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Biomedical subjects

J Dolovich

Publications and source records attributed to J Dolovich.

At least 163 records · Page 9Linked to original sources

Reactions during hemodialysis caused by allergy to ethylene oxide gas sterilization.

In patients receiving long-term hemodialysis (HD), we have examined the presence of IgE-dependent sensitization to ethylene oxide (EO) gas, which is used for sterilization of disposable medical products including dialyzers. Serum was obtained from 25 patients who experienced acute allergic reactions during HD, five patients receiving HD with isolated eosinophilia, and 37 unselected patients receiving HD. Sera from 22 of 25 of the allergic reaction group and from five of 35 of the unselected group were demonstrated to contain IgE antibodies with specificity for EO. Corresponding IgG antibodies were also present. No such antibodies were detected in serum from normal controls or ragweed-allergic patients. The serum from one patient with isolated eosinophilia had a borderline elevated IgE antibody level. These results demonstrate a close relationship between the presence of IgE antibodies to EO and HD-related allergic reactions in this patient population.

Ethylene Oxide↗

Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis.

Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year, placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract, in ragweed pollen-induced rhinoconjunctivitis. At the beginning of the study, subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year. There was random allocation of half to active treatment and half to placebo treatment. Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections (group 1), and the remaining 26 received six injections (group 2). Before the second season all subjects received 10 injections. Doses increased by half a log concentration each week unless there were adverse reactions. The mean total dose received by group 1 in year 1 was 385 micrograms of protein (28.9 micrograms AgE) and received by group 2 was 218 micrograms of protein (16.4 micrograms AgE). In year 2 the mean total dose was 1829 micrograms (137.2 micrograms AgE). Sixty-six percent of injections elicited no reaction or a mild local reaction; the remaining injections produced local redness and swelling more than 2 inches in diameter. Four percent of injections produced systemic symptoms. PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years, but increases in ragweed specific IgE antibody were significant only in group 1 in year 1. The magnitude of the IgG antibody changes was directly related to the total dose injected. At the beginning of the second year, PEG-modified ragweed-treated subjects still had elevated IgG antibody levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heterogeneity of metachromatic cells in human nose: significance of mucosal mast cells.

The distribution and abundance of histochemically and morphologically distinct subpopulations of metachromatic cells were investigated in nasal secretions and scrapings from patients with allergic rhinitis, as well as in nasal biopsy specimens from other patients. These analyses of the metachromatic cells demonstrate that basophils and two distinct mast cell populations are present in nasal specimens. One mast cell subpopulation was analogous to the atypical mucosal mast cell of the rat and human intestine, whereas the other cell population was similar to the typical connective tissue mast cell type. In nasal scrapings greater than 80% of the metachromatic cells was mast cells, almost exclusively of the atypical "mucosal" type. However, basophils were the predominant metachromatic cell type in nasal secretions, and atypical mast cells were more abundant than typical mast cells. Few basophils were observed in biopsy specimens, but mast cells were widely distributed in various anatomic compartments. Atypical mast cells outnumbered the typical type in the epithelium and lamina propria, whereas the reverse was true in the submucosa. When the number and type of metachromatic cell in scrapings were analyzed in relation to clinical findings, there was a significant correlation with severity of symptomatology and nasal swelling and pallor. Atypical "mucosal" mast cells were the major cell type in all specimens, from those with mild to those with severe clinical findings. When the distinct spectrum of responsiveness to antiallergic compounds of atypical mast cells is considered, these observations have important therapeutic implications.

Adolescent↗

Increased numbers of circulating basophil progenitors in atopic patients.

