Search PubMed⌕ Search

Biomedical subjects

T B Strom

Publications and source records attributed to T B Strom.

At least 253 records · Page 14Linked to original sources
PubMed1985

Stability of renal allograft recipients after conversion from cyclosporine to azathioprine.

Forty-eight patients with stable renal function after allotransplantation have been converted from CsA/prednisone to azathioprine/prednisone to assess the short- and long-term effects upon renal function. Virtually all patients show an initial improvement in serum creatinine levels. Three patients developed chronic renal failure after 12 to 21 months, and three died of pneumonia 7, 12, and 19 months later. The mean serum creatinine level at latest follow-up (seven to 36 months) was 2.5 +/- 1.5 mg/dL for all 48 patients. Of interest, a control group of 21 patients not converted to azathioprine had serum creatinine levels of 2.5 +/- 0.8 mg/dL, over a follow-up period of five to 25 months. It is not immediately apparent that either group will have a superior overall outcome, although patients on azathioprine seem to have more of a risk for graft loss. More data are needed with various dosage schedules, and with randomized controls.

Acute Disease↗
PubMed1985

The events of primary T cell activation can be staged by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1.

A mitogenic anti-CD3 ("T3") monoclonal antibody (64.1), that stimulates polyclonal T cell activation by a mechanism believed to be similar to antigen via binding to the T cell receptor complex, was utilized in soluble (SOL) and Sepharose-bound (SEPH) forms to dissect the role of accessory cells (AC) and interleukin 1 (IL 1) in supporting T cell activation. The T cell activation pathway was dissected into "early" events including expression of interleukin 2 receptors (IL 2R), increased RNA content, IL 2 release, and "late" (DNA synthesis) events. Unseparated peripheral blood mononuclear cells progressed through all stages of activation when stimulated by either form of 64.1. Stringent AC depletion by plastic adherence, nylon wool adherence, and L-leucine methyl ester (selectively lyses AC) prevented early and late T cell responses to either form of 64.1. The addition of highly purified IL 1 replenished both early and late T cell responses to SEPH-64.1 but not to SOL-64.1. Although SOL-64.1 stimulation of purified T cells induced modulation of the CD3 complex, only SEPH-64.1 induced IL 1 responsiveness, and exogenous IL 1 was then able to support synthesis of RNA, secretion of IL 2, expression of IL 2R, and ultimately, DNA synthesis. Therefore, the stages of early T cell activation owing to stimulation of the CD3-T cell receptor complex and IL 1 responsiveness have been dissected.

Antibodies, Monoclonal↗
PubMed1985

Rapid stereospecific stimulation of lymphocytic metabolism by interleukin 2.

IL 2 maintains the viability of IL 2-dependent CTLL-2 cells. IL 2, a lymphocytotrophic factor, stimulates the cellular metabolism of IL 2 receptor-bearing CTLL-2 murine cytolytic T cells. Both aerobic (oxygen consumption) and anaerobic (lactic acid production) metabolism of CTLL-2 cell are stimulated by rIL 2. The effects of IL 2 upon murine T cells is blocked by an anti-IL 2 receptor monoclonal antibody but not by other monoclonal antibodies that bind to other proteins upon CTLL-2 cells. Changes in aerobic and anaerobic cellular metabolism occur rapidly after interaction with IL 2, whereas the effects on the cell cycle are relatively slow and may be dependent upon antecedent metabolic stimulation by IL 2. This effect of IL 2 on cell viability appears to be mediated by a direct effect on important aerobic and anaerobic metabolic pathways.

Anaerobiosis↗
PubMed1984

Renal artery stenosis in transplant patients.

