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Biomedical subjects

P Michielsen

Publications and source records attributed to P Michielsen.

At least 19 recordsLinked to original sources

Evidence that stimulator cell-derived IL-6 and IL-1 are released in the mixed lymphocyte culture but are not requisite for responder T cell proliferation.

We investigated whether IL-6 and (or) IL-1 are crucial costimulatory signals in the human MLC with purified responder T cells. With allogeneic PBMC as stimulators, IL-6 and IL-1 were rapidly produced, and reached plateau values of 100-300 U/ml and 200-500 pg/ml after 24 hr, respectively. Irradiated or mitomycin-c treated PBMC could easily be induced (with LPS) to produce IL-6 and IL-1 while no activity was measured after 48 hr in the supernatant of PHA-stimulated T cells, suggesting that in the MLC the monokines were entirely produced by stimulator PBMC. In cultures of responder T cells and stimulator B cells, no IL-6 and IL-1 activity was measured in the supernatant, and only a marginal proliferative response was found. Exogenous IL-6 and IL-1 increased in a dose-dependent way the B-cell-induced alloresponse and induced significant cytotoxicity in the responder cells. Antisera to IL-6 and IL-1 totally inhibited the induced response. The proliferation was accompanied by increased IL-2 production and IL-2R expression. Preincubation of B cells with IL-6 and IL-1 did not improve the proliferation, suggesting direct effects of IL-6 and IL-1 on the T cells. The proliferative responses induced by B cells and exogenous IL-6 and IL-1 represented a fraction of those induced by PBMC. Moreover, in PBMC-stimulated cultures exogenous IL-6 and IL-1 or antisera to these lymphokines did not significantly alter proliferative responses, cytotoxicity, IL-2 levels in the supernatant, or IL-2R expression on responder T cells. We conclude that a role for IL-6 and IL-1 in allogeneic T cell stimulation can be demonstrated in conditions of suboptimal stimulation with B cells. With PBMC, neutralizing antisera to these cytokines do not seem to inhibit the proliferative response, suggesting that these cells are superior in alloantigen presentation either by producing various costimulatory signals or by the fact that due to cell-cell contact stimulator cell-derived monokines cannot be blocked. This finding makes it unlikely that antimonokine therapy will be useful in transplantation.

Adult

Characterization of the pea ENOD12B gene and expression analyses of the two ENOD12 genes in nodule, stem and flower tissue.

The ENOD12 gene family in pea consists of two different members. The cDNA clone, pPsENOD12, represents the PsENOD12A gene. The second ENOD12 gene, PsENOD12B, was selected from a genomic library using pPsENOD12 as a probe and this gene was sequenced and characterized. The coding regions of the two genes are strikingly similar. Both encode proteins having a signal peptide sequence and a region with pentapeptide units rich in prolines. ENOD12A has a series of rather conserved repeating pentapeptide units, whereas in ENOD12B the number of pentapeptide units is less and these are less conserved. From the amino acid sequence it is obvious that the PsENOD12 genes encode proline-rich proteins which are closely related to proteins that have been identified as components of soybean cell walls (SbPRPs). Previously, Northern blot analyses had shown that ENOD12 genes are expressed in a tissue-specific manner. A high expression level is found in Rhizobium-infected roots and in nodules, whereas expression in flower and stem is lower. This raised the question of which gene is expressed where and when. The availability of the sequences of both ENOD12 genes allowed us to analyse the expression of the two genes separately. Specific oligonucleotides were used to copy the ENOD12 mRNAs and to amplify the cDNAs in a polymerase chain reaction. It was demonstrated that in all the tissues containing ENOD12 mRNA, both genes PsENOD12A and PsENOD12B are transcribed and that the relative amounts of PsENOD12A and PsENOD12B mRNA within each tissue are more or less equal. Moreover, the expression pattern during infection and nodule development is the same for the two genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Angiotensin-converting-enzyme inhibitors and anaphylactoid reactions to high-flux membrane dialysis.

In a retrospective study, 9 of 236 haemodialysis patients treated with high-flux polyacrylonitrile 'AN 69' membranes were found to have had anaphylactoid reactions. Treatment with angiotensin-converting-enzyme (ACE) inhibitors had been recently started in all 9 affected patients; only 5 of 227 unaffected patients had been treated with ACE inhibitors, and anaphylactoid reactions disappeared after discontinuation of ACE inhibitors.

Adult

Growing bone cysts in long-term hemodialysis.

