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Biomedical subjects

A A Gordon

Publications and source records attributed to A A Gordon.

9 recordsLinked to original sources
PubMed1994

Distinct T cell populations distinguish chronic myeloid leukaemia cells from lymphocytes in the same individual: a model for separating GVHD from GVL reactions.

Donor lymphocyte responses to minor histocompatibility antigen (mHA) differences are involved in allo-responses between HLA matched pairs causing GVHD and graft-versus-leukaemia (GVL). Since some mHA are tissue-restricted, GVHD and GVL responses may be separable. We studied donor lymphocyte responses to patients with CML in a series of 10 HLA-matched sibling and 10 unrelated donor-recipient pairs comparing proliferation to recipient PHA blasts and CML cells and attempting to selectively deplete responses to PHA blasts in vitro. Responses in counts per min (c.p.m) to CML cells and PHA blasts were, respectively, 2809 +/- 2205 (SD) and 7376 +/- 1877 in related and 12,107 +/- 7191 and 26,136 +/- 22,479 in unrelated pairs. Autologous responses to PHA blasts were significantly lower (mean 779 +/- 735) (p < 0.001). Results correlated with clinical outcome: higher responses to recipient cells correlated with transplant-related death (p = 0.02 for CML and p = 0.06 for PHA blasts). Higher responses to CML correlated with GVHD grade > or = II (p = 0.025). Donor lymphocytes exposed to recipient PHA blasts for 5 days and treated with a ricin-conjugated anti-CD25 antibody retained over 75% of their response to CML but < 10% to PHA blasts. Similarly, depletion of response to CML but not to PHA blasts occurred when CML was the primary challenge. These results indicate that distinct populations of donor T cells respond to recipient leukaemic and non-leukaemic cells, and provide the basis for a clinically applicable technique to selectively deplete donor GVHD reacting cells while conserving GVL.

Graft vs Host Disease↗
PubMed1994

Shaping elder care in the acute setting.

Caring for the elderly in the 1990s poses a challenge necessitating exploration of a number of variables which affect the patient, the family and the setting in which care is provided. Hence, nursing leadership is compelled to shape the processes of elder care. The authors share strategies, insights and approaches to address this growing mandate.

Acute Disease↗
PubMed1993

The in vitro effects of interferon-gamma, interferon-alpha, and tumour-necrosis factor-alpha on erythroid burst-forming unit growth in patients with non-leukaemic myeloproliferative disorders.

We have studied the effects of interferons gamma (IFN-gamma) and alpha (IFN-alpha), and tumour-necrosis factor-alpha (TNF) on circulating 14-day erythroid progenitor cell (BFU-E) growth in vitro from patients with non-leukaemic myeloproliferative disorders (MPD) compared with normal controls. IFN-gamma (1000 U/ml) inhibited BFU-E growth in all controls studied (mean growth +/- SE = 61% +/- 6%, n = 10). In 7 of 11 MPD studied there was no inhibition, and in some cases clear enhancement of BFU-E growth by IFN-gamma. When cultured in the presence of recombinant erythropoietin (rEpo) 1 U/ml, both IFN-alpha and TNF (at 100 and 1000 U/ml) produced a similar degree of inhibition of BFU-E growth in MPD and controls. The inhibition by 100 U/ml IFN-alpha was abrogated, partially in controls but completely in MPD, by increasing the dose of rEpo to 5 U/ml. Similarly, the increase in rEpo dose enhanced BFU-E growth in cultures with 100 U/ml TNF, but had little effect on cultures containing 1000 U/ml of either IFN-alpha or TNF. The aberrant in vitro response to IFN-gamma demonstrated in some of these patients may be of relevance to the pathophysiology of MPD. These results fail to demonstrate a differential in vitro effect for IFN-alpha on MPD BFU-E growth compared with controls and suggest that the in vitro suppression of haemopoiesis by IFN-alpha when used in MPD treatment is non-specific.

Cells, Cultured↗
PubMed1990

Recombinant interleukin 2 for acute myeloid leukaemia in first complete remission: a pilot study.

