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Biomedical subjects

J D Bignon

Publications and source records attributed to J D Bignon.

At least 73 records · Page 4Linked to original sources

Lymphocyte subsets, phytohaemagglutinin responsiveness of blood lymphocytes, and interleukin 2 production in sarcoidosis.

To test the possibility that T lymphocyte subset imbalance and interleukin 2 (IL2) play a part in the impairment of cellular immune response in sarcoidosis, the proportion of T lymphocyte subsets in peripheral blood and alveolar lavage fluid from 21 patients with sarcoidosis was studied, monoclonal antibodies OKT3, OKT4, and OKT8 being used. Lectin induced production of IL2 and phytohaemagglutinin (PHA) responsiveness of peripheral blood lymphocytes were investigated. The percentage of both OKT3+ and OKT4+ T lymphocytes was significantly lower in peripheral blood from patients with sarcoidosis than in control subjects (control 63% and 46%), more so in patients with chronic sarcoidosis (44% and 23%) than in patients with recent sarcoidosis (56% and 38%). PHA induced IL2 production from peripheral blood lymphocytes did not differ between patients with sarcoidosis and control subjects. There was a significant positive correlation between PHA responsiveness and the percentage of blood OKT3+ and OKT4+ cells. Peripheral blood lymphocyte PHA responsiveness was decreased only in patients with an OKT4/OKT8 ratio of less than 1.5. Finally, late addition of exogenous IL2 to the culture medium on day 5 increased 3(H)Tdr incorporation by PHA stimulated blasts in peripheral blood lymphocytes from normal subjects, but not from those of patients with sarcoidosis. The data suggest that the impairment of cellular immune response in patients with sarcoidosis could in part reflect a decrease in the percentage of blood T helper lymphocytes and impaired IL2 receptors at the surface of stimulated lymphocytes.

Adult↗

Preparative two-step purification of human IL-2 by HPLC and hydrophobic affinity chromatography.

Interleukin 2 (IL-2) has been purified by a protocol using gel filtration high performance liquid chromatography (HPLC) and hydrophobic affinity chromatography with blue-trisacryl M. Peripheral blood lymphocytes or tonsillar lymphocytes were stimulated with phytohemagglutinin (PHA). Serum free conditioned medium (CM) containing IL-2, other lymphokines and residual PHA molecules was analyzed after 3 variations of ammonium sulfate (AS) precipitation: (1) precipitation of CM with 50% AS yielded a precipitate containing most of the residual PHA but also a fraction of IL-2. (2) Precipitation with direct 80% AS of crude CM yielded both IL-2 and residual PHA. (3) A double step procedure (50% AS followed by 80% AS) yielded a precipitate containing IL-2 but free of residual lectin. HPLC purification of these various AS-precipitated materials or of lyophilized crude CM yielded 2 peaks with mitogenic activity as assayed with the CTLL2 murine clone or IL-2-dependent human Con A-stimulated lymphoblasts. IFN was easily separated from IL-2 and PHA, but BCGF still copurified with IL-2. Peak I (25 kDa) was enriched 400-fold for IL-2 while peak II (68 kDa) contained the residual PHA. The IL-2-containing fractions eluted from HPLC were further purified by blue-trisacryl M chromatography. The IL-2 eluted with 0.4 M NaCl. The entire protocol (HPLC followed by blue-trisacryl) led routinely to 8000-fold IL-2 enrichment. Preparative HPLC directly applied to lyophilized crude (CM) enriched IL-2 activity 400-fold with yield averaging 60% of the IL-2 input. The final material was free from interferon and IL-1, but BCGF still copurified with IL-2. The 2-step purified material (HPLC and blue-trisacryl) gave 2 bands in SDS-PAGE both of which contained IL-2.

Ammonium Sulfate↗

Influence of HLA-A, B, and DR matching on the outcome of kidney transplant survival in preimmunized patients.

The outcome of 893 prospectively typed (HLA-A, B, and DR) and matched cadaveric kidney transplants--all first grafts, with patients being transfused before transplantation--was studied using actuarial survival methods. The effect of HLA-A, B and DR matching was only found to be significantly beneficial to graft survival in the group of 289 presensitized recipients: 70% and 43% graft survival at two years in the case of best-matched (4-6 HLA-A, B, and DR) identities versus mismatched (0 and 1 HLA-A, B, and DR) identities, respectively (P = 0.05). Although a cumulative effect of matching for antigens belonging to the 3 HLA-A, B, and DR series was observed among the group of preimmunized recipients, a trend arose in favor of the prominent role of the HLA-B alleles. No significant difference related to HLA matching was observed in the group of nonsensitized recipients. These results confirm previous observations and support efforts to give priority for matched kidneys to preimmunized patients.

Actuarial Analysis↗

HLA DR4 and giant cell arteritis.

We reported the data of HLA-DR frequencies in a new series of 40 unrelated patients suffering from giant cells arteritis (Horton's disease). As previously reported by us, a large increase of HLA-DR4 antigen frequency is noted in patients compared with 146 healthy controls. Moreover, gathering together these 40 patients with the 48 other patients of our first published data, increase of the DR4 frequency is largely confirmed with a Pc less than 0.001.

Arteritis↗

[Populations of circulating T lymphocytes in patients with alcoholic cirrhosis].

