A mechanism for tobacco smoke-induced allergy.

Normal CFW mice, when exposed to tobacco smoke, showed a significantly increased susceptibility to the lethal effects of histamine. The LD50 for mice subjected to smoke was 45 mg/kg of histamine, whereas in normal CFW mice the LD50 was 1,100 mg/kg. The histamine susceptibility of smoked mice was markedly diminished by injecting the animals with isoproterenol. Normal CFW mice, as well as sham control mice, exhibited an epinephrine-induced hyperglycemia, whereas the blood glucose values for smoked mice given epinephrine were essentially the same as those for sham mice given only saline. This observation indicates that tobacco smoke may contain a component which causes an autonomic imbalance, hence rendering the mice more susceptible to histamine. This tobacco smoke-induced allergy is probably related to a blockade of adrenergic receptors and not to an immunologic phenomenon.     

Human peripheral blood lymphocyte transformation by concanavalin A in a chemically defined medium

Human small lymphocytes from peripheral blood were cultured for 72 hours in a chemically defined medium consisting of NCTC 109 supplemented with methyl cellulose, glucosamine, and hormones. About two thirds of the cells died during the first 24 hour period, but thereafter the counts were fairly stable. The addition of concanavalin A stimulated the production of transformed cells, although during the 72 hour observation period none of these was seen in mitosis. As the amount of concanavalin A added to 3 ml. cultures was increased from 5 to 40 μg, the number of small lymphocytes in the defined medium that underwent transformation increased from 34 per thousand to 61 per thousand.     

Relationships between physical and mental illness

A random sample of the general population of a southeastern county was studied to examine some relationships between reported physical illness and mental disorders. Results, obtained from epidemiologic data, indicate that lower socioeconomic status is probably the most fundamental factor associated with high risk for both physical and mental illness.     

Histamine suppression of in vivo eosinophil accumulation and histamine release in human allergic reactions

Although it has been shown that histamine inhibits antigen-induced in vitro histamine release from basophils, it is unclear whether histamine inhibits in vivo mediator release in human allergic reactions. We report effects of exogenous histamine on histamine release and inflammatory cell responses in antigen-challenged skin sites in eight ragweed-sensitive individuals. Four heat-suction blisters in each subject were unroofed, and a collection chamber was appended to each blister base. Chamber A contained 1000 PNU/ml ragweed extract; chamber B contained buffered saline (control fluid); chamber C contained 1000 PNU/ml ragweed and 50 ng (5 x 10(-7) M) of histamine; and chamber D contained histamine alone (50 ng). Comparative analyses of chamber histamine levels in individual subjects showed that (1) histamine levels in chamber A were significantly greater than those in chamber B (p less than 0.01) and that histamine levels in chamber C were not significantly different than those in chamber D (p less than 0.5). Likewise, comparison of eosinophils attaching to membrane filters appended to the chamber bases for 2 hr showed that there were significantly more eosinophils in chamber A than in chamber B (p less than 0.01) and that there was no significant difference in eosinophil numbers on filters appended to chamber C vs chamber D. In three of four subjects studied, addition of exogenous histamine (50 ng/ml) to ragweed before intradermal injection inhibited the ultrastructural mast cell alterations seen within 10 min after injection of ragweed alone. In the one subject in which mast cell alterations were not prevented, exogenous histamine also did not inhibit antigen-induced histamine release or subsequent eosinophil accumulation in the skin chambers.     

Profile of multiple lymphocyte functional defects in acquired hypogammaglobulinemia,derived from in vitro cell recombination analysis

Immunoregulatory defects in patients can be assigned to B cells, T helper cells, or T suppressor cells by means of a modification of the in vitro PWM-stimulated Ig biosynthesis assay. When lymphocyte subpopulations from patient and normal are recombined, multiple internal comparisons within a single experiment reveal the functional activity of each subpopulation. By this technique we studied nine adult patients with acquired panhypogammaglobulinemia and one with isolated IgG deficiency. Low total Ig production by the B cell fraction was demonstrated in seven of the nine panhypogammaglobulinemic patients. In four of these seven, IgG and IgA secretion was markedly reduced compared with IgM. In the two patients with normal total Ig production, elevated IgM compensated for lower IgA and IgG. The one patient with no surface Ig⁺ cells had a B cell defect, but no T cell defect. Reduced T help and excessive T suppression characterized two of the four patients with the most severe B cell defects. Three patients were anergic by delayed hypersensitivity skin testing and failed to sensitize to DNCB, but the patient with the most severe T cell defects in vitro was not among them. One of these three patients showed a mild T cell help defect and suppressor excess and the other two had pure B cell defects. Thus, anergy and T regulator function were not correlated. In three instances where hypersuppression was more evident by adding patient unfractionated cells than by adding patient T cells, suppression by the T-depleted fraction could be demonstrated. No cases of radiation-resistant T suppression were revealed among the seven patients tested. Subnormal total protein synthesis, noted in six of seven patients with low Ig production, was invariably less marked than the Ig defect and often affected both T and B cells. One additional patient with pure IgG deficiency of 2 yr duration was essentially normal in her in vitro lymphocyte function. The general applicability of this experimental design for analysis of positive or negative immunoregulatory abnormalities is emphasized.     

