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Biomedical subjects

D A Morgan

Publications and source records attributed to D A Morgan.

At least 145 records · Page 8Linked to original sources

The management of locally advanced carcinoma of the breast by Nolvadex (tamoxifen): a pilot study.

Fifty-one postmenopausal women with locally advanced breast cancer were treated initially by Nolvadex (Tamoxifen, ICI) alone and followed prospectively between 1974 and 1982. Twenty-three patients (40%) showed an objective response to therapy of whom 17 (75%) remain in remission at median follow-up of 36 months. Patients who failed to respond to Nolvadex therapy were treated by radiotherapy which achieved local control in 64%, with 10 months median duration. Nolvadex therapy conveys a good quality lengthy remission to a sizeable minority of patients. The majority of those who fail to respond are satisfactorily managed by radiotherapy.

Aged↗

Phenotypic diversity within clones of human normal T cells.

Human normal T cells were selected for in vitro cloning according to the expression of T4, T8 or T10 antigens on individual cells. Clones were produced from each of these cells irrespective of the antigenic phenotype of the parental cell. The cloned progeny manifested, in many cases, shifts in antigen expression. Thus, T4+T8- cells gave clones expressing predominantly T4-T8+ and vice versa. The clonal expression of T4 and T8 seemed to be mutually exclusive. Antigenic shifts were recorded also in clones derived from T4-T8-T10- cells, resulting in T10+ clones which were also either T4+ or T8+ and from T4+T8-T10+ cloned cells yielding clones of either T4+ or T8+ cells. Testing functional properties we found that NK activity was mediated not only by T10+ cells but also, in some cases, by T4+ and T8+ cells. Moreover, TCGF production, which may reflect helper activity, was mediated not only by T4+ cells. Only the cytotoxic (CTL) activity seems to be confined to the T8 phenotype. Thus, it appears that T antigens, which seemed to be molecular markers of differentiation, are not markers for terminal differentiation and do not always reflect defined functional properties. These conclusions are drawn from cloning of normal T cells which manifest properties different from those of T-cell lines or T hybridomas.

Antibodies, Monoclonal↗

Gonadotrophin-producing seminoma: a distinct category of germ cell neoplasm.

Gonadotrophin-producing seminomas can be identified in two ways: detection of human chorionic gonadotrophin (HCG) in the serum or urine, or histological identification of syncytiotrophoblastic giant cells, which can be shown to contain HCG by means of indirect immunoperoxidase techniques. A review of the histories of 14 patients with such tumours shows that they are associated with a worse prognosis than that of 'typical' seminomas, and tend to present with a more advanced stage of disease. These tumours are thus distinct, clinically and biologically, from typical seminomas, and their treatment needs to be planned accordingly.

Chorionic Gonadotropin↗

Production of human T-lymphocyte clones. I. monoclonal culture and functional cytotoxic maturation.

Well-defined clones of human T-lymphocytes were produced and monoclonal T-cell cultures were maintained for long periods of time. Single T-lymphocytes were isolated with the help of a micropipette from PBL cultures prior to any cellular stimulation (MLC), collected separately at the bottom of a 200 microliter tissue culture microwell under the control of stereomicroscopic observation, and cultured with irradiated lymphoid cells in the presence of TCGF. After 12 days, 20-50% of the seeded wells exhibited clones of 3 x 104-105 T-lymphocytes, which were transferred to larger tissue culture wells (2 ml, LINBRO) for long-term culture. Recloning of the growing cloned cells under the same conditions as the primary culture was carried out successfully. In the preliminary cytotoxic assays performed in 11 clones (a) a marked activity directed against lectin-coated targets was observed in may clones; (b) an important NK-like activity was exhibited by the clone 45B9 (65% of the tested cells lysed K562 cell targets); (c) 2 clones did not demonstrate cytotoxic activity against either PHA-coated L-1210 cells or K562 cell targets. These results could be explained hypothetically by the difference of functional maturation of T-cells within each clone.

Cell Differentiation↗

The role of intrarenal vascular reconstruction for arteriovenous fistula.

Recent reports on the use of embolization to treat intrarenal arteriovenous fistula have suggested that there is little need for surgical reconstruction. We report the successful use of intrarenal vascular reconstruction in a patient who presented with a large intrarenal arteriovenous fistula and hypertension to emphasize the fact that there still are cases that need surgical repair.

