ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Evidence suggests that metabolic abnormalities are responsible for the widespread microvascular complications of insulin-dependent diabetes mellitus (IDDM). Interest in endocrine pancreas replacement therapy, including pancreas transplantation, is based on the hope that such treatment will reverse the complications of IDDM by providing more precise metabolic control than conventional therapy. To determine if whole pancreas transplantation is capable of reversing well-established metabolic abnormalities of diabetes mellitus (DM) and maintaining strict metabolic control for life, we performed monthly metabolic studies for 2 years in 141 nondiabetic control rats, 273 diabetic control rats with alloxan-induced DM, and 267 diabetic rats that received syngeneic whole pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of DM with alloxan. Whole-pancreas transplantation in rats with long-standing DM permanently reversed the metabolic disorders. Elevated plasma glucose concentrations were permanently reduced to normal, depressed plasma insulin levels were permanently increased to normal, elevations of BUN and serum creatinine were permanently normalized, and there was a striking gain in body weight. Hyperglycemia during glucose tolerance tests was of lesser magnitude and shorter duration than normal, as a result of greater-than-normal plasma insulin levels. The only abnormality the persisted was hyperglycemia and is of unknown significance. These results indicate that whole-pancreas transplantation produces the most complete and sustained correction of the metabolic abnormalities of experimental DM of any available therapeutic modality.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The expression of Ia-like (class II MHC) antigens on canine hemopoietic cells was investigated using a cytotoxic murine monoclonal antibody, WM-2, reactive with dog Ia-like antigens. Another monoclonal antibody, WMD-1, reactive with canine Thy-1 antigen, was used as a positive control. Depletion of Ia+cells from dog bone marrow by complement-mediated lysis with WM-2 antibody failed to inhibit growth of granulocyte-macrophage progenitors (CFUgm) in vitro, while WSMD-1 produced complete inhibition of CFUgm.Lethally irradiated dogs receiving bone marrow autografts depleted of Ia positive cells ex vivo showed initial engraftment, followed by prolonged pancytopenia, and eventual complete recovery of marrow function in the majority of animals. In contrast, dogs receiving autografts treated with WMD-1 and complement all died of marrow failure. We interpret these results as indicating: (1) that Thy-1 antigen is present on hemopoietic stem cells essential for marrow engraftment; (2) that the expression of Ia antigens on hemopoietic stem cells essential for marrow engraftment; and (2) that the expression of Ia antigens on hemopoietic cells is heterogeneous and related to the level of stem cell maturation. While Ia appear to be present on a stem ell population at an earlier stage than CFUgm, as evidenced by the transient phase of graft failure seen in dogs receiving Ia-depleted marrow, the most primitive stem cell, responsible for long -term engraftment, is effectively Ia-negative.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The frequency, timing, and specificity of the humoral antibody response to a murine monoclonal antibody (OKT3, IgG2a) were measured in 21 consecutive renal allograft recipients. These patients received i.v. OKT3, 1–5 mg/day for 10–20 days as treatment for acute graft rejection. Maintenance immunosuppression consisted of azathioprine and corticosteroids. Using three different assays, n antibody response was detected in 75% of the 20 patients with adequate samples. The ELISA assay of the overall IgM and IgG reactivity to OKT3 revealed that IgM anti-OKT3 in 50% of the patients, reaching a peak 20–33 days after the last dose of OKT3 The IgM preceeded the IgG in most cases (p<0.02) and in 8 cases was detected during therapy. One patient had high levels of IgM anti-OKT3 before therapy, yet responded normally to OKT3. Interference with the therapeutic effectiveness was evident in one patient who developed IgG antibodies during therapy. His serum blocked the binding of F-OKT3 to normal lymphocytes in the presence of normal BALB/c serum. The blocking assay, done by flow cytometry, measured anti-idiotypic (Id) reactivity since the sera did not affect the binding of OKT8 (another IgG2a) or anti-Leu4 (another anti-T3), and the blocking activity remained after affinity absorption with normal mouse IgG. Using this assay, 60% of