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Biomedical subjects

F Horak

Publications and source records attributed to F Horak.

At least 73 records · Page 4Linked to original sources

Purification, characterization and N-terminal amino acid sequence of a new major allergen from European chestnut pollen--Cas s 1.

Pollens from trees of the order Fagales (e.g. birch, alder, hazel, and hornbeam) all contain one major allergen--the main cause for tree pollen allergy. So far the major allergens from birch (Bet v 1), alder (Aln g 1), hazel (Cor a 1), and hornbeam (Car b 1) have been characterized, showing high sequence similarity with each other (1-4). We present the molecular and immunologic characterization of Cas s 1, the major allergen from the European chestnut (Castanea sativa). From aqueous pollen extracts from European chestnut a protein was purified to homogeneity and was subjected to further investigation. The protein revealed a Mr of 22 kDa and was shown to represent the major allergen of the European chestnut (immunoblotting, histamine release) and designated Cas s 1. Despite a marked difference in Mr, Cas s 1 shows significant amino acid sequence similarity at the N-terminus and is antigenically closely related to the major birch pollen allergen Bet v 1 (17 kDa), as shown by binding to the anti-Bet v 1 monoclonal antibody BIP-1 and by IgE-inhibition tests using recombinant Bet v 1.

Allergens↗

Allergens from birch pollen and pollen of the European chestnut share common epitopes.

Type I allergy to pollen of the European chestnut (Castanea sativa) represents a major cause of pollinosis in (sub) Mediterranean areas. Using sera from 14 patients with established allergy to pollen of the European chestnut, 13/14 sera (92%) showed IgE-binding to a 22 kD protein, 2/14 (14%) displayed additional binding to a 14 kD protein and 1/14 (7%) bound only to the 14 kD protein of European chestnut pollen extract. Two monoclonal mouse antibodies, BIP 1 and BIP 4, directed against different epitopes of Bet v I (the major birch pollen allergen), and a rabbit antibody to recombinant birch profilin (rBet v II) were used to characterize the proteins of the European chestnut pollen. The recombinant birch pollen allergens, rBet v I and rBet v II (profilin) were employed to show common allergenic structures on proteins from both birch and European chestnut pollen by IgE-inhibition experiments. Despite the fact that the 22 kD protein displayed a higher molecular weight in comparison to the 17 kD major birch pollen allergen, Bet v I, we could demonstrate reactivity of both monoclonal antibodies, BIP 1 and BIP 4, with this protein. A complete inhibiton of IgE-binding to this 22 kD protein was shown by pre-incubating sera with purified recombinant Bet v I. In addition, the 14 kD protein could be identified by IgE-inhibition studies with recombinant Bet v II and by using a rabbit anti-profilin antibody as the profilin from pollen of the European chestnut.

Allergens↗

Effects of H1-receptor antagonists on nasal obstruction in atopic patients.

The aim of this study is to investigate whether H1-receptor antagonists, besides their effect on nasal itching and sneezing, also have a measurable effect on nasal obstruction caused by allergen challenge. The antihistamine used was astemizole (10 mg) versus placebo, in a double-blind, cross-over, randomized study of two groups. Between the two sessions there was a wash-out period of at least 4 weeks. Seven patients of both sexes, with proven allergy to grass pollen, underwent a specific long-term provocation with grass pollen in the Vienna challenge chamber. Using a physiological method of challenge and a sensitive method for evaluating nasal function, we were able to prove H1-receptor antagonist influence on nasal airway obstruction. The main parameters obtained are nasal flow and nasal resistance at 75, 150 and 300 Pa, evaluated by active anterior rhinomanometry. We also investigated subjective symptom scores (0-3) of nasal, eye, and lung symptoms. It can be shown that the nasal flow under astemizole treatment is statistically significantly higher than the nasal flow under placebo treatment (P = 0.034). This is in accordance with the findings in subjective nasal itching and sneezing.

Adult↗

Seasonal allergic rhinitis. Newer treatment approaches.

