PubMed Health⌕ Search

Biomedical subjects

W H Stimson

Publications and source records attributed to W H Stimson.

At least 73 records · Page 4Linked to original sources

Hormonal manipulation of the immune response in systemic lupus erythematosus: a drug trial of an anabolic steroid, 19-nortestosterone.

Ten patients (8 female, 2 male) with systemic lupus erythematosus (SLE) were entered into an open trial with the anabolic steroid 19-nortestosterone (19-nor). Their clinical condition did not improve, nor were significant changes observed in the majority of laboratory data. However, overall the platelet count rose, and in patients with abnormal levels of T lymphocytes bearing receptors for IgG Fc treatment returned the values to normal. Despite this latter result, suppressor cell activity remained slightly below the normal range throughout the study period.

Clinical Trials as Topic↗

Studies of thyroglobulin autoantibody synthesis using a micro-ELISA assay.

Thyroglobulin autoantibody synthesis by Hashimoto lymphocyte cultures has been studied using an ELISA, a plaque assay and tanned red cell haemagglutination. The ELISA system was found to be the most suitable and using this method IgG-class thyroglobulin antibody synthesis was detectable in cultures of mitogen-stimulated lymphocytes from all 10 Hashimoto patients studied, but not in cultures of lymphocytes from 4 normal donors. The ELISA was also sufficiently sensitive to detect thyroglobulin antibody synthesis in mitogen-free lymphocyte cultures from 4 out of the 10 Hashimoto patients and consequently it should be possible to use this system to study the effect of various pathophysiological factors on autoantibody synthesis which would otherwise be masked by mitogenic stimulation.

Adult↗

Screening for metastases in breast cancer: an assessment of biochemical and physical methods.

Ten tumor markers were measured in serum or urine at approximately three month intervals in patients with breast cancer following mastectomy but before development of overt metastatic disease. In 23 patients who later had metastases, only three markers, alkaline phosphatase, carcinoembryonic antigen (CEA), and gamma-glutamyl transpeptidase (gamma-GT) were consistently abnormal prior to the development of detectable metastases in more than one patient. In half the patients, a "lead interval" of three months or more was obtained using these three markers and little advantage was obtained by the addition of any other biochemical marker. The value of these three measurements was then assessed in a larger group of patients and compared with other tests for metastases. Alkaline phosphatase, CEA, gamma-GT, clinical examination, and chest x-ray were the best indices of the metastatic state in breast cancer, being collectively abnormal in 98% of patients at first presentation with metastases. The authors recommend screening patients postoperatively with these five tests for metastases; more detailed tests should only be carried out if results of one or more these are abnormal.

Alkaline Phosphatase↗

Pregnancy-associated beta 1-macroglobulin (beta 1-PAM): a new serum protein associated with pregnancy serum-derived immune complexes and ovarian cancer.

A new pregnancy-associated serum protein, beta 1-PAM, was identified following low pH dissociation and separation, by gel chromatography, of pregnancy serum-derived immune complexes. A sandwich-type micro-enzyme immunoassay was developed and blood from various groups of subjects examined for the presence of beta 1-PAM. In addition to pregnant women, only subjects with ovarian cancer (70%) had consistently high levels of the antigen. beta 1-PAM isolated from both pregnancy and ovarian cancer serum was shown to be antigenically identical and to share the same isoelectric point (pH 5.25) and ammonium sulphate precipitation range (1.1--1.5 M). The serum protein had a molecular weight of 1.5 x 10(6), especially when obtained from ovarian cancer patients. However, it was apparent that other molecular weight forms were present, particularly in material isolated from pregnancy serum, which were probably related to the subunit nature of beta 1-PAM and its association with immune complexes.

Adult↗

The effects of nandrolone, testosterone and their decanoate esters on murine lupus.

Treatment of NZB/NZW F1 (B/W) female and castrated male mice with testosterone or 19-nortestosterone (nandrolone), either by implantation in silastic tubing or by subcutaneous injections of their decanoate esters, reduced in a dose-dependent manner symptoms associated with murine lupus (proteinuria, IgG antibodies to DNA) and prolonged survival. These phenomena were observed under both prophylactic (start at 3-4 weeks) and therapeutic treatments (start 27-29 weeks). Nandrolone and its decanoate ester were at least as potent as testosterone and testosterone decanoate. As the unwanted androgenic properties of nandrolone and its ester are significantly less pronounced than those of testosterone and its ester, also in these NZB/NZW mice, the beneficial effect on murine lupus does not seem to be associated with these properties.

