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Biomedical subjects

C R Zeiss

Publications and source records attributed to C R Zeiss.

At least 91 records · Page 5Linked to original sources

Immunoglobulin E-mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure.

Two workers are presented who were exposed to diphenylmethane diisocyanate (MDI) while coating pipes with a polyurethane foam. After a latent period of exposure, worker A developed immediate-onset asthma and worker B developed a clinical picture of hypersensitivity pneumonitis for which he was hospitalized. The antibody response of these workers to a conjugate of MDI with human serum albumin (MDI-HSA) was measured by gel precipitation, total antibody binding of 125I MDI-HSA, and specific IgG and IgE antibody by polystyrene-tube radioimmunoassay (PTRAI). Worker B had precipitating antibody to MDI-HSA by double immunodiffusion in gel. Both workers had high levels of IgG antibody specific for MDI-HSA which had some cross-reactivity with a conjugate or toluene diisocyanate and HSA. Total serum antibody binding of 125I MDI-HSA was 15 microgram/ml in worker A and 900 microgram/ml in worker B. Both workers had serum IgE antibody specific for MDI-HSA as measured by two PTRIA techniques. These results indicate that a marked immunologic response to MDI is possible in exposed workers and that hypersensitivity pneumonitis can occur subsequent to the inhalation of a low-molecular-weight chemical in the industrail setting.

Adult↗

A linear correlation between histamine release and degranulation of human basophils by specific antigen or the ionophore A23187.

Simultaneous kinetic measurements have been made of basophil degranulation and of histamine release. Both antigen and ionophore A23187 were studied. Cells from the same donor under the same conditions undergo both reactions at a similar rate. Regression analysis indicated a statistically highly significant correlation between these two parameters for activation by either antigen or ionophore. In addition, the mean slope of the regression lines approached unity indicating a close direct correspondence between the number of cells degranulated and the quantity of histamine released. At any time during histamine release almost all of the cells identifiable as basophils were confluently stained and only rarely were partly degranulated cells observed. These results suggest that: (1) histamine release is not synchronous for populations of basophils; (2) individual cells are fully activated to begin histamine release at different times during the release period and then release all or almost all of their histamine in a short time relative to the total release period; (3) some cells release essentially none of their histamine and the number of these cells varies among donors and experimental conditions accounting in large measure for the incompleteness of histamine release.

Anti-Bacterial Agents↗

Detection of antibodies in human serum using trimellityl-erythrocytes: direct and indirect haemagglutination and haemolysis.

Utilizing trimellityl-erythrocytes (TM-E), antibodies were detected in sera of seven workers with trimellitic anhydride (TMA) induced airway syndromes by direct haemagglutination, indirect haemagglutination with anti-human IgG, IgA or IgM or by haemolysis. Detectable levels of antibody were obtained with all three methods. The most sensitive technique was indirect haemagglutination using anti-IgG. When added as an inhibitor, TM-human serum albumin produced a 10- to 800-fold reduction in titres. TM-ovalbumin of similar epitope density was less inhibitory and sodium trimellitate the least inhibitory on a molar basis. All of the assays using haptenized human red cells were also capable of detecting anti-TM antibodies in Rhesus monkeys whose airways had been exposed to TMA. These assays are useful for detecting anti-TM antibodies and may also be adapted to demonstrate antibodies induced against other inhaled haptens in sera of environmentally exposed individuals or in animal models of such exposure.

Animals↗

Antibodies in hemodialysis patients against hapten-protein and hapten-erythrocytes.

Serum samples obtained from hemodialysis patients with immediate-type hypersensitivity reactions and hemodialysis patients with no reactions were analyzed for antibody activity against hapten-protein complexes prepared from PA and MDI. These chemicals, used in preparation of plastics, have been shown to be associated with immunologically mediated disease in other studies. IgE and IgG antibodies against P-HSA and MDI-HSA were detected in several sera, but symptomatic patients could not be differentiated from asymptomatic patients by antibody levels. Antibodies capable of agglutinating or hemolyzing P-E were also detected in some sera from hemodialysis patients. These studies demonstrate that although no clinical disease has yet been correlated with these antibodies, sufficient exposure of hemodialysis patients to protein-reactive chemicals occurs to elicit an immunologic response against hapten-protein or hapten-cells. Such antibodies may have immunopathogenetic significance in subjects systemically exposed to fluids which have been in contact with plastics.

Albumins↗

Pulmonary haemorrhage and haemolytic anaemia due to trimellitic anhydride.

