RNAs were of normal size, as estimated by Northern blotting, and encoded normal-sized light chains. The deduced light-chain sequence from patient Arn was related to the V kappa 1 subgroup, and included ten residues that had not been previously reported at these positions, only one of which (Leu-21) was located in a beta-sheet (4-2). The unusual presence of Asn-70 determined a potential N-glycosylation site. The sequence of the light chain from patient Air belonged to the V lambda 1 subgroup, and included three unusually located amino acid residues, one of which had already been reported in an amyloidogenic lambda-chain. The sequence of the light chain from patient Aub was related to the V lambda 3 subgroup, and contained five amino acid residues that had not previously been described at the corresponding positions; two of them (His-36 and Ser-77) were located in beta-sheets (3-1 and 4-3 respectively). This sequence was also peculiar because of the presence of numerous acidic residues in the complementarity-determining regions. Such unusual primary structures might be responsible for the amyloidogenic properties of these light-chain precursors.

Amino Acid Sequence↗
PubMed1992

NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.

Animals↗
PubMed1992

Primary structure of a monoclonal kappa chain in myeloma with light chain deposition disease.

Previous data suggest that structural abnormalities of immunoglobulin light chains may be responsible for non-amyloid light chain deposition disease (LCDD). We report on the complete primary sequence deduced from complementary (c)DNA analysis of a normal-sized kappa chain in a case of myeloma-associated LCDD. The patient's urine contained a kappa type Bence-Jones protein made of monomers and dimers of an unglycosylated kappa chain. The bone marrow myeloma cells contained intracellular kappa and gamma chains by immunofluorescence. Biosynthesis experiments showed the production of normal-sized gamma chains and of kappa chains with the same apparent molecular mass (Mr) in SDS gels as the urinary kappa chain (26,000-27,000). These kappa chains were secreted as assembled IgG molecules and as a large excess of free monomers and dimers. The complete sequence of two identical cDNA clones derived from a normal-sized kappa messenger RNA indicated that this kappa chain belonged to the rare V kappa IV subgroup. The kappa mRNA had an overall normal structure made up of the V kappa IV sequence rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable region differed from the V kappa IV-J kappa 1 germline sequence by 17 amino acid substitutions. The peculiar sequence of the variable region of this kappa chain of a rare subgroup might relate to its tissue deposition.

Aged↗
PubMed1991

[Glomerulopathies in monoclonal dysglobulinemias].

Glomerular lesions in monoclonal gammapathies include AL amyloidosis, light chain and monoclonal immunoglobulin deposit disease (LCDD), cryoglobulinemias, Waldenström's macroglobulinaemia and a new entity, atypical membranous glomerulonephritis with organised monoclonal IgG deposits. Present data on deposited material of immunoglobulin origin and immunoglobulin synthesis in amyloidosis and LCDD are reviewed.

Glomerulonephritis↗
PubMed1991

Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease.

That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.

Amino Acid Sequence↗
PubMed1990

[Articular manifestations in Wegener's disease. Report of 13 cases].

Seventeen cases of Wegener's granulomatosis have been reviewed in search of articular involvement. Articular symptoms were present in 13 cases (76 p. cent), and were inaugural in 9 cases (53 p. cent). Six of these patients experienced arthralgias, which were most often migratory, and were inaugural in 3 cases. Seven patients had arthritides, which were inaugural in 6 cases; they were fixed and additive in 6 of these 7 cases, making up a distal polyarthritis in 3 patients, and an oligoarthritis in the 3 other ones; they were transient and migratory in 1 case. The 3 cases of distal polyarthritis were inaugural and fulfilled the ARA criteria for rheumatoid arthritis; two of them were accompanied by nodules which were quite identical to rheumatoid ones. There was no axial involvement. Joint involvement was not destructive and had a favourable course under disease treatment. Myalgias were present in 3 cases, one of which simulated Horton's disease. Biological manifestations chiefly consisted of marked inflammatory changes. Antineutrophil cytoplasm antibodies were present in 11 out of 16 patients in whom they were searched; among 6 of these patients who had active disease, they were present in 5. The antibody level decreased as treatment reduced disease activity and suppressed joint involvement. Joint involvement in Wegener's granulomatosis seems to be the inconstant hallmark of disease activity. It requires no specific treatment.

