Biomedical subjects
Publications and source records attributed to B Charpentier.
The authors report a case of renal and pancreatic transplantation in a patient with renal failure and type I diabetes. The entire pancreas and duodenum were transplanted, the duodenum was drained into the bladder in order to assay the urinary amylase which is an early criterion of rejection of the exocrine pancreas.
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Cytomegalovirus (CMV) has close relationship with the immune system. Latency, reactivation and transforming effect are common features seen during its cellular localization, explaining the main importance of cellular immunity in the host defence. Host-graft induced immunosuppression and drugs are 2 important parameters involved in the frequency and the severity of CMV infection in organ transplantation. On the other hand, CMV and cellular rejection are tightly implicated both inducing the other and vice versa. In the host defence, NK cells, cytotoxic T lymphocytes and antibody dependent cell cytotoxicity are 3 lytic mechanisms successively involved and limiting or curing acute or chronic infection. Moreover, CMV has a transforming effect and could be implicated in some Kaposi sarcoma.
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Ten antegrade endoprostheses were inserted in renal transplant patients. Eight dilatations and 2 intubations were performed. Six stenoses had recurred after 6 months.
123 vascular surgical procedures were performed ex situ in the course of 534 renal transplantations performed between 1982 and 1987. This study demonstrates that the elongation of the renal vein facilitates the transplantation and significantly reduces the risk of arterial stenosis and that arterial repairs, in the case of multiple arteries, constitute a reliable technique. The elongation of the renal vein means that all donor right kidneys must be procured with the infra-renal inferior vena cava. Donor kidneys with multiple arteries without patch graft can be repaired on the table in the great majority of cases.
The factors affecting graft survival in transplant recipients receiving cyclosporin (CsA) are still being debated. Our report is based on an analysis of 202 successive transplantations performed in our institution from May 1984 to December 1986, using low-dose CsA as the basic means of immunosuppression. A total of 142 patients received the triple combination CsA, azathioprine (AZA), and corticosteroids. Sixty patients received a prophylactic combination of CsA, corticosteroids, and antilymphocyte globulins (ALG). From January to December 1986, both regimens were compared in a prospective randomized trial. The factors that affect graft survival were analyzed using the Cox multivariate hazard analysis. The relative risks were calculated for pretransplant baseline risk factors and for outcome-dependent post-transplant risk factors for surviving grafts at 1 month. Transplants performed with a prolonged ischemia time and patients whose graft did not function immediately were statistically at higher risk of graft loss. Adding prophylactic ALG to CsA was associated with better graft survival. Patients who experienced more than 1 rejection crisis and patients whose 1-month CsA dose was lower than or equal to 5 mg/kg per day were also at significantly higher risk of further graft loss. Neither HLA matching, peak panel reactivity, age of the recipient, occurrence of post-transplant renal dysfunction nor 1-month renal function affected the short-term graft outcome.
We report three cases of nodular regenerative hyperplasia of the liver: the clinical onset of hepatic disease occurred between 24 and 30 months after renal transplantation. Nodular regenerative hyperplasia was associated with peliosis hepatitis in two cases, and with veno-occlusive disease in one case. Two patients developed portal hypertension, but are doing well. The third patient developed jaundice and died of septic shock. We discuss the aetiological role of renal transplantation, cytomegalovirus infection, and azathioprine in the development of nodular regenerative hyperplasia of the liver.
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The authors report two cases of aneurysm in renal transplantation: one after removal of the transplant and the other with the transplant in place. In both cases, repair was preceded by excision of the aneurysm and consisted of interposition of an inverted autologous vein graft.
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Cells participating in the rIL 2-induced proliferation of resting PBMC were identified by using different methods of cell purification. NK cells recovered in the light density fraction of Percoll gradients responded, as already known, directly to rIL 2 by strong proliferation. In contrast, large T lymphocytes co-purifying with NK cells, and small T cells sedimenting in the high density area of the Percoll gradients, were virtually unresponsive when cultivated in the sole presence of rIL 2. However, the addition of either irradiated autologous monocytes or highly purified IL 1 allowed both kinds of T cells to undergo cell division. Stringent elimination of possibly contaminating NK cells (NKH-1+) and/or activated T cells (TNKTAR, Tac+, HLA-DR+) from the high density T cells by complement lysis did not impair rIL 2-induced cell proliferation, indicating entire responsiveness of these cells to the synergistic action of IL 1 plus IL 2. Both high density CD4+ and CD8+ participated in this phenomenon, with an apparent advantage for CD4+ cells. All Tac+ cells emerging in a 6-day culture of these cells expressed the WT31 antigen, which indicates that T cells involved in rIL 2-induced proliferation are conventional mature T cells. The relative precursor frequencies of NK cells, large T lymphocytes, and small T lymphocytes that proliferated in response to rIL 2 were analyzed by limiting dilution analysis. The frequencies of clonal growth of NK cells and low density T lymphocytes were approximately the same (1/103 vs 1/185), whereas that of high density T cells was four times lower (1/458). Thus, we clearly demonstrate that resting T cells, defined as such by morphological, density, and phenotypic criteria, are able to proliferate in response to IL 2 in the presence of IL 1 without antigenic or mitogenic triggering.
