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Biomedical subjects

N F Adkinson

Publications and source records attributed to N F Adkinson.

At least 163 records · Page 9Linked to original sources
PubMed1983

Assessment of venom-specific IgG antibody in patients treated for hymenoptera allergy.

The IgG antibody (Ab) response achieved with specific venom immunotherapy was explored in 32 patients with Hymenoptera hypersensitivity. Venom-specific IgG Ab was quantitated before and after 1 year of immunotherapy using two solid phase radioimmunoassay (SPRIA) methods. An agarose-based test using 125I-Staphylococcus aureus Protein A (SPRIA) was used to determine specific IgG for five Hymenoptera species: yellow jacket (YJ), honeybee (HB), yellow-faced hornet (YH), white-faced hornet (WFH), and Polistes (POL). A cellulose disk test using 125I-anti-IgG (IgG RAST) was available only for YJ and HB venoms. Acceptable agreement (90% concordance) was observed with IgG anti-HB levels measured in the two assays. For the YJ-IgG, however, 17/69 (25%) of sera positive in the SPRIA were negative in the IgG RAST, whereas the converse was not observed. This result suggests that the IgG RAST is insufficiently sensitive to detect YJ-IgG responses in all patients on maintenance level immunotherapy. Using the Protein A SPRIA, there was excellent agreement between the venom used for immunotherapy and the specificity of the IgG Ab response. In 31 patients treated with a total of 90 venom species, 90/90 venom IgG levels were increased or maintained at high pretreatment levels in response to immunotherapy. In the same patients venom IgG levels obtained for venom species not included in therapy were undetectable or declined in 55/60 cases; in 4 cases treatment with YJ venom stimulated a WFH and/or YH IgG response, the remaining case, YJ venom stimulated a small rise in POL IgG. These apparent discrepancies can be explained by variable cross-reactivity among vespid and POL venoms. Among 32 patients with a combined total of 87 positive venom skin tests, 1 year of specific immunotherapy resulted in greater than 5 micrograms/ml of venom-specific IgG in 61 instances. In 25 instances, the level of venom IgG was detectable but less than 5 micrograms/ml, and in 1 case venom IgG could not be detected. Based on recent analyses by Golden et al., some or all of these latter 26 cases may represent suboptimal therapy despite a standard immunotherapy regimen. We conclude that venom IgG measurements can provide a specific and quantitative assessment of the immunologic response to venom therapy, and that such assessment may be clinically useful in detecting instances of suboptimal immunotherapy.

Antibody Specificity↗
PubMed1983

Mediator release after nasal airway challenge with allergen.

An in vivo model of human allergic disease has been developed in which nasal challenge with antigen leads to physiologic changes, together with a release of increased amounts of inflammatory mediators into nasal secretions obtained by washing the nose with saline. In 105 experiments involving 35 subjects, only allergic subjects consistently demonstrated an increase in the concentrations of the mast cell mediator, histamine, and the putative mast cell mediators, TAME-esterase and PGD2. The release of each mediator was significantly (p less than 0.001) related to the physiologic change (sneezing). The release of each mediator also correlated significantly with the release of the other 2 mediators (p less than 0.001). This system, for the first time, clearly relates an in vivo symptom and mediator release and thus should provide an excellent tool for the further study of the allergic response and nasal pathophysiology.

Adolescent↗
PubMed1983

Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells.

