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Biomedical subjects

G Kunkel

Publications and source records attributed to G Kunkel.

At least 73 records · Page 4Linked to original sources
PubMed1993

Comparison of fiberglass-based histamine assay with a conventional automated fluorometric histamine assay, case history, skin prick test, and specific serum IgE in patients with milk and egg allergic reactions.

A microfiberglass-based histamine assay (HRM) was compared with an automated fluorometric histamine assay (HRA). Twenty-four subjects with and 24 without a case history (CH) of milk and/or egg allergy were tested by HRM and HRA, skin prick test (SPT), and specific serum IgE (RAST). Six different concentrations of milk, egg, and anti-IgE were used to stimulate washed leukocytes (250 microliters for HRA) and whole blood samples (25 microliters for HRM) in parallel. When we compared scores representing basophil sensitivity, correlation coefficients (rs) were positive (r(anti-IgE) = 0.88, r(egg) = 0.95, r(milk) = 0.88, P < 0.001), but no significant correlations were found after exclusion of the negatives in both tests. In some individual dose-response curves, the scores obtained by HRM were shifted to higher allergen and anti-IgE concentrations. A high degree of concordance was found in positive and negative responses between the two tests: anti-IgE 91%, egg 92%, milk 86%. Finally, we found a good concordance between, on one side, HRM and, on the other, CH, SPT, and RAST (HRM vs. CH/SPT/RAST): egg 92/82/82%; milk 89/74/67%. We conclude that HRM is in good qualitative, but poor quantitative, agreement with the autoanalyzer-based fluorometric histamine assay.

Adolescent↗
PubMed1993

Ramiprilat increases bradykinin outflow from isolated hearts of rat.

To establish that bradykinin is formed in the heart we measured bradykinin in the venous effluent from rat isolated hearts perfused with Krebs-Henseleit buffer. In addition, we examined the effect on bradykinin outflow of the angiotensin converting enzyme (ACE) inhibitor, ramiprilat. From rat isolated normoxic hearts a bradykinin outflow of 0.85 +/- 0.1 ng ml-1 perfusate g-1 wet weight was measured. Perfusion with ramiprilat increased the bradykinin concentration to 2.8 +/- 0.3 ng ml-1 perfusate g-1 wet weight. During ischaemia bradykinin outflow maximally increased 8.2 fold to 7.0 +/- 0.5 ng ml-1 perfusate g-1, and in ramiprilat-perfused hearts 5.8 fold to 16.0 +/- 1.8 ng ml-1 perfusate g-1. In the reperfusion period bradykinin outflow normalized to values measured in the respective pre-ischaemic period. The presents data show that bradykinin is continuously formed in the rat isolated heart. Ischaemia increases bradykinin outflow from the heart. Presumably by inhibiting degradation of kinins, ACE inhibition significantly increased the bradykinin concentration during normoxia, ischaemia and reperfusion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Role of the major allergen (Fel d I) in patients sensitized to cat allergens.

Forty patients with a positive case history and specific serum IgE to cat allergens were evaluated using titrated skin prick test (SPT), histamine release studies (HR) and immunoblotting studies. To determine the relevance of the major allergen, a monospecific antibody to Fel d I was preincubated in different concentrations with the cat allergen dose required for maximum response in the HR assay (10 SQ/ml). Dose-dependent inhibition of histamine release (n = 30, x = 66% +/- 5% IC30 = 0.36 micrograms/ml) was found in all patients sensitized to cat allergens as shown by antigen-induced HR. The greater the HR response to the cat allergen extract the higher were the antibody concentrations necessary for inhibition (p < 0.05). Immunoblot experiments (n = 22) using SDS-PAGE demonstrated five different locations of IgE binding in 15 sera: 18, 35, 46, 54 and 66 kD. IgE binding at 18 kD was found in 14 patients. Anti-Fel d I possessed two strong bands at about 18 and 35 kD which are representative of the major allergen Fel d I. Our findings emphasize the major role of Fel d I in patients sensitized to cat allergens.

Adolescent↗
PubMed1993

Bronchial hyperreactivity in patients with moderate pulmonary circulation overload.

