PubMed Health⌕ Search

Biomedical subjects

M Waer

Publications and source records attributed to M Waer.

At least 127 records · Page 7Linked to original sources
PubMed1992

Bilateral nephrectomy of the native kidneys reduces the incidence of arterial hypertension and erythrocytosis in kidney graft recipients treated with cyclosporin. Leuven Collaborative Group for Transplantation.

Since the use of cyclosporin (CsA) the incidence of post-transplant arterial hypertension and erythrocytosis has increased sharply. In a retrospective analysis of 707 consecutive first cadaveric kidney graft recipients treated with CsA as basic immunosuppression, the effect of bilateral native nephrectomy on arterial hypertension and erythrocytosis was studied. Patient and graft survival as well as kidney function of the 264 nephrectomized patients were identical to those of the 443 non-nephrectomized patients. In the nephrectomized patients the mean number of rejections during the first year was 0.62 +/- 0.88 versus 0.78 +/- 1.02 in the non-nephrectomized patients (P = 0.0285). At 1 year after transplantation, 65.8% of the non-nephrectomized patients needed hypotensive drugs versus 45.3% of the nephrectomized patients (P < 0.0001). Notwithstanding the use of more antihypertensive drugs, diastolic blood pressure in the former group was significantly higher than in the latter group (87 +/- 25 versus 83 +/- 10 mmHg; P < 0.02). During the first year 44 (9.9%) of the non-nephrectomized patients had haemoglobin levels higher than 17 g/dl versus only six (2.3%) of the nephrectomized patients (P < 0.0001). Comparable differences were also found up to 5 years after transplantation. These findings indicate that native nephrectomy is helpful in controlling arterial hypertension and erythrocytosis.

Blood Pressure↗
PubMed1992

Factors involved in peripheral T cell tolerance: the extent of clonal deletion or clonal anergy depends on the age of the tolerized lymphocytes.

After injection of SEB (staphylococcus enterotoxin B), normal adult mice, or thymectomized irradiated mice (TX irr.) reconstituted with lymphocytes taken from normal adult mice became specifically tolerant of SEB. At the same time the percentage of Vbeta8 positive CD4 lymphocytes known to be responsive to SEB was almost 50% decreased, indicating that a high level of clonal deletion was realized. In contrast, mice with an exclusively old T cell compartment (old thymectomized mice, TX irr. mice reconstituted several months previously) became tolerant of SEB without deleting their Vbeta8 + CD4 + cells, indicating that clonal anergy was the major mechanism in play in the induction of tolerance. Finally, TX irr. mice reconstituted with single positive thymocytes known to become recent thymic emigrants developed tolerance for SEB together with a high level (70%) of clonal deletion. Altogether these results indicated that the mechanism involved in peripheral tolerance depended on the age of the lymphocyte: very young lymphocytes underwent mainly clonal deletion whereas long lived lymphocytes underwent predominantly clonal anergy.

Animals↗
PubMed1992

Purulent meningitis due to aspergillosis in a patient with systemic lupus erythematosus.

We report a 39-year-old female patient with systemic lupus erythematosus under immunosuppressive therapy who developed persistent neutrophilic meningitis, for which no infectious agent could be identified. Intensifying the immunosuppressive therapy induced a short amelioration of the clinical picture. At autopsy, basal meningitis was found to be due to Aspergillus sp.

Adult↗
PubMed1992

The influence of neonatal thymectomy on the development of radiation myelopathy in rats.

To investigate the possible contribution of cellular immunity in the development of radiation injury of the central nervous system, Wag/Rij rats were thymectomized at birth and irradiated to the cervical spinal cord at the age of 3 months. At the time of paralysis or at the end of the follow-up period (when rats were 1-year-old) the animals were sacrificed and the mediastinum was examined histologically. In 95% of the neonatally thymectomized animals no thymus was left. These rats showed a firm impairment of the cellular immunity, as they had a 40% reduction of the T-lymphocytes in the spleen, and a 70% reduction of the mixed lymphocyte reaction, compared to age-matched controls. Both single dose and two-fraction irradiation experiments were performed. No modification of the latency time to develop paralysis was observed comparing thymectomized and age-matched controls. The incidence of foreleg paralysis after cervical spine irradiation (single dose or two-fraction) was identically distributed in the follow-up period for both neonatally thymectomized and control Wag/Rij rats. The ED50 value derived in the single dose experiments was 20.3 Gy for the control animals, and 20.9 Gy for thymectomized rats, and in the two fraction experiments 29 Gy for controls and 29.6 Gy for thymectomized rats. None of these differences are significant. It appears that neonatal thymectomy, in spite of its firm suppression of the cellular immunity, has no major influence on the development of radiation myelopathy in rats.

Animals↗
PubMed1992

Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T cells and decrease of "naive" (CD4-CD45R) T lymphocytes.

Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or "memory" T cells recovered completely, while the CD4-45R or "naive" T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells ("activated" T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. We propose that the recovery of the CD4 cells is limited to the CD4-w29 ("memory") population because of thymic dysfunction in older humans. The impact of the observed immune modulation on the low susceptibility for infections after local irradiation, and on putative antitumour immune responses is discussed.

