Induction of persistent tolerance to urushiol in humans

Young nonimmune subjects were injected intramuscularly multiple times with small amounts of urushiol oil derived from poison oak. One week after the last injection this group and another group of age-matched controls were exposed to a sensitizing dose of the oil painted on the skin. All were challenged at 1 mo, then each year for 7 yr. Initially all experimental subjects were tolerant to high challenge doses; this persisted for 1 yr, at which time experimental subjects were no longer completely tolerant but were clinically tolerant (hyporeactive). This state persisted for at least 4 yr, and this represents complete tolerance followed by long-lasting hyposensitization.     

Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers

Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples "disappeared," and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [14C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for.     

Leukocyte inhibition factor in delayed-onset food allergy

To investigate the possibility of a cellular immune hypersensitivity reaction in patients who developed allergic symptoms 2 or more hours after ingestion of a particular food, two in vitro tests were employed: leukocyte migration inhibition factor (LIF) and lymphoblastogenesis. Of the children and adults with food allergy, 73% (30 of 41) had a positive LIF test with whole cow's milk or its fractions or corn. Of nonallergic or grass-pollen sensitive controls, 15% (four of 26) had positive LIF. Lymphocyte transformation often correlated with LIF results in food-allergic patients but was also positive in 77% of controls (seven of nine). We suggest that many patients with delayed-onset food-induced allergy symptoms may have a cellular immune component to their sensitivity. Serum IgA, where measured, was absent or low in half of these patients.     

The natural history of food sensitivity

The natural history of food sensitivity has long been the subject of anecdotes about children “outgrowing” their problem, but prospective systematic studies are not easily found that document these opinions. Children who had had adverse reactions to foods during double-blind food challenges 1 to 7 yr prior to this study were evaluated. In children over 3 yr of age, 19% of the previously positive food challenges were negative at the time of the follow-up; in children 3 yr of age or younger, 44% of the food challenges that had been positive were negative. The data collected thus far suggest that children who have their food sensitivity diagnosed at older ages tend not to outgrow the problem. Skin testing was performed over a period of years on some of the subjects, and skin sensitization was found to be markedly persistent, even in subjects who could consume the sensitizing food without symptoms.     

Ocular allergy and immunology.

The eye may be the target of allergic inflammation in a large number of systemic immunologic conditions. Ocular signs and symptoms can often be the most striking and disabling aspects of such diseases. The eye is also affected by several local conditions in which immunologic mechanisms are thought to play a significant role. Certain anatomic and physiologic features appear to endow the eye with a unique immunologic reactivity which has made this organ of special interest to allergists and immunologists.     

Transfer of contact sensitivity to beryllium using dialyzable leukocyte extracts (transfer factor).

Transfer factor derived from lymphocytes of donors with strong cellular immunity against beryllium was intradermally or subcutaneously injected into unprimed or subclinically primed human recipients who were patch test-negative. These recipients were challenged with beryllium at weekly intervals thereafter. Subjects who had been subclinically primed and received transfer factor either intradermally or subcutaneously showed transient patch test reactivity to the challenge. Subjects who received transfer factor but were not primed and subjects who had been primed but did not receive transfer factor showed no such conversion. This is the first demonstration of transfer of contact sensitivity in man using transfer factor, and it suggests that subclinical priming is necessary for such transfers.     

Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate.

Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.     

Cutaneous immediate hypersensitivity in man: effects of systemically administered adrenergic drugs.

In in vitro models of hypersensitivity, beta adrenergic drugs inhibit the antigen-induced release of histamine and other mediators from mast cells and basophils. Epinephrine, an agent with both beta and alpha adrenergic properties, is clinically useful for treating immediate hypersensitivity reactions. We examined the effects of intravenously administered adrenergic drugs on cutaneous wheal-and-flare reactions to antigens and histamine in 7 normal men. Both epinephrine and isoproterenol, a beta agonist, inhibited skin reactions produced by antigen or histamine. Phenylephrine, an alpha adrenergic agonist, produced no effect. These results suggest that epinephrine's inhibition of cutaneous immediate hypersensitivity in vivo is mediated by beta, rather than alpha, receptors. This inhibitory effect in vivo is probably not mediated solely in preventing allergic release of inflammatory mediators since the skin reactions to histamine were inhibited as well.     

In vitro induction of tumor-specific immunity. VI: analysis of specificity of immune response by cellular competitive inhibition: limitations and advantages of the technique.

The cellular competitive inhibition 51Cr-release assay makes two distinct contributions to the in vitro study of cell-mediated immunity. It allows target cells which are not amenable to isotopic labelling to be investigated for their antigenic specificity, and it provides a means, complementary to the direct cytotoxicity assay, of estimating qualitative and quantitative differences in antigen expression on intact normal and neoplastic cells. Various parameters of a micro-51Cr-release inhibition assay have been studied, and it was found that the assay conditions markedly influenced both the sensitivity and specificity. It is concluded that optimal assay conditions for specificity include: 1) moderate levels of lysis on the linear part of the CL/T titration curve, 2) avoidance of prolonged assay times, and 3) low ratios of blocker to target cells. When tumor cells with large cell volumes are used as competitive inhibitor (blocker) cells, non-specific blocking will occur; limits have been defined for this particular micro-inhibition assay which, in general, exclude these effects.     