Adult↗
PubMed1989

[Anti-cytoplasmic antibodies of neutrophil granulocytes in systemic vasculitis].

Autoantibodies to the cytoplasmic components of neutrophil polymorphonuclear granulocytes (ACPA) were searched for by indirect immunofluorescence on ethanol-fixed smears from normal white blood cells in 248 sera from patients with Wegener's granulomatosis, Kawasaki disease and various other vasculitides, connective tissue diseases, nephropathies and infiltrative pulmonary diseases. Apart from a weak positivity in a few Kawasaki disease sera, ACPA were found in Wegener's granulomatosis (and micropolyarteritis) only, with a correlation between ACPA titers and disease activity. These results confirm the value of ACPA in the diagnosis and evaluation of activity of Wegener's granulomatosis.

Antibodies↗
PubMed1989

Retinal and choroidal ischemic syndrome, digestive tract and renal small vessel hyalinosis, intracerebral calcifications and phenotypic abnormalities: a new family syndrome.

A new family syndrome is described that affected three of seven siblings and another patient who had been abandoned at birth but came from the same area of France. All four patients were young women with a very peculiar phenotype, poikiloderma and greying of the hair, and idiopathic non-arteriosclerotic cerebral calcifications. Pathological studies demonstrated small-vessel hyalinosis due to basal membrane thickening, mainly in the digestive tract, kidneys and calcified areas of the brain. The clinical and biological expressions of these vascular changes varied. Peripheral retinal ischemic syndrome and chorioretinal scars were found in the ocular fundi of three patients. Malabsorption and protein-losing enteropathy was the main problem in all four, and was the cause of one patient's death. A subarachnoid hemorrhage due to a right sylvian aneurysm also occurred in two of the three sisters and was lethal for one. Nephropathy with renal failure and systemic hypertension is the major problem of the two surviving patients.

Abnormalities, Multiple↗
PubMed1989

Nephrotic syndrome associated with chronic lymphocytic leukemia: an immunological and pathological study.

Three patients with B chronic lymphocytic leukemia and the nephrotic syndrome had atypical membranous glomerulonephritis or lobular membranoproliferative glomerulonephritis with subepithelial and subendothelial deposits containing IgG1 kappa, IgG1 lambda or IgM and IgG by immunofluorescence, respectively. A monoclonal cryoglobulin was intermittently found in the serum in one case. In two patients, kidney deposits were made of organized microtubular structures. Intracytoplasmic immunoglobulin inclusions in the two patients' lymphocytes showed a very similar electron microscopic pattern. The immunologic phenotype of leukemic lymphocytes was analogous in the three cases (with expression of CD2) and suggestive of a late maturation step. A complete remission of the nephrotic syndrome was observed after therapy with chlorambucil (and prednisone). These observations suggest a direct role of monoclonal immunoglobulins in kidney disease.

Aged↗
PubMed1988

Diffuse small intestinal lymphoid infiltration in nonimmunodeficient adults from Western Europe.

In two white adults born, raised, and living in central France and presenting with long-lasting malabsorption, massive and diffuse lymphoid infiltrate of the lamina propria associated with crypt scarcity was found along the whole small bowel. It was mostly composed of mature lymphocytes, focally mixed with plasma cells and reactive germinal centers. There was no evidence of celiac disease, systemic or intestinal immune deficiency or alpha-chain disease, overt lymphoid malignancy, or stagnant-loop syndrome. By immunofluorescence the infiltrate was constituted in 1 case of polyclonal B cells and, in the other, of a large majority of T11, T8, T10, and class II-positive T cells associated with a population of monotypic B cells. A gluten-free diet and parenteral nutrition proved ineffective. A dramatic and protracted clinical response was observed in both patients after the onset of oral tetracycline therapy, and still persists after 8 and 5.5 yr, respectively, together with morphologically unchanged small bowel infiltrate. These cases may be the equivalents, in people from Western developed countries, of the predominantly lymphocytic variety of the immunoproliferative small intestinal disease described in people from developing countries.

Adult↗