Improved treatment approaches for seasonal allergic rhinitis are based on the increasing knowledge about allergic inflammation and on the improved efficacy of newer drugs. The current management concept includes an individualised composition of the different approaches including allergen avoidance, topical treatment and the use of systemic drugs and specific immunotherapy. Allergen avoidance, supported by pollen information, leads to a remarkable reduction of daily challenge situations. There is an increasing trend towards topical use of corticosteroids (e.g. budesonide and fluticasone) and mast cell stabilisers [e.g. sodium cromoglycate (cromolyn sodium), nedocromil and isospaglumic acid (N-acetylaspartylglutamic acid)] because of the potency of these drugs to impair the destructive activity of allergic inflammation. Potent histamine H1-receptor antagonists (e.g. azelastine and levocabastine) are approved for local treatment and lead to prompt relief of troublesome symptoms. A new generation of orally active antihistamines (e.g. astemizole, cetirizine, loratadine and terfenadine) have tended to be called 'antiallergics' because of activity other than H1-blockade. Furthermore, these newer compounds are less likely to cause sedation. Immunotherapy is still an integrated component in the treatment strategy. Standardised allergen extracts of high quality raise the treatment efficacy and safety. Overall, forming an individual combination of treatment approaches gives the best result.

Adrenal Cortex Hormones↗

Pharmacodynamic dose finding of dimetindene in a sustained release formulation.

A sustained release form of dimetindene (dimethindene maleate, Fenistil, CAS 3614-69-5) was developed based on a micropellet technique. Aim of the study was to evaluate the efficacy and duration of two doses of dimetindene in a sustained release pellet formulation with a standardised grass pollen provacation model (Vienna Challenge Chamber; VCC). The study with 12 grass pollen allergic volunteers--verified by case history, skin prick test (SPT), and radio allergo sorbent test (RAST)--was carried out in a placebo controlled, double blind, cross-over design. 12 h before a 4-h-lasting continuous challenge with permanent 1000 dactylis grass pollen in the VCC, administration of dimetindene (Fenistil R Pellets) in doses of 4 mg, 8 mg or identically appearing placebo was scheduled in three sessions. Nasal flow and resistance, nasal secretion and subjective symptoms were recorded at 15-min intervals during this long-term challenge under reproducible conditions. In comparison to placebo, dimetindene leads to a statistically significant reduction (p < 0.05) of nasal response and clinical symptoms for at least 16 h after treatment. The efficacy of 8 mg dimetindene was pronounced over 4 mg, however, the differences between both active treatments were not statistically significant. Therefore 4 mg dimetindene once a day is the adequate treatment for usual pollinotic disease conditions.

Adult↗

Horse chestnut (Aesculus hippocastanum) pollen: a frequent cause of allergic sensitization in urban children.

We investigated the incidence of allergic sensitization and the risk factors underlying sensitization in 214 urban children exposed to horse chestnut pollen. By means of the Phadezym RAST, we found IgE specific to horse chestnut pollen in 12.6% of the urban children, whereas it occurred in only 1.9% of control subjects recruited from a rural area. Reports of allergic symptoms in spring during the horse chestnut pollen load coincided with the presence of specific IgE in 5.1% of the urban group as against 1.4% of the recruited from the rural area. Environmental factors other than those related to urban living and higher horse chestnut pollen counts had no significant impact on allergic sensitization. Increased total IgE levels (greater than 100 kU/l), however, and the sensitization to pollen of other species significantly raised the odds for sensitization to chestnut pollen. They were highest in highly atopic children with sensitization to pollen, especially to that of plane trees (OR = 73.9). These results suggest the relevance of horse chestnut pollen because of the high allergic sensitization rate among urban children, and they should also be borne in mind when it comes to the planting of trees in urban areas.

Allergens↗

Onset and duration of the effects of three antihistamines in current use--astemizole, loratadine and terfenadine forte--studied during prolonged, controlled allergen challenges in volunteers.

In a three-way, double-blind, crossover study the onset of action and effects at the end of the dosing interval of 10 mg/day astemizole, 10 mg/day loratadine and 120 mg/day terfenadine forte given for 3 days to six atopic volunteers were assessed using the Vienna challenge chamber (VCC). With each treatment, two long-term pollen challenges were performed in the VCC: the first to assess the onset of action started 1 h before the first dose and lasted continuously for 5 h; the second to assess the effects at the end of dosing took place 21 h after the last of the three doses and lasted 3 h. All three drug treatments initiated 1 h after the beginning of challenge with grass pollen reversed the adverse effects of challenge on the subjective symptoms (runny, blocked or itchy nose, sneezing, itchy eyes, tears) and the objective parameters (nasal secretions, nasal resistance, nasal flow, flow increase, nasal peak flow) within 1-3 h. The mean time to onset of action was 107 min for astemizole, 117 min after treatment for loratadine and 153 min for terfenadine forte. During the second allergen challenge, 21-24 h after intake, astemizole consistently provided better protection for all parameters than did loratadine or terfenadine forte; however the differences were not statistically significant.