Recruitment of basophils to sites of homocytotropic antibody-mediated hypersensitivity reactions has been well documented in both experimental and clinical situations. Mechanisms underlying tissue basophil accumulation, however, remain unclear and may involve chemotaxis, cell proliferation, or both. We have recently reported the presence in human blood of circulating basophil/mast cell progenitors on the basis of histamine content of granulocyte colonies grown in methylcellulose. In the current studies we have analyzed the peripheral blood of 30 patients with atopy and 25 comparable control subjects for frequency of basophil/mast cell progenitors by analysis of the histamine content of individual granulocyte colonies. Forty percent of granulocyte colonies in cultures of atopic patients contained histamine in comparison to only 11% in cultures of control subjects (p less than 0.001). Histamine content per colony as well as mean histamine per cell in each colony was higher in granulocyte colonies of atopic subjects and could not be related to colony size or culture conditions. Granulocyte colony growth was enhanced by antigen-stimulated, peripheral blood lymphomononuclear cell--conditioned media of atopic patients. Histamine-positive colonies were found more frequently in active versus quiescent atopic disease (p less than 0.05). These results are consistent with the hypothesis that basophils accumulate at sites of allergic reactions at least in part by recruitment of progenitors from circulation and subsequent differentiation in situ in response to lymphokines. Further studies by use of hemopoietic assays could elucidate the contribution of basophil production to the development of allergic conditions.

Adolescent↗

Isolated late asthmatic reaction due to nickel sulphate without antibodies to nickel.

A worker with occupational exposure to nickel developed asthma a few months after starting work. Skin prick tests to nickel sulphate were negative. Inhalation challenge with nickel sulphate, at a concentration of 10 mg/ml for 30 min induced a late asthmatic reaction, starting 3 hr after the end of exposure leading to severe nocturnal attack. Tests for antibodies with nickel reactivity were negative.

Adult↗

Associated cutaneous findings in nickel contact sensitivity.

A clinical survey of patients with nickel dermatitis has provided evidence of a significant association with one or more of the following reactions: contact reaction from adhesive tape, reaction from mosquito bites which lasts 1 week or longer, and a history of hives. The association of nickel contact dermatitis with at least one of the other reactions is termed contact sensitivity syndrome.

Adult↗

Skin tests for chymopapain allergy.

Skin prick tests with therapeutic chymopapain (CP) solution, 10 mg/mL, were administered prior to CP injection. Three of 232 (1%) of patients with negative skin tests and 5/6 (83%) of patients with positive skin tests reacted to the therapeutic injection of CP. A positive CP skin test is a contraindication to therapeutic CP injection.

Anaphylaxis↗

Occupational asthma due to pepsin.

A 30-year-old atopic worker exposed to pepsin powder, herb, and pollen extracts at work developed an increase in asthmatic symptoms. Monitoring of peak expiratory flow rate revealed more important fluctuations at work. Skin prick tests yielded a large immediate reaction to pepsin. Specific inhalation challenges confirmed the diagnosis; an intense early response was documented after exposure to pepsin. The pepsin IgE RAST was positive and selectively inhibited by pepsin.

Adult↗

Prediction of late asthmatic responses to inhaled allergen.

Relationships between cutaneous and bronchial responses to allergen were examined in nineteen atopic asthmatics. Allergen inhalation tests elicited an isolated early asthmatic response (EAR) in ten subjects and a dual asthmatic response (DAR) in nine subjects. Ragweed IgE RAST, performed with the sera of those patients tested with ragweed antigen, yielded higher values in all but one patient who experienced DAR than any of the patients with EAR. In one patient with annual symptoms in the ragweed season, positive skin tests with ragweed antigen and DAR to inhaled ragweed extracts, the IgE RAST was entirely negative and the serum IgE concentration was low. Dilutions of the allergen used in each individual for inhalation were also used in skin-prick tests. Early cutaneous allergic response (ECAR) mean wheal diameters were obtained at 10 min and late cutaneous allergic response (LCAR) mean diameters at 6-8 hr. Early asthmatic response (EAR) subjects differed modestly from DAR subjects in the relationships between ECAR and LCAR; in the EAR group, a significantly larger wheal diameter (P less than 0.01) was required before an LCAR ensued, however there was some overlap. Once LCAR developed, there was no difference between EAR and DAR groups in the magnitude of the LCAR. There was a trend (not significant) towards a requirement for a higher antigen concentration in the EAR group to elicit an LCAR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Allergy to ethylene oxide in chronic hemodialysis patients.