We treated nine patients in first remission from AML with rhIL-2. The toxic effects of rhIL-2 infusion were, malaise, pyrexia, and hypotension, which resolved rapidly on cessation of rhIL-2 infusion. No patient required transfer to an intensive care unit. Following rhIL-2 infusions patients developed eosinophilia, and a modest lymphocytosis, involving both NK cells, and T lymphocytes. Relapse occurred in six patients at a median of 39 weeks from remission. A particular concern was rapid relapse in the two patients with AML FAB type M5. There was no survival advantage from rhIL-2 treatment when compared to a similar group of chemotherapy only treated AML patients from this institution.

Actuarial Analysis↗
PubMed1990

Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and growth-promoting activity.

Megakaryocyte growth-promoting activity (MK-GPA) was scored on a scale of 0-3 in the serum of 23 patients up to 120 d following bone marrow transplantation (BMT) for leukaemia. Nine of 19 allografts and two of four autografts had thrombocytopenia requiring platelet transfusion more than 30 d after BMT. There was a close correlation between MK-GPA and platelet count. MK-GPA reached a maximum before day 30 after BMT but remained elevated in patients with persisting thrombocytopenia secondary to poor engraftment, graft-versus-host disease (GVHD) or relapse. Recent platelet transfusion did not suppress serum MK-GPA. Two of four patients undergoing autologous BMT for acute myeloid leukaemia (AML) showed delayed platelet recovery and persistence of MK-GPA in the serum. Seven further AML remission marrows were tested for megakaryocyte production before or after autologous BMT, using pooled sera with known MK-GPA activity. Megakaryocyte generation was reduced before BMT and absent in post transplant samples. This failure of MK production was not corrected by T-cell depletion or by the presence of adherent cells from normal marrow. We conclude that thrombocytopenia after BMT is associated with an appropriate increase in MK-GPA levels in response to a reduction in the megakaryocyte pool rather than the platelet pool, and that persisting thrombocytopenia after autologous BMT is due to decreased numbers of available megakaryocyte precursors.

Adolescent↗
PubMed1990

Interleukin-2 treatment-associated eosinophilia is mediated by interleukin-5 production.

During a trial using recombinant human interleukin-2 (rhIL-2) immunotherapy for acute myeloblastic leukaemia (AML) in remission, eosinophilia was observed in all patients. We used in-vitro clonogenic assays to investigate the mechanism of the eosinophilia in five patients. The mean eosinophil count increased from 0.05 x 10(9)/l before rhIL-2 to 0.98 x 10(9)/l within 48 h of stopping the infusion, and an exponential correlation between the pretreatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. RhIL-2 did not stimulate eosinophil colony formation by normal bone marrow. However, serum collected from patients during rhIL-2 infusion was a potent stimulator of eosinophil colony forming units (CFU-Eo), but had no significant stimulatory effect on granulocyte-macrophage colony forming units (CFU-GM). The CFU-Eo stimulation by pre-treatment serum was 2.8-fold higher than control serum. Serum collected during treatment stimulated CFU-Eo 12 times more than control serum (P less than 0.05). By pre-incubating patient serum, collected during rhIL-2 treatment, with monoclonal antibodies to murine IL-5, or human granulocyte-macrophage colony stimulating factor (GM-CSF), a reduction of 80% and 38% respectively in eosinophil and GM colony production was found. The CFU-Eo stimulating effect of patient serum was in the range of the CFU-Eo stimulating effect of normal serum, after the addition of 5 u/ml of recombinant murine IL-5. The results suggest that eosinophilia was caused by IL-5 and GM-CSF production by rhIL-2 stimulated CD4 positive lymphocytes. The location on chromosomes 5 of the genes for IL-5, GM-CSF and IL-3 may be associated with regulation of expression, by a common mechanism, of all the factors known to be involved in eosinophil production. This mechanism may be activated by IL-2 stimulation. The separate location on chromosome 17 of the G-CSF gene may explain the ability of IL-2 to produce a distinct stimulus to eosinophil but not neutrophil production.

Adult↗