The clinical course of congestive heart failure (CHF) and mitral valve stenosis (MVS) is accompanied by episodes of dyspnea, wheezing, and cough, symptoms also observed in patients with bronchial hyperreactivity. However, it is still controversial whether bronchial hyperreactivity is demonstrable in patients with chronic overload of the pulmonary circulation. In order to examine the effects of CHF on the respiratory function, we performed pulmonary function tests, titrated bronchial acetylcholine provocations, and left and right heart catheterization in 21 patients with impaired left ventricular function (mean ejection fraction, 37 percent, NYHA class 3), 5 patients with MVS, and 17 control patients with coronary artery disease (mean ejection fraction, 63 percent). Bronchial hyperresponsiveness was defined as an obstructive response to increased doses of inhaled acetylcholine. A 20 percent fall in forced expiratory volume in the first second (FEV1), a 100 percent increase in total airway resistance (Rtot), and a 60 percent reduction of pulmonary conductance (SGtot) were considered positive. Patients with impaired left ventricular function showed significantly higher airway resistance, and lower airway conductance at the maximal tolerated acetylcholine dose compared with control patients. Patients with MVS had a significant lower airway conductance. The induced bronchial obstruction was completely reversible upon inhalation of a beta 2-mimetic. We conclude that chronic overload of the pulmonary circulation is accompanied by bronchial hyperreactivity that may augment the symptoms of dyspnea in patients with CHF and MVS.

Acetylcholine↗
PubMed1993

Regulation of beta-adrenergic receptors on endothelial cells in culture.

This study aimed to determine the density of vascular beta-adrenergic receptors in cultured endothelial cells and to study the regulation of endothelial receptors after exposure to catecholamines and the ACE inhibitors, lisinopril and ramiprilat. Membranes from bovine aortic endothelial cells (BAEC) and bovine pulmonary artery endothelial cells (BPAEC) showed saturable binding of the radioligand [125I]iodocyanopindolol (ICYP). The beta-receptor density and binding affinity were comparable in both types of endothelial cells. Isoproterenol induced significant down-regulation of beta-receptors (-50%; P < 0.01). Incubation (24h) with the ACE inhibitors lisinopril 10(-5) M (+28.8%; P < 0.05) and ramiprilat 10(-5) M (+33.7%, P < 0.09) augmented the beta-receptor density in BAEC, but lower ACE inhibitor doses had no affect. Incubation with lisinopril 10(-5) M for 24 h resulted in significantly lower cAMP baseline levels, but did not affect cAMP concentrations after stimulation with isoproterenol. These results indicate that down-regulation of endothelial beta-receptors occurs during prolonged exposure to beta-stimulation, and that high concentrations of ACE inhibitors may affect the density of endothelial beta-receptors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Kinin generation following methacholine nasal airway challenge of non-allergic subjects.

Following nasal challenges with the muscarinic neurotransmitter methacholine in 14 patients with chronic non-allergic rhinitis, kinin generation was induced. This occurrence was inhibited by pretreatment with anticholinergic agents (ipratropium bromide) and by an overdose of neurotransmitter, indicating that a muscarinic receptor is stimulating the liberation of kinin. These observations suggest that patients with chronic non-allergic rhinitis exhibit cholinergic neurotransmitter-induced kinin generation.

Adolescent↗
PubMed1992

Modulation of IgE-mediated histamine release from human leukocytes by a new class of histamine H2-agonists.

A new class of phenyl (pyridylalcyl) guanidines, acting as potent histamine H2-agonists, inhibits IgE-mediated human basophil histamine release in a nanomolar range. IC30-level of three substitutes of this group (arpromidine, BUA-75, and FRA-19) were found to be 0.02, 0.015 and 0.008 microM. The inhibition appeared with a fast onset (plateau after 10 min. preincubation) and claimed its maximum (60 +/- 2.9%, 63 +/- 1.8%, and 61 +/- 3.1%, n = 7) with 10 microM of the compounds. H2-mediated inhibition was totally blocked by 10 microM famotidine, a potent histamine H2-antagonist. The amount of anti-IgE or antigen for the initiation of the immunological release influenced the strength of inhibition of H2-agonist FRA-19 (p less than 0.05). Combined preincubation of FRA-19 with zardaverine, a cAMP-specific phosphodiesterase III/IV inhibitor, produced a synergistical inhibitory effect of leukocyte histamine release, which might explained by their different sites of action on intracellular cAMP levels. The capability of histamine to inhibit its own release is mediated by H2-receptors exclusively. New, potent H2-receptor stimulating compounds with positive inotropic effects possess additional potent anti-allergic properties.