the pateints made an anti-Id response. One made only anti-Id, and several had anti-Id at times when other reactivities were undetectable. Antibodies to non-idiotypic, presumably isotypic, determinants represented on OKT8 occurred in only 44%, while other reactivity (OKT4; IgG2bk) was less common (12%) and weaker.While no adverse allergic reactions occurred in this group of patients, the anti-Id antibodies, which are a prominent feature of the immune response to this and probably other monoclonal antibodies, can block their therapeutic effectiveness and can arise despite intense immunosuppression. This response may require the use of different idiotypes for prolonged or repeated courses o therapy and may be the major obstacle to the use of human monoclonal antibodies.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Thirty-one episodes of biopsy-proved acute rejection (R) in 28 patients maintained on cyclosporine did not respond to high-dose steroids an were treated with antilymphocyte globulin (ALG). Cyclosporine was discontinued in all but three during ALG administration. (A) Twenty-four patients received 26 courses of ALG within 90 days of transplant (11 1st R, 15 2nd or 3rd). Seven treatment courses were cut short due to infection (4), ongoing R (2) and a combination of infection and rejection (1). Only 1 of 7 has a functioning graft. Of the remaining 19 full ALG courses (17 patients) (8 1st R, 11 2nd or 3rd), 13 (11 patients) responded (7 1st R, 6 >1st). The remaining 6 Five patients were treated after 6 months posttransplant; two responded but no grafts currently function. (c) Overall 7 patients developed systemic infection (7 viruses, 1Candida) with 1 death, and 2 additional patients developed severe thrombocytopenia an leukopenia. Patients responding to their ALG course were restarted on cyclosporine. We conclude that ALG is not as effective I reversing steroid-resistant rejection in patients maintained on cyclosporine. We conclude that ALG is not as effective in reversing steroid-resistant rejection in patients maintained on cyclosporine as it has been in patients maintained on azathioprine. However, more than 50% of steroid-resistant rejection episodes are reversed.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Chronic mucocutaneous candidiasis (CMC) is typically associated with the inability of T lymphocytes to proliferate and produce lymphokines in response toCandidaantigen. A 7-year-old girl with CMC developed severe aplastic anemia and, after conditioning with cyclophosphamide, 200 mg/kg, underwent bone marrow transplantation from her HLA-identical sister. Engraftment was prompt and complete. Te patient is surviving more than 3 years after transplantation with normal donorderived hemopoiesis and immune function. Manifestations o CMC have resolved completely and she has not received antifungal therapy for more than 2 years.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In vitro IgG anti-tetanus toxoid (IgG anti-TT) antibody produced by peripheral blood lymphocytes (PBL) from 16 normal subjects (9 marrow donors and 7 random healthy subjects) and 17 marrow graft recipients from 45–1058 days postgrafting was measured with an enzyme-linked immunosorbent assay (ELISA). PBL from 11 of 13 seropositive (ant-TT ±1:1024) normal subjects produced IgG anti-TT in vitro, whereas the PBL from the 3 seronegative (IgG anti-TT <:1:1024) normal subjects did not. In our normal subjects, there was a high correlation between seropositivity and in vitro IgG anti-TT production (P=.0048, χ2, two-tailed). PBL from only one of 13 serospositive marrow graft recipients produced in vitro IgG anti-TT antibody.B and T cell functions of 8 marrow graft recipients were assessed by coculturing their T and B cells with those from their HLA-identical marrow donors. One short-term patient and 7 long-term patients (4 with and 3 without chronic graft-versus-host disease) were studied. Recipient B cells failed to produce antibody in the presence of donor T cells in 7 of these 8 cases. However, T cells fro long-term survivors provided helper activity to immune donor B cells in 7 o 9 evaluable cases.TT-specific helper T cell activity was present in most seropositive long-term recipients, and B cells from marrow recipients failed to produced specific antibody in the presence of normal donor TT-specific helper T cells. These results, TT-specific T cell helper activity, and normal circulating serum IgG anti-TT antibody levels in marrow graft recipients without postgrafting TT boosters suggest that specific immunity had been transferred from the marrow donor to the marrow recipient.