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N Matthews

Publications and source records attributed to N Matthews.

11 recordsLinked to original sources
PubMed1979

Tumour-necrosis factor from the rabbit. III. Relationship to interferons.

Tumour-necrosis factor (TNF) is growth-inhibitory or cytotoxic to certain tumour cell lines, and is present in the serum of rabbits injected i.v. with BCG and endotoxin 2 weeks apart (TNF serum). TNF serum also has interferon activity, and as TNF and interferons have a number of properties in common their relationship has been investigated further. TNF was assayed by cytotoxicity in vitro against L cells and interferon by a CPE-inhibition assay with Semliki Forest virus.TNF appears not to be an interferon, on the following bases:1. TNF activity could be separated from the Type I interferon of TNF serum by passage through a Cibacron blue-agarose column or by sequential salt precipitation, ion-exchange chromatography and gel filtration.2. Preparations of Type I interferon induced by poly I, poly C or virus lacked TNF activity.3. Though it was not possible to compare TNF with rabbit Type II interferon (as methods used to induce Type II interferon in other species were unsuccessful in the rabbit) rabbit TNF has a number of properties which distinguish it from the Type II interferons of other species.4. Rabbit TNF inhibited the growth of a human melanoma cell line, and also had effects on certain mouse and rabbit cell lines, whereas the anti-cellular effects of interferons are reported to be species-specific.

Animals↗
PubMed1978

Tumour-necrosis factor from the rabbit. I. Mode of action, specificity and physicochemical properties.

Sera from rabbits injected with BCG and then with endotoxin contain a factor (tumour-necrosis factor TNF) which, even at high dilutions, is cytotoxic in vitro for mouse L cells and some other cell lines. Using a 51Cr-release assay, cytotoxicity was detected as early as 7-8 h after addition of TNF serum to L cells and cell death was evident microscopically by 24 h. TNF was cytotoxic at 37 degrees C but not at 21 degrees C or 4 degrees C, and acted on both dividing and non-dividing cells. The antimetabolites sodium azide and dinitrophenol partially protected L cells from TNF, suggesting that actively metabolizing cells are the most sensitive. Treatment of L cells with trypsin did not delay cytotoxicity nor was cytotoxicity inhibited in the presence of various saccharide derivatives of cell-surface glycoproteins. Rabbit TNF was remarkably stable with a mol. wt. of 40-50,000. It was eluted with the more acidic serum proteins on ion-exchange chromatography, but precipitated in 50%-saturated ammonium sulphate. Sensitivity to TNF could not be correlated with tumourigenicity of several animal and human lines tested nor with the production of C-type viruses.

Animals↗
PubMed1978

Tumour-necrosis factor from the rabbit. II. Production by monocytes.

Mononuclear cells from normal rabbit blood were cytotoxic to a number of cell lines in vitro. The cytotoxic cells were contained in the monocyte-enriched fraction adherent to plastic. Supernatants of the monocyte-enriched fraction had the same cytotoxic specificity as the parent cells. The cytotoxic factor precipitated in 50% saturated ammonium sulphate solution and on gel filtration was heterogeneous with a mol.-wt. range of 30--50,000 u. On the basis of specificity and molecular characteristics, this cytotoxic factor closely resembles rabbit tumour-necrosis factor (TNF) suggesting that TNF or a closely related factor is a normal product of mononuclear phagocytes.

Animals↗
PubMed1978

Meningococcal infection and proteolytic control.

Cascade enzyme inhibitors (C1-esterase inhibitor, C3b inactivator, antithrombin III) and other major proteolytic enzyme inhibitors (alpha 1 trypsin inhibitor, alpha 1 chymotrypsin inhibitor, inter-alpha-trypsin inhibitor, alpha 2 macroglobulin) as well as C3 and alpha 1 acid glycoprotein, have been examined in the sera of Nigerian patients suffering from meningococcal infection of varied severity. Patients with meningococcaemia had lower serum concentrations of important inhibitors than did patients with localised meningitic infection. Within the coccaemic group, those who died had the lowest values, notably of antithrombin III and alpha 2 macroglobulin (and also of C3). The clinical end-result of meningococcal infection may be related to the degree of disequilibrium of the linked system of proteolytic control induced by the meningococcal endotoxin.

Antithrombin III↗
PubMed1976

Lymphoid cell fractionation by aggregated immunoglobulin-agarose columns.

Fractionation by columns of aggregated rat immunoglobulin (Agg Ig)-agarose was investigated as a method of separating different populations of lymphoid cells. With rat spleen cells, Agg Ig columns retained phagocytes, IgM- and IgG-antibody-forming-cells, cells mediating antibody- or PHA-induced lysis of chicken erythrocytes, and specifically immune splenocytes lytic to chicken erythrocytes without exogenous antibody. Agg Ig columns did not selectively remove 'B lymphocytes' (surface-Ig-bearing lymphocytes with or without EAC' receptors), or T lymphocytes capable of PHA-induced proliferation or graft-versus-host reactivity. With mouse spleen cells, Agg Ig columns retained alloimmune cytotoxic T cells.

Animals↗
PubMed1976

Characterization of cytotoxic spleen cells and effects of serum factors in a syngeneic rat tumour system.

Splenocytes from inbred Wistar rats bearing a syngeneic squamous cell carcinoma (Spl) were fractionated by several techniques to characterize the lymphoid cells cytotoxic to the tumour in vitro. The anti-tumour cytotoxicity is presumably mediated primarily by T lymphocytes because it was greatly reduced by removal of T lymphocytes with heterologous anti-T serum plus complement but not by removal of other cell types. Cytotoxicity could be blocked at the tumour cell but not at the effector cell by sera taken late in tumour growth. Sera taken earlier in tumour growth could induce cytolysis of tumour cells by normal splenocytes but only if the tumour cells were treated with serum and washed before addition of the effector cells. Although splenocytes from normal and tumour-bearing rats were equally effective at lysing antibody-coated target cells it is unlikely that this mechanism is important in vivo as sera from early in tumour growth onwards contained factors (immune complexes?) which inhibited antibody-induced lymphocytolysis.

Animals↗
PubMed1975

Analysis of inhibition of lymphocyte cytotoxicity in human colon carcinoma.

Serum inhibition of autochthonous lymphocyte cytotoxicity for tumour cells has been studied in 112 cases of colonic carcinoma. Addition of patient's serum to the lymphocyte tumour cell reaction mixture resulted in decreased cytotoxic reactivity of lymphocytes from 8 of 39 cytotoxic positive cases. It was also shown that sera could inhibit if separately preincubated with the lymphocytes (4 cases) or the target cells (2 cases). A tumour antigen preparation inhibited only when incubated with the lymphocytes. Inhibition by serum or antigen appeared to be specific for colon carcinoma. Four cases were specially studied to determine the mode of lymphocyte killing of tumour cells: in 3 it was mediated largely if not entirely by T lymphocytes, and in the fourth by both T and non-T cells. The findings support the view that T lymphocytes lose their anti-tumour reactivity in vivo in the presence of circulating antigen or antigen-antibody complexes such as would occur with progressive tumour growth.

Adult↗