Purified human lung mast cells released histamine, leukotrienes, prostaglandin (PG) D2, thromboxane B2 (TxB2), and PGF2 alpha in response to anti-IgE stimulation. Incubation of the cells for 24 h with 10(-6) M dexamethasone, a treatment that inhibits mediator release from human basophils, had no effect on the release of these mediators from mast cells. Dexamethasone treatment of human lung fragments led to little or no inhibition of anti-IgE-induced release of the mast cell-derived mediator, histamine, but produced a significant inhibition of the release of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. As was the case with purified mast cells, the steroid did not inhibit the release of PGD2 or TxB2 from human lung fragments. Comparison of the quantities of PGD2 and TxB2 produced by purified cells and human lung fragments reveals that the mast cells produce quantities of these metabolites sufficient to account for the entire amount produced by challenged lung fragments. Dexamethasone inhibited spontaneous release from lung fragments of all cyclooxygenase products measured. These results suggest that the human lung parenchymal mast cell phospholipase is not inhibited by dexamethasone, whereas other phospholipase(s) in the lung are inhibited by the steroid. These results may be useful in explaining the resistance of acute allergic reactions, including anaphylaxis, to steroids, despite the potent antiinflammatory activity of steroids on subacute and chronic inflammation, such as in bronchial asthma, which may be initiated by IgE-dependent mechanisms.

Autacoids↗
PubMed1983

Heterogeneity of human mast cells.

Enzymatically dispersed human lung parenchymal cells were fractionated according to size by countercurrent centrifugation elutriation. Human lung mast cells eluted throughout the procedure indicating heterogeneity of mast cell diameters. In seven individual lung elutriations, the mean histamine content ranged from 2.5 +/- 0.5 pg/mast cell for the smallest diameter mast cells (8-10 microns) to 10 +/- 2.5 pg/mast cell for the largest (16-20 microns). Intermediate sized mast cells had correspondingly intermediate histamine contents. The maximum release of histamine after anti-IgE stimulation varied with mast cell size. Small mast cells consistently released less histamine (10 +/- 3.6% net) than the largest diameter mast cells (38 +/- 6% net). This differential histamine release could not be explained by cell surface IgE content which was similar in mast cells of all sizes. The concentration of anti-IgE for maximum histamine release was the same (2 micrograms/ml) for mast cells of all sizes. The generation of PGD2, the predominant cyclooxygenase metabolite of the human lung mast cell, also was correlated positively with mast cell size and to the quantity of histamine released. Studies to date indicate no clear pattern in agonist receptor activities as judged by the inhibition of histamine release by PgE2, the beta-adrenergic agonist, fenoterol, and adenosine. We conclude that human lung mast cells are heterogeneous with regard to size and function.

Cell Separation↗
PubMed1983

In vivo demonstration of inflammatory mediator release following nasal challenge with antigen.

An in vivo model system was developed to recover inflammatory mediators from the nose after antigen stimulation. In 105 experiments involving 35 subjects, antigen was introduced into the nose. Allergic individuals demonstrated an increase concentration of histamine, TAMe esterase and PgD2 during the physiologic changes of nasal obstruction and sneezing. Clinical symptoms and mediator release were highly correlated; moreover, the release of each mediator was significantly correlated to the others.

Airway Resistance↗
PubMed1982

A comparison of immunotherapy schedules for injection treatment of ragweed pollen hay fever.

In 44 patients highly sensitive to ragweed, we compared weekly injections of single doses of ragweed extract (RW-Wk, 15 patients) with clustered doses of ragweed extract at 3-wk intervals (RW-Cl, 18 patients) for effects on ragweed hay fever symptom-medication scores and immunologic variates. Patients were matched and randomly assigned to treatment groups. Ragweed doses were advanced to the highest tolerated dose. Doses and number of visits were lower in the RW-Cl group than in the RW-Wk group. Despite lower doses, systemic reactions were not reduced and antiragweed IgE levels increased significantly more in the RW-Cl group than those in the RW-Wk group. Both the RW-Cl and RW-Wk groups had significant increases in antiragweed IgG levels, decreases in seasonal rise in antiragweed IgE levels, and lower symptom-medication scores (p less than 0.01) in comparison with the placebo group. We conclude that the RW-Cl regimen offered no important advantage over RW-Wk. Seventeen patients had previously received Rinkel-method immunotherapy with 0.5 ml of end-point dilution of ragweed extract for 1 to 2 yr without significant clinical improvement or immunologic changes. After adequate treatment with either RW-Wk or RW-Cl, these patients had significantly lower symptom-medication scores than those of the placebo groups and immunologic changes similar to those of the entire active-treatment group. Therefore, treatment failures on Rinkel immunotherapy respond well to adequate dose immunotherapy by either schedule.