Adult↗

[Quality control in the allergy laboratory--4 years "Allergy Ring Trial" in Austria].

In 1988 the Austrian Society for Allergology and Immunology initiated an external quality control program for the in vitro allergy diagnosis. In 12 mailings, 62 sera from allergic patients were sent to selected laboratories in order to determine total and antigen specific IgE according to the laboratory-specific methods. The values for total IgE varied considerably (73.9% were within +/- 1 SD, 94.3% within +/- 2 SD and 99.1% within +/- 2 SD, but only 0.9% beyond that). Sources of error were mainly attributable to inappropriate equipment and low quality reagents, but also bad test performance, with respect to personnel and the routines. In contrast, antigen specific IgE against pollen, mites, moulds, insect venoms, animal danders, drugs, parasites, environmental and food antigens revealed quite homogeneous results. Out of 1492 data, only 46 (3.1%) had to be declared as "wrong", and the variability of the RAST-classes was low. Whereas the quality of the reagents from all the different suppliers was not absolutely reliable at the beginning of the study, it improved considerably with time, as consequence of our complaints. The comparability of the methods for detecting total-IgE were non-satisfactory, whereas those for antigen specific IgE were generally good. The variety of methods employed (radio- and enzyme immunologic, fluoro- and nephelometric methods, etc.) should entail appropriate consequences, especially critical comparisons within one and the same laboratory; in addition, international standardization of the "normal" values should replace company-standards, and quality control programs for each test system before it is marketed should be mandatory. Our results confirm, that external control should be obligatory for any laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Direction and amplitude precuing has no effect on automatic posture responses.

Automatic postural responses of leg muscles to the sudden displacement of standing support were investigated under four different conditions of information given to subjects in advance. Results from three groups of subjects were compared: 6 normal subjects, 10 patients with cerebellar disease, and 9 patients with Parkinson's disease. Specifically, each subject was provided with visual information about the direction and/or the amplitude of an upcoming platform tilt. For the control situation no advance information on the characteristics of platform tilt was provided. Neither the latencies nor the integrals of postural EMG-responses showed alterations with advance information. In contrast, in a control experiment in which 3 normal subjects had to perform large or small forward or backward voluntary movements of the body around the ankle joint, shorter onset-latencies of leg muscle EMG responses were observed with increasing complexity of the advance information. These results suggest that, unlike voluntary movements, postural responses to rapid surface tilts do not benefit from advance visual information on direction or amplitude of a postural disturbance.

Adult↗

Pollen sensitization and allergy in children depend on the pollen load.

We investigated the influence of grass and birch pollen load on specific IgE response, skin prick test reactivity, and manifest allergic disorders of the eyes and respiratory tract. The study population was two groups of 200 children each, matched in sex and age, who were domiciled in areas with high and low pollen load, respectively. In the children from the area with high pollen load, the grass pollen load was 1.7 times higher than in the other and only specific IgE to grass pollen was found to be present more frequently (23.5% as against 12.5%; P less than 0.01). In the same area, the birch pollen load was 2.8 times higher, which caused specific IgE in 10.5% as against 3.5% of the other group (P less than 0.01) as well as positive skin prick test in 9.0% as against 3.5% (P less than 0.05). Reports of subjective complaints were rare among the group with high pollen load but the total number did not amount to a statistically significant increase. There was no difference between the two groups concerning sensitization and allergy to house dust mite. This suggests that the influence of the pollen load is strongest on the development of specific IgE, and less on skin test reactivity and manifest allergies.

Air Pollutants↗

Risk of vocal chord dysplasia in relation to smoking, alcohol intake and occupation.

The significance of tobacco smoking, alcohol consumption and occupation as risk factors for the development of vocal chord dysplasia was evaluated in a case-control study. Twenty-seven male patients with dysplasia of the vocal chords were chosen from the I. ENT-University Clinic in Vienna (1985-1988) and compared with 54 controls. The main results are: The relative risk (RR) of a smoker compared to that of a non-smoker for vocal chord dysplasia is 7.27 (6.81-7.73); the RR adjusted for occupation is 3.58 (2.31-4.84). The most important risk factor, however, is occupational exposure. The relative risk of a blue collar worker compared to that of a white collar worker is 11.04 (10.61-11.46), which is reduced only to 10.02 (10.61-11.46) after stratification according to smoking habits.