Immunologic mechanisms in hypersensitivity pneumonitis: I. Evidence for cell-mediated immunity and complement fixation in pigeon breeders' disease

Immunologic studies were performed on 5 patients with pigeon breeders' disease. Intradermal injection of pigeon serum produced an immediate wheal-and-flare reaction within 15 minutes and a secondary Arthus-type reaction within 4 to 8 hours. Immunofluorescent studies of the secondary reaction site showed IgG, C3, and C4 in 2 patients. Patients' sera produced multiple precipitin bands with pigeon serum when reacted by double diffusion in gel. IgG antibody isolated from each of the patients' serum formed precipitating immune complexes that fixed large amounts of complement (C4) when added to fresh human serum. Peripheral blood lymphocytes from 4 of the 5 patients produced macrophage migration inhibitory factor (MIF) when challenged with dilute pigeon serum. These studies are the first to show complement fixing antibodies and macrophage MIF production by lymphocytes from patients with hypersensitivity lung disease and suggest that both humoral and cellular immunity may be important in the pathogenesis of these disorders.     

The relative merits of cromolyn sodium and high-dose theophylline therapy in childhood asthma

The use of cromolyn sodium (SCG) and high-dose theophylline (HDT) in the treatment of chronic perennial asthma in children is reviewed. It is noted that the regimens are only suitable for children with persistent symptoms uncontrolled by simpler forms of treatment. The methods of administration and dosage based on pharmacologic data are considered, and the potential importance of long-acting theophylline and nebulized cromolyn preparations is noted. Short-term studies have confirmed the efficacy of both drugs, and a comparative study showed little difference between them. Long-term studies of SCG have demonstrated its value to some 66% of children without serious side effects. No formal long-term studies have been carried out on HDT. Side effects from theophylline can often be eliminated by careful control of blood levels. From published evidence, neither SCG nor HDT is effective in steroid-dependent asthmatic children, and they contribute little, if anything, to management in such cases. The difference in cost of the drugs is small when all factors are considered, and either regimen is justified by the saving in medical expenses when used for carefully selected patients.     

Identification of a new physically induced urticaria: cold-induced cholinergic urticaria

Four patients with symptoms suggestive of either cold urticaria or a combination of cold and cholinergic urticaria were studied. However, all patients were negative to an ice-cube test or cold-immersion test and had no urticaria after exercise in a warm environment. When each patient was seated in a cold room (4° C) for 5 to 15 min, generalized urticaria appeared, consisting of punctate wheals and surrounding erythema as seen in cholinergic urticaria. Two patients had weakly positive methacholine skin tests and the other two had completely negative tests. When serial venous blood samples were obtained to test for mediator release, three of four patients had evidence of histamine release and the time course was similar to that previously reported for patients with cholinergic urticaria. These four cases represent a new syndrome with features suggestive of cold and/or cholinergic urticaria, but the results of all the tests usually utilized to diagnose these conditions were negative. We have called this disorder cold-induced cholinergic urticaria to indicate that it is cold dependent and visually indistinguishable from cholinergic urticaria.     