Animals↗

An assay for antigen-antibody complexes in human sera using C1q-enzyme conjugates.

An assay for soluble immune complexes employing enzyme-C1q conjugates is described. The method is sensitive, rapid and precise, and should prove suitable for monitoring patients. The test gave positive results for complexes in normal pregnant women and indicated significantly increased levels in subjects with pre-eclampsia.

Antigen-Antibody Complex↗

Androgen binding cytosol receptors in the rat thymus: physicochemical properties, specificity and localisation.

Normal rat-thymus cytosol was shown to contain a 5 alpha-dihydrotestosterone-binding species characterised by low capacity and high affinity (Kd-6 X 10(-10) M). The principal binding moiety had a sedimentation coefficient of 8 S at low ionic strength. Competitive binding studies with 61 compounds showed that the specificity was highly androgenic while comparison with similar data from the prostate indicated that the thymic androgen receptor had a different specificity pattern. The thymus was not found to be capable of 5 alpha-reduction; unlike the prostate, it rapidly metabolised testosterone to androstenedione. Androgen receptor levels were significantly higher in intact females than males and the binding species was positively identified only in medullary tissue--thymocytes were devoid of the receptor. This data supports the idea that the thymus is an androgen-responsive tissue and that at least part of the immunoregulatory effects of androgens are mediated through the thymus.

Animals↗

Effects of steroids on the secretion of immunoregulatory factors by thymic epithelial cell cultures.

Rat thymic epithelial cells were cultured for 39 days in the presence of various concentrations of oestradiol, testosterone, progesterone and corticosterone and the supernatants assessed for effects on the stimulation of cells from the thymus, bone marrow, lymph nodes and spleen, with several agents. All the steroids, except progesterone, were found to significantly regulate the secretion of immunoregulatory factors by the epithelial cells at physiological levels but the effects were dose dependent. Fractionation of active supernatants indicated that the capacity to enhance or depress cellular proliferation was mainly associated with substances having molecular weights greater than 30,000 or less than 1000, respectively. This study supports the idea that certain steroids can influence the immune response indirectly through the thymus.

Animals↗

Are pregnancy-associated serum proteins responsible for the inhibition of lymphocyte transformation by pregnancy serum?

Certain pregnancy-associated serum proteins, namely pregnancy-associated alpha 2-glycoprotein, pregnancy-specific beta 1-glycoprotein, alpha-foetoprotein, human placental lactogen and human chroionic gonadotrophin, have been proposed as immunosuppressive factors. A pregnancy serum was constructed from a number of such sera to produce high serum levels of these compounds. Each of the proteins was then removed sequentially from the serum by affinity chromatography and the remaining materials examined for inhibitory activity on lymphocyte transformation. Only the removal of pregnancy-associated alpha 2-glycoprotein decreased suppression by the serum. However, a large proportion of the serum inhibitory activity could not be accounted for, indicating the presence of other suppressor factors.

Adolescent↗

Studies on the maternal immune response to placental antigens: absence of a blocking factor from the blood of abortion-prone women.

The leucocyte migration-inhibition assay was employed to assess the reactivity of cells from postpartum women to placental antigen preparations. Leucocytes from normal primigravidae responded to their own placental antigens and displayed a limited degree of cross-reactivity with allogeneic preparations. Autologous plasma suppressed this antigen recognition and the factor responsible was shown to be an IgG antibody. Leucocytes from five women with spontaneous abortions also responded to autologous placental preparations but no immunosuppressive factor could be detected in their blood. It is suggested that target antigens for maternal lymphocytes are present on the placenta, a structure critical to the continuance of pregnancy, and that the presence of the blocking antibody is necessary for fetal well-being.

Abortion, Habitual↗

The anti-inflammatory profile of dapsone in animal models of inflammation.

Dapsone has been shown to possess anti-inflammatory activity in a variety of animal models. It possesses oral anti-oedema activity especially pronounced in novel models of acute inflammation, viz. anti-IgG and reversed passive Arthus oedemas. However, it is not very active in the guinea pig u.v. erythema model. It is effective in chronic models such as adjuvant arthritis and the cotton pellet granuloma although multiple administration may also produce cyanosis. Antipyretic and analgesic effects for dapsone have been demonstrated and are similar to those produced by phenylbutazone. It inhibits zymosan-induced beta-glucuronidase release from cultured macrophages and also the activity of this enzyme. Dapsone does not appear to be ulcerogenic in the rat.

Animals↗

Serum biochemical markers in lung cancer.

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy.

Adult↗