The characteristics, the origin and the role in the determinism and/or in the course of hepatocellular necrosis of immune disorders in patients with alcoholic liver cirrhosis still remain unclear. In this study, the T-lymphocyte population was determined by sheep-rosette formation and labelling with OKT3-monoclonal antibodies. T-cell subsets were investigated using OKT4 and OKT8 monoclonal antibodies in the peripheral blood of 40 alcoholic patients with cirrhosis (CA) and of 23 non-cirrhotic alcoholic (ANC) patients. The results were compared to those in 34 healthy volunteers. A decrease in the percentage of T-lymphocytes in the two groups of alcoholic subjects was noted. However, this decrease was significant only in the CA group and only when OKT3 antibodies were used as markers. The lymphocyte-subset identified by OKT4 antibodies was decreased as well in the CA and ANC groups; however the OKT8+ subset was significantly decreased in the CA group only (p less than 0.001). No correlation was found between this decrease in OKT8+ subpopulation or between the increased OKT4/OKT8 ratio and all biochemical parameters of hepatic function measured in this study. The significance of this T-cell imbalance in CA has still to be elucidated, concerning both the functional activity of the reduced pool of OKT8+ cells (suppressor or cytotoxic?) and the mechanism of this decrease.

Adult↗

HLA-AB and -DR types in patients with infectious mononucleosis (IM).

The frequency of HLA-A, -B and -DR antigens in 48 infectious mononucleosis (IM) patients was studied and the antigen frequencies were compared with those of a local panel. The resulting data do not confirm the association of IM and HLA-B35 as reported in a previous work. A high and significant frequency of blank HLA-DR phenotypes was noticed in IM population during the acute phase, but HLA-DR phenotypic expression was restored after recovery. This lack of expression could be the result of modified HLA-DR expression on circulating EBV infected B lymphocytes.

Adolescent↗

Plasma exchange in early kidney graft rejection associated with anti-donor antibodies.

Patients with early rejection of kidney allografts associated with anti-donor antibodies have been randomized in two groups which received, respectively, either the conventional corticosteroid/azathioprine treatment or extensive plasma exchanges (PE) plus the conventional treatment. Data on the monitoring of anti-T or anti-B donor lymphocytes, as well as anti-panel or autoreactive cytotoxicity are described. Although the titer of anti-donor antibodies is decreased in the PE-treated group there is no sustained improvement of graft function compared to the control group. Thus, in these stereotyped rejection episodes, which are likely to be antibody mediated, there is no significant effect of extensive and early plasma exchange.

Antibodies↗

[Effects of blood transfusions on kidney transplants].

In a retrospective study involving 24 transplantation centres and 858 cadaveric kidney recipients, a number of transfusion factors affecting transplant survival were identified. The best results were observed with the most intensive transfusion schedules including at least one transfusion per month. The optimal number of transfusions varied from 6 to 20. However, it was impossible to determine whether a minimal interval was required between the last perfusion and transplantation, or whether the effect of each transfusion was limited in time. Qualitatively, it appeared that whole blood and packed red cells gave better results than leucocyte-deprived blood. Moreover, fresh blood taken less than 3 days before the transfusion clearly proved more effective than blood stored for more than 5 days. All this suggests that live leucocytes and platelets may be important factors. The mechanism by which blood transfusions improve the outcome of kidney transplants remains unknown.

Blood Transfusion↗

HLA antigens and Berger's disease.

We have studied the frequencies of HLA-A, -B antigens in 73 Berger's disease patients, plus HLA-DR antigens in 35 of them, and compared the percentages of antigens frequencies with those of a local and national panel. This study does not confirm the positive associations with HLA-Bw35 or HLA-B12 which have been previously reported. The HLA-DR typing only showed increased frequency of blanks in the patients (P smaller than 0.01, but no significant corr.P). Patients with Berger's disease and renal failure have a higher (but still not significant) HLA-Bw35 frequency than those without renal failure. The reasons for the discrepancy between our group and others are analysed.

Glomerulonephritis↗

Systematic transfusion in hemodialyzed patients awaiting grafts: kinetics of anti-t and b lymphocyte immunization and its incidence on graft function.

Since June 1977, a systematic blood transfusion (BT) policy (160 ml of leukocyte-poor washed erythrocytes given every 6 months) has been applied to 126 hemodialyzed patients awaiting a first kidney graft. Only patients who had anti-T or B lymphocyte (T or BLY) antibodies (Ab) killing fewer than 10 or 20% of the panel cells, respectively, entered the protocol. Screening of anti-T and BLY was performed 8, 15, and 21 days after each BT. Patients were removed from the protocol if they developed Ab against more than 10 or 20% of the T or BLY panel cells. The cumulative immunization (all Ab types) averaged 90% after four BTs. Anti-BLY (63%) were more frequent than anti-TLY (49%) after for BTs. No anti-HLA-DR specificity could be attributed to the anti-BLY, whereas 20% of the anti-TLY displayed a particular anti-HLA-A,B specificity. Patients that had had BTs or pregnancies before entering the protocol had a higher degree of immunization. The kinetics of the anti-B or TLY pattern differed greatly both at the level of their detection after 8, 15, and 21 days following one BT and in their development after repeated BTs. Forty-three patients received transplants at various stages of the protocol. Recipients grafted without Ab had the best graft outcome (87 versus 66 actuarial percentage at 3 months), even though their HLA (A,B and DR) matching was inferior. There was no significant difference in recipients who had different subgroups of Ab. These data indicate that immunization is very high even after a few BTs when careful controls are performed and they suggest that BTs do not act via active enhancement.

Antilymphocyte Serum↗

[A further case of albumin auto-agglutination in a blood donor].

A blood donor is described whose serum contains an albumin active agglutinin reacting with autologous as well as normal donors red cells. Natrium caprylate present in some commercial albumin preparations is show to be co-responsible for this unusual reaction which cause difficulties or errors in Rh grouping.

Adult↗