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T R Zerbe

Publications and source records attributed to T R Zerbe.

30 records · Page 2Linked to original sources
PubMed1987

Myosin content and myosin isoenzyme distribution in the heterotopic rat heart allograft.

Heterotopic cardiac transplants are vascularly perfused organs that can be used to study the regulation of myocardial protein content. Prior studies have demonstrated that cardiac isografts undergo marked atrophy with a decrease in weight and myosin content. In the present studies we have investigated the changes in size, myosin content and myosin isoenzyme distribution in the heterotopic cardiac allografts. Six days after transplantation allograft hearts were not spontaneously beating and histologically showed evidence of necrosis and cellular infiltration. Total heart weight (816 +/- 16 mg) and protein content (117 +/- 7 mg) were significantly greater in the allografts compared to in situ hearts (471 +/- 11 and 90 +/- 5 mg respectively, (P less than 0.01). In contrast to the increase in weight there was a simultaneous decrease in myosin ATPase (26%), the V1 isoform of the myosin isoenzyme (43%), and myosin content (53%) in the allograft heart. These studies demonstrate that similar to cardiac isografts, allograft hearts undergo a decrease in myosin content and a shift in myosin isoenzymes. In contrast to the marked atrophy of the cardiac isograft, the allograft heart weight is increased most likely due to rejection with cellular infiltration and an increased water content.

Adenosine Triphosphatases↗
PubMed1987

EKTACHEM bilirubin fraction Bc as a predictor of liver transplant rejection.

Bilirubin fractions Bc and DELTA, not routinely available prior to the EKTACHEM Chemistry Analyzer and its slide methodology, were studied in an outpatient population of liver transplant recipients. A preliminary evaluation by the authors has shown that direct bilirubin (DBILI) levels in the normal range consist almost exclusively of DELTA (protein-bound conjugated bilirubin), while at elevated DBILI levels, an increasing amount of Bc (non-protein-bound conjugated bilirubin) is measured as well. The present study evaluated the clinical significance of Bc in the serum of 80 liver transplant recipients as a means of identifying episodes of rejection. Each patient was classified into rejection or nonrejection categories based on clinical status, liver biopsy results, and/or response to therapy. Eighteen patients were classified as experiencing an episode of rejection during the period of this study. Fourteen of these (77.8%) had Bc levels that ranged from 0.1 to 6.8 mg/dl. Sixty two patients were classified in the nonrejection category. Fourteen (22.6%) of these patients had Bc levels that ranged from 0.1 to 0.6 mg/dl. In our outpatient liver transplant recipients with Bc greater than or equal to 0.1 mg/dl, the relative risk of rejection (% of rejection patients with Bc/% of nonrejection patients with Bc) was 3.44. This value indicates that Bc determination may be a helpful adjunct in the assessment of rejection.

Bilirubin↗
PubMed1986

Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients.

Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Diagnostic procedures in allergy III. Office screening for immune deficiency.

Using the screening tests discussed in this review, the practicing allergist can obtain an adequate assessment of the patient's immune system. Using the clinical nature of the particular patient's infectious history as a guide to the selection of the few simple assays described, the physician can identify those patients who require further evaluation of their immune system. In addition, he can assure those who have concerns about their own or their children's immune system that it is functioning normally.

Antibodies, Monoclonal↗
PubMedDate not supplied

Presence of CD4, CD8 double-negative and T-cell receptor-gamma-delta-positive T cells in lymphocyte cultures propagated from coronary arteries from heart transplant patients with graft coronary disease.

Previous studies have shown that the interleukin-2-induced propagation of lymphocytes from endomyocardial biopsy specimens, an indicator of cellular rejection, is associated with the development of graft coronary disease in heart transplant patients. To further investigate the concept of cell-mediated immune responses in graft coronary disease, we have applied the methodologies of interleukin-2-induced propagation of lymphocytes from arterial tissues. In a group of 23 patients, which included 6 heart, 6 kidney, and 11 liver transplant recipients, we observed that arterial lymphocyte growth was significantly associated with obliterative vasculopathy (p less than 0.03). T-cell phenotyping analysis of coronary artery-derived lymphocyte cultures from three heart transplant patients with graft coronary disease showed significant numbers of CD4, CD8 double-negative T cells and T-cell receptor-gamma delta cells, especially when the cultures were established with relatively high doses of 400 U/ml of interleukin-2. These data suggest that the subset of CD4-CD8-, T cell receptor-gamma delta+ T cells may play a role in the pathogenesis and progression of graft coronary disease.

CD4-CD8 Ratio↗
PubMedDate not supplied

Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography.

Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Actuarial Analysis↗
PubMedDate not supplied

Lymphocyte growth from cardiac allograft biopsy specimens with no or minimal cellular infiltrates: association with subsequent rejection episode.

Histologic features of endomyocardial biopsy specimens are essential in the monitoring of heart transplant patients. Significant cellular infiltrates accompanied by myocyte damage are diagnostic of transplant rejection, whereas no or minimal infiltrates (grades 0 and 1) suggest absence of rejection. Biopsy specimens were cultured on the basis of the principle that the allograft is infiltrated by activated lymphocytes, which can be expanded in the presence of interleukin-2, a lymphokine that induces proliferation of activated T cells. Although frequency of cell cultures was proportional to histologic rejection grade, 39% of biopsy specimens with grades 0 and 1 cultured during the first month posttransplantation yielded lymphocyte growth. Cell growth was observed in 28% of biopsy specimens with grades 0 and 1 obtained during the first 10 days posttransplantation. In this group (growers) 73% showed clinical rejection after 9.8 +/- 5.0 days. In contrast, 55% of nongrowers were treated for rejection after 19.1 +/- 13.8 days. For biopsy specimens obtained 11 to 20 days posttransplantation, subsequent rejection episodes were observed in 61% of growers, but in only 33% of nongrowers. For biopsy specimens obtained 21 to 30 days posttransplantation the incidence of clinical rejection was 60% versus 14%, respectively. A sequential analysis of biopsy specimens obtained during the first month posttransplantation enabled us to identify 16 persistent nongrowers; only 6 (37%) experienced clinical rejection during the first 3 months posttransplantation. Most of the persistent nongrowers were found among patients on the immunoprophylactic rabbit antithymocyte globulin protocol. These data suggest that in vitro cultures of biopsy specimens with no detectable or minimal cellular infiltration may be useful in identifying patients at risk of developing rejection.

Adult↗
PubMedDate not supplied

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Device explant protocol.

An explant protocol was developed to investigate the effects of implantation of a left ventricular assist system (LVAS) manufactured by Novacor Division, Baxter Healthcare Corporation on the function of end organs (such as the brain, the kidney, the liver), with particular interest in examining possible complications due to LVAS support. Emphasis was placed on an analysis at the time of device removal and/or autopsy of 1) the local LVAS-host interface; 2) remote cardiovascular and end-organ effects; and 3) the impact of chronic circulatory support on the native heart. To accomplish these objectives, tissue and device samples must be obtained in an appropriate fashion to ensure photographic documentation, microscopic examination, microbiologic and biochemical assays, and compliance with regulatory and manufacturer requirements. This article describes the techniques and protocol that were proposed to ensure the quality of device explant and tissue analysis.

Autopsy↗