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M Waer

Publications and source records attributed to M Waer.

At least 109 records · Page 6Linked to original sources

The influence of donor age on initial and long-term renal allograft outcome. Leuven Collaborative Group for Transplantation.

To investigate the impact of donor age on the immediate and long-term graft outcome, 808 primary cadaveric renal allograft recipients, transplanted between January 1983 and December 1992, were divided into six groups according to donor age: 10-19 years (n = 142), 20-29 years (n = 214), 30-39 years (n = 136), 40-49 years (n = 146), 50-59 years (n = 142), 60-69 years (n = 28). The six groups were comparable with regard to donor origin (local/distant), serum creatinine, cold ischemia and reanastomosis time, recipient sex, degree of presensitization, number of pretransplant blood transfusions, number of HLA-B and B/DR mismatches. The incidence of delayed graft function was linearly correlated with increasing donor age, from 11.9% (donors 10-19 years) to 39.3% (donors 60-69 years) (P<0.0001). Graft survival at 3 years was not influenced by donor age (from 89.3% for the youngest donors to 84.4% for donors 60-69 years). After the 3rd decade, the creatinine clearance linearly decreased with donor age (6.2 ml/min, P < 0.01). This progressive decline could not be attributed to the recipient age (-7 ml/decade for 485 recipients < 50 years, and -6.1 ml/decade for 323 patients > or = 50 years). Despite the decreased function in older kidneys, recipient renal function remained remarkably stable between 1 and 3 years after transplantation within each donor age group.

Adolescent↗

Clonal deletion and clonal anergy in allogeneic bone marrow chimeras prepared with TBI or TLI.

The evolution of Vbeta6-expressing C3H (H2k, Thy 1.2, Mls a-) lymphocytes was investigated in C3H recipients mice pretreated with total body irradiation (TBI) or total lymphoid irradiation (TLI) and infusion of AKR (H2k, Thy 1.1, Mls a+) cells. After TBI (9.5 Gy) all Vbeta6+ Thy 1.2 (C3H) cells, which are capable of reacting against the Mls a antigen that like expressed by AKR mice, were deleted in the thymus and the periphery in stable bone marrow (BM) chimeras obtained by infusion of 5 x 10(6) T-cell-depleted (TCD) AKR BM cells. When, in the opposite combination, 30 x 10(6) C3H spleen cells were infused into TBI-treated AKR cells, all animals developed graft-versus-host disease (GVHD) with no clonal deletion and in contrast, showed an increase in Vbeta6+ C3H cells. After injection of 30 x 10(6) AKR BM cells into TLI-treated C3H mice no C3H cells were detected in the thymus and only a small percentage in the periphery. Within these C3H cells Vbeta6+ cells were only partially deleted and anergized as they did not respond in vitro after stimulation with Mls a+ AKR cells or anti-Vbeta6 mAb. Cells suppressing anti-Mls a-reacting C3H cells were not found. After injection of 15 x 10(6) AKR cells more C3H cells were found in the thymus, but only a minority of Vbeta6+ cells persisted in the periphery of these animals. In conclusion in TBI-prepared chimeras only clonal deletion occurred, whereas in TLI-prepared chimeras both clonal deletion and anergy occurred in maintaining tolerance.

Animals↗

Flow cytometry analysis of lymphocyte subpopulations in peritoneal fluid of women with endometriosis.

PROBLEM: We investigated the lymphocyte subpopulations in peripheral blood (PB) and peritoneal fluid (PF) of women with and without endometriosis to evaluate if the decreased natural killer (NK)-mediated cytotoxicity in women with endometriosis was due to a quantitative defect or not. METHOD: The PB and PF mononuclear cells of 59 women undergoing a diagnostic laparoscopy for pain and/or infertility were analyzed by flow cytometry. RESULTS: The number and concentration of PF mononuclear cells (MC) was increased in women with endometriosis compared to women without endometriosis. The monocyte/macrophage marker (CD14) was expressed on 70.3 and 66.9% of PFMC of women with and without endometriosis, respectively. The CD4/CD8 ratio was inverted in the PF, and this was more pronounced in women with endometriosis. In the PF of women with endometriosis, 41.3% of the lymphocytes were CD8 positive, compared to 34.3% in women without endometriosis. The percentage of NK positive lymphocytes in PF, using three different monoclonal antibodies directed against NK cell markers (CD57, CD16, and CD56) were not different between women with and without endometriosis. In women with endometriosis, 12.7, 9.5, and 28.8% of lymphocytes were CD57, CD16, and CD56 positive, respectively. CONCLUSION: PFMC consisted mainly of phagocytic and human leukocyte antigen (HLA)-restricted or HLA unrestricted cytotoxic cells capable of reacting to various antigens entering the cavity from the lower genital tractus. Furthermore, the decreased NK activity reported in PB and PF of women with endometriosis was not likely to be caused by a quantitative defect, since the percentage of NK positive lymphocytes was not different between women with and without endometriosis.

Ascitic Fluid↗

Lymphokine-activated killer activity in women with endometriosis.

The aim of the present study was to investigate whether women with endometriosis displayed a decreased lymphokine-activated killer (LAK) activity. In 15 women with and 7 women without endometriosis the cytotoxicity against four different tumor cell lines--K562, the endometrium carcinomas AN3CA and RL95, the natural-killer (NK)-resistant Daudi cell line--was investigated, using either freshly isolated peripheral blood mononuclear cells (PBMC) or recombinant interleukin (IL)-2-stimulated PBMC. In 5 additional women collagenase-DNase-digested endometrium was used, to investigate whether recombinant IL-2-activated lymphocytes displayed an increased cytotoxicity against fresh and cultured endometrial cells. The cytotoxicity of unstimulated PBMC toward K562, AN3CA and RL95 target cells was decreased in women with endometriosis compared to women without endometriosis (p < 0.05, for all). After recombinant IL-2 stimulation the cytotoxicity toward the four different target cells increased significantly, both in women with and without endometriosis. There was no difference in LAK-mediated cytotoxicity against the four tumoral cells between women with and without endometriosis. Significant LAK activity was demonstrated against both fresh and cultured (72 h) endometrial cells. The cytotoxicity of autologous lymphocytes against cultured endometrial cells was 31.0 +/- 17 versus 67.4 +/- 5.8%, using lymphocytes cultured in medium without and with recombinant IL-2, respectively (paired t test, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

CO2-laser excision of endometriosis does not improve the decreased natural killer activity.

OBJECTIVE: We recently described a decreased lymphocyte-mediated cytotoxicity to autologous endometrium and to natural killer-sensitive targets in women with endometriosis. The purpose of the present study was to investigate whether the defect remained after CO2-laser excision of the endometriotic lesions. DESIGN: In 15 women with endometriosis the cytotoxicity assays were performed before and three to four months after complete removal of the endometriotic lesions with CO2-laser excision. CA-125 serum levels were measured before and after laser laparoscopy, in order to confirm that endometriosis had been treated properly. RESULTS: After removal of the endometriotic lesions the decreased natural killer activity (K562-assay) and the impaired cytotoxicity of autologous and even heterologous lymphocytes to the endometrium remained unchanged, and those cytotoxicity assays were still significantly decreased compared to the women without endometriosis. CA-125 serum concentrations, however, were still significantly decreased three to four months after CO2-laser excision of the endometriosis. (paired Student's t-test p < 0.007). CONCLUSIONS: These data suggest a primary deficiency in natural killer activity in women with endometriosis and are in accordance with our clinical experience as endometriosis is relapsing frequently after treatment.

Carbon Dioxide↗

Transforming growth factor-beta activity is increased in peritoneal fluid from women with endometriosis.

OBJECTIVE: To investigate the presence of transforming growth factor-beta in peritoneal fluid of women with and without endometriosis. METHODS: Fifty-two peritoneal fluid samples, obtained during laparoscopies performed for tubal ligation (n = 10), infertility (n = 38), or pain (n = 4), were examined for the presence of transforming growth factor-beta using the Mv1Lu cell growth inhibition assay. At laparoscopy, 26 women had endometriosis. The other 26 women had no endometriosis; 16 of them had infertility, and ten who had no pelvic pathology at tubal sterilization served as fertile controls. RESULTS: The concentration of transforming growth factor-beta was increased in the peritoneal fluid from women with endometriosis (11.4 +/- 3.3 ng/mL) compared to both the fertile control group without endometriosis (1.1 +/- 0.29 ng/mL) and the infertile control group without endometriosis (3.6 +/- 1.4 ng/mL). Twenty-five of the 52 women (48%) demonstrated levels of transforming growth factor-beta higher than 2 ng/mL. Patients with endometriosis were significantly more likely to have elevated concentrations of transforming growth factor-beta than were women without endometriosis (16 of 26, 61.5%, versus nine of 26, 34.6%). CONCLUSIONS: These findings demonstrate the presence of transforming growth factor-beta in peritoneal fluid. Elevated levels in women with endometriosis could be important in the pathophysiology of this disease.