Almost a decade ago, a single chronic hemodialysis patient in Hamilton, Ontario, Canada, who was experiencing recurrent acute reactions during hemodialysis was found to have become allergic to ethylene oxide gas (EO). This observation recently provided a stimulus to examine the possibility that others exhibiting acute allergic-type reactions during hemodialysis might be similarly sensitized. Serum was obtained from 27 reacting patients and tested in a radioallergosorbent test (RAST) for antibodies to EO. The test was positive for 22 of these sera. EO-related specificity of the antibodies was confirmed. However, EO sensitization was not found in other hemodialysis patients with isolated eosinophilia. In a survey of the current Hamilton chronic hemodialysis population for EO-related antibodies, 9% had a positive allergy skin test and 12% had a positive RAST. The sensitized individuals had no distinctive symptoms. The lesser sensitivity of the skin test contrasts with usual findings in allergic individuals; however, the use of histamine and codeine in chronic hemodialysis and peritoneal dialysis patients might well explain a reduced sensitivity of the EO-related allergy skin test. Chronic peritoneal dialysis could not be invoked as a source of sensitization. None of these patients had a positive skin test or RAST for EO-related antibodies that could be attributed to peritoneal dialysis.

Antibodies↗

Occupational asthma from nickel sensitivity: I. Human serum albumin in the antigenic determinant.

Occupational asthma from nickel sensitivity was confirmed in a male worker (SB) by allergy skin tests and inhalational challenge. In an ammonium sulphate coprecipitation test 63Ni was selectively precipitated from SB plasma indicating antibody with nickel related specificity. Preincubation of 63Ni with human serum albumin (HSA) increased the specificity of the coprecipitation test. Blocking experiments with nickel and copper(II) salts effectively inhibited the binding of 63Ni to antibody of SB plasma but did not affect control tests or that for antibodies to an unrelated antigen, ampicillin. Co2+ slightly inhibited the binding of 63Ni, while Zn2+ and Mn2+ failed to inhibit. This deactivation pattern corresponds to the known sequence of binding of these metals to the primary copper binding site of HSA. It is concluded that the antigenic determinant depends on the combination of Ni2+ with HSA at this specific copper/nickel plasma transport site.

Antibody Specificity↗

Occupational asthma from nickel sensitivity: II. Factors influencing the interaction of Ni2+, HSA, and serum antibodies with nickel related specificity.

Serum from an individual with occupational asthma from nickel sulphate inhalation was shown by ammonium sulphate (Farr) and anti-IgG coprecipitation tests to contain antibodies which bind 63Ni2+. This binding was absent from 30 control sera. Ligand competition studies with serum and plasma from the propositus and controls are described, and include serial additions of HSA, L-histidine, EDTA, and the tripeptide gly-gly-L-his. The results, like those from metal ion blocking experiments, clearly showed that the formation of the reactive antigenic determinant depends on the selective binding of Ni2+ at the native Cu2+/Ni2+ transport site of HSA. Corroborating evidence is derived from the similar dependence on pH of the Ni2+-HSA formation and the ammonium sulphate 63Ni2+ coprecipitation reactions.

Antibodies↗

Cellular binding and/or uptake of nickel(II) ions.

L-Histidine (L-His) and human serum albumin (HSA) at physiological concentrations, like the exogenous ligands D-penicillamine (D-PEN) and EDTA, are shown to inhibit the uptake of physiological levels of Ni2+ by B-lymphoblasts of human origin, human erythrocytes and rabbit alveolar macrophages. Evidence is also presented that illustrates the ability of these ligands to sequester Ni2+ from cells preloaded with this ion. The experimental observations are interpreted to indicate that serum concentrations of HSA and amino acids (especially L-His) exert a controlling influence on the cellular accumulation of Ni2+ in vitro, and further suggest the necessity to standardize the concentrations of these and related constituents in cell-culture media for meaningful comparisons of cellular uptake and toxicity of Ni2+ and other metal ions. Cells were lysed and the fractional distribution of 63Ni2+ in the lysate and residual pellet were assessed. About 60% of the radiolabel occurred in the pellet and 40% in the lysate for B-lymphoblasts, compared to 70 and 30% respectively for the alveolar macrophages. Diethyldithiocarbamate (DDC), unlike the other complexing agents, enhanced the cellular uptake of Ni2+ and prevented its removal from loaded cells. DDC also induced a transfer of the 63Ni2+ from the lysate to the residual pellet, suggesting that it promotes the deposition of Ni2+ in the lipid-rich components of cells (tissues). It is concluded that cellular association of Ni2+ is favoured by ligands forming lipophilic complexes, and extracellular localization by those giving hydrophilic complex compounds. The relevance of these contrasting roles in nickel detoxification by endogenous ligands and chelating drugs is discussed.

