ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Chronic denervation of the heart leads to depletion of tissue catecholamines, giving rise to metabolic abnormalities, including a reduction in cardiac glucose oxidation. Impaired glucose oxidation could cause an increased oxidation of fat, which in turn could lead to development of coronary artery disease. Cardiac glucose oxidation (using14C-(U),D-glucose) was studied in female baboons, before, and three to five weeks after, autotransplantation. Systemic arterial and coronary sinus samples were analyzed for total CO2content, O2content,14CO2, glucose, lactate, pH, PCO2, and PO2. Tissue for metabolite assays (adenosine-5‘-triphosphate7[ADP] and creatine phosphate [CP]; glucose-6-phosphate [G6P] and fructose 6-phosphate [F6P] was obtained from the right ventricle before and after auto-transplantation in some animals. There were no significant changes. Tissue was also obtained postmortem for analysis of noradrenaline, soluble tyrosine hydroxylase activity, and contractile and regulatory proteins. There was a large decrease in tissue noradrenaline, suggesting almost total sympathetic denervation. The level of tyrosine hydroxylase activity shows that the denervated heart can synthesize dopamine. There were no detectable changes in the contractile or regulatory proteins. In six of the nine baboons successfully studied, there was a distinct decrease in the oxidation of glucose after auto-transplantation (P<0.05). This indicates that the removal of the sympathetic and parasympathetic nerve supply to the heart affects the ratio of glucose oxidized to other substrates.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The use of vasopressin to limit the polyuria of the brain-dead organ donor is a controversial subject. It is held that the associated vasoconstriction may result in ischemic damage to transplantable organs. However, the derangements in the intravascular—and thereby interstitial and intracellular—fluid and electrolyte balances associated with diabetes insipidus may lead to gross fluid shifts in the organ donor. Aggressive resuscitation with crystalloid solutions may aggravate these fluid shifts, contribute to the development of interstitial and intracellular edema, and ultimately result in cardiovascular failure and the rejection of the organs for transplantation.Theoretically, a minute amount of vasopressin is required for the maintenance of normal intravascular fluid and electrolyte balance, and it is best administered as a continuous i.v. infusion.We report on our study of an animal model of a brain-dead organ donor, in which polyuria, hypernatremia, and hyperosmolality developed. The administration of low-dose (2—10 μU/kg/min) vasopressin by continuous infusion maintained plasma sodium and osmolality in the normal range over the course of the experiments (24hr) in the experimental group. Cardiovascular function remained stable in both control and experimental vasopressin-infusion) groups, with the only significant difference being a moderate rise in pulmonary artery pressure.It would appear that early low-dose vasopressin supplementation by continuous i.v. infusion may improve donor management. The maintenance of intravascular homeostasis may contribute to the quality and number of organs for transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Of 68 consecutive allogeneic bone marrow transplant patients, 53 survived more than three months after transplantation. Twenty-two (42%) developed chronic graft-versus-host disease (GVHD). Chronic GVHD was more common among patients who had previously experienced cytomegalovirus (CMV) infection (20/36, 56%) than among those without signs of active CMV infection (2/17, 12%) (P<0.01). The CMV infections preceded the development of chronic GVHD by a median of 128 days (range 23–322 days). Children below 14 years of age who had had CMV infection developed chronic GVHD as often as older patients (8/14 vs. 12/22). CMV infection may pave the way for chronic GVHD.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Eight recipients of a bone-marrow graft from HLA-identical, MLR-nonreactive sibling donors who had developed grade II—IV acute graft-versus-host disease (aGVHD), were given 14 consecutive daily injections of 5 mg of a murine anti-T-cell monoclonal antibody (MCA) called OKT3. Four patients with grade II aGVHD showed a complete response; two patients with grade II had a partial response, and two patients (one with grade II and one with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the first injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence, and flow cytometry. Circulating T3+T cells dropped to virtually zero within 1 hr following the first injection. Low numbers of E-rosetting cells were still demonstrable during OKT3 therapy. During the second week of treatment, T-cell markers (T3, T4, T8) started to increase again, in spite of excess antibody in the circulation. At that time, T cells showed weaker fluorescence with OKT3 than before OKT3 therapy, suggesting modulation of the T3 antigen. After cessation of OKT3 therapy, T cells reached pretreatment levels within one week. None of the six patients studied developed anti-mouse-Ig antibodies. These results suggest that OKT3 therapy is effective in limited aGVHD. The absence of anti-mouse-Ig antibody formation may allow repeated courses of MCA that may add to their therapeutical potential.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Skin biopsies from 3 patients receiving one-haplotype-matched bone marrow grafts have provided a unique opportunity to demonstrate the presence of donor cells in situ using immunohistological techniques and a monoclonal antibody directed against an epitope common to HLA-A2 and HLA-A28 antigens. The infiltrating cells were also analyzed in consecutive tissue sections with a panel of monoclonal antibodies to human leukocyte antigens, T cells, and epidermal Langerhans cells. Most of the infiltrating cells were shown to be T lymphocytes of donor origin, regardless of whether the histological changes were consistant with graft-versus-host disease (GVHD) or were eczematous. Donor T cells were also shown to colonize histologically normal skin soon after transplantation. Epidermal keratinocytes, dermal endothelium, and adnexal structures did not express the donor HLA type (i.e., were host derived) but the origin of the epidermal Langerhans cells could not clearly be established. The data show that donor cells preferentially migrate to certain sites in skin after transplantation and are not always associated with GVHD.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