Basophils↗
PubMed1992

Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma.

Six atopic subjects with grass pollen allergy and six nonallergic healthy volunteers were enrolled into this study. Substance P-like immunoreactivity (SP-LIR) and beta-endorphin-like immunoreactivity (beta E-LIR) were determined in bronchoalveolar lavage (BAL) and nasal lavage (NAL) fluids before and after allergen (grass pollen) provocation. A significant increase in the baseline concentration of SP-LIR and beta E-LIR was seen in BAL of allergic subjects. In NAL of allergic subjects an increased baseline concentration of SP-LIR was found (beta E-LIR not detectable). After allergen provocation there was a rise of SP-LIR and beta E-LIR in BAL fluids of allergic subjects immediately after provocation. In NAL fluids of allergic subjects allergen challenge resulted in a rise of SP-LIR within 10 minutes. Allergen provocation did not influence SP-LIR and beta E-LIR concentration in BAL and NAL in nonallergic controls. The demonstrated higher baseline levels of SP-LIR and beta E-LIR as well as the increase after provocation in the BAL and NAL of allergic subjects but not in nonallergic controls support the hypothesis that these neuropeptides contribute to allergic reactions in airways of humans.

Adolescent↗
PubMed1992

Comparison between MAGIC LITE- and CAP-system: two automated specific IgE antibody assays.

The MAGIC LITE system, a newly developed immunochemiluminometric assay for specific and total IgE antibody using paramagnetic particles coupled with standardized allergens as solid phase, was compared to the CAP system, a recently introduced immunoassay based on a cellulose polymer encased in a capsule. A total of 357 serum samples of patients with suspected inhalant allergies and a positive skin prick test (SPT) to common allergens (birch, timothy-grass, mugwort, cat dander, Dermatophagoides pteronyssinus, Alternaria) were investigated. Fifty SPT negative subjects served as controls (total number of tests in each assay = 1600). Both assays were highly precise (overall intra-assay and inter-assay coefficients of variation were 2.9% and 4.5% in MAGIC LITE, 4.7% and 5.5% in CAP) and showed excellent linearity (mean r2 of eightfold log2 serum dilutions were 99.7% and 99.3% in MAGIC LITE and CAP). Good correlations were found between the absolute specific IgE antibody values detected by both methods (correlation coefficient r: birth 0.86, grass 0.93, mugwort 0.96, cat 0.91, D. pteronyssinus 0.73, Alternaria 0.90). Excellent specificity (greater than or equal to 98%) occurred in both assays and with all allergens, and sensitivity was related to the allergen (MAGIC LITE/CAP): birch 91%/89%, grass 83%/90%, mugwort 50%/69%, cat 83%/83%, D. pteronyssinus 72%/78%, Alternaria 75%/81%. Our results indicate that both in vitro tests are useful tools for the detection of specific IgE antibody.

Allergens↗
PubMed1992

IgE, IgG, IgG1 and IgG4 patterns in yellow jacket allergic patients during immunotherapy with a venom depot extract.

Using immunoblot studies, detailed antibody patterns were performed with the sera of 10 yellow jacket allergic patients undergoing specific immunotherapy with a yellow jacket venom SQ-depot extract (ALK, Denmark). Five males and five females (age range 10-65, mean 48 years) were investigated. All patients had a history of systemic reactions after an insect sting and a positive skin-prick test at a dose of at least 100 micrograms/ml yellow jacket venom. Yellow jacket venom (ALK) was separated on a 7.5-20% SDS-PAGE, transferred to nitrocellulose (NC), and then the NC-strips were incubated with the patients' sera. For detection of IgE, IgG, IgG1 and IgG4, an alkaline phosphatase linked 2nd antibody was used. Prior to immunotherapy, a strong IgE binding was detected at 25 kD in nine of 10 patients, representing Antigen-5 (Ag-5) as major allergen. Reactivity to this antigen was also present with the other immunoglobulin classes, although not as marked. In addition, a second frequent IgG and IgG1-binding band was seen at 35 kD (phospholipase A). Only weak or no binding to this band was found with IgE and IgG4. Binding to hyaluronidase (43 kD) was seen only in three cases. During immunotherapy, a significant increase in IgG and particularly IgG4 staining was found with Ag-5, whereas hyaluronidase induces mainly an IgG1 response and phospholipase A showed only a weak IgG response. In addition, the formation of new IgG4 binding to proteins in the region of about 70-90 kD was found in most patients. The dose necessary for the induction of this antibody formation was greater than or equal to 150.00 SQ yellow jacket venom.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Comparison of the Phadebas RAST with the Pharmacia CAP system for insect venom.

