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Biomedical subjects

N Matthews

Publications and source records attributed to N Matthews.

103 records · Page 6Linked to original sources

Inhibition of K cell function by human breast cancer sera.

Sera from breast cancer patients and from female controls were tested for inhibition of lysis of antibody-coated target cells by human leukocytes (K cells). Sera from 39% of breast cancer patients, but from only 8% of controls, inhibited lysis by more than 30%. This inhibition was unrelated to the stage of the disease, the patient's age or whether the patient was pre- or post-operative. Inhibition was apparently not due to anti-HLA antibodies and did not correlate with the IgG level or anti-complementary activity of the serum. On fractionation by gel-filtration, inhibitory activity was found in fractions of higher molecular weight than IgG. As no IgG could be detected in these fractions, inhibition is probably not due to immune complexes containing IgG antibody. The inhibitory factor may well contribute to the immunosuppressed status of a proportion of breast cancer patients.

Adult↗

Characterization of serum factors modulating splenic cytotoxicity in a syngeneic rat tumour system.

During the terminal stages of tumour growth (6-8 weeks) in Wistar rats bearing a syngeneic squamous cell carcinoma (Sp1), their sera can block in vitro anti-tumour cytotoxicity by immune splenic T lymphocytes. At an earlier stage of tumour growth (4-6 weeks) the sera do not block this cytotoxicity, but can induce anti-tumour cytotoxicity by non-immune spleen cells in the absence of complement. Sera taken at these 2 stages of tumour growth have been fractionated by ion-exchange chromatography, using DEAE-cellulose. The fractions have been examined by immunoelectrophoresis and tested for anti-tumour reactivity. Blocking activity was found in the Week-8 serum fraction eluted with 0-005M phosphate buffer, pH 7-4, whilst the "cytotoxic" activity of Week-4 serum was eluted with 0-02M phosphate buffer, pH 6-2. It is suggested that different IgG sub-classes are responsible for the 2 activities.

Animals↗

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↗

Characterization of the normal lymphocyte population cytolytic to Burkitt's lymphoma cells of the EB2 cell line.

The normal human lymphocyte population which exhibits "spontaneous" cytolysis of EB2 Burkitt's lymphoma cells has been characterized. The effector cell has EA and EAC' receptors but lacks E receptors and probably surface Ig. "Spontaneous" anti-EB2 cytotoxicity was not reduced by preincubation of the effector cells with plastic or iron carbonyl or by passage through cotton wool or agarose columns but was reduced by passage through nylon wool columns. Thymocytes were not cytotoxic to EB2 cells, and chronic lymphocytic leukaemia cells (of B cell characteristics) had reduced cytotoxicity compared with normal lymphocytes. Cells from various lymphoid organs of rats and guinea-pigs were also cytotoxic to EB2 cells with reactivity in spleen greater than or equal to blood greater than lymph nodes. Spleen cells from neonatally thymectomized rats had increased cytotoxicity compared with normal rat spleen cells, suggesting that T lymphocytes are not essential. The effector cell in rat spleen did not adhere to cotton wool or agarose columns, indicating some resemblance to its counterpart in human peripheral blood.

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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↗

Use of the defined antigen substrate spheres system as a model for analysing possible mechanisms of inhibition-blockade of anti-tumour lymphocytotoxicity.

The defined antigen substrate spheres (DASS) system was employed for analysing reactions between solid state antibody or antigen and soluble immune complexes. Sepharose beads covalently coupled with ovalbumin were used to represent tumour cells and beads coupled with antibody against ovalbumin were used to represent anti-tumour lymphocytes; the ovalbumin and corresponding antibody simulated tumour-derived antigen and antibody to tumour respectively. Binding of soluble complexes to the beads was measured by fluorimetry and/or radiometry of fluorescein or 125-I-labelled ovalbumin or antibody. Antigen-antibody complexes in antibody excess bound less effectively to the antibody beads than antigen alone, but complexes in slight or moderate antigen excess bound more effectively. Complexes in antibody excess were most effective in the complex before levelling off and then decreased in extreme antibody excess. The model demonstration of augmentation by antibody of antigen binding to solid state antibody might by analogy reflect a mechanism of inhibition of lymphocyte cytotoxicity. Complexes in a wide range of antibody excess should also be effective in blocking lymphocytotoxicity at the target cell level.

Animals↗

alpha 2HS-glycoprotein is expressed at high concentration in human fetal plasma and cerebrospinal fluid.

The concentration of alpha 2HS-glycoprotein (alpha 2HS), a human homologue of the fetal protein fetuin, has been measured in plasma and cerebrospinal fluid (CSF) of fetuses from 14 to 37 weeks of gestation and in cord blood from newborn babies. The levels were highest in both plasma and CSF in the younger fetuses, but even in the newborn the concentration of alpha 2HS in plasma was nearly twice the adult level. Two of six fetuses in the 14- to 19-week group had levels of alpha 2HS over 200 mg/100 ml, which is similar to the levels of fetuin in some fetal animals.

Adult↗