IgG subclasses of cytomegalovirus (CMV) antiviral antibodies were determined in 37 donor-recipient pairs of bone marrow transplants (BMT). Bone marrow transplant recipients, like healthy persons, have a restricted immune reactivity, producing mainly two types of anti-CMV IgG: IgG1 and IgG3. Passively transfused specific antibody subclasses were readily measurable. Take of the transplant could be detected from the production of subclass IgG antiviral antibody 1–3 months after BMT of seronegative recipients with marrow from seropositive donors.Patients with protracted CMV infections or other severe diseases initially also produced CMV IgG1 and IgG3, but anti-CMV subclass titers then decreased. In severe disease, CMV was isolated from blood cells as well as from urine. In moderate infections, in which the patients recovered, CMV was isolated from urine but usually not from blood, and a strong and durable antiviral subclass response was measured.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient compatibility based on public rather than private HLA-A,-B specificities influenced the beneficial effect of HLA matching on outcome. HLA compatibility was calculated considering match and mismatch based on common private or various public (crossreactive group, [CREG]) specificities. Donor-recipient compatibility using certain CREG assignments provided an equivalent means of stratifying graft outcome by the degree of HLA-A,-B match or mismatch, and other CREGs assignments did not. Multivariate Cox regression analysis of donor-recipient compatibility based on certain public antigens showed as high an association (P< 10−5) between good matching and decreased graft rejection as did matching for private antigens alone. Patient stratification by HLA match provided a stronger association with graft outcome than by HLA mismatch, irrespective of whether private or public antigens were considered. The likelihood of finding a better match was significantly increased using CREG assignments, and patients with at least one matched private antigen had equivalent or better graft survival when additional public antigens were matched.These findings indicate that with conventional immunosuppressive therapy: (1) matching of private or public HLA-A,-B antigens plays a highly significant role in decreasing renal allograft rejection; (2) matching based on certain public antigens can provide the same or a better association with outcome as private antigens; and (3) the association (crossreactivity) of various HLA specificities can be defined on a functional basis in terms of graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We are participating in a multicenter trial testing the efficacy of a murine monoclonal antihuman peripheral T lymphocyte antibody (OKT3.PAN) as immunosuppressive therapy for the treatment of acute cadaveric renal allograft rejection. Although clinical data indicate that administration of this antibody clears the circulating lymphocyte pool of T3-positive cells, some in vitro studies have called into question whether the antibody is indeed lymphocytotoxic. Other in vitro data suggest that the antibody is a potent mitogen. To address these problems and investigate the effect of the antibody on T cell function, we have studied spontaneous blastogenesis, response to the lee tins phytohemagglutinin (PHA) and concanavalin A (ConA), and response to donor-specific and non-donor-specific alloantigen in a one-way MLC in 9 patients treated with anti-T3 for acute rejection and 9 steroid-treated controls. Patient cells were harvested with standard techniques and studied after transplantation, but prior to acute rejection, on days 3 and 12 of therapy and 1 week after cessation of therapy. All patients received baseline immunosuppression with azathioprine and steroids. Acute rejection was reversed with αT3 antibody (5 