All patients with chronic renal failure undergoing hemodialysis for more than 10 years in the university hospitals of Leuven were selected for this study. The medical records and radiographs of these 21 patients were studied retrospectively. Skeletal surveys were examined for the presence and location of subchondral cysts. The predialysis films and the films taken after 5, 10, 15 and 20 years of dialysis were reviewed. Subchondral cysts that grew in size and number were found in the wrist, humeral head, hip, and patella. Accurate measurements were made of cysts in the wrist and compared with a control group. In the dialysis group, cystic involvement of the wrist was more common and the size and number of the cysts were larger. Soft tissue swelling was seen in the dialysis group but not in controls. Soft tissue swelling was assessed on shoulder radiographs by measuring the acromiohumeral distance (ACD) and in the knees by ultrasonic measurement of synovial thickness. In 11 patients synovial or bone biopsies or aspirated synovial fluid were available. All these patients had swollen joints and multiple subchondral periarticular cysts. Amyloid deposition was found in ten of these patients, and this proved to be composed of B2 microglobulins in seven.

Amyloidosis

Azathioprine hypersensitivity in a renal transplant recipient.

Hypersensitive reactions to azathioprine have been reported infrequently, and always in nontransplanted patients. Here, a renal transplant recipient with a severe hypersensitive reaction to azathioprine is described. We suggest that, until recently, hypersensitivity to azathioprine was suppressed in transplant recipients by the association of high doses of corticosteroids. Since the introduction of cyclosporin, azathioprine therapy is usually associated with corticosteroids in a much lower dose, so an increasing occurrence of azathioprine hypersensitivity in transplanted patients might be expected.

Adult

Induction of mixed lymphocyte reaction nonresponsiveness after chimeric thymus transplantation.

Discussion still continues regarding whether self-tolerance is imparted within the thymus by the thymic epithelial cells (TEC) or by the bone marrow-derived (BMD) dendritic cells and macrophages. Many experiments suggest that BMD cells may be the major cells responsible for inducing tolerance within the thymus. In order to address this question and to see whether thymus chimerism could play a role in establishing transplantation tolerance, we looked in the present experiments at the induction of in vitro tolerance after transplantation of chimeric thymuses. Chimeric thymuses were constructed by injecting T-depleted C3H (H2k) bone marrow into lethally irradiated BALB/c (H2d) mice and were thus composed of TEC of BALB/c and BMD cells of C3H origin, something which was verified with immunoperoxidase staining. Subsequently, chimeric thymuses were transplanted into thymectomized BALB/c mice that were lethally irradiated and reconstituted with T-depleted syngeneic BALB/c bone marrow. In 8 out of 11 BALB/c mice this procedure was successful, and in all chimeric thymus graft-bearing mice, specific tolerance for C3H (H2k) antigens was documented in the mixed lymphocyte reaction (MLR). These experiments thus show that: (1) immunological tolerance can be imparted by BMD cells in the thymus and (2) the presence of chimerism within the thymus could be one of the mechanisms involved in the establishment or maintenance of transplantation tolerance.

Animals

Efficacy of interferon alfa-2b with or without prednisone withdrawal in the treatment of chronic viral hepatitis B. A prospective double-blind Belgian-Dutch study.

A prospective, double-blind study was carried out to assess the efficacy of interferon alfa-2b, with or without pre-treatment prednisone withdrawal, in patients with chronic hepatitis B. A total of 57 Belgian and Dutch patients were included in the study. Patients were divided into four treatment groups: Group A, prednisone withdrawal followed by interferon 5 million units per day; Groups B and C, placebo followed by interferon 5 or 1 million units, respectively; and Group D, untreated controls followed for 1 year. All treated patients received interferon for 16 weeks. Two of the 14 control patients lost hepatitis B e antigen during the year of study, and only one of 15 patients in the interferon 1 million units group. Among the 28 patients receiving 5 million units of interferon (with or without prednisone withdrawal), ten (36%) cleared hepatitis B e antigen during the study or within 6 months of the end of therapy. This was associated with a marked improvement in serum transaminase levels. When comparing Groups A and B, it was found that prednisone withdrawal therapy enhanced the response to interferon in patients with pre-treatment serum alanine aminotransferase levels below 100 IU/l, bringing the seroconversion rate up to 50%, compared to 17% on interferon alone. This effect was not seen in patients with high pre-treatment transaminase levels. All treatment responders showed a marked improvement in Knodell index score, whereas in the 15 non-responders from groups A and B, overall inflammatory activity remained the same in six, improved in five and worsened in four.(ABSTRACT TRUNCATED AT 250 WORDS)

Belgium