Two young men who had been exposed at work to epoxy resin powder containing trimellitic anhydride (TMA) presented with haemolytic anaemia and repeated haemoptyses. They did not return to work at the factory and the symptoms and the anaemia resolved spontaneously. Seven similar cases have lately been presented at meetings, so it seems that TMA, already known to cause respiratory syndromes such as asthma, can also lead to several extrapulmonary toxic effects, including haemoptyses and haemolytic anaemia. Studies on these patients' sera with TMA haptenised protein and cells pointed to an immunological mechanism.

Adolescent↗

The immune response of patients with ragweed hay fever treated with polymerized ragweed antigens.

This report describes the immune response of patients with ragweed hay fever treated with polymerized ragweed antigens (PRW). Their IgG antibody responses to crude ragweed extract, antigen E, antigen K, and antigen Ra3 were determined by a solid-phase radioimmunoassay. The results indicate that PRW contains an array of clinically important antigens that are available for immunologic processing and result in an immune response in patients treated with this new form of immunotherapy for ragweed hay fever.

Analysis of Variance↗

Reduced allergenicity of high molecular weight ragweed polymers.

Polymerized ragweed antigens of different molecular weight ranges were studied to determine if the degree of allergenicity was dependent on molecular size of the polymers. In this study, allergenicity is defined as the ability to elict IgE-mediated skin reactivity. Ragweed antigen treated with glutaraldehyde was fractionated into one preparation with a molecular weight range of 200,000 to 20,000,000 and another with molecular weights less than 200,000. Except for the difference in molecular sizes of the two molecular sizes of the two preparations, all ragweed polymers had been treated in an identical fashion. The low molecular weight fraction had cutaneous endpoint reactivity greater than 10(5) to 10(8) times that of the high molecular weight materials. In these and other studies, immunogenicity defined as the ability to induce an IgG antibody response was retained by the high molecular weight material. The results are consitent with the hypothesis that allergenicity decreases as the molecular weight of the polymerized allergen increases.

Allergens↗

Quantitation of IgE antibody specific for ragweed and grass allergens: binding of radiolabeled allergens by solid-phase bound IgE.

IgE antibody specific for multiple allergens extracted from grass and ragweed pollens was measured by radioimmunoassay. The assay depends on the interaction between IgE antibody bound to a polystyrene solid phase, , 125I-labeled grass allergens (GA), and ragweed allergens (RW). The binding of 125I RW by serum IgE antibody from 37 allergic patients ranged from 0.2 ng to 75 ng RW protein (P) bound per ml. This binding of 125I RW by patient's IgE was paralleled by their IgE binding of 125I antigen E (AgE), a purified allergen from ragweed pollen (r = 0.90, p less than 0.001). Inhibition of patient's IgE binding of 125I RW by highly purified AgE ranged from 25% to 85% indicating individual differences in patient's IgE response to inhaled ragweed pollen. The binding of 125I GA by serum IgE antibody from 7 grass-sensitive patients ranged from 0.6 ng GA P bound per ml to 15 ng. This assay should be useful in the study of IgE responses to environmental agents containing multiple allergens and has the advantage that other antibody classes cannot interfere with the interaction between IgE antibody and labeled allergens.

Allergens↗

Poylmerized whole ragweed: an improved method of immunotherapy.

A single-blind study compared the effectiveness of glutaraldehyde-treated polymerized ragweed with nonpolymerized monomeric ragweed. These studies are an extension of those previously reported for polymerized AgE using a readily available ragweed preparation containing all ragweed antigens. Nineteen ragweed-sensitive patients were randomized into 2 groups; 10 received the polymerized form and 9 received the monomeric form. Four parameters were followed: serum-specific IgE against antigen E, total blocking antibody against antigen E, local and systemic reactions to injection therapy, and symptom score indices. Pretreatment levels of antigen E--specific IgE and blocking antibody activity were similar in both groups. After a total of 15,000 protein nitrogen units (PNU) had been given, blocking antibody activity in the monomer group rose from a mean of 170 ng AgE bound per ml to a mean of 2,813. The rise in blocking antibody activity in the polymer group was from a mean of 181 ng AgE bound per ml to 1,574. At 15,000 PNU, blocking antibody activity levels were not statistically different in the 2 groups. After 1 year of treatment, no consistent decrease in postseasonal specific IgE rise could be shown in either group. Forty times less erythema and 15 times less induration were found with polymerized ragweed. There were 7 systemic reactions with the monomer and none with the polymer. Both groups experienced symptomatic improvement with treatment.

Adult↗

Comparison of immune reactivity to polyvalent monomeric and polymeric ragweed antigens.

