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Biomedical subjects

C J Bishop

Publications and source records attributed to C J Bishop.

At least 19 recordsLinked to original sources
PubMed1989

T lymphocytes in infectious mononucleosis; effect of IL-2 on the outgrowth of Epstein-Barr virus-infected cells.

The addition of interleukin-2 (IL-2) to lymphocyte cultures from acute infectious mononucleosis (IM) donors dramatically increased the incidence of regression in such cultures and resulted in the emergence of an IL-2 dependent, CD3 Epstein-Barr virus nuclear antigen (EBNA)-negative cell population. Corresponding cultures seeded in the absence of IL-2 rarely regressed and were quickly dominated by IL-2 independent, CD3-negative, EBNA-positive cells. Lymphocyte cultures from Epstein-Barr virus (EBV) seropositive donors showed enhanced regression in the presence of IL-2 but failed to regress after the removal of the E-rosetting population. Cultures from EBV-seronegative donors showed no evidence of regression in the presence or absence of IL-2. E-rosetting cells isolated from cultures from acute IM donors that had been cultured in the presence of IL-2 lysed autologous and allogeneic lymphoblastoid cell lines.

Antibodies, Viral↗
PubMed1987

The role of reactive oxygen metabolites in lymphocyte-mediated cytolysis.

To examine the possible role of reactive oxygen metabolites in lymphocyte-mediated cytolysis, the morphology of cell death following the exposure of cells to reactive oxygen metabolites in vitro was compared with the morphology of cell-mediated killing in vitro of tumour cells by natural killer (NK) cells. Ultrastructural examination of human tumour cells that were dying following incubation for 60 min with the oxygen metabolite generating systems, xanthine-xanthine oxidase or t-butylhydroperoxide, showed that cell death in both instances was exclusively by necrosis. It was unclear which oxygen metabolites were involved in killing. Cell death was not decreased by the addition of superoxide dismutase, a scavenger of the superoxide anion, to the xanthine-xanthine oxidase mixture. Although the cells were not killed by incubation with 1 mM-hydrogen peroxide, the addition of catalase, a scavenger of hydrogen peroxide, to the xanthine-xanthine oxidase mixture significantly reduced cell death. The addition of scavengers for the hydroxyl radical to either the xanthine-xanthine oxidase mixture or t-butylhydroperoxide gave inconsistent protection. In contrast, tumour cell killing mediated by natural killer cells was by apoptosis, a morphologically distinct mode of cell death with a different basic mechanism, indicating that reactive oxygen metabolites are not directly involved in lymphocyte-mediated cytolysis.

Cell Line↗
PubMed1986

The ability of microfilariae to evade in vitro cell-mediated cytotoxicity.

When microfilariae (Mf) of Dirofilaria immitis, both uterine and systemic, were incubated in an in vitro cytotoxicity assay with neutrophils and sera from dogs with occult infections, some Mf remained free of adherent cells and consequently evaded cytotoxicity. The ability to evade cytotoxicity could not be related to the age of the Mf, and host albumin was not detected on any Mf, either uterine or systemic. However, it was shown that some Mf failed to bind IgM, IgG and C3 when incubated with occult sera. It is suggested that the ability of some Mf to evade serum-dependent, neutrophil-mediated cytotoxicity in vitro was related to differences in their antigenicity.

Age Factors↗
PubMed1986

Stimulation of neutrophil respiratory burst and iodination reaction by opsonized microfilariae of Dirofilaria immitis.

It has been shown that the interaction of Dirofilaria immitis microfilariae (Mf) opsonized with sera from infected but amicrofilaraemic dogs (occult dogs) stimulated the respiratory burst and degranulation of neutrophils as measured by chemiluminescence and iodination. Sera from normal and microfilaraemic dogs gave either low level or non-significant reactions. Since the sera required were also those required for neutrophil-mediated cytotoxicity to D. immitis Mf in vitro, the results suggested that the products of oxygen reduction as well as the myeloperoxidase system could be involved in the killing of Mf by neutrophils. However, whether these pathways have a major role to play in neutrophil-mediated cytotoxicity to Mf is uncertain, as various chemical and enzymatic inhibitors of the products of the respiratory burst were unable to prevent or reduce cytotoxicity. Azide, which is a known inhibitor of the iodination reaction, also failed to reduce cytotoxicity.

Animals↗
PubMed1986

T lymphocyte lines from arthritic synovial fluid: establishment and function.

