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Biomedical subjects

R C Rees

Publications and source records attributed to R C Rees.

At least 145 records · Page 8Linked to original sources
PubMed1983

Rat natural killer cell activity against lymphoid and nonlymphoid tumor cells and normal rat cell lines.

Natural cytotoxicity in the rat was assessed against solid tumors and normal and embryonic rat monolayer culture lines, and the results were compared with rat natural killer activity towards syngeneic, allogeneic, and xenogeneic lymphoma targets. The targets tested showed a very wide range of susceptibility to lysis by peripheral blood and spleen effector cells in both 4- and 18-hr cytotoxicity assays. Cytotoxicity toward the mouse lymphoma, YAC-1, and rat sarcoma LT1 targets was relatively high in a 4-hr assay, compared with that toward the other cell lines used in the study. At 18 hr, increased killing was seen against YAC-1, LT1, SP3 (rat pheochromoblastoma), F2304 (rat embryonic cells), and normal rat kidney cells, while a significant increase in susceptibility with time was not observed with other rat targets: W/Fu-T (sarcoma); ERTh/V-G (sarcoma); R35 (mammary tumor); and W/Fu-P21 (embryo fibroblasts) targets. The cytotoxicity against all of the targets tested was not age restricted and was potentiated by rat interferon. Natural cytotoxic reactivity was seen with effector cells from the blood, spleen, and peritoneal cavity of both W/Fu (euthymic) and Rowett nude (congenitally athymic) rats. Cytotoxic effector cells from the blood were present in the low-density fractions recovered from discontinuous Percoll density gradients and, as shown previously for lymphoma target cells, a strong correlation was observed between the killing of embryonic, normal, and solid tumor targets and the presence of large granular lymphocytes. These results indicate that the naturally cytotoxic rat effector cells for normal fibroblast and bone marrow targets, lymphomas-leukemias, embryonic cell lines, and solid tumor targets are all included in the large granular lymphocyte subpopulation.

Aging↗
PubMed1982

Depressed spontaneous natural killing and interferon augmentation in patients with malignant lymphoma.

A substantial proportion (44%) of peripheral blood lymphocyte samples from 41 patients with malignant lymphoma have been shown to have depressed or undetectable levels of natural cytotoxicity against the leukaemic cell line K562 in a 4-hr [51Cr]-release assay. No correlation was found between low levels of natural killer (NK) cell activity and either the age of the patients, total or differential white blood counts, or the type or stage of disease. Furthermore, pre-treatment of lymphocytes with human lymphoblastoid (Namalva) interferon failed to enhance NK levels in 5/11 patients with Hodgkin's disease and 5/8 patients with non-Hodgkin's lymphoma, and was in contrast to the response of control peripheral blood lymphocytes assayed under the same test conditions. The lack of responsiveness to interferon of peripheral blood NK cells from lymphoma patients was not wholly associated with those patients shown to have low levels of spontaneous NK activity.

Adolescent↗
PubMed1982

Properties of a Herpes virus-transformed hamster cell line--I. Growth and culture characteristics of sublines of high and low metastatic potential.

A Herpes virus hominis type 2-induced tumour line of the Syrian hamster, designated HSV-2-333-2-26, exhibited a low level of spontaneous metastasis from the primary subcutaneous tumour mass. Two lung foci, met A and met B, were resected and transplanted s.c.; both lines showed an elevated metastatic potential compared with the parent cell line such that all animals inoculated with these cells developed metastatic disease within 40 days after resection of the primary tumour. Neither the rapidity of cell growth in vivo or in vitro, nor anchorage-independent growth or degree of attachment to a solid substrate in vitro are implicated in the altered behaviour of the metastatic cell lines.

Animals↗
PubMed1982

Natural killer cell activity and response to phytohaemagglutinin compared with the histological diagnosis of patients with transitional cell carcinoma of the bladder.

In vitro tests of immune reactivity in patients with transitional cell carcinoma (TCC) of the urinary bladder were compared with the clinical and histological diagnosis. Response of peripheral blood lymphocytes to the mitogen phytohaemagglutinin (PHA) tended to be reduced in patients with more advanced disease, although the difference between patients with advanced disease and those with early disease or controls was not statistically significant (P greater than 0.05). Assessment of natural killer (NK) cell activity in the same patients showed no change in levels of reactivity at any stage of the disease. There was no difference between the NK cell activity of patients with TCC of the bladder and normal controls.

Aged↗
PubMed1982

Studies on the antitumour effects of N-137.

The antitumour properties of the drug N-137 were assessed in vivo in two murine T lymphoma models and two naturally metastatic hamster fibrosarcomas of Herpesvirus hominis aetiology. N-137 therapy caused a significant delay in the subcutaneous growth rate of both lymphomas (EL4 and TLX9) and in many cases completely prevented tumour appearance when administered at high doses. The antitumour effect observed in both systems was shown to be dose dependent. In contrast, N-137 therapy failed to influence the growth of two hamster fibrosarcomas (HSV-333-2-26 Met A and Met B lines), and drug administration prior to or following resection of Met B tumours failed to influence the development of natural metastases as measured by monitoring animal survival.

