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Biomedical subjects

N Matthews

Publications and source records attributed to N Matthews.

At least 91 records · Page 5Linked to original sources
PubMed1981

Tumour-necrosis factor from the rabbit. V. Synthesis in vitro by mononuclear phagocytes from various tissues of normal and BCG-injected rabbits.

Tumour-necrosis factor (TNF) is an anti-tumour factor released into the serum of BCG-primed rabbits after i.v. injection of endotoxin. Although negligible amounts of TNF are produced in normal, unprimed animals after endotoxin injection, monocytes from these rabbits can produce TNF after endotoxin challenge in vitro. This paper (a) establishes the optimal conditions for TNF production in vitro by mononuclear phagocytes from various tissues and (b) compares tissues from normal and BCG-injected rabbits for TNF production in vitro. Optimal amounts of TNF are produced by mononuclear phagocytes in the presence of endotoxin. The TNF is newly synthesized, mainly in the first 7 h of culture, and has similar gel-filtration and ion exchange behaviour irrespective of its source. For both normal and BCG-injected rabbits, alveolar and peritoneal macrophages are the most potent producers, followed by blood monocytes, spleen macrophages and marrow cells. The liver is also an important site of TNF synthesis. In the tissues of BCG-injected rabbits there are more mononuclear phagocytes than in normal rabbits, and these cells have enhanced capacity to produce TNF. Taking both factors into account it can be calculated that, after injection of endotoxin in vivo, over 20 X more TNF would be produced by BCG rabbits than normal rabbits, assuming that the major sources of production are the lungs, blood, spleen and liver.

Animals↗
PubMed1981

Serum and salivary immunoglobulin A and free secretory component in ulcerative colitis.

Patients with ulcerative colitis have been investigated for evidence of defects in secretory immunity. Total serum IgA concentration, serum IgA antibody titres to Candida albicans, salivary IgA and free secretory component concentrations have been measured in thirty-six patients with ulcerative colitis and thirty-six normal controls. None of the parameters was significantly different between patients with proctitis and patients with extensive colitis or between the colitis patients and normal controls.

Adolescent↗
PubMed1981

Production of an anti-tumour cytotoxin by human monocytes.

Human monocytes incubated in vitro for 20 hr at 37 degrees release a factor which is cytotoxic to a number of human and murine tumour cell lines: untransformed cells appear to be less susceptible. A similar factor is produced under comparable conditions by myelomonocytic leukaemic cells and by macrophages derived from monocytes by in vitro culture for 8 days. Maximum production of the factor occurred in the presence of foetal calf serum or autologous plasma and endotoxin. The factor is newly synthesized in culture as its production is reduced if the monocytes are treated with cycloheximide or actinomycin D or incubated at lower temperatures. Freshly isolated monocytes do not release the factor on freeze--thaw or hypotonic lysis. The monocyte cytotoxin has apparent molecular weights of 34,000 on Ultrogel AcA54 gel filtration and 140,000 on gradient polyacrylamide gel electrophoresis; it has beta 2--gamma 1 electrophoretic mobility in polyacrylamide gel and does not appear to be C3a or arginase.

Animals↗
PubMed1980

Tumour-necrosis factor from the rabbit. IV. Purification and chemical characterization.

Serum from rabbits with BCG/endotoxin-induced shock is growth inhibitory or cytotoxic to a range ot tumour cell lines. The active component, tumour-necrosis factor (TNF), has been purified 1000-fold by sequential salt precipitation, ion-exchange chromatography and gel-filtration. TNF had a mol. wt of 67,000 on gradient PAGE and 39,000 on Ultrogel AcA44 gel-filtration. The isoelectric point was pH 5.1-5.2. TNF was susceptible to the proteolytic enzyme pronase, but resistant to trypsin or papain. On isopycnic ultracentrifugation it had a buoyant density of 1.27, confirming that it is protein in nature, with little or no carbohydrate. This is also suggested by its failure to bind to a range of lectins.

Animals↗
PubMed1980

Agglutinins to bacteria in Crohn's disease.

Sera from patients with Crohn's disease were tested for antibodies against organisms which are thought to cause inflammatory bowel disease in animals, or have been implicated in human Crohn's disease. Control sera were collected from healthy individuals and patients with ulcerative colitis. Sera from Crohn's disease and controls failed to agglutinate Clostridium colinum or Campylobacter sputorum subsp. mucosalis and two strains of Mycobacterium paratuberculosis (M26 and M27). Most of the sera agglutinated a Citrobacter freundii variant, Mycobacterium paratuberculosis (M28) and Mycobacterium avium (M41) but Crohn's disease sera did not differ from controls. A complement fixation test against Chlamydia gave more positive reactions in patients with Crohn's disease and colitis than in healthy controls. There was a clear difference between the sera from patients with Crohn's disease and other sera, including ulcerative colitis, in agglutination tests with the commensal coccoid rods of the genera Eubacterium and Peptostreptococcus; in these tests 54% of sera from Crohn's disease were positive compared with 11% in ulcerative colitis and none of the sera from healthy controls. All the results were essentially negative with the exception of those from Eubacterium and Peptostreptococcus and these bacteria merit investigation.

Agglutination Tests↗
PubMed1980

Recurrent meningococcal infections associated with a functional deficiency of the C8 component of human complement.

A patient is described who had a functional deficiency of the C8 complement component. His serum contained abnormal C8 which lacked some of the antigenic determinants of normal C8. The defect was associated with recurrent meningococcal infections due at different times to at least two strains. The patient's serum contained antibodies to meningococci and could induce phagocytosis and intracellular killing of the cocci by polymorphs. However, the serum was bactericidal only after the addition of C8-containing serum. As the patient did not give a history of susceptibility to other pyogenic organisms and has normal polymorph function, the circumstances of meningococcal infection must be unusual in that the plasma bactericidal activity critically determines the outcome: it may be that if large numbers of meningococci are not killed in the plasma, the polymorphs are overwhelmed.

Adolescent↗
PubMed1980

Immunogenicity of lipid-conjugated antigens. II. Anti-complementary activity and antigen trapping in the spleen.

The most immunogenic of various acylated human serum albumin (HSA) preparations also showed the greatest anti-complementary activity. This is due in part to their ability to activate the alternative pathway and consume complement components. Such molecules also adsorbed radiolabelled complement components readily and were themselves rapidly removed from the circulation after their intravenous injection. Highly lipidated C14 HSA (C14, fatty acid side-chains with 14 carbon atoms) was not itself mitogenic: unlike HSA it localized heavily to the red pulp as well as to cells of dendritic form in the splenic white pulp. The increased immunogenicity is found in lipidated HSA species which show the following features: hydrophobicity, anti-complementary activity, ability to activate complement, heavy localization in the red pulp and an unusual tendency to localize to dendritic cells of the while pulp.

Acylation↗
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↗