Induction of delayed hypersensitivity to protein antigens in mice without Freund adjuvants

Three ways for inducing tuberculin-type delayed hypersensitivity (DH) in mice to purified protein antigens without Freund adjuvant are described. Four strains of mice compared for susceptibility to sensitization with several antigens ranked SJL > CF-1 > CAF₁ = C57B1. Females were more easily sensitized than males. The first way of sensitizing without Freund adjuvant was simply to inject antigen intradermally in saline, but it could be used only with the potent antigen methylated human serum albumin (HSA). Six-mercaptopurine injections during the first 5 days of sensitization enhanced such sensitization in CF-1 but inhibited it in CAF₁ mice. The second way sensitized with a weaker antigen, chicken conalbumin (CA), and thus is more versatile. It consisted of injecting a saline solution of antigen into a 24-hr strong DH dermal reaction to an unrelated antigen (dextran). The third way was simplest and best: Freund adjuvant was replaced with aqueous Evans blue dye. Thus, distilled water solutions of antigen (CA or chicken ovalbumin) and dye injected subcutaneously induced DH indistinguishable from that induced with the same antigens in Freund adjuvant. Neither antigen in distilled water alone sensitized. The dye also intensified Arthus sensitization. This diazo dye therefore may be a practical, harmless water-soluble substitute for Freund adjuvant for inducing DH or cell-mediated immunity and for intensifying Arthus sensitization.     

Factors related to the incidence of psychosomatic illness

The three-year incidence of psychosomatic illness in a sample of the general population was analyzed in relation to a variety of sociodemographic, cultural, and psychopathologic factors and stressful life events. Persons who were older, female, black, previously married, and of lower socioeconomic status were more likely than others to develop psychosomatic symptoms and conditions, but the risk was significantly higher only in those of lower socioeconomic status. The authors discuss the various factors related to poverty that may contribute to the development of psychosomatic illness.     

Specific immunoglobulin E antibodies in tear secretions of patients with vernal conjunctivitis

Twenty-two patients with vernal conjunctivitis (VC) were studied by radioallergosorbent test (RAST) for specific IgE antibodies to the inhalant pollen allergens in tear secretions. Specific IgE antibodies were detected in the tear secretions of 12 (54.5%) patients with VC. Six patients had a positive tear RAST, but the corresponding serum RAST and immediate skin test reactivity were negative. The specific tear IgE antibodies appeared to correlate with the seasonal prevalence of the pollen in the environment and the period of maximal symptomatology. Six patients had both positive serum and tear RAST determinations. A double ratio formula with transferrin as a marker for the leakage of plasma proteins into tear secretions and the “specific activity” ratios of IgE antibody to total IgE between the tear secretions and the serum indicated that almost all (79% to 99%) of the tear IgE antibodies were locally produced. IgE antibodies were also detected in the tears of four of 10 patients with allergic conjunctivitis (AC) and of three with allergic rhinitis (AR). However, the “specific activity” ratio in the patients with AC and AR with measurable tear IgE suggested that the IgE antibodies were derived from the leakage of serum proteins into the tear secretions. These findings suggest that the pathogenesis of VC may be IgE mediated in some patients and lends support to the concept that specific IgE antibodies can be produced locally by the target organ, i.e., conjunctival tissues.     

Allergy to murine antigens in a biological research insitute

Symptomatic and immunologic responses to allergens from laboratory mice were studied in a research institute. Subjects who had been exposed to mice and 50 unexposed subjects were studied by questionnaire and by prick tests with seven prevalent aeroallergens and allergens from mouse urine and pelts. Of the 121 exposed subjects. 39 (32.2%) had respiratory, ocular, or cutaneous symptoms after exposure to mice; occurrence of these symptoms correlted with positive skin tests to purified mouse urinary proteins (MUP) and pelt allergensfrom CBA/H mice. Serum levels of IgG antibodies correlated with the frequency of mouse exposure. In subjects with seasonal allergic rhinitis, nasal symptoms from exposure to mice, positive prick tests to MUP, and IgE antibodies to MUP were significantly more prevalent. The possibility of genetic influences on susceptibility to mouse allergy were also suggested by a negative association between the incidence of HLA-DRW6 and positive prick-test responses to urinary proteins from C57BL and BALB/c mice among the 54 subjects who were exposed to mice and tested for DR locus antigens (p = 0.05). However, no significant differences in any of the loci studied culd be shwn in subjects with and without nasal symptoms from exposure to mice.     

The presence of IgE on the surface of lymphocytes in nasal polyps

The presence of IgE-bearing lymphocytes in nasal polyps was correlated with the patients' atopic status. Following surgical removal, the polyp tissue was treated with hyaluronidase and a single-cell suspension was obtained. Lymphocytes were isolated by gradient centrifugation, and the fluorescent antibody technique was used to study the presence of various immunoglobulin markers on the surface of lymphocytes. The presence of IgE-bearing cells was correlated with serum IgE levels, history of allergy, and skin test reactions. Patients with a positive atopic history had intermediate to high serum IgE levels. There was no correlation between IgE level and skin reactivity in these patients. Good correlation was obtained between the number of IgE-bearing cells in nasal polyps and serum IgE levels in atopic patients. The IgE-bearing cells represented 10 to 40 per cent of total immunoglobulin-bearing lymphocytes. No IgE-bearing cells were detected in five of six patients with a negative atopicf history and negative skin tests. Thus IgE may be synthesized within nasal polyps of atopic patients, and the polyps in atopic patients may have a different etiology from those in nonatopic patients.     