Animals↗
PubMed1982

Comparative studies of transformed hamster cells by Herpesvirus hominis types 1 and 2.

Hamster embryo cells transformed by Herpesvirus Type 2 (HSV-2) virus (two separate cell lines) and by HSV-1 virus (one cell line) were inoculated into hamsters. The morphological appearance of tumours was studied by both light and electron microscopy, and the results compared to similar studies of tumours induced by SV40 virus. The tumours were also tested for immunogenicity, and for susceptibility to contact suppression with BCG. The results indicated that the tumours induced by inoculation of HSV-transformed cells were distinct from those of other DNA viruses; that the two cell lines transformed by HSV-2 were very similar but distinct from the cell line transformed by HSV-1; that all 3 HSV tumour cell lines were weakly immunogenic, and 2 were susceptible to contact inhibition with BCG. The relevance of the morphological and immunogenic properties of the animal tumour is discussed with relation to the possible importance of the findings to human malignant disease.

Animals↗
PubMed1981

Corynebacterium parvum stimulation of adherent and non-adherent cytotoxic cells in mice.

Two naturally occurring cytotoxic cell populations have been identified in the peritoneal cavity of mice inoculated with C. parvum (CP), and are distinguishable on the basis of target-cell reactivity and intrinsic properties. The first effector cell was non-adherent to nylon wool and glass and non-phagocytic. These cells were selectively cytotoxic to the NK-sensitive target cell line K562, and present in the peritoneal cavity of mice 2 days after treatment with 700 micrograms of CP. The second cytotoxic effector cell was adherent to nylon wool and glass, and killed EL4 lymphoma cells derived from in vivo tumour transplants; these target cells are susceptible to phagocytic cell killing, but not NK-cell cytotoxicity in short-term (4h) assays. The adherent cytotoxic population of effector cells was present 4 days after inoculation of CP. In vivo studies showed that CP injected i.p. induced resistance to i.p. challenge with lymphoma EL4 cells, but no resistance was evident when the challenge dose was administered s.c. Adoptive-transfer studies showed that the effector cell type responsible for inhibiting tumour growth was nylon-wool adherent, probably CP-activated macrophages.

Animals↗
PubMed1981

Antitumour effects of tilorone hydrochloride on the in vivo growth of chemically induced and spontaneously arising rat tumours.

Inhibition of subcutaneous tumour growth, following treatment with tilorone hydrochloride, was observed with two transplantable methylcholanthrene-induced rat sarcomas (Mc7, Mc4), but similar drug treatment was ineffective against two rat hepatomas induced by dimethylaminoazobenzene (D23, D30). Successful therapy of sarcoma Mc7 and Mc4 subcutaneous growth was not accompanied by the development of specific antitumour immunity, although with hepatoma D30, which grew out following tilorone hydrochloride treatment, specific immunity was demonstrated, indicating that drug treatment does not prevent the initiation of an antitumour response during progressive tumour development. Under defined experimental conditions tilorone hydrochloride also prevented pulmonary metastases from a subcutaneous tumour graft of epithelioma SP1 and mammary carcinoma SP22, as measured by an increased survival or treated rats.

Adenoma↗
PubMed1979

High nonspecific reactivity of normal lymphocytes against mycoplasma-infected target cells in cytotoxicity assays.

Several rat tumor cell cultures were deliberately infected with three species of mycoplasma commonly found as contaminants of cell lines grown in vitro, and the effect of mycoplasma infection on the results of cytotoxicity assays was examined. Lymph node cells and spleen cells from normal animals showed an apparently high spontaneous cytotoxic activity against tumor cells infected with either M. arginini or M. hyorhinis, but the reactivity against cells infected with M. orale was not significantly higher than that against uninfected cells. The high reactivity towards tumor cells infected with M. arginini and M. hyorhinis bore a close resemblence to natural cell-mediated immunity in that spleen cells were much more reactive than lymph node cells, spleen cells from nude mice were as effective as spleen cells from normal mice, and the reaction crossed both strain and species barriers. However, closer examination revealed that the cytotoxic effects were directly caused by depletion of arginine or other essential nutrients from the medium. These findings imply that a cautious approach should be taken when interpreting certain aspects of spontaneous cell-mediated cytotoxicity, and that the greatest care be taken to ensure that the cells used as targets in any cytotoxicity test are mycoplasma-free.

Animals↗
PubMed1979

Tumorgenicity of herpesvirus hominis type 2-transformed cells (line 333-8-9) in adult hamsters.