Determination of specific IgE by RAST is a well-established method in the diagnosis of immediate allergic reactions. In this study, we have compared the RAST with the ImmunoCAP, a novel test system which is based on a new type of solid phase. A total of 123 sera from 111 insect venom-allergic patients (74% female) were investigated. All patients had their diagnosis confirmed on the basis of their history and skin tests with insect venom. The patients' age showed a mean +/- S of 44.2 +/- 14.6 years. The total serum IgE levels ranged from 4-1712 kU/l, with a median of 108 kU/l. The results of specific IgE, as determined by RAST and CAP, showed a significantly higher sensitivity, by almost one class, with the CAP compared with the RAST system. The quotient of specific IgE to total IgE, determined with the CAP system, could not be shown to be an expression of sensitization, compared with the severity of sting reactions (Müller classification (16)). A conversion factor for vespid venom RAST to CAP was calculated from the present data by subtracting the RAST from the CAP values. The mean delta value +/- SD was found to be 0.9 +/- 0.65, with a range from -0.8 to 2.7 and a median of 0.9. The data clearly show the differences between RAST and CAP-RAST classes, indicating that the CAP-system has a higher sensitivity and that patients with a low level sensitization are missed by the RAST method.

Adolescent↗
PubMed1992

Yellow jacket allergy. Comparison of skin prick tests and intradermal tests with three different yellow jacket venom extracts.

The aim of the present study was to compare yellow jacket venom extracts from two different companies and to compare skin prick test (SPT) with intradermal test (IDT). IDT and SPT with yellow jacket venom (ALK and Pharmacia Reless) were performed on 54 yellow jacket allergic patients and 44 symptom-free volunteers. Venom was diluted to 300, 100, 10 and 1 microgram/ml for SPT and 10(0), 10(-1), 10(-2), 10(-3) and 10(-4) micrograms/ml for IDT, according to the manufacturers' instructions. Skin tests were performed on both forearms. Both extracts showed approximately the same relationship between sensitivity and specificity, but the Pharmacia Reless yellow jacket venom extract showed a 5-10 fold higher biological activity in both SPT and IDT. Thus yellow jacket venoms of ALK and Pharmacia Reless are not comparable in allergen activity at the same venom concentrations. Using extracts from the same company, SPT and IDT were comparable with regard to sensitivity and specificity at an allergen concentration 1000 times higher for SPT than for IDT.

Adolescent↗
PubMed1992

Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits.

Histamine release (HR) studies were performed in 40 birch pollen-allergic patients (positive case history, positive SPT, positive birch pollen-specific serum IgE: RAST > or = 3) with (n = 20, A) and without (n = 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose-dependent HR (apple peel = apple pulp > peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit-related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens.

Adult↗
PubMed1992

Inhibition of IgE-mediated histamine release from human peripheral leukocytes by selective phosphodiesterase inhibitors.

Several phosphodiesterase (PDE) inhibitors with the capacity to inhibit the PDE IV isoenzyme produce dose-dependent inhibition of IgE-mediated histamine release (HR) from human peripheral leukocytes in vitro. Inhibition reached a maximum after 20 min of preincubation (IC30: 6-30 microM, IC50: 30-80 microM). Motapizone--a potent inhibitor of the isoenzyme PDE III--was much less effective, thus giving indirect evidence that PDE IV plays a predominant role in the control of cAMP cleavage in human basophils. The inhibiting effect of PDE-III/IV-selective compounds on IgE-mediated HR did not exceed the action of PDE-IV-selective inhibitors. The inhibition of anti-IgE-induced HR by zardaverine (a PDE-III/IV-inhibiting compound) was synergistically enhanced in the combined presence of forskolin or the recently synthesized histamine H2-agonist FRA 19).