The proteins of an aqueous extract of ragweed pollen (RW) were precipitated at 90% saturation with (NH4)2SO4, solubilized, and sieved through Sephadex G-15. The excluded fraction, termed the monomeric form (MRW), was cross-linked with glutaraldehyde to form polymerized ragweed (PRW). As compared with MRW, PRW is more immunogenic in rabbits in the production of antibody against RW antigen E (AgE). MRW and PRW resulted in equal peak reaginic responses in rabbits but the duration of reagin production was longer after immunization with MRW than with PRW. Both MRW and PRW have exposed antigenic determinants of AgE but PRW had approximately 1/3 the number as shown by neutralization of human antibody against RW AgE. PRW had 100-to 1,000-fold less human cutaneous reactivity than MRW. PRW may be a more easily effective therapeutic agent for human RW immunotherapy than currently used aqueous extracts and may be more readily obtainable than polymerized AgE.

Antibody Formation↗

Evaluation of severe (anaphylactic) reactions.

The clinical course of twenty-one patients who presented with life-threatening symptoms, appearing to be allergic in aetiology, is described. In ten of these patients clinical evaluation established a diagnosis, for example: drug allergy, food allergy, a curious form of hospital addiction syndrome, an underlying malignancy, systemic mast cell disease or a complement abnormality. In the remaining subjects, it was found that their condition could be stabilized with sympathomimetics, antihistamines and corticosteroids. In those in whom no aetiology could be found, there was usually a spontaneous subsidence of the frequency and severity of attacks or spontaneous remission. No fatalities occurred.

Adolescent↗

Human antihapten antibodies in trimellitic anhydride inhalation reactions. Immunoglobulin classes of anti-trimellitic anhydride antibodies and hapten inhibition studies.

Inhalational exposure to trimellitic anhydride (TMA) produces an immediate-type asthmatic or a late respiratory systemic syndrome in certain workers after a latent period of work exposure. TMA has been found to react with proteins to produce a hapten-protein complex (trimellitate [TM] protein) or become hydrolyzed in aqueous, alkaline solutions to produce a salt, NaTM. Using a solid-phase radioimmunoassay technique, antibodies of different Ig classes were detected against TM-protein conjugates. IgE antibody was detected in three of five workers with asthma. IgG and IgA antibodies were detected in most exposed workers but higher levels of antibody were found in symptomatic workers even after long periods without direct TMA exposure. IgM antibody activity against TM-human serum albumin (TM-HSA) was detected but did not differentiate symptomatic from asymptomatic workers. NaTM served as a hapten for study because it does not react with proteins to form a hapten-protein complex as TMA does. The NaTM only partially inhibited IgG antibody activity against TM-HSA and much smaller amounts of TM-HSA than of NaTM were required to neutralize IgG antibody. A similar result was found with TM-ovalbumin. The latter results suggest that some IgG antibody is directed against a TM-protein moiety, probably a TM-amino acid determinant. In contrast to IgG, marked inhibition by NaTM of IgA and IgM antibody against TM-HSA was found in the sera studied.

Anhydrides↗

Low molecular weight C1q-precipitins in hypocomplementemic vasculitis-urticaria syndrome: partial purification and characterization as immunoglobulin.

A lupus-like syndrome involving chronic urticaria with cutaneous vasculitis, systemic symptoms, hypocomplementemia with preferential depletion of C1q, and low m.w. (7S) C1q-precipitins has recently been defined. The C1q-precipitin activity (C1q-p) seems to represent a diagnostic marker of the disease, but its chemical nature is not yet clear. We have partially purified and characterized C1q-p from the serum of two patients with this syndrome and compared its activity with the C1q-precipitating activity of aggregated human gamma-globulin (AHGG) anti-C1q antibodies, and several polynucleotides including DNA and polyinosinic acid. C1q-p was found to partition with IgG during precipitation by ammonium sulfate and low ionic strength buffer as well as during column chromatography on DEAE-cellulose and G-200 Sephadex. Like AHGG, but in complete contrast to the polynucleotides, the C1q-precipitating activity of C1q-p was sensitive to pepsin, trypsin, and acidic conditions, but unaffected by DNAse or RNAse; the C1q-precipitating activity of anti-C1q antibody was not diminished by any of these procedures. Thus, C1q-p consists of gamma-migrating protein of low m.w., and its C1q-precipitating activity is indistinguishable from that of AHGG. These results are consistent with the concept that C1q-p is comprised, at least in part, of IgG that binds C1q via the Fc portion of the molecule.

Binding, Competitive↗