The effect of the castor bean toxin, ricin, on rat IgE and IgG responses.

IgE responses are closely regulated in non-atopic humans and low IgE responder animals. After an initial period of IgE production following antigen exposure, IgE synthesis appears to be actively suppressed. Inhalation of the dust of castor beans induces persistent IgE responses in atopic and non-atopic humans alike. This phenomenon was investigated in animals. Hooded Lister rats were immunized intraperitoneally with different preparations of castor bean. These had been heated for different lengths of time, 60 and 15 mins, to inactivate the toxin ricin. Immunization with as much as 100 micrograms of the extract heated for 60 min failed to produce an IgE response, while injection of 100 micrograms of the extract heated for 15 min produced a marked IgE response to castor bean proteins. Thus the component of castor bean extract which induces the IgE response appears to be heat labile. The IgE potentiating component in castor bean was found to enhance IgE responses to other antigens such as ovalbumin and when 0.8 microgram of an unheated castor bean extract was administered together with an optimal dose of ovalbumin, there was a substantial increase in ovalbumin-specific IgE but not IgG in all animals. In addition, total serum IgE but not IgG increased up to 20-fold. The effect of castor bean was more sustainable than that of an established IgE-specific adjuvant, Bordetella pertussis, and was able to boost an IgE response that had diminished and maintain an ongoing IgE response when re-administered at weekly intervals. In addition, it was possible to reproduce the IgE potentiating effects with purified castor bean ricin at 25 ng/rat. The way that it produces this effect is not known but it is possible that ricin blocks the normal IgE suppressive mechanisms that regulate IgE responses.

Effect of ricin on the proliferation of rat spleen and mesenteric lymph node cells.

The effect of the castor bean toxin, ricin, on rat spleen and mesenteric lymph node cell cultures was tested. Rat lymphocytes were cultured for 2 days in the presence of optimal doses of the mitogens phytohaemagglutinin, conconavalin A, and lipopolysaccharide. At concentrations of 10(-3) to 10(-5) mg/ml ricin, spontaneous and mitogen-driven proliferation were inhibited. At lower concentrations, spleen but not mesenteric lymph node cells showed enhanced proliferation. Studies are continuing to identify subpopulations of lymphocytes with increased or decreased sensitivity to ricin and their role in the regulation of IgE.

The relationship between total serum IgE and castor-bean-specific IgE antibodies in castor-bean-sensitive patients from Marseilles.

The relationship between serum IgE and castor bean (Ricinus communis)-specific IgE was studied in a group of dockworkers and other residents of Marseilles who were diagnosed as having castor bean allergy. The diagnosis was made because they had asthma or other allergic symptoms together with a positive skin test to castor bean. Total serum IgE was found to be higher in castor-bean-allergic patients (mean = 174 IU/ml) than in a control group of local blood donors (mean = 66 IU/ml). IgE levels were not as high as those found in the sera of a previously identified group of castor-bean-allergic dockworkers from Port Sudan (mean = 902 IU/ml). Castor-bean-specific IgE was demonstrated in the serum of 91% of the allergic group and there was some correlation with total IgE (r = 0.53, p less than 0.01). The proportion of IgE antibody specific for castor bean was determined in 20 castor-bean-sensitive patients using the radioallergosorbent test and was found to vary between 9 and 64% (mean = 38% or 265 ng/ml). No castor-bean-specific IgE antibody was detected in the control group.

Allergy to castor bean. I. Its relationship to sensitization to common inhalant allergens (atopy).

The IgE response to castor bean (Ricinus communis) was studied in 96 castor bean-allergic patients from Marseilles, France. All had positive skin tests to castor bean. The IgE response to grass, cat, dust mite, olive, and Parietaria was also measured, and a positive RAST to one or more of these allergens was taken to indicate atopic status. Castor bean-specific IgE antibodies, measured by RAST, were found in 87 (91%) of the castor bean-allergic patients, in two of 13 atopic Marseilles residents living close to the castor bean mills, in three of 42 allergic subjects who had no known contact with castor bean, and in none of a control group of 111 Marseilles blood donors. Very high levels of castor bean-specific IgE (maximum class 4 readings on the Phadebas RAST score) were found in 54 (56%) of the castor bean-allergic patients, but the level of IgE antibody to castor bean was not significantly different in atopic and nonatopic subjects. The frequency of a positive serological test (RAST) for atopy in castor bean-allergic subjects (32%) was very similar to that found in the local population (36%). These data indicate that castor bean is an extremely potent sensitizer for both atopic and nonatopic individuals. The magnitude of the specific IgE antibody response is not related to the atopic status of the patient and may be a function of the physiochemical characteristics of the allergen itself.

Allergy to castor bean. II. Identification of the major allergens in castor bean seeds.

Castor bean proteins were separated and identified by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted onto nitrocellulose paper. The capacity of the castor bean proteins to bind human IgE was probed with sera from castor bean-sensitive patients and radiolabeled anti-IgE. It proved difficult to identify allergens with isoelectric focusing. However, three allergens were identified when proteins were first separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis: the 2S storage albumin, the 11S crystalloid proteins, and a third protein doublet with molecular weights of 47 and 51 kd. Specific IgE antibody to the 2S storage albumin, measured by RAST, was detected in most (96%) castor bean-sensitive patients, confirming it as the major allergen. We would like to suggest that the 2S albumin be named Ric c I, that the crystalloid proteins be named Ric c II, and that the 47/51 kd doublet be named allergen 3.

A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma.

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.

The role of friction in the measurement of slipperiness, Part 1: friction mechanisms and definition of test conditions.

Friction has been widely used as a measure of slipperiness. However, controversies around friction measurements remain. The purposes of this paper are to summarize understanding about friction measurement related to slipperiness assessment of shoe and floor interface and to define test conditions based on biomechanical observations. In addition, friction mechanisms at shoe and floor interface on dry, liquid and solid contaminated, and on icy surfaces are discussed. It is concluded that static friction measurement, by the traditional use of a drag-type device, is only suitable for dry and clean surfaces, and dynamic and transition friction methods are needed to properly estimate the potential risk on contaminated surfaces. Furthermore, at least some of the conditions at the shoe/floor interface during actual slip accidents should be replicated as test conditions for friction measurements, such as sliding speed, contact pressure and normal force build-up rate.

The role of friction in the measurement of slipperiness, Part 2: survey of friction measurement devices.

This paper seeks to address questions related to friction measurement such as how friction is related to human-centred assessment and actual slipping, and how repeatable friction measurements are. Commonly used devices for slipperiness measurement are surveyed and their characteristics compared with suggested test conditions from biomechanical observations summarized in Part 1. The issues of device validity, repeatability, reproducibility and usability are examined from the published literature. Friction assessment using the mechanical measurement devices described appears generally valid and reliable. However, the validity of most devices could be improved by bringing them within the range of human slipping conditions observed in biomechanical studies. Future studies should clearly describe the performance limitations of any device and its results and should consider whether the device conditions reflect these actual human slipping conditions. There is also a need for validation studies of more devices by walking experiments.