Inoculation of adult hamsters with greater than 1.5 X 10(2) Herpesvirus type 2 (HSV-2) transformed hamster embryo fibroblasts induced rapidly growing tumours at the site of inoculation, in more than 50 per cent of animals. The tumours were examined by light and electron microscopy, and were histologically anaplastic fibrosarcomas. Lung metastases were frequently found in tumour-bearing animals; these were usually only seen microscopically, and were cytologically similar to the primary tumours. The nature of tumour development showed similarities with naturally occurring tumours of man, and HSV-2 tumour is probably a better model of human cancer than other virus-induced tumours studied in the past.

Animals↗
PubMed1979

Spontaneous development of cytotoxic activity in cultured lymphnode cells from tumour-bearing rats.

Incubation in vitro of lymphnode cells (LNC) from rats bearing a transplanted syngeneic methylcholanthrene-induced sarcoma (Mc7) resulted in the generation of a potent cytotoxic activity. Four to seven days' culture was required for development of cytotoxic activity, which was shown to be mediated by a heat-stable soluble factor. The cytotoxicity was not detectable in a 3 h or 15 h 51Cr-release assay, but was demonstrated in a 48 h microcytotoxicity assay, where post-labeling with isotopically labelled cell precursors was used to quantitate cell survival. The cytotoxicity of the cultured tumour-bearer LNC and their supernatant factor was shown to be cross-reactive for tumour cell lines other than sarcoma Mc7, and was also expressed against adult or embryonic fibroblasts.

Animals↗
PubMed1978

Immune response of the draining and distal lymph nodes during the progressive grwoth of a chemically-induced transplantable rat hepatoma.

The immunological and histological changes occurring in the lymph node draining the site of a progressively growing intramuscular tumour (D192A) implant were monitored during a 4-week time course. Cell-mediated cytotoxicity against hepatoma-D192A and 15-day rat embryo cell targets, was detected with cells derived from the draining "lumbar" lymph node 4 days after tumour implantation and persisted up to the 2nd week of tumour growth, decreasing rapidly during the 3rd week. The observed lymph-node anergy demonstrated in cytotoxicity tests correlated with the histological findings, in that an initial marked paracortical (T-dependent) response also declined towards the end of the 3rd week of tumour growth. The B-dependent cortex showed active lymphocyte follicles in the 2nd week of the time course, and plasma-cell production continued until the experiment was terminated. These changes were shown to occur with the progressive increase in lymph-node mass. Serum antibody specific for the developing tumour was detected during the latter stages of tumour growth. The immunological and histological changes displayed were out of phase with those shown by the draining lymph node.

Animals↗
PubMed1978

Studies on the microcytotoxicity test. II. The uptake of amino acids ([3H]leucine or [75Se]methionine) but not nucleosides ([3H]thymidine or [125I]IUdR) or 51CrO24-provides a direct and quantitative measure of target cell survival in the presence of lymphoid cells.

We have studied the suitability of various commonly used radioactive materials for the direct post-labeling of adherent rat target cells in long-term cytotoxicity tests. The use of nucleosides at high concentration avoids the necessity of adding fluorodeoxyuridine to enhance nucleoside uptake by target cells, and reduces the degree of non-specific inhibition of nucleoside uptake caused by products released from effector lymphoid cells. However, when [125I]iododeoxyuridine was used for labelling, such inhibition was not completely avoided even at very high nucleoside concentration, necessitating the washing of target cells prior to labelling. Similarly, without prewashing, the uptake of 51CrO24-ions frequently failed to correlate well with the numbers of surviving target cells as assessed by cell counting. On the other hand, radiolabelled amino acids, when present at semi-saturating concentrations, were taken up quantitatively by target cells under all conditions tested. Furthermore, in comparison to [125I]iododeoxyuridine, radioactive amino acids showed little if any toxicity to target cells. The use of the gamma-emitting amino acid analogue, [75Se]selenomethionine, is particularly recommended.

Animals↗
PubMed1976

Studies on the microcytotoxicity test. I. Evidence that the effects of normal lymphoid cells on tumour cell growth in microtest plates may be caused by non-immunological modifications of the culture medium.

Lymph node cells from normal Wistar rats were found to affect the growth/survival of syngeneic chemically-induced solid tumour cells in the microcytotoxicity test. Whether inhibition or enhancement of tumour cell numbers occurred depended on the particular tumour cell type and, in some cases, on the particular in vitro subline used. Fractionation of LNC on nylon wool columns revealed that the two effects were mediated by distinct subpopulations of lymphoid cells: column-retained cells showed predominantly an inhibitory effect and column-eluted cells predominantly an enhancing effect. When column-retained and column-eluted cells were cultured under the conditions of the microcytotoxicity test but in the absence of tumour cell growth. The inhibitory activity was maximal within one hour of lymphocyte culture, while the enhancing effect developed slowly during incubation. Furthermore, the tumour cells themselves were found to produce growth-enhancing activity. It is proposed that interaction between these various supernatant activities accounts at least in part for the non-specific effects of normal lymphoid cells in the microcytotoxicity test.

Animals↗