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Biomedical subjects

W L Ryan

Publications and source records attributed to W L Ryan.

8 recordsLinked to original sources

A new platelet function test.

A method for screening EDTA(K3) blood samples for platelet function is described. The general availability of whole blood platelet counters in the clinical laboratory suggested their use to measure platelet aggregation. To simplify the collection and storage of blood samples, a method utilizing EDTA collected blood is described. Addition of calcium and citrate restores platelet function to blood samples even when stored at room temperature for several hours. Thus, the blood sample used to assay RBC, WBC and platelet parameters may also be employed in platelet aggregation. A comparison of this method with aggregometry on 120 subjects indicated a similar response to arachidonate, collagen, ristocetin and ADP.

Adenosine Diphosphate

Initiation-promotion skin carcinogenesis: inhibition by cyclic and non-cyclic nucleotides.

The effect of nucleotides on initiation-promotion skin carcinogenesis in Swiss mice was investigated. Cyclic AMP was given before initiation with DMBA, between initiation and promotion, and at the same time as promotion with croton oil. Cyclic AMP was more effective in inhibiting tumor development when injected at the same as promotion with croton oil. 5'-adenosine-monophosphate (5'-AMP) and cyclic GMP were as effective as cyclic AMP in inhibiting tumor development under these conditions. However, adenosine, dibutyryl-cyclic AMP and 5'-guanosine-monophosphate (5'-GMP) were ineffective.

9,10-Dimethyl-1,2-benzanthracene

Antibody stimulation of benzo(a)pyrene carcinogenesis.

Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.

Animals

Stimulation of malignant skin cells by antibody to normal skin cells of mice.

The ability of antibodies developed against normal skin cells to stimulate skin cells transformed by 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Primary cultures of normal skin, containing both fibroblasts and epithelial cells, were established from epidermis of the back skin of adult strain A/J mice. Malignant skin cells were obtained by treating a subculture of normal cells with DMBA. Transformation was demonstrated by increased growth rate, growth in soft agar, and production of tumors in strain A/J mice. Antisera developed in New Zealand White rabbits against the normal cells were cytotoxic to both normal and malignant cells in the presence of complement of 1:320 dilution. However, greater dilutions of the antisera (1:500-1:1,000) in the absence of complement produced growth enhancement of the malignant but not of the normal cells. The growth-enhancing properties were present in the gamma-globulin fraction of the antisera that contained IgG, IgM, and IgA antibodies. Immunofluorescence studies indicated that antibodies from the sera bound to the membranes of both normal and malignant cells. These data indicate that antibodies to normal cells are stimulatory to DMBA-transformed cells and confirm previous data obtained with spontaneously transformed cells.

9,10-Dimethyl-1,2-benzanthracene

Initiation-promotion skin carcinogenesis and immunological competence.

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

9,10-Dimethyl-1,2-benzanthracene

Adenylate cyclase stimulation by trypsin.

Adenylate cyclase activity of a rat embryo fibroblast cell line (F111) is markedly increased by brief treatment with 1:300 trypsin. The degree of stimulation depends upon the length of time the cells are treated and the concentration of trypsin. Crystalline trypsin produced a stimulation similar to that obtained with 1:300 trypsin. Further, the addition of soybean trypsin inhibitor blocked the stimulation of adenylate cyclase by 1:300 trypsin. Trypsin-treated adenylate cyclase responds to PGE1, but there is no increase over that of untreated enzyme. This result and the increase in fluoride-stimulated levels of activity suggest that the trypsin is acting upon the catalytic unit of the enzyme.

Adenylyl Cyclases

Serum sperm agglutinating antibody formation in vasectomized men treated with dexamethasone.

The effect of immunosuppression with dexamethasone on sperm antibody formation following vasectomy in men was determined. Vasectomized men were treated with dexamethasone (4 mg) tablets starting two days prior to vasectomy and each day thereafter for a total of eight days for a total dose of 30 mg. There was no significant difference in serum sperm agglutinating antibody, cholesterol, triglycerides, or lipoproteins between the dexamethasone and placebo groups. The finding that immunosuppression at the time of vasectomy did not inhibit sperm antibody formation in man was surprising because in a similar study with Cynomoglus monkeys treatment at the time of vasectomy with dexamethasone inhibited sperm antibody development. The difference between the two studies may be that in monkeys sperm antigen presentation comes at the time of vasectomy and therefore immunosuppression at this time can prevent an immune response, but in man sperm antigen presentation comes at some later time following vasectomy. This species difference in sperm antigen presentation following vasectomy in man compared to monkeys may affect subsequent atherosclerosis development and explain why no cardiovascular disease is found in man following vasectomy.

Antibody Formation