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Biomedical subjects

D Glotz

Publications and source records attributed to D Glotz.

At least 19 recordsLinked to original sources
PubMed1992

Vascular complications in the adult kidney transplant recipient.

Vascular complications of renal transplantation occurred in 15% of the cases. They are thrombotic infarct, arterial stenosis, arterio-venous fistula, and chronic arterial diseases. From 900 renal transplantations performed, only 120 (made since 1989) were studied with color flow Doppler (CFD). Lack of arterial signal is indicative of main arterial thrombosis (or of renal infarct if thrombosis is limited). At the site of arterial stenosis, high velocity and turbulence are found. If the stenosis is more than 70%, the rising systolic time is longer than 0.07 sec in the post-stenotic artery. Arterio-venous fistulas are frequent after renal biopsy. They provoke vibrations transmitted to peri-vascular tissues and seen with CFD as a large area of turbulence. In the feeding artery, Fast Fourier Transformation (FFT) showed a high velocity with a low resistive index and pulsed flow in the outgoing vein. Chronic arterial diseases include cyclosporine A intoxication and chronic rejection. These two diseases cannot be diagnosed by CFD alone.

Arteriovenous Fistula↗
PubMed1991

[Extramembranous glomerulopathies].

Membranous nephropathy is defined by the presence of immune deposits localized on the epithelial side of the glomerular basal membrane. Its mechanism has been elucidated through numerous experimental models and is thought to be the consequence of in situ formation of immune complexes. Membranous nephropathy is clinically discovered by a nephrotic syndrome of unknown long-term evolution: 25% of the patients undergo complete spontaneous remission and 20% show progressive renal failure. As of today, no prognostic criteria are available. Numerous studies using steroids, immunosuppressive agents, or a combination of both, have tried to modify the natural history of the disease, but none of these protocols clearly seem to have changed the course of the disease.

Adrenal Cortex Hormones↗
PubMed1991

[Anti-idiotype antibodies].

The discovery of idiotypes by Oudin and Kunkel, followed by the idiotype network theory by Jerne have opened a new field of investigation of the humoral immune response and of its regulation. The presence of anti-idiotypes behaving like "internal images" and the ability of anti-idiotypes to modulate the immune response in animals lead the way to new therapeutic regimens in very various fields such as auto-immune diseases or vaccinations. However, many theoretical as well as practical problems need to be solved before the actual use of such reagents in clinical medicine.

Animals↗
PubMed1991

Wegener's granulomatosis presenting as diffuse pulmonary hemorrhage.

A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management.

Adult↗
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↗
PubMed1990

Specificity and cross-reactive idiotypes of anti-glomerular basement membrane autoantibodies in HgCl2-induced autoimmune glomerulonephritis.

Mercury-induced autoimmune glomerulonephritis in the Brown-Norway (BN) rat is characterized by the successive appearance of linear and granular glomerular IgG deposits. Anti-laminin autoantibodies represent the major part of the anti-glomerular basement membrane (GBM) antibodies produced in this model. Fusions were performed in this model and four anti-GBM monoclonal antibodies (mAb) were obtained. Three of them were laminin specific. Using rabbit anti-idiotype antibodies, cross-reactive idiotypes (CRId) were characterized on anti-laminin antibodies. They were expressed on the three anti-laminin mAb, on kidney-eluted and circulating anti-laminin antibodies. CRId-bearing immunoglobulins were detected transiently in the circulation and paralleled the anti-laminin antibody activity. By immunofluorescence studies on kidney cryostat sections two different CRId were defined. One was localized close to the antigen-combining site since it was not revealed on kidney-bound antibodies, in contrast with the second CRId. This latter CRId was also found deposited in a typical linear pattern in the early phase of the disease and in a granular pattern in the late phase, demonstrating that these CRId are components of immune deposits. Taken together, these results suggest that in this model of T-dependent polyclonal B cell activation, restricted sets of V genes encode for at least a part of the anti-GBM autoantibodies.

Animals↗
PubMed1989

A natural neonatal hybridoma autoantibody to the T200 antigen.

We report on the production and characterization of a murine hybridoma generated from neonatal (less than 24 h from birth) unstimulated BALB/c splenocytes that produces an IgG2b kappa-antibody (21G10) reacting with a cell surface Ag of murine lymphocytes. By immunoprecipitation technique we determined that the Ag recognized by autoantibody 21G10 has an apparent m.w. of 200 kDa and is present on both T and B lymphocytes but not on fibroblasts. Together with the pattern of immunoprecipitation and the cell lineage distribution we suggest that autoantibody 21G10 likely recognizes the common leukocyte Ag T200. This is further inferred by using a mutant (T200-) cell line and a reference anti-T200 mAb in immunodepletion experiments. Functionally, autoantibody 21G10 blocks (greater than 90%) the incorporation of [3H]TdR by T lymphocytes stimulated in vitro with Con A, and inhibits the production of IL-2 by these cultures. This report demonstrates the existence of autoantibodies directed against lymphocyte cell surface Ag within the natural preimmune repertoire. The implication of this finding with regard to T-B cells interaction early in ontogeny is discussed.