Adult↗

[What happens to vocal cord dysplasias in variable smoking behavior?].

UNLABELLED: The influence of smoking with regard to the development and course of laryngeal dysplasias was examined. The case histories of 63 patients with histologically proven dysplasias of the larynx were evaluated in the light of their answers to a questionnaire covering their lifetime smoking habits. RESULTS: 1. The percentage of smokers in the patient group significantly exceeds the percentage of smokers in the general population. 2. The disease is more likely to lead to deteriorated histological findings in smokers. 3. A change in smoking habits at the time of diagnosis has no significant effect on the further course of disease. 4. Non-smokers have higher levels of dysplasia at first biopsy, but the disease is less likely to progress. The development of malignancy was not observed in the non-smoker group.

Humans↗

[Chronic allergic rhinitis and vasomotor rhinopathy].

The allergic rhinitis and the hyperreactive rhinitis are closely related not only in terms of symptoms. However it is possible to split both components by a subtile diagnostic management. In terms of treatment it is much easier to control allergic reactions than alter hyperreactivity.

Allergens↗

Evaluation of the efficacy and safety of loratadine in perennial allergic rhinitis.

Loratadine, a new nonsedating antihistamine, was evaluated for efficacy and safety in 228 patients with perennial allergic rhinitis. Taken at a dose of 10 mg once daily, loratadine was significantly more effective than placebo and comparable to terfenadine, 60 mg taken twice daily, in reducing combined symptom scores in this patient population. Efficacy was maintained throughout the 28-day course of treatment. The overall incidence of side effects with loratadine was low (14%) with few occurrences of sedation (3%) and dry mouth (4%).

Adolescent↗

A multicentric study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis.

This multicentric study compared 14-day treatment with loratadine (Clarityne) 10 mg once daily, terfenadine 60 mg twice daily and placebo in outpatients with seasonal allergic rhinitis. Of 275 patients enrolled, 256 (87 in the loratadine group, 89 in the terfenadine group and 80 in the placebo group) were evaluable for efficacy and 266 (90, 91 and 85 in respective groups) were evaluable for safety. Investigators graded the severity of 4 nasal and 4 nonnasal signs/symptoms and investigators and patients rated overall disease condition and therapeutic response on treatment days 3, 7 and 14; patients recorded when signs/symptoms of rhinitis were relieved, as well. Hematology and blood chemistry tests were conducted before and after therapy, and patients were questioned throughout the study about possible adverse experiences. At all visits, loratadine and terfenadine were significantly superior to placebo (p less than or equal to 0.004), and the two active medications were statistically comparable, based on mean totals of sign/symptom severity scores and ratings of overall disease condition and therapeutic response. By patients' last valid visit, mean totals of sign/symptoms severity scores improved by 56% and 53% for loratadine and terfenadine groups, respectively, but exacerbated by 5% for the placebo group. Moreover, an excellent or a good therapeutic response was observed in 58/87 (67%) loratadine-treated patients and 58/89 (65%) terfenadine-treated patients, as compared to 13/80 (16%) placebo-treated patients (p less than 0.01). A total of 61/76 (30%) patients in the loratadine group and 57/78 (73%) in the terfenadine group versus 22/71 (31%) in the placebo group experienced relief within the first 3 days of therapy (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A critical examination of vestibular function in motor-impaired learning-disabled children.

This study examined the role of the vestibular system in balance and coordination problems found in motor-impaired, learning-disabled (LD) children. Vestibulo-ocular reflex (VOR) and vestibulo-spinal tests (moving platform posturography) were performed on 15 learning disabled and 54 normal children. Twelve LD children had normal VOR scores suggesting normal peripheral vestibular inputs. All 15 LD children had abnormal posturography. Motor-impaired LD children could not appropriately integrate vestibular information with visual and somatosensory inputs for postural orientation. Results suggest that the best discriminator of abnormal sensorimotor function in LD children are posturography trials requiring orientation to gravity despite absent or inaccurate visual and somatosensory cues, rather than traditionally relied on VOR and Romberg tests.

Child↗