Although hypertension appears not infrequently among recipients of kidney transplants, renal artery stenosis is relatively rare as a causative factor. A 23-year experience of patients receiving kidney grafts at the Brigham and Women's Hospital was reviewed to ascertain the incidence of renal artery stenosis and its surgical management. Risk factors leading to the condition and selection of patients for operation are emphasized. The incidence of arterial stenosis severe enough to require operation was 2.7% of 914 kidney transplants; the overall incidence in these patients is unknown, although operated patients comprise about one-half of those undergoing arteriography to diagnose hypertension. The mean time for development of the condition was 21.4 months from date of engraftment. A successful outcome as measured by fall in blood pressure and/or serum creatinine was achieved in 14 of 21 patients (67%) in whom surgical repair of the effected artery was undertaken. Reparative surgery was unsuccessful in seven patients, although hypertension was improved in one of these individuals following transplant nephrectomy. Surgery was never undertaken in four patients because of chronic rejection noted on biopsy. There was no mortality. Operative repair should be offered to patients with renal artery stenosis leading to unmanageable hypertension or renal dysfunction, but withheld from those with documented chronic rejection regardless of major arterial compromise.

Adult↗
PubMed1984

Experience with cyclosporine and steroids in clinical renal transplantation.

We have reviewed the results of patient survival and transplant function of the last 100 recipients of renal allografts treated with cyclosporine (CyA) plus low-dose steroids since November 1981; the follow-up varies between 3 months and 2 years. A group of 56 individuals transplanted between January 1980 and October 1982 and immunosuppressed with azathioprine (Aza) and steroids were used as comparison. There were five deaths among 100 patients treated with CyA and two among 56 treated with Aza. There were, however, marked differences in allograft function. Using actuarial curves, 2-year allograft survival from 24 living, related, one haplotype matched donors was 83%, as compared to an unsatisfactory 60% graft function among 24 nonrandomized, comparable, Aza-treated recipients. The 2-year actuarial survival of 76 allografts from cadaver donors was 76%; that of 36 grafts in patients treated with Aza, 48%. Interestingly, function of first cadaver allografts was 84% at 2 years, far better (p less than 0.002) than cadaver graft function (58%) in patients who had been previously transplanted; these latter results are comparable to Aza-treated cadaver recipients. Side effects and complications of this difficult drug, as well as its benefits, have been stressed in this article.

Actuarial Analysis↗
PubMed1984

Conversion from cyclosporine to azathioprine in renal allograft recipients.

Fifty seven recipients of renal allografts initially treated with CsA and low-dose prednisone were switched to azathioprine and low-dose steroids. Ten had prolonged (greater than 28 days) allograft nonfunction after transplantation (group 1), 8 had ongoing, poorly controlled rejection (group 2), and 39 had stable functioning grafts (group 3). With a mean follow-up period of 5 +/- 3 months after conversion, 50 grafts remained functional including 6 of 10 in group 1, 6 of 8 in group 2, and 38 of 39 in group 3. Thirty-seven (65%) had improved function, 12 (21%) had stable function, and 8 (14%) experienced declining renal function. Three of these latter 8 patients required reinstitution of CsA therapy. There were 20 episodes of acute rejection in 18 patients; one graft lost function because of acute rejection unresponsive to therapy. Reasons for the 6 other graft losses were persistent primary nonfunction in 3 patients from group 1, untreated rejection in 2 patients who had multiple prior rejection episodes while on CsA, and chronic rejection in one patient. Although renal function has improved or stabilized in the majority (86%) of individuals changed to azathioprine therapy, there was substantial risk of acute rejection (32%) complicating this procedure. Patients most likely to benefit from conversion to azathioprine therapy are those with prolonged graft nonfunction after transplantation and those with serum creatinines greater than 2.0 mg/dl.

Adult↗
PubMed1984

Decreased expression of human class II antigens on monocytes from patients with acquired immune deficiency syndrome. Increased expression with interferon-gamma.