A possible heterogeneity of peripheral receptors for CCK26-33 [Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] (CCK8) was investigated by replacement of the flexible Gly29 residue, reported to be crucially involved in the CCK8 folding, by a D-Lys residue in Boc[Nle28,31]CCK27-33, a derivative as active as CCK8. The linear peptide Boc-Asp-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 was cyclized through amide bond formation between the side chains of Asp26 and D-Lys29 to give the peptide Boc-Asp-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2. Analogues 1 and 2 were shown to stimulate secretion of amylase from rat pancreas with a potency that was respectively 40 and 80 times lower than that of CCK8. In contrast, both peptides acted as weak antagonists (EC50 approximately 10(-5) M) of the CCK8-induced contractions of guinea pig ileum. Peptides 3 and 4 obtained by removal of the phenylalanine from 1 and 2 were inactive in all bioassays despite amidification of their C-terminal Asp32 residue, a modification known to induce antagonist properties in CCK7. Cyclization between residues 28 and 31 in Boc[Asp28,Lys31]CCK27-33 gave compound Boc-Tyr(SO3H)-Asp-Gly-Trp-Lys-Asp-Phe-NH2, which was inactive in all bioassays. The pharmacological properties of these first described cyclic analogues of CCK8 were in agreement with their binding affinity to brain and pancreas receptors, suggesting the existence of a heterogeneity of peripheral receptors and emphasizing the usefulness of cyclic peptides in structure-activity studies.
Cytomegalovirus (CMV)-specific immune T-cells, present in the circulation of previously infected kidney transplant recipients (anti-CMV serum antibody titer greater than 1/40) can be reactivated to give rise to specific helper and cytotoxic effector cells by co-culturation with fresh autologous blasts coated with CMV antigen in vitro. The reactivated cells are able: 1) to proliferate when stimulated with CMV antigen, 2) to kill the autologous target coated with CMV antigen and not autologous blasts alone when assayed in 51Cr release test. These specific effector cells lie in the E+ T cell subset by removing NK cells with sheep-erythrocytes rosetting. When the reactivated cells are tested against allogeneic CMV coated blasts the level of cytotoxicity is in general related to the extent of HLA-A and B antigen sharing between effector and target cells. The results provide strong evidence that: 1) only previously infected individuals can generate immune T cells against CMV in vitro, 2) there is a correlation between the index of proliferation and cytolysis, 3) there is an HLA restriction of immune T cell cytotoxicity of CMV, 4) monoclonal antibodies directed at several antigenic sites of CMV are able to block cytolysis.
An increased incidence of Kaposi's sarcoma is well known in renal transplant recipients in whom it may represent up to 3 p. 100 of all de novo tumours. This sarcoma has a close relationship with the potential oncogenicity of the cytomegalovirus (CMV) and with chronic immunological deficiency. Anti-CMV immunity is based on the integrity of cytotoxic cellular functions such as those of cytotoxic T lymphocytes (CTL), "natural killers" cells, and K cells which function in the antibody-dependent cell cytotoxicity (ADCC) system. Two cases of Kaposi's sarcoma were observed out of a total of 700 renal transplant recipients; they underwent the following investigations: lymphocyte sub-group counts by murine monoclonal antibodies, lymphocyte proliferation to lectins and allogenic cells, NK activity and generation of specific auxiliary and cytotoxic anti-CMV cells. Both cases of Kaposi's sarcoma were seropositive for CMV and seronegative for LAV. In one case, an abnormal number of peripheral OKT9 + lymphocytes (normally a thymocytic marker) was observed with small numbers of OKT4/OKT8, a reduced proliferative response to mitogens and allogenic cells. All these in vitro changes persisted despite reduction of immunosuppressive therapy and clinical improvement. A clinical and biological cure was only obtained after withdrawal of immunosuppressive therapy and return to haemodialysis. In the second case of Kaposi's sarcoma, the initial biochemical changes were minimal and a clinical cure was obtained by decreasing the immunosuppressive therapy. These two cases illustrate the complex dysregulation of the immune system in Kaposi's sarcoma.
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Fifty-six renal artery stenoses involving transplanted kidneys among a series of 819 renal transplants performed from 1978 to 1986 were treated. Forty-two patients underwent surgery. Surgery was the initial treatment in 38 cases and followed failed or complicated dilatation in four cases. Surgical treatment ensured successful control of hypertension in 85% of cases with a mean time lag of 26 months. Recurrence rate was 12%. Two patients died in the perioperative period. Percutaneous dilatation was performed in 18 renal artery stenoses and ensured control of hypertension in 61% of cases with a mean time lag of 19.6 months and a 33% recurrence rate.