Adult↗

Polyenzymatic activation of cellular hydrolases induced by interferon; its role in cell lysis and other interferon--related phenomena.

Treatment of human cultured T cells by interferon (IFN), which enhances cell-mediated cytotoxicity directed against human K562 cell targets (NK-like activity) induces an activation of cell hydrolases. Treatment of mouse cultured L929 cells by IFN and double strand RNA enhancing cell autolysis induces first an activation of tested hydrolases (hexosaminidase, beta-glucuronidase, acid and alkaline phosphatases). Polyenzymatic activation of hydrolases induced by IFN is similar to coordinate enzymatic induction described by Hosli which occurs by lack of specific enzyme when non-digestible substrates are absorbed by cells. It is hypothesized that the polyenzymatic activation which accounts for cell lysis is a general defense mechanism which might also explain other actions related to IFN such as antiviral effect, inhibition of cell division, diminution of protein synthesis and cell surface alteration.

Animals↗

Evidence for cytotoxic functions in well-defined human T cell clones.

Long-term cultures of T lymphocytes from PBL of normal individuals and cancer patients grown in presence of TCGF exhibited cytotoxic activity directed against a variety of targets. In order to separate the subpopulations responsible for the different cytotoxic activities, cultured T lymphocyte cloning was performed. Production of T cell clones were obtained at a high yield by direct isolation and culture of single T cells. Preliminary analysis of cell-mediated cytotoxicity showed that 8 out of 11 clones were cytotoxic against both PHA pretreated L1210 and K562 target cells. In addition, within a clone, only a percentage of cells expressed the cytotoxic function. We suggested that this finding is due to the different stage of maturation of the cloned cells and this hypothesis correlate with their morphology, which is not identical for all the cells within a clone.

Animals↗

[Identification of cytotoxic cells responsible for lysis of target cells pretreated with concanavalin A in spleen populations of pregnant mice with suppressive activity].

During an alloimmunization, killer cells which lyse target cells only in the presence of a lectin are generated. That these cells, as well as suppressive cells, share immunocytological properties with specific killer cells, leads to the hypothesis that these cells may be concerned with the mechanism of immunosuppression. Two experimental results presented in this paper are consistent with this hypothesis: 1) Spleens from H-2k mice pregnant by H-2d males which bear a high suppressive activity also contain a relatively large number of killer cells having the ability to lyse Concanavalin A treated target cells and 2) supernatants of suppressive systems generated through an MLC block the cytolysis of specific target cells by the bound killer cells.

Animals↗

Functional and morphologic characterization of human T cells continuously grown in vitro.

Long-term growth (now over 13 months) of thymus-derived lymphocytes from numerous normal human bone marrow and peripheral blood cell samples was accomplished by using a factor present in media obtained from mitogen-stimulated human peripheral blood lymphocytes. This long-term growth could neither be initiated nor maintained by mitogens alone. All cell cultures were greater than 90% E rosette-positive, whereas the tests for B cell markers, surface IgG and IgM, and EAC rosette were routinely negative. There was no evidence for the presence of granulocytes, monocytes, and their precursors in these cultures. The E rosette-positive cells were then tested to see if they had T cell functions. PHA, Con A, and pokeweed mitogens stimulated lymphproliferative responses in these cultures comparable to those of fresh peripheral blood cells. These proliferating cells were also able to release cell mediators, such as interferon and colony-stimulating activity. Further evidence for the T lymphocyte nature of these cultured cells was obtained from one-way mixed leukocyte cultures in which these cells responded to but were unable to stimulate allogeneic cells. The functional and morphologic characteristics of these cultured cells show that these cells are T cells that grow continuously in vitro.

Cells, Cultured↗

Selective in vitro growth of T lymphocytes from normal human bone marrows.

Selective growth of T lymphocytes occurred when unfractionated normal human bone marrow cells were cultured with conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes (Ly-CM). Cultures of up to 90 percent T cells have been maintained for more than 9 months. The T cells exhibited a strict growth dependence upon Ly-CM and were consistently negative for Epstein-Barr viral information.

Bone Marrow Cells↗