Animals↗
PubMed1989

Molecular characterization of the VH region of murine autoantibodies from neonatal and adult BALB/c mice.

We report on the molecular characterization of the heavy (H) chain variable (V) region of two murine autoantibodies reacting with a conventional self antigen, thyroglobulin (Tg), originated from unimmunized/unstimulated neonatal mice (clone B10H2) and from an adult hyperimmunized mouse (clone 62), respectively. Serologically, both hybridoma antibodies express the same idiotype (Id). By cloning and sequencing we demonstrated that their VH regions are encoded by identical VDJ gene elements including the VD and DJ joints. This VH belongs to the VH 7183 gene family, the most 3'-end proximal family in the murine genome. The D segment is unique and only 50% similar to any murine D segment. The J segment utilized is germ-line JH4. The cloned DNA rearrangement was transfected into the J558L myeloma cells and the secreted antibody was found to express the reference Id on the H chain, hence proving that the productive VDJ rearrangement had been identified. These results show that a spontaneously arising and an antigen-induced autoantibody use an identical VDJ gene rearrangement and that after hyperimmunization somatic mutation did not occur. The significance of this finding with respect to ontogeny of the B cell repertoire is discussed.

Animals↗
PubMed1989

Autoantibody idiotypy and neonatal B cell repertoire.

During ontogeny, antibody variable (V) regions are subjected to selection events at the level of B-cell clones bearing on their surfaces Ig molecules useful to the developing organism. Antigenic determinants of immunoglobulin V regions (idiotypes) are believed to play an essential role in molecular recognition and immune responsiveness to exogenous and self antigens. Recent data indicate that reactivity with self-antigens is prevalent within the natural neonatal repertoire, suggesting that self-antigens are involved in the selection and shaping of the immunologic repertoire. One implication of the above considerations is that V regions having regulatory idiotypes are borne preferentially on antibodies that react with self-antigens. Here, we report on the molecular characterization of the idiotype 62 expressed by BALB/c autoantibodies to a classic self-antigen, thyroglobulin. We show that under appropriate experimental conditions, Id62 can modulate the autoantibody response through a process requiring the activation of regulatory T cells. We also demonstrate that self--reactive V regions bearing Id62 are present in newborn mice and report on the primary structure of the V-region genes encoding Id62. Lastly, we provide evidence that hybridomas derived from unstimulated splenocytes of normal neonatal BALB/c mice express Ig molecules that react prevalently with self-antigens.

Amino Acid Sequence↗
PubMed1989

Early ontogeny of rheumatoid factor antibodies. Characterization of a murine neonatal hybridoma autoantibody to IgGl in BALB/c mice.

The ontogeny and the function of rheumatoid factors (RF) are poorly understood. Here we describe a stable neonatal hybridoma cell line of BALB/c origin that secretes a RF autoantibody of the IgM class. By a series of in vitro assays we determined that this RF reacts specifically with the murine IgGl heavy chain. It also binds IgG of several mammalian species. By using mutant IgGl molecules, the reactive epitope was mapped to the CH3 domain of the constant region of IgGl. These findings indicate that clones with reactivity to autologous IgGl exist in normal mice at birth.

Animals↗
PubMed1988

Isotype, VH genes, and antigen-binding analysis of hybridomas from newborn normal BALB/c mice.

In this study we report on the characterization of a panel of 62 hybridomas generated by fusing unstimulated spleen cells from neonatal (less than 24 hr old) normal BALB/c mice with the non-secreting Sp 2/0 cell line. The vast majority (98%) of these hybridomas secreted Ig but only 20% produced IgM. The isotype of the remaining hybridomas was determined as being IgG2b. Interestingly, when splenocytes from 1-day-old mice were stimulated with LPS for 48 h prior to the fusion event, 84% of the hybridomas were secreting IgM. The hybridoma supernatants were screened either by ELISA or RIA for binding reactivity using a panel of 17 Ag, proportionally divided between self and non-self. A binding reactivity could be assigned in 44% of cases. Of these, 29% were monoreactive, i.e., reactivity occurred with one Ag only, while the remaining 15% were multireactive. The majority (21 of 27) of hybridomas with a defined reactivity were directed against self-Ag. These included autologous red blood cells, DNA, histone H1, thyroglobulin, and Ag of the cell surface of T cells. The frequency of utilization of VH genes was determined using DNA probes for eight VH gene families. While all VH gene families appeared to have been used, one, VH 7183, had a slight but significant (p less than 0.02) higher utilization than expected by random expression. The frequency of all the other VH gene families was not significantly different from random utilization. No correlation was found between Ag reactivity in the supernatants and the utilization of a particular VH gene family. These findings indicate that early in the ontogeny the predominant reactivity of B cells is for self-Ag and, unlike what it is commonly believed, the IgM isotype is not dominant within these endogenously activated B cells at this time of ontogeny when genes from all VH families are utilized.

