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Biomedical subjects

W H Stimson

Publications and source records attributed to W H Stimson.

At least 91 records · Page 5Linked to original sources

Comparison of the effects of human pregnancy serum and anti-inflammatory compounds on the release of lysosomal enzymes from macrophages.

Human sera and anti-inflammatory drugs were compared for their ability to inhibit the zymosan-induced release of beta-glucuronidase from cultured rat peritoneal macrophages. Late pregnancy serum was the most potent in this respect and produced a dose-related suppression with a maximum of 94% when 15% (v/v) serum was incorporated into the culture medium. The effect was not shown by male serum and was associated with compounds of low molecular weight. However, steroids, commonly elevated in level during pregnancy, did not appear to be responsible for the inhibition of enzyme release.

Animals↗

Identification of pregnancy-associated alpha-macroglobulin on the surface of peripheral blood leucocyte populations.

Pregnancy-associated alpha-macroglobulin (PAM) was identified on the surface membranes of human peripheral blood leucocytes by immunofluorescent staining. Subjects having a high serum-level of the glycoprotein (pregnant and contraceptive steroid-treated women) were shown to possess a significantly greater proportion of PAM-positive cells than those (normal males) with a low concentration. However, no correlation was found between the serum values and the percentage of PAM-associated leucocytes. Studies employing purified leucocyte-types and the simultaneous detection of PAM and lymphocyte surface markers indicated that only subpopulations of T lymphocytes (23%) and monocytes (40%) were associated with this serum protein.

Adult↗

Preclinical warning of recrudescent mammary cancers by pregnancy-associated alpha-macroglobulin.

Nine of 30 mammary cancer patients developed metastases during 13-94 months after mastectomy. All 9 patients had elevated blood levels of pregnancy-associated alpha-macroglobulin (PAM) 1-21 months before conventional detection of metastases. Seven of the clinically well patients had PAM rises exceeding 90 per cent above the baseline and in 4 of these the PAM later fell to lower levels. PAM appears to have potential as an indicator of the growth of micrometastases.

Adult↗

Studies on the immunosuppressive properties of a pregnancy-associated alpha-macroglobulin.

A pregnancy-associated serum glycoprotein was shown to have an inhibitory effect on several in vitro methods of immunological assessment. This suppressing activity was evident at physiological concentrations and did not appear to be due to cytotoxicity. Transformation, induced by agents often regarded as preferential stimulators of T lymphocytes (concanavalin A, phytohaemagglutinin, allogeneic cells and tuberculin) was significantly depressed by the alpha-globulin. However, this phenomenon was much less evident when lipopolysaccharide or goat anti-human F(ab')2 serum was employed to selectively stimulate B-cells. The glycoprotein also blocked antigen-induced inhibition of leucocyte migration and caused a significant reduction in the number of lymphocytes binding sheep erythrocytes, in the spontaneous rosette test. It is proposed that the non-specific inhibitory activity of the alpha-macroglobulin depends upon some direct effect exerted on the lymphocyte itself and that it is levelled primarily at the cell-mediated immune response.

Adult↗

Identification of an immunosuppressive factor in pregnancy serum.

Complement-inactivated allogeneic serum was found to contain a factor capable of suppressing BCG-induced inhibition of leukocyte migration in vitro. Although serum from late pregnancy was the most potent in this context, the ability to antagonize the leukocyte response appears to be an intrinsic property of human serum. The inhibitory factor was purified by salf fractionation and gel chromatography and the effect found to be associated with alpha-globulins of high lipid content which are probably alpha-lipoproteins. Estrogens, progesterone, or corticosteroids, associated with the lipoprotein, did not appear to be the cause of the observed suppression. The factor appears to block the immune response at the level of the lymphocyte and its nonspecific immunosuppressive properties could contribute to acceptance of the fetus by the mother.

BCG Vaccine↗

Correlation of the blood-level of a pregnancy-associated alpha-macroglobulin with the clinical course of cancer patients.

The variations in serum level of a pregnancy-associated alpha-macroglobulin (P.A.M.) were studied during the treatment of breast-cancer patients. Good correlation was found between P.A.M. concentrations and the course of the disease--levels rose prior to the clinical recognition of metastatic disease and decreased significantly on successful treatment. Periodic P.A.M. determinations may allow detection of tumour recurrence while it is still at a treatable stage.

Alpha-Globulins↗

The effect of Corynebacterium parvum therapy on immunoglobulin class and IgG subclass levels in cancer patients.

Detailed serological studies have been undertaken in a small group of cancer patients receiving nonspecific immunotherapy with Corynebacterium parvum (C. parvum). These patients included 4 cases of recurrent malignant melanoma, 2 of stomach cancer and 2 of recurrent breast cancer. They all received an initial i.v. infusion of 20 mg of a formol killed suspension of C. parvum followed by 2 mg (i.m.) at weekly intervals for 10-11 weeks. This protocol consistently resulted in an increase in the circulating IgG levels of all patients but had a variable effect on their IgA, IgM and IgE levels. Increases in the concentration of all 4 IgG subclasses contributed to the overall increase in IgG levels and these changes ranked IgG2 greater than IgG1 greater than IgG3 = IgG4. It also had an inconsistent effect upon the levels of alpha-macroglobulin in pregnancy but the levels of normal serum alpha2-macroglobulin were virtually unchanged. Pre-existing antibodies to C. parvum were noted in all the patients. Titres rose appreciably following C. parvum administration and remained at high, though fluctuating levels, throughout the 100-day period of observation. Absorption studies suggested that the development of antibodies to C. parvum accounted in part for the increased IgG levels noted following this form of therapy. The significance of these changes in relation to the possible anti-tumour effect of C. parvum is discussed.

Adult↗

Variations in the level of a pregnancy-associated alpha-macroglobulin in patients with cancer.

The concentration of a pregnancy-associated alpha-macroglobulin (PAM) was determined in the blood of patients with various cancers. PAM was detectable in subjects with all types of malignant disease studied, and the level of the serum protein correlated well with the course of the disease: the concentration increased before clinical recognition of metastases and decreased significantly on successful treatment. Periodic PAM determinations may allow detection of tumour recurrence while it is still at a treatable stage and could aid in the evaluation of therapy.

Female↗