The expression of HLA-DR (a class II histocompatibility antigen) on monocytes isolated from the peripheral blood of normal individuals and patients with acquired immune deficiency syndrome (AIDS) was investigated by the use of dual fluorescent staining and cytofluorometry. In animal models the absence of class II positive monocytes is linked to a failure of T cells to respond to antigens. We now report that patients with AIDS have a paucity of HLA-DR+ monocytes. The percentage of HLA-DR+ monocytes among eight normal individuals ranged from 49.3 to 95.0%+, and only one individual had less than 50% HLA-DR+ monocytes. HLA-DR expression on monocytes from homosexual male patients with lymphadenopathy was similar to that of normal subjects (range, 58.0 to 97.4%+). In contrast, seven of nine patients with AIDS had less than 50% HLA-DR+ monocytes (range, 13.4 to 78.8%+). The in vitro incubation of monocytes from AIDS patients with cloned human interferon-gamma resulted in an increase of the expression of HLA-DR to near normal levels.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Cyclosporine: a new immunosuppressive agent for organ transplantation.

Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.

Animals↗
PubMed1984

Accessory cell requirement for activation antigen expression and cell cycle progression by human T lymphocytes.

Stringent accessory cell (AC) depletion by a three-step procedure--plastic adherence, nylon wool adherence, followed by simultaneous treatment with two anti-AC monoclonal antibodies + complement--has allowed the demonstration of several AC-dependent stages in the T cell activation pathway. Simultaneous analysis of DNA content and cell surface immunofluorescence (correlation of activation antigen expression with cell cycle position) or DNA and RNA content (cell cycle position) of cultured cells was accomplished by dual parameter flow cytometry. AC-depleted, PHA-stimulated human peripheral blood T lymphocytes (PBTL) failed to exhibit "early" indicators of activation, including increased RNA content, expression of three activation-associated cell surface proteins (IL 2 receptor, transferrin receptor, and 4F2 protein), and the production of IL 2. The AC-depleted PBTL that failed to express these "early" markers of activation also failed to progress into the "late" phase of activation, DNA synthesis. All indicators of PHA responsiveness were fully replenished upon addition of AC but were only reconstituted to intermediate levels by addition of excess quantities of either highly purified IL 1 or crude AC-conditioned medium with lymphocyte-activating factor activity. These data suggest that the AC membrane plays a key and as yet undefined role in the stimulation of T cells by PHA.

Antigen-Presenting Cells↗
PubMed1984

Interactions between T lymphocyte subsets supported by interleukin 2-rich lymphokines produce acute rejection of vascularized cardiac allografts in T cell deprived rats.

A series of adoptive transfer studies were performed to define both the role of lymphocyte subpopulations and of lymphokines in the reestablishment of immunologic responsiveness towards vascularized organ allografts in T cell-deprived B rats. Acute rejection of otherwise indefinitely surviving cardiac allografts (10.9 +/- 2.9 days) occurred when sensitized T cells were adoptively transferred with a course of partially purified, lectin-free IL 2-conditioned medium (IL 2CM), whereas rats receiving T cells alone rejected their grafts at 19.8 +/- 4.6 days (p = 0.025). Rejection is mediated primarily by alloactivated T helper cells highly enriched for W3/25 phenotype. The relationship between the mean allograft survival time and the cell number transferred was of exponential order. In contrast to rejection occurring after the transfer of intact T cells, that produced by W3/25+ cells was independent of the administration of exogenous IL 2CM. W3/25+ T helper cells were also found to be less potent in mediating graft rejection than were whole T cells when limited cell numbers were transferred. The OX8+ T cytotoxic/suppressor cell subpopulation, even when supplied with a course of IL 2CM, was unable to bring about rejection, but induced transient graft enlargement in about 50% of the animals. Recombination of individual subsets caused acute rejection at a rate comparable to that of unseparated T cells when IL 2CM was supplied (10.8 +/- 1.0 days), in contrast to those rats which received the recombined inoculum in the absence of IL 2CM (16.8 +/- 2.2 days, p = 0.025). Lymphocyte migration studies revealed a more vigorous homing of OX8+ cells to the allograft as compared to W3/25+ cells. However, to produce maximal accumulation of transferred cells in the graft, both T cell subsets supplemented by lymphokines must be introduced together into T cell-deprived hosts.

