Biomedical subjects
Publications and source records attributed to P C Frei.
The hepatitis infections can rather be characterized by an intensive pathogenetic contribution of the most than by a lytic effect of the causative organism, as it is the case for instance in the lymphocytic choriomeningitis of the mouse and perhaps in the chronic polyarthritis.
Untoward allergic reactions were monitored prospectively in 98 patients undergoing hyposensitization with depot type preparations of house dust mites (42 patients) or grass pollens administered before the pollen season (56 patients). 44% of the patients experienced at least one major local reaction, usually when injected with high doses of allergens. A mild systemic reaction (benign crisis of rhinitis or asthma within 12 hours after the injection) was reported at least once by 9% of the pollen-treated and 52% of the mite-treated patients. A severe systemic reaction, which improved rapidly with adrenaline, was noted in 3% of the pollen-treated and 5% of the mite-treated patients. These data indicate that untoward allergic reactions during hyposensitization are not uncommon, and this type of treatment therefore requires a strict indication.
The antigen from a non-A, non-B antigen-antibody system previously described was purified and, when tested by immunodiffusion, was shown to produce patterns of identity with all antigen-positive sera of the system. The sedimentation coefficient S20,w of the antigen was estimated by rate zonal ultracentrifugation to be 48. Isopycnic ultracentrifugation in CsCl gradient of non-A, non-B antigen generated a single sedimentation peak at the density of 1.28. SDS-polyacrylamide-agarose gel electrophoresis showed that I125-labelled antigen migrated as a single band (molecular weight 3.0 X 10(6)); in addition, labelled material also migrated to the albumin region. With SDS-PAGE under reducing conditions, the antigen was shown to consist of seven polypeptides. Spherical particles of 23 nm in diameter, demonstrated by electron microscopy, could be aggregated by purified non-A, non-B antibody. They probably represent the antigen and not a complete viral particle. The characteristics of this antigen associated with non-A, non-B hepatitis appear therefore to be close to those of hepatitis B surface antigen.
The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a similar mechanism is involved in hepatitis A. In the present paper, immune reactivity to hepatitis A antigen (HAAg) was measured in 13 patients at the time of recovery from hepatitis A, by using the leukocyte migration inhibition test (LMIT) under agarose with purified HAAg as antigen. Eleven normal subjects without history of hepatitis and 4 patients convalescent from hepatitis B were used as controls. Inhibition of leukocyte migration by HAAg was found in 11 of the 13 patients, with an average migration index (MI) of 77.0% (SEM 3.5). No such inhibition was found in any of the controls: MI = 100.8% (SEM 1.0), P less than 0.0001. These findings show that, like for HBsAg in hepatitis B, an immune response specific for HAAg can be demonstrated by the LMIT after HAV infection. This response could perhaps be related to the liver injury associated to hepatitis A.
To enable shorter and more convenient testing, the Phadezym RAST and Phadezym IgE PRIST procedures for the determination of specific and total IgE were modified in three ways: (i) allergen-coupled paper discs were tested in microtitre wells; (ii) the incubation times were reduced to 1 hr with serum and 2 hr with the anti-IgE by shaking the plates at room temperature; and (iii) the fluorogenic substrate used reduced the development time to 15 min. Determination of IgE antibody specific for fifteen inhalation allergens by the modified fluorescence test (FEIA) and by the conventional Phadezym RAST (EIA) was performed on the serum of thirty-two patients suffering from asthma/rhinitis: correlation studies for these sera showed that 96.1% of the results fell in the same class. In these patients, both FEIA and EIA detected the same proportion of skin-prick tests (SPT) positive results (67%). With the FEIA, 4/165 (2.4%) class 1 results were found in eleven non-atopic subjects (symptom free, fifteen negative SPT, total IgE lower than 80 kU/l), compared to 1/165 (0.6%) with the EIA. In twenty cord sera, both FEIA and EIA found 4/300 (1.3%) class 1 results. For the determination of total serum IgE, the microtitre FEIA showed a detection limit of 0.5 kU/l and an excellent correlation with Phadezym IgE PRIST (n = 66 serum, r = 0.99). These data indicate that the adaptation of Phadezym RAST and Phadezym IgE PRIST to microtitre plates and fluorescence technology has resulted in a time-saving and easy to perform within-day assay which provided results as reproducible, sensitive and specific as those of the conventional procedure.