Adolescent↗
PubMed1982

Cyclooxygenase metabolites in human lung anaphylaxis: airway vs. parenchyma.

We studied the generation of arachidonic acid cyclooxygenase metabolites (AACMs) during in vitro anaphylaxis of passively sensitized human lung parenchymal and airway fragments. Prostaglandins E, F2 alpha, D2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 (PGE, PGF2 alpha, PGD2, 6-keto-PGF1 alpha, TXB2, respectively) were assayed by radioimmunoassay. Results with airway tissue were compared with subpleural parenchymal fragments from the same lungs similarly challenged. Spontaneous generation of prostacyclin (PGI2), as measured by its stable metabolite 6-keto-PGF1 alpha, exceeded by two- to threefold other spontaneous AACM release in both bronchial and parenchymal fragments. In airway antigen produced variable AACM responses, but in general the rank order was 6-keto-PGF1 alpha greater than PGE congruent to PGF2 alpha greater than PGD2 greater than TXB2. The rank for antigen-induced AACM release from parenchyma was 6-keto-PGF1 alpha congruent to PGD2 much greater than PGF2 alpha greater than TXB2 congruent to PGE. In airway, as in parenchyma, very little AACM production during anaphylaxis can be attributed to smooth muscle contraction per se. Histamine released from bronchi (0.67 +/- 0.30 micrograms/g lung) was significantly less than from parenchyma (3.7 +/- 0.70 micrograms/g) despite comparable histamine content. At comparable levels of histamine release, the parenchyma produced greater quantities than bronchi of all AACMs except PGE. The comparatively limited bronchial capacity to generate PGF2 alpha, PGD2, TXB2, and histamine (airway constrictors) along with predominant generation of PGI2 and PGE (airway relaxants) may help preserve airway patency.

Anaphylaxis↗
PubMed1981

The quantitation of parasite-specific human IgG and IgE in sera: evaluation of solid-phase RIA and ELISA methodology.

We have developed a non-competitive solid-phase radioimmunoassay (SPRIA) to quantitate both human IgE and IgG antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite causing extensive infection throughout the tropics. Previously enzyme-linked immunosorbent assays (ELISA) had been used to detect microgram/ml levels of IgG anti-B.m., but IgE antibodies were difficult to detect in this system. Since the SPRIA successfully quantitates both IgG and IgE anti-B.m., we sought to examine the reasons for the SPRIA's apparent superiority in detecting IgE anti-B.m. by extracting specific IgG from sera with high levels of IgE and IgG anti-B.m. antibodies. IgE anti-B.m. was then quantitated in these sera using both the SPRIA and ELISA methods. Results indicate that IgG anti-B.m. does not interfere with detection of specific IgE antibody in the SPRIA but does interfere in the ELISA. While ELISA permits detection of IgE anti-B.m. in the absence of competing IgG anti-B.m., as levels of specific IgG increase, the IgE is no longer detectable. These differences between SPRIA and ELISA can be explained by the SPRIA's antigen excess conditions which assure that there are sufficient antigens both to detect all anti-B.m. antibodies present in the serum and to adequately represent all antigen specificities in the crude B.m. extract. Our findings commend the use of SPRIA methods over ELISA in assessment of B.m.-specific IgE antibody in filariasis and indicate a potential role for SPRIA methods in absolute quantitation of specific serum antibodies.

Animals↗
PubMed1981

Indomethacin modification of immediate-type immunologic airway responses in allergic asthmatic and non-asthmatic subjects: evidence for altered arachidonic acid metabolism in asthma.