T lymphocyte lines have been established, with the addition of interleukin-2 (IL-2), from the synovial fluid (SF) of patients with arthritis. Characterisation of seven of these SF-derived T cell lines showed them to be T3+, T11+, and to contain a significant proportion of T8+ cells (mean 41%). The proportion of T4+ cells varied among the lines, with a mean T4+/T8+ ratio of 0.6. A significant autologous mixed lymphocyte reaction (AMLR) was observed only in one of four T cell lines assayed. Two of four lines assayed showed natural killer (NK) cell-like activity, while one line displayed a significant suppressor activity, suggesting that the T cell population in SF contained NK-like cells or suppressor cells, or both, either of which may be selected in the establishment of SF-derived T cell lines.

Arthritis↗
PubMed1985

Regulation of the glucose phosphotransferase system in Brochothrix thermosphacta by membrane energization.

Uptake of 2-deoxyglucose, alpha-methylglucopyranoside, and glucose into intact cells of Brochothrix thermosphacta (formerly Microbacterium thermosphactum, ATCC 11509) was stimulated by KCN or CCCP. The glucose analogs were recovered almost totally as the sugar phosphates. Membrane vesicles were isolated from protoplasts and shown to be right side out by freeze fracturing and by using ATPase as a marker for the cytoplasmic membrane surface. Uptake of glucose into vesicles was dependent on the presence of phosphoenolpyruvate. NADH oxidation, K+ -diffusion gradients, and externally directed lactate gradients (pH greater than 7 initially) were used to generate transmembrane potentials across membrane vesicles. Above a threshold value of about -50 mV, uptake of glucose into membrane vesicles was reduced. Likewise, the maximum uptake of glucose and its two analogs into cells occurred when the protonmotive force was less than about -50 mV.

Adenosine Triphosphatases↗
PubMed1985

Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity.

A light and electron microscopic study of antibody-dependent lymphocytotoxicity was carried out with the object of elucidating the mechanisms responsible for the cell killing, the basis for the research being the relationship that has recently been shown to exist between the morphology of cell death and its pathogenesis. Chang liver cells coated with a rabbit anti-human antibody were used as targets and normal human peripheral-blood lymphocytes as effector cells. Cytotoxicity assays using release of 51Cr demonstrated extensive K-cell killing, thus validating the suitability of the model for morphological studies. Cell death displaying the features of apoptosis correlated with K-cell activity. A small amount of cell death by classical necrosis was observed, but its extent appeared to be unrelated to the presence of lymphocytes, to pre-treatment of the target cells with antibody, or to the magnitude of 51Cr release. The results support evidence indicating that lymphocytotoxicity depends on activation of a self-destruct program within the target cell. They do not favour a mechanism involving the production of plasma membrane lesions analogous to those responsible for complement-mediated immune cytolysis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

T lymphocytes in infectious mononucleosis. I. T cell death in vitro.

A large proportion of T lymphocytes isolated from the peripheral blood of acute infectious mononucleosis (IM) patients rapidly die when cultured in vitro, with greater than 50% dying within 12-15 h of seeding and up to 80% dying within 24 h. The cells die by apoptosis, a morphologically distinct mode of cell death that occurs in circumstances where death is a regulated event such as in embryonic development and hormone-dependent atrophy. In contrast, the level of cell death remained low in cultures of lymphocytes from controls and in the T cell depleted subpopulation from acute IM patients, with less than 2% and 10% of the lymphocytes dying by apoptosis after 36 h in culture, respectively. The rapid death of acute IM T cells in vitro does not involve soluble factors (including the serum fraction) or T cell to T cell contact. It is suggested that this observation may necessitate a re-evaluation of IM T cell function in vitro.

Cell Communication↗
PubMed1985

T lymphocytes in infectious mononucleosis. II. Response in vitro to interleukin-2 and establishment of T cell lines.

The addition of 20% interleukin-2 (IL-2) significantly reduced the percentage of T lymphocytes dying in vitro after being isolated from the peripheral blood of acute infectious mononucleosis (IM) patients. Moreover, the immediate addition of 20% IL-2 to freshly isolated blood allowed IM T cell lines to be readily established from the peripheral blood of acute IM patients. Characterization of seven of these IM T cell lines showed them to be T3+, T11+, T4-, T9- and generally T10-. Over half of the lines characterized were T8+. It will now be possible to re-evaluate IM T cell effector functions as previous assays of IM T cell functions may have been influenced by the presence of rapid and extensive T cell death in vitro.