The FAST assay (Allergenetics) for the determination of specific IgE has recently been introduced. The results of this test, graded in classes 0 (negative), 1 (equivocal) and 2 to 6 (positive) were compared with those of another commercially available test (Phadezym RAST, Pharmacia), graded from class 0 (negative) and classes 1 to 4 (positive). In 52 adults suffering from rhinitis/asthma, a total of 114 positive skin prick tests (SPT) were obtained for common respiratory allergens. In 67% of these tests the Phadezym RAST was positive and in 63% the FAST was positive (classes 2 to 6). In these patients there were 151 negative SPT: 6% corresponded to a positive Phadezym RAST (all class 1) and 34% to a positive FAST (classes 2 to 6). The serum of nine nonatopic volunteers who had negative SPT for 12 common allergens were tested. In none did the Phadezym RAST give any positive results; the FAST was positive in all nine sera, detecting between five and 11 allergens. When both assays were performed on 14 unselected cord blood samples, the Phadezym RAST was positive in three samples (with class 1 results to a maximum of two allergens), and the FAST was positive in 12 samples, detecting between one and seven allergens. Thus, in our hands, the FAST gave an abnormally high number of positive results in patients with negative SPT, in nonatopic volunteers, and in cord blood.
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Anti-HTLV-III antibody was tested in frozen sera from high-risk individuals, collected between 1974 and 1985 in Switzerland. All but one of the 262 sera of a control group were negative. Among drug addicts, none of the 78 samples collected from 1974 to 1979 was positive. Antibody was first detected in 1980 and thereafter with progressively increasing frequency. Three of 63 samples from 24 dialyzed patients who had received multiple transfusions showed borderline positive values. None of the seropositive subjects has developed AIDS or AIDS-related complex.
Nonsteroidal anti-inflammatory drugs and certain food or drug additives are known to induce acute bronchospasms, angioneurotic edema, and urticaria in susceptible patients. Thirty-four patients (17 with asthma and 17 with urticaria), whose case history suggested such intolerance, were challenged orally with increasing doses of seven compounds: acetylsalicylic acid, glafenine, sodium benzoate, sulfur dioxide, potassium sorbate, sodium glutamate, and tartrazine. Among 162 oral provocation tests, 38 were positive (20% decrease in peak flow rate or appearance of acute urticaria/angioneurotic edema). Twenty-four of the 34 patients (nine with asthma and 15 with urticaria) were intolerant to at least one compound. However, no serious reaction was observed. In 20 of these 24 patients (six with asthma and 14 with urticaria), a diet free of additives and nonsteroidal anti-inflammatory drugs resulted, within 5 days, in a marked improvement of symptoms, which persisted 8 to 14 mo after starting the diet. Age, prevalence of IgE-mediated allergy, and nasal polyposis were similar in patients with or without reactions of intolerance. Under the conditions used, oral provocation tests proved to be feasible, safe, and useful in many patients not helped by existing methods.
It has been shown that (+)-cyanidanol-3 [+)-catechin) is able to stimulate in vitro the cell-mediated immune response specific for hepatitis B surface antigen (HBsAg), and might contribute to the elimination of hepatitis B virus (HBV) during HBV infection. In the present study, the possible action of two of its derivatives, palmitoyl-3-catechin and heptyl-3-catechin, on this type of immunity was investigated by adding the substances to leucocyte migration inhibition tests performed in presence of PPD and HBsAg, with leucocytes from individuals sensitized to these antigens. In normal individuals sensitized to PPD, the addition of palmitoyl-3-catechin and heptyl-3-catechin amplified the inhibition of migration by resp. 7.2% (p less than 0.05) and 13.5% (p less than 0.001). In patients previously infected by HBV and sensitized to HBsAg, the maximum amplification was resp. 12.7% (p less than 0.001) and 7.6% (p less than 0.05). This effect was dose-dependent. These substances did not modify the leucocyte migration measured in the absence of antigen. Palmitoyl-3-catechin and heptyl-3-catechin therefore seem capable of amplifying the cell-mediated immune response. The effect of the two derivatives, which were selected because of their liposolubility, was more pronounced than the effect of (+)-cyanidanol-3. It is thus possible that the two new catechin-derivatives, not yet in therapeutical use, will also stimulate cell-mediated immunity to HBsAg, and that a more marked clinical effect might be expected.