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Two murine monoclonal antibodies (URO-4 and URO-4a)—which detect different epitopes of a proximal tabular cell glycoprotein antigen the adenosine-deaminase-binding protein (ABP)—have been formatted into sandwich enzyme immunoassay for detection of ABP in the urine. Serial urine samples from 34 renal transplant patients during the first six months posttransplant were analyzed to determine the correlation of this test with clinical rejection and cyclosporin (CsA) nephrotoxicity.In 29/29 acute rejection episodes the ABP level was elevated, beginning 1–7 days prior to treatment of rejection. Eighteen patients were treated fro rejection with courses of OKT3 or antithymocyte globulin: 0/6 whose ABP level fell to normal during therapy had rerejection; 10/12 whose ABP level remained elevated had rerejection within 7 had no rejection or drug toxicity; all 7 and normal ABP levels. The remaining 8 had CsA nephrotoxicity, all in association with elevated ABP levels that rapidly fell to normal with decreased CsA dose. An additional 7 patients with creatinine elevations more than 6 months posttransplant were studied: 5 had chronic vascular changes on biopsy, no response to increased immunosuppression, and normal ABP levels; 2 had a cellular infiltrate on biopsy, response to increased immunosuppression, and elevated ABP levels. We conclude that the urinary ABP assay provides information useful in the management of renal transplant patients with acute and chronic rejection and CsA toxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The survival of 100 consecutive patients with diabetic nephropathy after treatment with hemodialysis, peritoneal dialysis, or renal transplantation was reviewed at our institution from 1976 to 1982. Standard actuarial survival analysis revealed an overall survival of 83% and 61% at one and two years, respectively. Coronary angiography was used as a screening procedure for renal transplantation. In the dialysis group, 27 patients were considered acceptable transplant candidates on the basis of the coronary angiography but were not transplanted for other reasons. When the survival analysis was limited to those “transplant candidates” the survival rates were 78%, 51% and 8% 1, 2, and 5 years, respectively. In comparison, survival after transplantation was 81%, and 45%, at 1, 2, and 5 years, respectively. I order to eliminate bias, survival comparisons were subsequently made using the Cox Proportional Hazard Model to take into account the time the transplant patients spent on dialysis prior to renal transplantation. When this analysis was performed, there was no significant difference in survival between transplantation and dialysis for the first two years, but overall survival after five years was significantly better after renal transplantation even when the comparison was limited to acceptable transplant candidates who remained on dialysis (P=.04). Survival for patients with significant coronary disease (>70% stenosis of a coronary vessel or moderate to severe left ventricular dysfunction) was analyzed according to therapeutic modality. Although overall prognosis was poor in this group as a whole (1, 2, and 5 year survivals were 76%, 45%, and 19%, respectively), the cardiac patients had a trend to better survival were 76%, 45%, and 19%, respectively), the cardiac patients had a trend to better survival after renal transplantation than when maintained on dialysis (P=.22). In addition to other factors such as quality of life, rehabilitation, and progression of other diabetic complications, the benefit of renal transplantation of patient survival must be considered when deciding between renal transplantation and maintenance dialysis therapy for diabetic patients with renal failure.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We studied the effectiveness of plasma exchange for reversing antiplatelet alloimmunization in 18 patients undergoing marrow transplantation. Patients received one-to-three daily exchanges. Most exchanges occurred during the pretransplant conditioning phase. Overall, eleven of 18 patients had a beneficial response to plasma exchange, defined as an improvement in post-platelet-transfusion increments. More patients responded who had received to or more exchanges. Patients who had lymphocytotoxic antibodies pretransplant were more likely to benefit from the exchange. Our results show that plasma exchange may improve the posttransfusion platelet increments in alloimmunized patients undergoing marrow transplant.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID