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Biomedical subjects

M Waer

Publications and source records attributed to M Waer.

At least 181 records · Page 10Linked to original sources
PubMed1985

Treatment of cadaveric renal transplant recipients with total lymphoid irradiation, antithymocyte globulin, and low-dose prednisone.

The ability of preoperative total lymphoid irradiation (TLI) to reduce the need for chronic immunosuppression after cadaveric renal transplantation was examined in 25 recipients who were given a brief course of antithymocyte globulin (ATG) postoperatively with daily low-dose prednisone (0.1-0.2 mg/kg) as the sole maintenance immunosuppressive drug. Patients were selected for the study on the basis of their low levels of cytotoxic antibodies. Grafts were not HLA-matched, and the mean interval between completion of TLI and transplantation was 9 days. During an observation period of up to 25 months, 2 grafts were lost because of rejection. There were two deaths due to disseminated viral infections and two to late cardiovascular complications. At the last observation point, the mean serum creatinine of the 19 patients with functioning grafts was 1.5 mg/dl, and the mean dose of prednisone was 10.2 mg/day. 10 of these patients did not have a rejection episode. Comparison of patients given TLI with a group given cyclosporin at the same institution showed similar graft survival but better graft function in the TLI group.

Adult↗
PubMed1985

Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI).

The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Low dose prednisone was given after transplantation. Profound and long-term immunosuppression has been achieved in all patients. Six patients live already more than one year (greater than 2 years in 3 of them) and 7 for less than one year with a functioning kidney graft. Two out of these 13 patients had repeated rejection episodes necessitating a supplementary immunosuppressive treatment with cyclosporine A. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia). The amount of steroids and azathioprine administered to these patients was substantially lower than in the case of conventional immunosuppression. The preliminary results are thus encouraging. However, the treatment schedule as used in the present study can not yet be considered as optimal since the majority of patients still had one or more rejection episodes. Further investigations are warranted. The optimal dose of radiation, the importance of the interval between TLI and organ transplantation, the influence of splenectomy on the immunity, etc., are still to be assessed.

Adult↗
PubMed1985

[Acute renal insufficiency: 1st manifestation of familial sarcoidosis].

We report an unusual case of sarcoidosis remarkable for: 1) The presentation as acute irreversible renal failure with interstitial granulomas and ischemic glomerular lesions. This leads to a discussion of the possibility of perivascular granulomas or the existence of a vasculitis. 2) The unusual localisation of other lesions in the stomach and cutaneous tissues with a necrotising epidermal vasculitis, unusual in sarcoidosis. 3) The existence, in the patient's mother, of nasal mucosal sarcoidosis and also a carrier of the B8 and DR3 antigens.

Acute Kidney Injury↗
PubMed1984

Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells.

Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

Animals↗
PubMed1984

Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation.

Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. In the TLI-treated group only a low maintenance dose of prednisone (15 mg) was given. Immunologic monitoring was performed after transplantation at regular intervals and was compared in both groups. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI (less than 15% of pre TLI value) and again no recovery occurred during the first year. Natural killer (NK) cell activity progressively decreased from a mean value of 53% lysis before transplantation to 15% lysis at the end of the first year after transplantation in the conventionally treated patients. In TLI-treated patients, however, the NK activity, which declined during irradiation from 46% specific lysis to 12%, recovered rapidly after TLI to reach levels of 35 to 40% of specific lysis from the second month on after TLI. In both groups of patients the ratio of helper-inducer (TH) to suppressor-cytotoxic (TS) lymphocytes, as determined with monoclonal antibodies, progressively declined during the first 2 mo after transplantation to a low value of about 1.2. In TLI-treated patients however, this fall progressed further, so that very low levels (less than 0.6) were noticed from the third month on after TLI. The decline of the TH:TS ratio after TLI is due to an absolute increase in the number of suppressor cells. This is in contrast with the conventionally treated patients, where the low ratio is mainly provoked by a more important decrease of the helper cell population. These changes in the balance between TH and TS subpopulations are more frequently associated with positive functional suppressor cell assays in the TLI-treated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver↗
PubMed1984

Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice.

When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 X 10(6) C57 B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 X 10(6) were added to the BM inoculum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

Animals↗
PubMed1984

Allogeneic bone marrow transplantation in mice after total lymphoid irradiation: influence of breeding conditions and strain of recipient mice.