Adult↗
PubMed1992

The natural killer activity of peritoneal fluid lymphocytes is decreased in women with endometriosis.

OBJECTIVE: To investigate the local natural killer (NK) activity of the peritoneal fluid mononuclear cells (PFMC). DESIGN PATIENTS: In a prospective way, the NK activity (K562-assay) was measured in peripheral blood (PB) and peritoneal fluid (PF) of 44 women who underwent a laparoscopy for infertility and/or pain at the University Hospital of Gasthuisberg, Leuven, Belgium. MAIN OUTCOME MEASURE: The NK activity of peripheral blood mononuclear cells and PFMC, the number and concentration of PFMC, the percentage of lymphocytes versus macrophages by May-Grünwald-Giemsa staining and the estradiol and progesterone concentration of the PF were correlated together and with the severity of endometriosis. RESULTS: We demonstrated that there is a significant NK activity in PF and that this activity is decreased in women with endometriosis. This defect was more pronounced in the follicular phase of the cycle compared with the postovulatory phase. In PB of the same 44 women, the decreased NK activity correlated with the severity of the disease. This confirms our previous report on another 34 women. CONCLUSIONS: The NK activity is decreased in women with endometriosis and correlated significantly with the severity of the disease in both the PB and PF of women with endometriosis.

Ascitic Fluid↗
PubMed1992

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↗
PubMed1992

1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice.

The active form of vitamin D, 1,25(OH)2D3, can prevent various forms of experimentally induced autoimmune disorders. The aim of this study was to confirm these findings in NOD mice that spontaneously develop an autoimmune type of diabetes mellitus. Therefore, the effect of a long-term 1,25(OH)2D3 treatment on the incidence of insulitis, the histological lesion preceding diabetes, was studied. Forty-three NOD mice were treated with 1,25(OH)2D3 (5 micrograms/kg) i.p. every other day from age 21 days on, when no insulitis was present yet. At day 100, 16 control mice receiving the treatment vehicle (arachis oil) had an incidence of insulitis of 75%, whereas only 41% of the 1,25(OH)2D3-treated animals developed insulitis (P < 0.025). Calcemia, determined 24 h after the last 1,25(OH)2D3 injection was 2.5 +/- 0.1 mM, which was higher than in control animals (2.3 +/- 0.1 mM), but was well tolerated. Cellular immunity, as assessed with the mixed lymphocyte reaction performed at day 100, was not impaired significantly. This study demonstrates that long-term treatment with high doses of 1,25(OH)2D3 is able to decrease the incidence of insulitis in spontaneous autoimmune diabetes without major side effects.

Animals↗
PubMed1991

A subset of asialo GM1+ cells play a protective role in the occurrence of graft-versus-host disease in mice.

In three different murine models of bone marrow (BM) transplantation the capacity of asialo GM1+ cells to suppress graft-vs-host disease (GVHD) was investigated. In a first model, total lymphoid irradiation (TLI)-treated BALB/C mice were given 1 mg of anti-asialo GM1 antibody. This led to the disappearance of functional suppressor cells after TLI. Injections of anti-asialo GM1 into TLI-treated BALB/C mice before infusion of 30 x 10(6) fully allogeneic (C3H) BM cells, led to a significantly decreased survival rate as compared to TLI-treated mice injected with control serum before BM transplantation (survival 29 and 83%, respectively, at 120 days after transplantation, p = 0.0032 log rank). The mortality of the former group was due to GVHD as 1 degree all dying animals showed clinical and histologic signs of GVHD, 2 degrees all animals were chimeric and 3 degrees mice receiving no or syngeneic BALB/C BM had excellent survival rates excluding BM aplasia or increased susceptibility for infections as reason for the mortality of the allogeneic BM recipients. In a second model, asialo GM1+ cells were removed in vitro from the C3H BM inoculum before injection into lethally irradiated (9 Gy) BALB/C recipients. In mice kept in specific pathogen-free conditions, this procedure resulted into a significant mortality (12/12) as compared to mice receiving BM pretreated with control serum (1/12, p = 0.0001 log rank). When kept in conventional housing, GVHD occurred in both groups but much earlier in the group receiving anti-asialo GM1-treated BM (median survival time 6 vs 46 days for the control mice, p = 0.001 log rank). No animal receiving anti-asialo GM1 and treated with syngeneic BM died, thus excluding toxicity, increased susceptibility to infections, or decreased graft take as a cause of mortality. In a last model, asialo GM1 cells were removed from syngeneic BM in a BM transplantation model in which T cell-depleted syngeneic (BALB/C) and non-T cell-depleted allogeneic (C3H) BM was administered to lethally irradiated (9 Gy) BALB/C mice. Also in this model GVHD-related mortality only occurred in the group of mice receiving syngeneic BM from which asialo GM+ cells were depleted before infusion (3/12). Our experiments thus clearly show that asialo GM1+ cells from both recipient (the TLI model) as well as donor origin (the TBI experiments) can suppress the occurrence of GVHD.

Animals↗
PubMed1991

Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium.

OBJECTIVE: The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, PATIENTS: Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. MAIN OUTCOME MEASURE: The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. RESULTS: The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. CONCLUSION: The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.

Chromium Radioisotopes↗