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Biomedical subjects

F Balkwill

Publications and source records attributed to F Balkwill.

50 records · Page 3Linked to original sources
PubMed1985

Antiviral and antiproliferative effects of interferons in quiescent fibroblasts are dissociable.

Quiescent mouse Swiss 3T3 cells or human fibroblasts treated with interferon for only 2 hr before the addition of serum are effectively protected against virus infection for up to 24 hr after the addition of serum and the removal of interferon. In sharp contrast, exposure of quiescent fibroblasts to interferon only before addition of serum or the peptides epidermal growth factor and insulin, has no inhibitory effect on cell proliferation. Further, even when interferon is added after the addition of growth factors, an exposure of several hours is required to inhibit stimulation of DNA synthesis. These findings strongly suggest that the antiviral action of interferons is dissociable from their ability to inhibit cell proliferation. The implications of these findings for elucidating the molecular events leading to the biological responses elicited by interferon are discussed.

Animals↗
PubMed1985

Use of interferon in the management of patients with subacute sclerosing panencephalitis.

Six patients (five male, one female) with subacute sclerosing panencephalitis were treated with purified lymphoblastoid interferon, using a combination of intravenous and lumbar intrathecal routes. The first symptoms of the disorder occurred between seven and 16 years of age, and the length of the illness before treatment varied from 1 1/2 to 12 months. All six patients were in the first clinical stage of the disorder. After a limited period of follow-up there has been no clinical improvement. Nil or low levels of interferon were found in CSF two hours after intravenous injection, but CSF levels of interferon were maintained for at least 24 hours after intrathecal injections. Side-effects of interferon included pyrexial reactions, especially after high-dose intravenous therapy (six), lethargy (four), a transient rise in blood pressure (two) and a reduction in platelet count (six). Staphylococcus epidermidis was grown from the CSF of one patient.

Adolescent↗
PubMed1984

Monoclonal antibodies that distinguish between subspecies of human interferon-alpha and that detect interferon oligomers.

Monoclonal antibodies to human interferons (HuIFN) of the alpha-class have been prepared by screening against 125I-labeled IFN in a rapid liquid-phase radioimmunoassay. All of the six antibodies produced react with HuIFN-alpha 2 and with some components of HuIFN-alpha N (Namalwa); three of the antibodies also bind HuIFN-alpha 1, and these either do not bind or bind very weakly the 25K component of Namalwa. Reaction of the antibodies with IFN components blotted onto nitrocellulose after separation on reducing gels suggests that two of the antibodies are against conformational determinants, whereas the epitopes recognized by the other antibodies are not destroyed by reduction or SDS treatment; these antibodies can be used to detect the presence of oligomers in IFN preparations. From the reaction of the antibodies with different alpha-IFN in immunoblots, in an antiviral assay, and in an ELISA, it was concluded that at least five different epitopes are recognized by the six antibodies, only one of which is non-neutralizing.

Animals↗
PubMed1983

A paralytic disease in nude mice associated with polyoma virus infection.

Nude mice (nu/nu), heterotransplanted with human tumours and kept in isolators, were found to suffer from wasting and posterior paralysis. Electron microscopy of spinal cord tissue revealed virus particles in the oligodendrocytes consistent in size (35 to 40 nm), morphology and distribution with those of the polyoma--SV40 sub-group of papovaviruses. Serology and restriction enzyme analysis of the virus genome showed that the virus was the murine polyoma A2 strain. Inoculation of uninfected nude mice with 10(7) TCID50 of polyoma A2 strain virus produced a similar disease in these mice with wasting and, after 10 to 23 weeks, paralysis of the hind legs of all surviving mice. Extensive myelin disruption was seen throughout the brain stem and sacral region of the spinal cord and high titres of polyoma virus were found in the whole brain (10(8.8) TCID50/brain) and in the spinal cord (10(6.8) TCID50/spinal cord).

Animals↗
PubMed1980

Demyelination and wasting associated with polyomavirus infection in nude (nu/nu) mice.

Nude (nu/nu) mice bearing human tumour heterografts were affected with posterior paralysis and wasting. There was demyelination and infection of the oligodendrocytes of the spinal cord with a papovavirus. Similar virus particles and inclusion bodies were found in the bronchial epithelium, which showed histopathological changes. Similar changes were shown by the epithelia of the renal pelvis, ureter and choroid plexus. The virus was found in a transplantable human tumour, and evidence of spread by contact was also obtained. Intracerebral injection of spinal cord suspension from infected mice resulted in virus infected cutaneous carcinomata, demyelination with virus particles in the oligodendrocytes and posterior paralysis with wasting in adult nude mice. The suspension injected intraperitoneally into newborn Syrian hamsters produced tumours similar to those produced by murine polyoma. No evidence of infection was found in mice from the colony of origin. The virus was identified as murine polyoma Wild Type A2.

Animals↗
PubMed1978

Inhibition by lymphoblastoid interferon of growth of cells derived from the human breast.

Human lymphoblastoid interferon inhibited the growth in vitro of fibroblasts and epithelial cells from normal, hyperplastic and neoplastic human breast tissue. At an interferon concentration of 10(3) inter-national units (IU) per ml, the inhibitory effects on monolayer growth were completely reversible but the growth potential of cells at lower density in colony-forming cultures was not completely recovered. Studies on the cell cycle distribution of interferon-treated cells demonstrated that the growth-inhibitory effect was not due to an effect on one specific phase of the cell cycle, but to a lengthening of all phases.

Breast↗
PubMedDate not supplied

The effect of cytokines on cultured mononuclear cells from patients with B cell chronic lymphocytic leukemia.

In the past 5 years a number of cytokines have been identified that control B cell development, proliferation, and maturation. The role of such cytokines in the evolution, pathophysiology, and treatment of B cell malignancies is an area of great interest. The in vitro response of freshly isolated peripheral blood mononuclear cells from patients with B cell chronic lymphocytic leukemia (B-CLL) and a high white cell count, to four cytokines, IFN-alpha, IFN-gamma, IL-2 and TNF, was studied. No culture condition or cytokine resulted in a significant increase in cell number over 4 days, cells survived better in autologous serum than in heat inactivated foetal calf serum, and a small but significant increase in blast cells was seen when the cells were cultured in IL-2. There was a discrepancy between uptake of thymidine and increase in cell number which can be explained by the low labelling index of these cultures and the fact that cells can incorporate [3H]-thymidine without going into mitosis. The majority of cultures produced biologically active TNF at levels ranging from 1 to 40 pg/ml. In IFN-alpha treated cultures TNF levels were decreased. Cultures contained biologically active IL-6 at levels ranging from 2 to 2800 U/ml. IL-6 production was not influenced by other cytokines. Thirteen of 28 patients had detectable IL-6 in their serum, but in cells lysed no more than 2 h after removal from the patient, message for IL-6 could not be detected by Northern blotting. Cells also failed to express IL-1 beta mRNA but seven of eight patients had low levels of TNF message. Preliminary data using in situ hybridization techniques revealed that whilst no mRNA for IL-6 was detected, TNF and IL-1 beta mRNA were detected in a minority of mononuclear cells.

Antigens, Neoplasm↗