Animals↗
PubMed1987

Idiotype regulation of self responses, autoantibody V regions and neonatal B cell repertoire.

The role of autoantibodies themselves in immune regulation is still unknown. There is evidence that some autoantibody idiotypes (Id) may play a regulatory role in physiologic and possibly pathologic situations of the immune system. Here we present evidence that (1) certain autoantibody Id modulate the immune response to self antigens (regulatory Id), and (2) that the neonatal preimmune repertoire is primarily devoted to self recognition. The humoral and cellular events following immunization with regulatory Id suggest an active participation of T cells in the regulatory events. Based on immunochemical, structural and molecular genetics analysis, it appears that this regulatory Id is of germline origin as it exists within the neonatal preimmune repertoire. B cell hybridomas generated from unstimulated splenocytes of neonatal mice are primarily self-reactive, suggesting that the immune system essentially begins as a self-recognizing system. The findings are discussed with regard to the relationship between germline repertoire, autoantibodies, and regulatory idiotypes.

Animals↗
PubMed1986

Perturbation of the autoimmune network. II. Immunization with isologous idiotype induces auto-anti-idiotypic antibodies and suppresses the autoantibody response elicited by antigen: a serologic and cellular analysis.

We report on the humoral and cellular events following autologous immunization against an idiotype (Id62) borne on a murine monoclonal autoantibody to thyroglobulin, and their impact on the autoantibody response to thyroglobulin. BALB/c mice with a state of active auto-anti-idiotypic immunity and challenged with thyroglobulin in complete Freund's adjuvant 2 wk after the last immunization with idiotype were found to have a suppressed autoantibody response. This suppression could be adoptively transferred to syngeneic x-irradiated recipients by using whole spleen cells from idiotype-primed mice. Transfer of separate T and B lymphocyte populations proved instrumental in disecting humoral from cellular events and in establishing that whereas B cells were required for transferring an intact anti-idiotype antibody response, T cells from idiotype-primed mice were necessary to transfer suppression. These findings contribute to our understanding of the interrelationship between antigen, idiotype, and anti-idiotype in the immune response to self-antigens, and the role of certain idiotypes in regulating autoimmune responses.

Animals↗
PubMed1986

Detection of a regulatory idiotype on a spontaneous neonatal self-reactive hybridoma antibody.

To investigate the physiologic relevance of an idiotype-driven regulation of the immune system, we began a search for spontaneous self-reactive hybridomas in neonatal BALB/c mice. We sought hybridoma antibodies reactive with thyroglobulin (Tg) and expressing Id62, a recurrent idiotype with regulatory properties borne on induced adult autoantibodies to Tg. We describe herein such a neonatal Tg binding/Id62-positive monoclonal antibody (mAb) B10H2, and compare it with prototype mAb 62, an adult Tg-binding/Id62-positive mAb. Both mAb react with the same Tg epitope, as demonstrated by their abilities to totally inhibit the binding of the other to Tg. Moreover, as assessed by a double-reciprocal plot of their binding to Tg, their relative affinities for Tg are comparable. Likewise, mAb B10H2 appears idiotypically similar to mAb 62 because it totally inhibits the binding of mAb 62 to homologous anti-idiotype. Finally, as previously shown for mAb 62, mAb B10H2 expresses Id62 independently on both heavy (H) and light (L) chains, as evidenced by the immunoblot binding of a specific anti-Id62 probe to separated H and L chains. By molecular genetic analysis both antibodies appear to have made use of a member of the same VH 7183 gene family. Altogether, these findings suggest that neonatal mAb B10H2 and adult mAb 62 are very similar if not identical, and regulatory idiotype Id62 may be germline encoded. Furthermore this observation supports, in general, the concept of an idiotype-driven regulation for autoimmune responses.

Animals↗
PubMed1979

[The metabolism of colostomised laying hens with 15N-labelled wheat. 4. 15N-Incorporation in the corpuscular components of blood, in the blood plasma and the basic amino acids].

Three colostomised Laying hybrids received over four days a dosage of 672 mg 15N-excess (15N'), 20.3 mg lysine 15N', 23.0 mg histidine-15N' and 66.7 mg arginine-15N' with a ration customary in production. After feeding the same nonlabelled ration for another four days the hens were killed and the N-content of the blood as well as of its fractions (corpuscular components, plasma, free amino acids of the plasma) was determined.

Animals↗