Prophylactic intravenous immunoglobulin treatment influences serum immunoglobulin M repertoire development after allogeneic bone marrow transplantation.

Patients treated with allogeneic bone marrow transplantation (BMT) suffer from a deficient humoral immunity during the post-transplant period. To prevent infections patients may receive prophylactic intravenous immunoglobulin (IVIG) therapy from 1 week before to 3 months after BMT. We have studied the effect of IVIG treatment on reconstitution of immunoglobulin repertoires in transplanted patients. Sera obtained from 13 IVIG-treated and 31 non-IVIG-treated patients before and at different time points after BMT, ranging from 3 days to 3 years, and from 18 healthy controls, were analyzed using a quantitative immunoblot system. The average immunoglobulin (Ig)M and IgG reactivity profiles against antigens derived from human liver, muscle and skin as well as Staphylococcus epidermidis protein extracts were similar in both patient groups and in controls. Both IgG and IgM reactivity profiles are, however, less heterogeneous among the individuals in the IVIG-treated patient group. Around 1 year after BMT the heterogeneity of the IgM reactivity profiles against allogeneic protein extracts is much lower in the IVIG-treated group compared to the non-IVIG-treated group and the healthy controls. This effect remains months to years after the IVIG treatment has been completed. Our results suggest that IVIG influences selection of the natural antibody repertoire mediated by the variable (V)-region during reconstitution after BMT.

Functional diversity of natural IgM.

This paper proposes a method for the quantitative characterization of repertoire diversity of an unknown mixture of antibodies on the basis of its reactivity profile in the quantitative immunoblot (QIB). The QIB is calibrated by measuring the reactivity profiles of supernatants of known 'diversity' (i.e. known numbers of B cell clones). We define a quantitative 'index of variability' (IV) which decreases regularly as the diversity increases and the profiles tend towards a common 'convergence profile'. The calibration procedure is consolidated by a mathematical model based on the Poisson distribution; this theoretical model accounts correctly for the observed convergence behavior. On the basis of this calibration curve, it is possible to estimate the diversity of an unknown antibody mixture from a measure of its IV. We conclude that the functional diversity of natural serum IgM in mice can be estimated at approximately 16,000 clones.

Characterization of a protein species isolated from HeLa cell cytoplasm by affinity chromatography on polyadenylate-sepharose.

Chromatography of different soluble extracts from HeLa cells on poly(A)-Sepharose columns has allowed the isolation of a protein fraction eluted by 0.2 M NaCl and localized predominantly in the cytoplasmic supernatant and in the 0.5 M KCl ribosomal wash. This fraction is present in large amounts (around 3% of total cytosolic proteins) and appears to contain a major protein species that is acidic on electrofocusing (pI around 4.5) and phosphorylated. It runs on glycerol gradients and Sephadex G-200 chromatography close to the aldolase marker (158,000 daltons) and dissociates into apparently identical subunits of 38,000 +/- 2,000 daltons on sodium dodecyl sulfate-acrylamide gels, suggesting a tetrameric structure.

Use of the Cadzow procedure in 2D NMR for the reduction of t(1) noise.

A data processing approach is proposed for reducing the t(1) noise observed in multidimensional NMR spectra. This method is based on the use of the Cadzow procedure [Cadzow, J.A. (1988) IEEE Trans. Acous. Speech Signal Proc., 36, 49-62], and is demonstrated to be efficient for simulated cases as well as real experiments.

[Metabolic disorders in experimental hepatic insufficiency and parenteral feeding]. / Troubles métaboliques de l'anhépatie expérimentale et nutrition parentérale.

Anhepatia is a complete experimental model for the study of metabolic disturbances associated with hepatic insufficiency. The authors report their experience based upon 16 cases of total hepatectomy in the dog. The animals received different types of hepatic assistance : group 1 (2 dogs), carbohydrate assistance (glucose 7 g/kg/24 h) ; group II (2 dogs), carbohydrate and haemostatic assistance : homologous plasma 50 ml/kg body weight per 24 hours previously stored at - 80 degrees C ; group III (2 dogs) same nutrition as in group II, combined with amino acids : leucine 53, 3 mg, isoleucine 46, 6 mg ; valine 53,3 mg alpha-ketonic acid (lg/kg/24 h) ; group IV (10 dogs, same nutrition as in group III, combined with supplements in neuro transmitter precursors : 6 dopa 1,66 mg, 5 hydroxy-tryptophane 2 mg and choline 16, 66 mg/kg/24h. Metabolic disturbances and their course were analysed in detail. Results : (mean survival) - group I : 24 +/- 4 hours; group II : 36 +/- 9 hours; group III : 42 +/- 4 hours; group IV : 90 +/- 9 hours. The average survival differed significantly for groups III and IV (p less than 0,01) in comparison with control groups I and II. The replacement of essential hepatic functions such as blood glucose regulation, coagulation, detoxication and the provision of neurotransmitter precursors made possible 4 days survival after total hepatectomy.

Long-term persistence of oligoclonal serum IgM repertoires in patients treated with allogeneic bone marrow transplantation (BMT).

Immunoglobulin gene rearrangements in patients treated with BMT have restricted repertoire diversity. Clonal variability remains low for 3 months and reconstitution of the humoral immune system appears to follow a wave-like pattern. In the present study we analysed serum IgM and IgG repertoires in 44 patients from 1 week to 3 years after transplantation. We applied a quantitative immunoblot technique in combination with a newly developed method for estimation of repertoire diversity in complex mixtures of antibodies. Our results demonstrate that 60% of BMT patients have severely reduced diversity in the IgM repertoire during and after the first year post-BMT, compared with healthy controls. In contrast, the majority of patients have a polyclonal IgG repertoire, similar to that of healthy controls. Serum IgM repertoires remain oligoclonal even though the serum concentration of total IgM is within normal range around 6 months post-BMT. During the first years after transplantation IgM as well as IgG repertoires are less diverse in patients receiving a BM graft from a sibling donor compared with those receiving a graft from an HLA-matched unrelated donor. Patients in the latter group show a higher incidence of infections and minor antigen mismatches which may promote the development of a diverse immunoglobulin repertoire post-BMT.

[Hepatic regeneration in the rat after subtotal (90%) hepatectomy treated with testosterone]. / Régénération hépatique chez le rat après hépatectomie subtotale (90%) traité à la testostérone.

A single dose (120 mg/kg IM) of testosterone administered 1 month before subtotal hepatectomy (90%) in Rats, reduced liver steatosis and allowed complete liver regeneration.