Cell Line↗
PubMed1984

The role of apoptosis in atrophy of the small gut mucosa produced by repeated administration of cytosine arabinoside.

Progressive atrophy of ileal crypts and villi following daily administration of cytosine arabinoside to mice was found to be the result of suppression of mitosis and marked enhancement of apoptosis in the crypt epithelium. The amount of apoptosis produced by each dose decreased as the atrophy advanced. Mucosal regeneration after cessation of administration of the drug was due to increased mitosis in the crypts, and was associated with complete restoration of susceptibility of the crypt cells to further doses. During early regeneration, the wave of increased mitosis was accompanied by a wave of mildly increased apoptosis.

Animals↗
PubMed1984

Potentiation of anchorage-independent colony formation by sodium polyanethol sulphonate.

Sodium polyanethol sulphonate (SPS) when incorporated into rat erythrocyte lysate (REL) containing semi-solid agar medium at 1 mg ml-1. markedly enhanced colony formation by a number of anchorage-independent cell lines. REL usually needed to be included for the expression of SPS induced potentiation as in its absence SPS was generally cytotoxic. Studies suggested that SPS reduced the lag prior to colony initiation resulting in the earlier appearance of colonies and in a higher cloning efficiency. The effectiveness of SPS in potentiating colony formation by responsive cell lines was markedly influenced by the species of serum and to a lesser extent by differences between individual batches. Enhancement by SPS was greater with poorer foetal calf serum (FCS) batches than with better. This effect may have been partly due to SPS interfering with the action of a growth inhibiting serum component, possibly a lipoprotein. Studies in which delipidated FCS was substituted for normal FCS suggested that SPS was also able to compensate for the lack of a growth-promoting lipid component. Binding studies showed that initially 125I-SPS bound equally well at 4 degrees C and 37 degrees C with continued labelling occurring only at 37 degrees C. Autoradiography of cells labelled at 37 degrees C for 24 h revealed the presence of intracytoplasmic 125I-SPS.

Agar↗
PubMed1984

Immunological and ultrastructural aspects of the cell-mediated killing of Dirofilaria immitis microfilariae.

Neutrophils in the presence of serum from dogs with occult Dirofilaria immitis infections were shown to be cytotoxic to D. immitis microfilariae recovered from the blood of microfilaraemic dogs. This cytotoxicity was correlated with the presence of IgM and IgG antibodies on the cuticular surface of microfilariae incubated in the sera from occult dogs. Such antibodies were not observed on the surface of microfilariae incubated in sera from microfilaraemic or normal dogs. The neutrophil attack was directed at the cuticular crypts, at which sites the worms appeared to be structurally most vulnerable because of the absence of the outer layer of the cuticle. The IgM antibodies were shown to be bound preferentially to these sites. Our data suggested that the neutrophil-mediated toxicity involved both hydrogen peroxide release and degranulation.

Animals↗
PubMed1984

Effects of hypoxia on the kinetic and morphological characteristics of human melanoma cells grown as colonies in semi-solid agar medium.

An investigation was made of the cell populations that occur in the sequential strata of human melanoma ( MM96 ) colonies. Colonies were either grown for the full duration of culture in a 'physiological' atmosphere of 5% O2 (unperturbed colonies), or grown in this atmosphere followed by a final incubation in a hypoxic atmosphere of less than 0.1% O2. Both autoradiographic and ultrastructural studies indicated that cell changes similar to those which occur successively in monolayer cultures experiencing nutritional deficiency, exist concurrently in the sequential strata of the larger unperturbed colonies. At the margin with the necrotic core, approximately half of the cells showed morphological changes associated with death by apoptosis. The other half were undergoing necrosis. Observations on colonies incubated for the final 24 or 48 h in a hypoxic (less than 0.1% O2) atmosphere showed that many of these cells, although otherwise well preserved, developed oedema complicated by cytoskeletal rupture and extrusion of areas of damaged cytoplasm within membrane-bound vesicles. Although sudden-onset hypoxia did not appear to precipitate cell death in small colonies previously lacking a necrotic core, large colonies suffered a marked reduction in the width of their viable rims. Cell death under this circumstances was by necrosis, the same mode of death as occurs with infarction. The study indicated that apoptosis was associated with sub-acute cell death as occurs with progressive nutrient depletion and catabolite accumulation, whereas necrosis was associated with acute cell death as seen in previously compromised cells subject in addition to sudden-onset hypoxia.