Animals↗

Ethylene oxide allergy in a dialysis center: prevalence in hemodialysis and peritoneal dialysis populations.

Chronic hemodialysis (HD) and peritoneal dialysis (PD) patients in one dialysis center were examined for (EO)-related sensitization. Five of 56 (8.9%) HD patients and 0 of 30 PD patients skin tested with a conjugate of human serum albumin (HSA) and EO had positive skin prick tests. The sera of 13 of 107 (12.1%) HD patients including sera from 5 patients with negative skin tests were positive in an EO-HSA radioallergosorbent test (RAST). Sensitized patients in this population did not experience allergic-type reactions during hemodialysis. There were no positive EO-HSA RAST results which could be ascribed to PD. Non-specific cutaneous responsiveness of the renal failure patients was compared with that of normal adult subjects by the use of skin prick tests with codeine phosphate and histamine phosphate. A significantly reduced responsiveness is present in chronic renal failure patients which would be expected to lower the sensitivity of the diagnostic skin test by comparison with the RAST.

Adult↗

Sporobolomyces: a possible cause of extrinsic allergic alveolitis.

A 28-year-old horseback rider presented with symptoms, chest radiograph, and pulmonary function tests suggestive of extrinsic allergic alveolitis related to exposure to a horse barn. Exposure to the barn produced symptoms, fever, and a fall in VC commencing 4 hr after exposure. Precipitins were positive against Sporobolomyces, suggesting this might be the causative agent; precipitins were negative against other fungi and horses. Lymphocyte stimulation to Sporobolomyces in vitro was positive in the patient and negative in two control subjects. Sporobolomyces was grown from straw in the barn. Cessation of exposure to this barn (but continued exposure to horses) has resulted in improvement in clinical condition. A survey for immunologic sensitivity to Sporobolomyces revealed that eight of 30 atopic subjects had positive wheal-and-flare prick skin tests to Sporobolomyces antigen, whereas none of 30 laboratory controls or 30 grain handlers had precipitins against Sporobolomyces. Sporobolomyces is a common fungus in cereal grain growing areas. Its spore size is less than 5 micron, consistent with other causative agents of this disorder. In this patient, positive precipitins and lymphocyte stimulation to Sporobolomyces and negative precipitins to other known causes of extrinsic allergic alveolitis provide circumstantial evidence that Sporobolomyces was the cause of the syndrome.

Adult↗

Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure.

Serial measurements of symptoms, peak flow rates, methacholine bronchial responsiveness, and ragweed-specific IgE antibodies were made before and during the ragweed pollen season in 13 sensitized subjects. Allergen inhalation tests were carried out with aerosols of pollen extract out of season in nine subjects; isolated early asthmatic responses were provoked in four, and dual responses (early followed by late) were provoked in five. During the pollen season all subjects developed hay fever and eight had symptoms of asthma. There was a real increase in methacholine responsiveness during the ragweed season. This increase appeared before or after the occurrence of asthma symptoms and changes in flow rates and was greater in subjects with symptoms in the pollen season, dual responses after allergen inhalation tests, and higher levels of ragweed-specific IgE antibodies. The results confirm the occurrence of seasonal asthma and increases in nonallergic (nonspecific) bronchial responsiveness to methacholine from seasonal pollen exposure. They suggest that the occurrence of symptoms is closely linked to the allergic inflammatory reaction and the induction of increased nonallergic responsiveness.

Adolescent↗