Different groups of C57BL/ka or BALB/c mice received a dose of 34 Gy or 42 Gy of fractionated total lymphoid irradiation (TLI) before bone marrow transplantation with 30 X 10(6) BALB/c or C57BL nucleated bone marrow cells, respectively. BALB/c mice that were not bred in specific pathogen-free conditions before TLI showed a high morbidity and mortality rate after 34 Gy of TLI and allogeneic bone marrow transplantation as compared with BALB/c or C57BL that were bred in pathogen-free conditions before irradiation. Many of the conventionally bred BALB/c mice had clinical and histologic signs of graft-vs-host disease after TLI and allogeneic bone marrow infusion. Although leucocytosis and lymphocytosis and the immunologic competence as measured with in vitro tests were equally depressed after 34 Gy TLI in BALB/c and C57BL mice, chimerism was nevertheless significantly easier to obtain in BALB/c mice. The incidence of chimerism after TLI could be enhanced in C57BL mice by increasing the total radiation dose from 34 to 42 Gy. This augmentation of chimerism was paralleled by the induction of more suppressor cells after 42 Gy of TLI in C57BL mice.

Animals↗
PubMed1983

Facilitation of allogeneic bone marrow engraftment in mice by total lymphoid irradiation combined with total-body irradiation.

Different groups of C57BL/Ka mice received daily fractions of 2 Gy total lymphoid irradiation (TLI) in a total dose of 34, 24, or 14 Gy. On the day after the last irradiation, 30 X 10(6) allogeneic (BALB/c) nucleated bone marrow cells were infused into the irradiated animals. When the last one or two fractions of the radiation schedule were given to the whole body (combined total lymphoid-total-body irradiation, TLBI): (1) stable bone marrow chimerism with a higher number of donor-type cells in the peripheral blood was induced in a higher percentage of mice that had received 34 Gy TLBI compared with mice that received 34 Gy TLI. (2) bone marrow chimerism could also be induced after 24 Gy or 14 Gy TLBI, whereas 24 and 14 Gy TLI alone were ineffective. The tolerance to the TLBI schedules was excellent and no clinical signs of graft-versus-host disease were noticed. It is concluded that the addition of TBI can facilitate bone marrow engraftment after TLI and drastically reduce the number of radiation fractions needed to obtain successful chimerism after allogeneic bone marrow transplantation in mice.

Animals↗
PubMed1982

Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice.

Three groups of C57/BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. In the first group daily fractions of 2 Gy were given during 3 1/2 weeks. In the second group 4 to 5 fractions with 3 1/2 hr interval were given each day, thus delivering 17 fractions in 4 days. In the third group three fractions were given daily for two consecutive days and was repeated two times after 8 or 9 days interval, resulting in a total treatment time of 3 1/2 weeks. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different parameters involved in the transplantation.

Animals↗
PubMedDate not supplied

Role of CD4+ and CD8+ T cells in the rejection of heart or islet xenografts in recipients with xenotolerance in the innate immune compartment.

UNLABELLED: To further study the interactions between innate and adaptive immunity in xenotransplantation, we explored the relative contribution of T-cell subsets in vascularized (heart) and cellular (islets) xenografts in a model with established xeno-non-reactivity of the innate system. MATERIALS: Specific innate xenotolerance was induced in xenoheart (hamster) recipients (nude rats) by a tolerizing regimen (TR), consisting of donor antigen infusion, temporary natural killer (NK)-cell depletion and a 4-week administration of leflunomide. Hamster pancreatic islets were transplanted either 1 week after heart transplantation or alone and syngeneic T-cell adoptive transfer was performed 10 days later. Purified CD3(+), CD4(+), and CD8(+) T cells were given 2 weeks after withdrawal of all drugs. At the day of rejection, xenografts were removed for histology. Serum was taken and IgM and IgG xenoantibody titers were measured by flow cytometry. RESULTS: Both heart and islet grafts were rejected after CD4(+) reconstitution. After CD8(+) T-cell adoptive transfer, cellular grafts were not rejected but vascularized grafts were rejected, although only after several months. Rejection in CD4(+) reconstituted nude rats was accompanied by the generation of predominantly IgG xenoantibodies. CONCLUSION: CD4(+) T lymphocytes are able to rapidly initiate the rejection of islet xenografts in the presence of a xenotolerant innate immune system either by breaking the "innate tolerance" (e.g., by activating macrophages and NK-cells) or through a mechanism without any involvement of the innate tolerance (e.g., T-dependent IgG antibody production). In contrast, CD8(+) T cells provoke a late rejection of only xenoheart grafts.

Animals↗