Agar↗
PubMed1982

The effect of dietary restriction, adrenaline, hydrocortisone and surgery on the rates of death of 125IUdR-labelled, intravenously injected tumour cells in the lungs of mice.

Dietary restriction, adrenaline hydrocortisone or surgery reduced the rate at which pulmonarily arrested 125IUdR-labelled murine tumour cells were lost within 7 h of intravenous (i.v.) injection. Mice that had been adrenalectomised 10 days previously showed a normal intrapulmonary tumour cell loss rate with further surgery reducing this rate to approximately half that observed in normal mice that had been subjected to surgery. Thus, although it is likely that adrenal hormones play an important role in decreasing the rate of early intrapulmonary tumour cell loss, additional factors must be implicated. Mice subject to dietary restriction, adrenaline, hydrocortisone or surgery had reduced levels of in vitro growth inhibitor(s) in their sera. Despite this, individual surgically treated animals showed no correlation between serum in vitro-growth inhibitor levels and rate of loss of i.v. injected tumour cells from the lungs. Furthermore, the 24 h pre-incubation of tumour cells in inhibitor-rich serum did not influence the subsequent loss rate of such cells following i.v. injection into mice. Electron microscopic studies indicated that dietary restriction, adrenaline and surgery reduced the rate of intravascular tumour cell death. The decreased tumour cell death rate in mice receiving these treatments could not be related, however, to any consistent morphological change in the pulmonary vasculature. The decreased rate of intravascular tumour cell death in treated mice was followed by an increased number of lung tumours with only one of the tumour lines studied, indicating that the intravascular death rate need not be a major determinant of pulmonary tumour incidence.

Animals↗
PubMed1981

Biophysical and morphological correlates of kinetic change and death in a starved human melanoma cell line.

An investigation was made of the sequential biophysical and morphological changes that occur as cultured human melanoma cells (MM96) outgrow their supply of nutrient. Simultaneous buoyant-density and velocity-sedimentation fractionation experiments were used to characterize cells from 3 kinetically differing types of culture. Cells from exponential cultures were large, moderately dense and rapidly sedimenting; cells from post-exponential cultures were of intermediate size, less dense and much more slowly sedimenting; and dye-excluding cells from reproductively non-viable late post-exponential cultures were small, of widely variable though generally high density and sedimented moderately rapidly. Although reproductive viability was high in cells from both exponential and post-exponential cultures, depletion of clonogenic cells was seen at the extremes of the distribution profiles of cells fractionated by either method. This was particularly evident at the low-density extreme of the buoyant-density profiles where cells retained viability despite their loss of proliferative potential. As cells became post-exponential, nuclear size diminished in parallel with cell size, the number of microvilli declined, mitochondria condensed, cytoplasm vacuolated, the frequency of osmiophilic vacuolar inclusions rose, chromatin clumped and nucleoli became prominent. Progression to a reproductively non-viable late post-exponential state resulted in a continued parallel fall in nuclear size, increased cytoplasmic blebbing, further mitochondrial condensation, an increased proportion of cytoplasmic vacuoles containing osmiophilic material, the major part of which was melanin, and further clumping and margination of chromatin. Cells progressed rapidly from this newly described pre-apoptotic state to death by apoptosis, a process characterized by the budding and division of cells into a number of ultrastructurally well-preserved membrane-bound fragments.

Biophysical Phenomena↗
PubMed1981

The effect of 125I-5-iodo-2'-deoxyuridine labelling on murine tumour cells.

Labelling with 125IUdR at radioactivity concentrations commonly employed in studied with i.v. injected tumour cells (1.0-0.1 microCi/ml) was shown to reduce considerably the in vitro reproductive viability of mastocytoma tumour cells. Velocity sedimentation cell separation studies on mastocytoma cells that had been labelled for 12 h with 0.8 microCi/ml 125IUdR yielded a population that varied markedly between fraction with respect to distribution of label and, in parallel, with respect to induced loss of reproductive viability. A similar population of mastocytoma cells that had been labelled for 36 h with 0.01 microCi/ml 125IUdR yielded fractions where distribution of label was not associated with reduced reproductive viability. Although in vivo survival (as distinct from reproductive viability) of tumour cells injected i.v. and i.p. was not significantly altered within 7 h and 30 h respectively by the commonly used concentrations of 125IUdR, it is suggested that in studies of the fate of injected tumour cells exponentially growing cells be labelled with 125IUdR for intervals well in excess of population doubling times at concentrations less than or equal to 0.025 microCi/ml.

Animals↗