Basophils↗
PubMed1992

Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma.

Zardaverine is a newly developed selective phosphodiesterase III and IV inhibitor. This study investigates the bronchodilatory properties of zardaverine, administered by inhalation. Twelve patients with reversible bronchial obstruction (increase in forced expiratory volume in one second (change FEV1 % predicted) at least 15% after 200 micrograms salbutamol, median age 31 yrs, range 21-54 years) entered the double-blind, crossover study. Four puffs of either zardaverine (total dose 6 mg) or placebo were inhaled at 15 min intervals. Pulmonary function (specific airway conductance (sGaw) and FEV1 was measured by body plethysmography at regular intervals (5 and 12 min after each puff and, in addition, 30, 60, 120, 180 and 240 min after the last puff). Compared to placebo, sGaw and FEV1 increased significantly during the first hour of repeated inhalations, but not during the entire observation period of almost 5 h. The maximum mean difference between zardaverine and placebo for FEV1 was 0.3 l or 12% and occurred approximately 1 h after inhalation of the first puff. In seven patients FEV1 increased by > 15%. The duration of action varied considerably between patients. Three patients complained of side-effects (headache, drowsiness, vertigo, nausea), and one of these dropped out of the study due to vomiting. We conclude that inhalational administration of zardaverine has a modest and short-lasting bronchodilating activity.

Administration, Inhalation↗
PubMed1992

Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation.

We evaluated the levels of bradykinin, albumin, TAME-esterase activity, histamine, PGD2 and LTC4 in bronchoalveolar lavage fluid from asthmatics and from patients with pneumonia, sarcoidosis, fibrosis, and chronic bronchitis. Compared with the results of healthy volunteers and atopic asymptomatic asthmatics the bradykinin levels and TAME-esterase activity were significantly elevated. In all other groups, histamine was additionally elevated in asymptomatic asthmatics, whereas albumin was elevated in symptomatic asthmatics and fibrosis patients, and decreased in chronic bronchitis and pneumonia patients. Following local intrabronchial allergen challenge of mild grass pollen asthmatics out of season bradykinin levels increased significantly, correlated with albumin, histamine and TAME-esterase activity. In contrast to the increased mediator concentrations in the early phase reaction there was no change of BAL cells in asthmatics compared to baseline and healthy volunteers. The presence of bradykinin in the bronchoalveolar space of patients with active pulmonary inflammations and bradykinin generation in asthmatics as a result of intrabronchial allergen challenge provides strong evidence that kinins are involved in inflammatory disorders of the lower airways.

Asthma↗
PubMed1992

IgE-mediated inhalant allergy in inhabitants of a building infested by the rice weevil (Sitophilus oryzae).

The rice weevil (Sitophilus oryzae) is known as a stored product pest. Occupants living in a factory used previously as a granary and known to be contaminated by the rice weevil developed rhinitis and asthma. To study the role of the potential insect allergens, extracts were prepared from whole body and a grain dust of the rice and grain weevil (Sitophilus granarius). The extracts were coupled to cyanogen bromide-activated paper disks. Skin prick tests (SPT) were performed using common inhalant allergens as well as the insect allergen preparations. In cases of a positive SPT, specific serum IgE to the insect products was measured. Histamine release studies with peripheral leukocytes (HR) and studies using immunoblot techniques were performed. Fifteen of 39 subjects living in the infested rooms demonstrated positive SPT to the extracts of insect origin. Histamine equivalent wheal size induced by the whole body extract of the rice weevil required 3-160 micrograms protein/mL. Five of 15 subjects (with positive SPTs) had elevated specific IgE-levels to the insect material. RAST-inhibition studies indicated cross allergenicity between rice and grain weevils, and also between the frass of both beetles. Five of 15 subjects were positive in the HR assay (Ag30, allergen concentration for 30% HR for the whole body extract: range, 10(-3) to 400 micrograms protein/mL, maximum release: 26% to 89%). IgE binding was detected after SDS-PAGE by immunoblot techniques at different locations: 35-38, 54, 67, 70, and > 94 kD.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