Animals↗
PubMed1984

Cyclosporine therapy of rat heart allograft recipients and release of interleukins (IL 1, IL 2, IL 3): a role for IL 3 in graft tolerance?

LEW rat recipients of (LEW X BN)F1 strain heterotopic cardiac transplants treated with cyclosporine A (CsA) (15 mg/kg/day intramuscularly, 7 days) retain grafts indefinitely despite drug withdrawal. Donor-specific suppressor T cells that are active in passive transfer experiments have been harvested from long-term CsA-treated hosts. Although CsA is known to inhibit in vitro cytokine release, the in vivo effects of the CsA on the lymphokine cascade are not known. We investigated the action of the drug upon spontaneous and mitogen-induced interleukin 1 (IL 1), interleukin 2 (IL 2), and interleukin 3 (IL 3) release by spleen cells obtained from the following groups of rats: 1) normal, i.e., untreated and ungrafted; 2) grafted, acutely rejecting; 3) grafted, actively treated; and 4) under CsA-induced state of "tolerance." The results demonstrate that in vivo CsA therapy inhibits monocyte (IL 1 release) as well as lymphocyte function (IL 2 and IL 3 release) only during the inductive phase (the 7 days of treatment). During the "tolerant" phase, mitogen (Con A and LPS)-induced release of interleukins was quantitatively similar to that noted in normal animals. In contrast, a remarkable increase in the spontaneous production of IL 3 was observed in the "tolerant" group. Because cytokine release is not inhibited in the "tolerant" state, our data strongly support the concept that maintenance of the state of unresponsiveness is governed by the emergence of suppressor cells. The correlation of increased spontaneous production of IL 3 during this period leads us to postulate that this interleukin may be implicated in the activation or clonal expansion of suppressor cells, and hence may play a role in graft tolerance.

Animals↗
PubMed1984

Dual parameter flow cytometric analysis of DNA content, activation antigen expression, and T cell subset proliferation in the human mixed lymphocyte reaction.

This study provides direct correlation via dual parameter flow cytometry (simultaneous assessment of immunofluorescence and DNA content) between mixed lymphocyte reaction (MLR) responder cell entry into the S/G2/M phases of the cell cycle with the kinetics of expression of two activation-associated cell surface proteins, Tac (IL 2 receptor) and 4F2 (unknown metabolic function). A small population of activated cells was identifiable by expression of both Tac and 4F2 antigens before peak DNA synthesis in the MLR. This population of activation antigen-positive cells expanded linearly in size from days 3 to 7 of culture. Treatment of immature MLR cultures with anti-4F2 Mab and complement (C) before DNA synthesis (treatment on day 3, peak DNA synthesis on days 5 to 6) resulted in blunted proliferation and activation antigen expression when the same culture was analyzed after maturation on day 6, indicating that the activated population had been previously detected and removed by anti-4F2 Mab + C. The 4F2 antigen was expressed on a greater percentage of cells in the MLR at all times (days 3 to 9) than was Tac, was present on virtually all S/G2/M phase responder cells, and a large fraction of cells remained intensely 4F2+ subsequent to peak DNA synthesis. In contrast, after initially preceding responder cell entry into the S phase of the cell cycle, the kinetics of Tac antigen expression closely paralleled the kinetics of responder cell proliferation. A subpopulation of cycling responder cells was noted in all MLR cultures studied that expressed Tac antigen weakly or not at all. Cells within both T4 and T8 cell subsets proliferate with similar kinetics in response to alloantigen. The possibility that activation antigens can be utilized to study effector cell generation in the MLR and that this flow cytometric technique may be utilized to analyze the response to various alloantigens is discussed.

Antigens, Surface↗