Allergy to insects in Japan. II. The reaginic sensitivity to silkworm moth in patients with bronchial asthma

The reaginic sensitivity to extract of silkworm moth wing (silkworm wing) and to that of silkworm moth body (silkworm body) was studied in 50 randomly selected asthmatic patients. Although none of the patients had occupational exposure to silkworm moth, 34 (68.0%) of these patients showed positive reaction to silkworm wing while 28 (56.0%) patients reacted positively to silkworm body following intracutaneous injection(s). Radioallergosorbent tests (RASTs) showed that 22 (44.0%) of 50 sera were positive to silkworm wing and 11 (22.0%) sera were positive to silkworm body, with less uptake of ¹²⁵I-labeled anti-immunoglobulin E in silkworm body than in silkworm wing RASTs. This suggests that wing components are more common sensitizers than body components. A fairly high percentage of these 50 patients also showed reaginic sensitivity to the extracts of butterfly, moth, and mite. That is, 26 (52%), 22 (44%), and 32 (64%) of these 50 patients had butterfly-, moth-, and mite-specific IgE antibodies in their sera, respectively. The seasonal variations of silkworm wing-, butterfly-, moth-, and mite-specific IgE antibodies and mutual RAST inhibition tests revealed that IgE antibodies to silkworm wing, butterfly, and moth were identical but all differed from the antibody to mite. These data suggest that the extract of silkworm wing is useful for the detection of allergy to moth and butterfly and also provides a suitable allergen source of unlimited quantity and consistent quality. It was also shown that the allergy to Lepidoptera (moths and butterflies) in Japan is found as commonly as that to mite, but without cross-reactivity between them.     

Migraine

Instead of representing two sharply different entities, migraine and tension headache may best be thought of as occupying the two ends of a continuum, with mixed tension and vascular headache in the center. The author's assessment of current knowledge of mechanisms, symptoms, and acute and prophylactic treatments supports his statement that the major clinical difference between the variants of headache is differential pharmacologic effectiveness of the drugs used.     

Life events, risk factors, and coronary disease.

Are high levels of stress from life events correlated with increased levels of smoking, blood pressure, and cholesterol? The authors used a life events questionnaire to determine the level of presumptive stress in a sample of 575 middle-aged men who were initially selected for inclusion in the larger, collaborative Multiple Risk Factor Intervention Trial (MRFIT). Significant differences in stress levels were found only between smokers and nonsmokers. Therefore, the authors suggest that smoking behavior be included as a variable in studies of the relationship between psychological stress and illness.     

[Sar, Ala] angiotensin II in cerebrospinal fluid blocks the binding of blood-borne [I]angiotensin II to the circumventricular organs

There is a specific, high affinity uptake of angiotensin II in the circumventricular organs when the peptide is injected systemically.¹¹ The question of whether angiotensin II in cerebrospinal fluid can reach angiotensin receptors in the circumventricular organs was investigated in rats by determining the effect of intraventricular administration of the angiotensin II receptor blocking peptide [Sar¹, Ala⁸]angiotensin II (saralasin) on the binding of blood-borne [¹²⁵I]angiotensin II. Other rats received intraventricular saline, intraventricular ACTH^4–10 as a peptide control, or intravenous saralasin. The brains of the rats were then sectioned and subjected to radioautography. ACTH^4–10 had no effect on angiotensin II uptake. Intraventricular saralasin reduced the uptake of blood-borne angiotensin II in the median eminence and organum vasculosum of the lamina terminalis to the same degree as intravenous saralasin, and reduced uptake in the subfornical organ and area postrema to a lesser extent. Uptake was reduced 40% in the anterior lobe of the pituitary by intraventricular saralasin and 73% by intravenous saralasin, indicating that some saralasin entered the portal vessels. Uptake in the posterior lobe was unaffected by intraventricular saralasin, but reduced by intravenous saralasin.

The data indicate that saralasin, and so presumably angiotensin II, in the cerebrospinal fluid can reach angiotensin II receptors in the circumventricular organs which bind blood-borne angiotensin II. Consequently, the effects of intraventricular angiotensin II that are also produced by intravenous angiotensin II can probably be explained by the peptide acting on the circumventricular organs.     

Light-chain glomerulopathy with amyloid-like deposits

A 40-year-old man with rapidly progressive renal failure was found to have a lobular glomerulonephritis by renal biopsy. Immunofluorescent microscopy showed prominent glomerular deposition of both kappa and lambda light chains but no significant heavy-chain component. Ultrastructurally, electron-dense deposits in the mesangium and capillary basement membranes had a fibrillar appearance indistinguishable from amyloid. This case illustrates a "light-chain glomerulopathy" distinct from previously reported glomerulopathies associated with the deposition of light chains of a single subclass.     

Correlation of flunisolide plasma levels to eosinopenic response in humans

Plasma levels of flunisolide were measured in healthy male volunteers after the administration of single doses of the drug by the intravenous, oral, intranasal, and bronchial inhalation routes. The systemic availability of a 1-mg dose orally was only 21%. After a single dose of approximately 0.117 mg intranasally plasma levels ranged up to 1 ng/ml. When 1 mg was administered by bronchial inhalation, peak or near peak plasma levels were recorded at 2 min and remained near this level throughout the first hour before declining at a rate similar to that observed after flunisolide intravenously (plasma ). Gargling with an alcoholic mouthwash immediately after inhalation reduced plasma levels at 30 and 60 min but not earlier, suggesting rate-limiting dissolution of flunisolide in bronchial fluids or rate-limiting diffusion across the mucociliary blanket or pulmonary membrane. The systemic availabilities of the inhaled-mouthwash and inhaled-no mouthwash doses were 32% and 39%, respectively. Systemic potency of flunisolide, measured by eosinopenic response, was oral < inhaled < intravenous and correlated with the systemic availability of flunisolide after drug administration by these three routes. These pharmacokinetic properties of flunisolide are clinically advantageous in that relatively small doses are delivered topically to the target organs, i.e., the nasal mucosa and lungs, whereas a large portion of the dose is swallowed and subsequently extensively metabolized to relatively inactive metabolites.