Effect of moderate malnutrition on immediate hypersensitivity and immunoglobulin E levels in asthmatic children

Dermal reactions and IgE levels were compared in 51 asthmatic Colombian children identified on the basis of anthropometric measurements as nutritionally normal (25) or mildly (16) or moderately (10) undernourished. Twenty-five nonatopic children served as controls. Total serum IgE concentrations were significantly elevated in the asthmatic group as a whole. Moderately malnourished (grade 11) asthmatic children had more than twice as much serum IgE as normal or mildly malnourished (grade I) asthmatic subjects and seven times more than nonatopic children. Intestinal parasitism did not appear to contribute to these differences in IgE levels. Serum levels of IgA and IgD were similarly elevated in grade II asthmatics. Concentrations of serum IgG, IgM, and C3 and C4 complement were unaffected by nutritional or allergic status. Eosinophilia in nasal mucus was significantly reduced in grade I and grade II malnourished asthmatic children. Among asthmatics, the most frequent dermal reactions were to mite antigens (96%), house dust (67%), and grass pollens (35%). Significant levels of specific IgE were detected by the RAST to two species of mites in nearly all atopic children. There was no apparent influence of nutritional status on the distribution of reactivity to a particular allergen by either dermal reactivity or specific IgE assay. The clinical significance of hyper immunoglobulin E in atopic, moderately malnourished children remains to be elucidated.     

A volumetric study of winter fungus prevalence in the air of midwestern homes

Volumetric recoveries of airborne, mesophilic microfungi were made during winter months at three specific points in 150 single-family dwellings in southeastern Michigan. Mean levels of total isolates/m³ comprised a range of from less than 10 to over 20,000, although concurrent outdoor levels never exceeded 230/m³. Form species of Penicillium, Aspergillus, Cladosporium, and Rhodotorula as well as non-pigmented yeasts were the types encountered most widely indoors. Certain homes showed high recoveries of other types, including Cephalosporium, Sporobolomyces, Verticillium, and Sporothrix form species. A positive association between indoor fungus prevalence and bedroom relative humidity was strongly suggested, and high levels were observed in well-humidified homes despite the presence of electrostatic air cleaners. The data indicate characteristic patterns of (winter) air spora in specific homes and suggest that humidifying devices may serve as dispersion sources in addition to their permissive role in facilitating fungus growth.     

A technique for intense radiolabelling of pollen and pollen extract with 99mTc

Methods for radiolabelling Poa praetensis whole pollen grains and pollen extract with ^99mTc are described. Structurally intact and antigenically potent dry pollen grains with specific activities as high as 4.2 mc. per milligram pollen were obtained. The radiolabel is apparently confined to the nucleophilic groups of pollen outer wall. An almost identical procedure may be used for radiolabelling pollen extract.     

Harvester ant sensitivity: in vitro and in vivo studies using whole body extracts and venom.

Harvester ant stings by Pogonomyrmex maricopa (Pm) or Pogonomyrmex rugosus (Pr) resulted in serious reactions in 8 patients, 4 with generalized reactions and 1 with large local reactions. Exposure to one species in the genus Pogonomyrmex (P) appeared to cross-sensitize ant-sensitive patients to other species in the same genus as evidenced by skin testing and leukocyte histamine release, but these patients were less sensitive to extracts from other stinging Hymenoptera, including bee, wasp, yellow jacket, hornet, and Formica ant. Pr ant venom was obtained by electrical stimulation of live ants for leukocyte histamine release studies. The venom preparation was considerably more effective in inducing histamine release than a body extract derived from gasters, the posterior abdominal segments. Rabbits immunized with an extract from one species produced precipitating antibodies against the injected extract withich cross-reacted with extracts from other species of harvester ant, but not with other stinging Hymenoptera. Humans and rabbits appear to react to certain genus-specific antigens present in Pogonomyrmex whole body extracts. Proper identification of the offending ant is crucial for proper testing and treatment of ant-sensitive patients.