mg i.v./day−1× 14 days) in 8 of 9 patients and in 6 of 9 steroid-treated controls. Spontaneous blastogenesis was not enhanced by anti-T3 nor did it rise during therapy. PHA and Con A responsiveness were dramatically and significantly depressed by therapy with anti-T3 or steroids on days 3 and 12. Although PHA responsiveness rebounded past baseline 1 week after monoclonal therapy, it was depressed compared with the steroid-treated patients. On the other hand, Con A responsiveness was still significantly depressed one week after monoclonal therapy compared with prerejection values or with controls. Response to donor-specific and to non-donor-specific alloantigen was significantly depressed with anti-T3 therapy compared with steroid controls, and it did not rise during therapy. Donor-specific response tended to be slower in returning to pretreatment values in the OKT3 patients compared with steroid controls. In summary: (1) Anti-T3 antibody did not enhance spontaneous blastogenesis in patients treated for acute rejction; (2) Con A and PHA responses were dramatically depressed by anti-T3 therapy and returned to baseline following different time courses; (3) Non-donor-specific alloresponse and, more important, donor-specific alloresponse, was more depressed—and for longer periods—by anti-T3 than by conventional steroid anti-rejection therapy. We conclude that the clinical efficacy of anti-T3 antibody therapy in acute rejection may be mediated by depletion from the circulation of lymphocyte subsets responsive to PHA and Con A to donor-specific and non-donor-specific alloantigen.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We have studied serial samples of pretransplant and posttransplant sera for cytotoxic antibodies to lymphoid B cell lines (LCL) in 45 renal allograft recipients. A total of 48 rejection reactions occurred in 31 patients. A comparison of each patient's most reactive posttransplant serum showed a significantly higher reactivity in the ten patients with early allograft failure when compared with the 21 patients with reversible rejections and the 14 patients who had no rejections. Rejection reactions were easily differentiated by comparing the change in cytotoxic reactivity to LCL of recipients' sera drawn at the time of a rejection episode with the reactivity of their pretransplant sera. In 32 rejections considered non-antibody-associated cytotoxic reactivity of recipients' sera to LCL either decreased or remained essentially unchanged during the rejection. In 16 rejections considered antibody-associated the recipients' sera drawn during the rejection episode showed an increase in cytotoxic reactivity ranging from 40% to 100%. Response to antirejection therapy and three month graft survival had a significant correlation with changes in LCL antibody reactivity during a rejection. Only two of the 32 rejections considered non-antibody-associated failed to reverse compared with eight of the 16 antibody-associated rejections (P<.001). Graft survival at three months in patients with non-antibody-associated rejections was 90% compared with 27% in the 11 patients who had antibody-associated rejections (P<.001).Other parameters possibly related to the severity of a rejection reaction or to early allograft prognosis did not differ appreciably between the two types of rejections. This included the time posttransplant to the first rejection episode, the number of patients with multiple rejections in the first three months, and rejections requiring dialysis therapy.Determination of a change in cytotoxic reactivity to LCL during a rejection reaction enables one to predict the response to antirejection therapy and early allograft prognosis. This may ultimately be useful in selecting different types of antirejection therapy for individual patients.

ISSN:0041-1337    

出版商:OVID    

年代:1984

数据来源: OVID