To examine the role of arachidonic acid metabolism in the modulation of immediate-type immunologic airway responses, we compared the effects of indomethacin (50 mg every 6 h for 96 h) and placebo on responses to antigen inhalation challenge in allergic asthmatic subjects and a group of nonasthmatic subjects with allergic rhinitis. Sensitivity to antigen was determined for changes in one-second forced expiratory volume, specific airway conductance, and expiratory flow at 25% of the forced vital capacity measured from partial flow-volume curves. The groups differed in terms of prechallenge pulmonary function and non-immunologic airway reactivity as determined by methacholine challenge, but were comparable with respect to intradermal sensitivity to ragweed antigen. After placebo, asthmatic subjects demonstrated approximately 3.5-fold greater sensitivity to antigen than that of nonasthmatic subjects. Indomethacin had no effect on prechallenge pulmonary function in either group. However, after indomethacin, non-asthmatic subjects had a significant increase in antigen sensitivity. Indomethacin had no effect on antigen sensitivity in asthmatic subjects as measured by one-second forced expiratory volume or expiratory flow at 25% of the forced vital capacity, and produced a slight but significant decrease as measured by specific airway conductance. Indomethacin failed to alter methacholine sensitivity in atopic, non-asthmatic subjects. These findings indicate that products of arachidonic acid metabolism participate in vivo in the modulation of airway responses to immediate-type immunologic stimuli, and that this participation differs in asthmatic and non-asthmatic subjects.

Adult↗
PubMed1981

Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma.

Antigen challenge of passively sensitized chopped human lung resulted in the generation of several arachidonic acid cyclooxygenase metabolites (AACM): thromboxane A2 (TxA2) as measured by its stable metabolite TxB2, prostaglandin D2 (PgD2), prostacyclin (PgI2) as measured by its stable metabolite 6-keto-PgF1 alpha, prostaglandin F2 alpha (PgF2 alpha), and prostaglandin E (PgE). The kinetics of AACM release after antigen challenge paralleled histamine release. All AACM were released in an antigen dose-dependent manner and reached maximal release at antigen concentrations lower than those required for maximal histamine release. Quantitatively, of the AACM measured, PgD2 and PgI2 were found to predominate in anaphylactic reactions of human lung parenchyma. Generation of PgD2 and PgI2 were 3- to 7-fold greater than that of other AACM measured. Thromboxane B2 was generated in quantities comparable to PgE and PgF2 alpha. Studies were designed to test the hypothesis that lung smooth muscle contraction per se can account for the generated AACM that are released during anaphylaxis of the lung. The studies compared antigen-induced AACM generation with methacholine-induced (10(-4) M) AACM generation. The failure to confirm this hypothesis was especially evident for PgD2 where release was dependent on mast cell activation. Thromboxane A2, PgD2, and PgI2 have been reported to have potent effects on smooth muscle. Our data suggested that these AACM are generated in such sufficient quantities that they may function in important aspects of the modulation of hypersensitivity responses in human lungs.

Anaphylaxis↗
PubMed1981

Hyperlabile diabetes accompanied by insulin resistance.

It is generally held that high insulin antibody concentrations, by "buffering" abrupt swings in free insulin concentrations after injections of exogenous insulin, tend to stabilize blood glucose variations in diabetic patients. However, we encountered a patient with extremely labile diabetes coexisting with insulin resistance. This patient's injections were switched to pure porcine insulin from his usual mixed bovine/porcine insulin, in an effort to decrease his insulin requirement. This treatment was successful, and, as his insulin dosage decreased, his diabetic lability diminished substantially. His diabetes was eventually considered stabilized on about 22 units of porcine insulin daily. The serial decrease in his insulin antibody concentrations, monitored by use of solid-phase radioimmunoassay, paralleled the disappearance of his diabetic lability as well as the decrease in his insulin requirement.

Adult↗