The effect of amoxycillin and doxycycline on human granulocyte function was studied in vitro. The antimicrobial agents were added to tests of chemotaxis, random motility, yeast phagocytosis, and killing, at progressing concentrations. The effect was also evaluated in vivo by measuring chemotaxis and random motility (agarose technique) of granulocytes from rabbits injected with these antibiotics. Amoxycillin was shown to have a slightly stimulating effect on chemotaxis, demonstrable only at the highest concentration tested (100 micrograms/ml), and no effect on the other variables. Doxycycline had a dose-related inhibitory effect on chemotaxis, random motility, and phagocytosis, and no effect on killing. Chemotaxis and random motility were slightly, but not significantly, stimulated in vivo when rabbits were given amoxycillin. Chemotaxis (but not random motility) was significantly impaired when the rabbits were given doxycycline.
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A serological investigation was made on patients with viral hepatitis A and individuals with a past history of this disease. Titration of antibody in sequential samples was found to be of no help in diagnosis. Separation of early (IgM) from late (IgG) antibodies by protein A or by 2-mercaptoethanol did not prove to be convenient for the serodiagnosis. A chromatographic separation of late and early antibody was found to be satisfactory, and equivalent to a radioimmunoassay for IgM-antibodies.
This review is an attempt to discuss the basic conceptual tools that are a prerequisite for any clinical study of chemotactic defects. They include familiarity with definitions of common terms and with the merits and drawbacks of the several possible in vivo and in vitro assay methods. Cellular mechanisms involved in locomotion are complex. They include basic requirements for cell metabolism as well as receptor recognition, attachment to surfaces and contraction of the cytoskeleton of the cell. Of the many chemotactic factors reported, few are well characterized and universally agreed upon. Similarly, with the use of more stringent criteria, a number of clinical defects of chemotaxis have proven transitory or even artifactual.
Detailed histories taken in eighty-one patients suffering from perennial asthma and rhinitis were analysed independently by three trained allergists and their conclusions were compared to the results of three tests: (1) concentration of total serum IgE; (2) skin tests and (3) radioallergosorbent test (RAST). In eleven patients (14%), the three investigators disagreed when estimating the allergic nature of the symptoms. Ten out of forty-four patients (23%), unanimously predicted not to be allergic, had high levels of total serum IgE and skin tests and RAST clearly positive for one or more allergens. The allergists suspected 47% of the allergens detected by skin tests and 55% of those detected by RAST. The case history was the test which most often gave information at odds with that suggested by the other three tests. Our study indicates therefore that a case history not even suggestive of allergy should be complemented by additional tests.
26 patients with viral hepatitis were selected on the basis of negative responses to serological tests for hepatitis B virus and hepatitis A virus infections. The illness was acute in 19 patients and chronic persistent in the remaining 7. Immunodiffusion tests showed a single antigen-antibody system in the sera of all 26 patients. Each patient had at least one serum sample positive for antigen or antibody. In 1 post-transfusion case, the corresponding immunological marker was found in the donor. This system was considered specific for the disease, since the markers could not be detected in sera from patients with other liver conditions or immune complex diseases, or in sera from healthy blood donors without a history of hepatitis. The antigen could be separated from contaminating serum proteins. The purified preparation showed immunological identity with all our antigen-containing sera and with samples of a study already published. These results suggest the existence of an antigen associated with non-A, non-B, viral hepatitis and probably related to an infectious agent responsible for all the cases in this study.
A technical modification was introduced by the manufacturer (Pharmacia) of a commercially available RAST, with the use of an anti-IgE antibody specific for the domain epsilon 2 of the IgE molecule. Results of the previous and of the new RAST were compared in 100 patients suffering from bronchial asthma or chronic rhinitis. When the same serum was assayed by both techniques, the new RAST technique disclosed a higher positivity in 26% of the comparisons. The new RAST improved the overall correlation between RAST and skin-tests by 6%: individually by 12% for house dust, 8% for Dermatophagoides pteronyssinus and 15% for animal danders. However, the level of correlation was decreased by 8% for the moulds. In patients with a total IgE concentration larger than 100 PRIST units, the new RAST allowed the demonstration of specific IgE in a number of cases twice as large as the previous technique. Thus, the modification of the RAST provides a more sensitive test, the results of which better correlate with those of other diagnostic methods.