Ascitic Fluid↗

Immunohistochemical characterization of leucocyte subpopulations in endometriotic lesions.

Leucocyte subpopulations localized in endometriotic lesions were analysed using the avidin-biotin immunoperoxidase technique on 15 biopsies obtained by CO2 laser excision. Qualitative assessment of the leucocyte subpopulations was performed with a panel of antihuman monoclonal antibodies for leucocytes (anti-Hle-1), T-lymphocytes (anti-leu-4), T helper/inducer (anti-leu-3a), T suppressor/cytotoxic (anti-leu-2a), B cells (anti-leu-12), HLA-DR (anti-HLA-DR), macrophages (anti-leu-M3) and natural killer cells (anti-leu-7, anti-leu-11; anti-leu-19). Leucocyte common antigen (anti-Hle-1)-positive cells were present in all lesions and were the most frequent stromal leucocytes. Of these, the T lymphocytes are the most frequent subpopulation together with the macrophages. The CD4/CD8 ratio was 0.78. No anti-leu-7 and/or anti-leu-11-positive cells were found although a substantial amount of anti-leu-19-positive cells were found in each lesion. There were very few B cells present in the ectopic endometrial lesions. In conclusion, an important amount of cytotoxic lymphocytes (anti-leu-2a -and anti-leu-19-positive cells) and macrophages (anti-leu-M3) were found in the endometriotic lesions. The possible importance of these intraendometriotic leucocytes for the pathophysiology of endometriosis will be discussed.

Antibodies, Monoclonal↗

Lack of disease recurrence in diabetic BB/Pfd rats after syngeneic islet transplantation.

Restimulation of autoreactivity in two different BB rat sublines of the same origin (Ottawa, Canada) was investigated by syngeneic islet transplantation into diabetic animals. Despite identical methods and conditions recurrence of hyperglycaemia was observed in BB/OK rats (Karlsburg, Germany) but not in BB/Pfd rats (Leuven, Belgium). Pancreatic morphology at the time of transplantation revealed significant differences in islet volume density and the degree of insulitis. Additionally, marked differences in the phenotypical composition of cells infiltrating the islets were observed. A loss of autoimmune memory in BB/Pfd rats is discussed as a probable reason for the lack of disease recurrence in those animals.

Animals↗

Immunosuppressive activity of peritoneal fluid in women with endometriosis.

OBJECTIVE: To investigate the immunosuppressive effect of peritoneal fluid and follicular fluid on both natural killer-mediated cytotoxicity and phytohemagglutinin-induced lymphocyte proliferation. METHODS: The peritoneal fluid of women with endometriosis was compared to both fertile and infertile control fluids. Lymphocytes were pretreated for 2 or 20 hours with peritoneal or follicular fluids, and their cytotoxicity toward K562 tumor cells was measured. We also investigated the phytohemagglutinin-induced stimulation of lymphocytes cocultured with peritoneal or follicular fluid. RESULTS: Peritoneal fluid from women with endometriosis had a significantly greater immunosuppressive effect on natural killer-mediated cytotoxicity and on phytohemagglutinin stimulation of lymphocytes compared to peritoneal fluid of fertile women without endometriosis (P < .01 and P < .05, respectively). Using the peritoneal fluid of infertile women without endometriosis, these differences were significant only when compared to women with severe endometriosis. Inhibition of the natural killer activity increased when the incubation period was prolonged from 2 to 20 hours (P < .04). There was no correlation between the immunosuppressive effect of peritoneal fluid and the volume of peritoneal fluid, the day of the menstrual period, or estradiol, progesterone, prostaglandin E2, or prostaglandin F2 alpha levels. In peritoneal fluid, the factor responsible for inhibition of natural killer activity was not removed with charcoal treatment. In follicular fluid, on the other hand, the inhibition of natural killer activity decreased significantly after treatment with charcoal. CONCLUSION: Natural killer activity is suppressed by the peritoneal fluid of women with severe endometriosis; this may be important in the pathogenesis of endometriosis. The factor responsible for the inhibition of natural killer activity in peritoneal fluid is different from that in follicular fluid.

Ascitic Fluid↗