Replication of association between ADAM33 polymorphisms and psoriasis

Polymorphisms in ADAM33, the first gene identified in asthma by positional cloning, have been recently associated with psoriasis. No replication study of this association has been published so far. Data available in the French EGEA study (Epidemiological study on Genetics and Environment of Asthma, bronchial hyperresponsivensess and Atopy) give the opportunity to attempt to replicate the association between ADAM33 and psoriasis in 2002 individuals. Psoriasis (n = 150) has been assessed by questionnaire administered by an interviewer and a sub-sample of subjects with early-onset psoriasis (n = 74) has been identified based on the age of the subjects at time of interview (<40 years). Nine SNPs in ADAM33 and 11 SNPs in PSORS1 were genotyped. Association analysis was conducted by using two methods, GEE regression-based method and a likelihood-based method (LAMP program). The rs512625 SNP in ADAM33 was found associated with psoriasis at p = 0.01, the usual threshold required for replication (OR [95% CI] for heterozygotes compared to the reference group of homozygotes for the most frequent allele = 0.61 [0.42;0.89]). The rs628977 SNP, which was not in linkage disequilibrium with rs512625, was significantly associated with early-onset psoriasis (p = 0.01, OR [95% CI] for homozygotes for the minor allele compared to the reference group = 2.52 [1.31;4.86]). Adjustment for age, sex, asthma and a PSORS1 SNP associated with psoriasis in the EGEA data did not change the significance of these associations. This suggests independent effects of ADAM33 and PSORS1 on psoriasis. This is the first study that replicates an association between genetic variants in ADAM33 and psoriasis. Interestingly, the 2 ADAM33 SNPs associated with psoriasis in the present analysis were part of the 3-SNPs haplotypes showing the strongest associations in the initial study. The identification of a pleiotropic effect of ADAM33 on asthma and psoriasis may contribute to the understanding of these common immune-mediated diseases.     

Ultrastructure of epithelium and ciliary receptors in the parasitic turbellarian Urastoma cyprinae (Turbellaria, "Prolecithophora") and position of the species within Platyhelminthes

Ultrastructure of the epithelium of adult and juvenile Urastoma cyprinae has been studied. The epithelium of both adult and juvenile worms is cellular, ciliated and bears numerous microvilli. The cytoplasm is rich in large, numerous epitheliosomes of two types--electron-dense and with fibrillated content (fig. 1, a, [symbol: see text]; 2, a-[symbol: see text]). Besides large secrete granules small membrane-bounded vesicles were observed (fig. 2, a-[symbol: see text]). In juvenile worms the dense epitheliosomes are less abundant and the fibrillated content in the second type of granules has a different structure: the fibrils are very thin and more densely packed forming the structures of the less electron density (fig. 3, a, [symbol: see text], [symbol: see text] 1). The membrane-bounded vesicles in the epithelium of juvenile worms were not observed. All types of secrete are ejected by exocytosis (fig. 2, [symbol: see text]; 3, [symbol: see text], [symbol: see text]). The ultrastructure of the epithelium in juvenile U. cyprinae is strongly similar to that in parasitic turbellarian Kronborgia, especially to the epithelium in a male and a larva. The basal lamina consists of tree layers and forms numerous deep infoldings into the epithelium (fig. 1, a; 2, a; 3, a, [symbol: see text], [symbol: see text]). The basement membrane projects deep and numerous invaginations into the epithelium which may almost reach the apical membrane (fig. 1, a; 2, a, [symbol: see text], [symbol: see text]; 3, [symbol: see text]). Mitochondria are large and situated mainly near the projections of the basement membrane (fig. 2, [symbol: see text]-[symbol: see text]; 3, [symbol: see text]). Such ultrastructure implies an intensive process of the transmembrane transfer of the dissolved organic substances from the sea water. The same structures were found in the epithelium of Kronborgia. Uptake of organic compounds through the epithelium in the common ancestors of Urastoma and Kronborgia could be the preadaptation to the endoparasitic mode of life in Fecampiida. The differencies in ultrastructure of epithelium in U. cyprinae from the White Sea and from Mediterranean Sea (Noury-Sra?ri e. a., 1990) may be explained by the differences in the method of fixation or by the parasitizing the another host--the mollusk Mytilus galloprovincialis. The ciliary receptors of five types were revealed in U. cyprinae (fig. 3, e, [symbol: see text]; 4; 5; 6). They differ in the shape and length of the ciliary rootlets and in the content of the nerve processes. All receptors lack of the real collars typical for the receptors of Neodermata. Urastoma is most close to the Neodermata amond parasitic turbellarians studied thus far, and the absence of collars in receptors of this species testifies that the collars are the veritable synapomorphy of the Neodermata. The diversity in the ultrastructure and possible functions of receptors correspond to the complicated adaptations of this species. The modern molecular data as well as the ultrastructural evidence attest that parasitic turbellarians of the genera Urastoma, Genostoma and Ichthyophaga are relatives and cannot be included in any turbellarian order known. Therefore Urastoma, Genostoma and Ichthyophaga have been erected in the separate order Urastomida ord. nov. The diagnosis of the new order is given.     

Comparative study of the diagnostic value of new cholera eltor bacteriophages ctx+, ctx-, and KhDF-3, 4, and 5

The comparative evaluation of the diagnostic value of new cholera eltor bacteriophages ctx+ and ctx-, as well as monophages X[symbol: see text]-3, 4, 5, demonstrated their high activity and specificity. Using of these bacteriophages epidemic potential of 95% Vibrio cholerae eltor strains ctx+ and 84.5% of V. cholerae eltor stains ctx- was determined. Commercial monophages X[symbol: see text]-3, 4, 5 were inferior to bacteriophages ctx+ and ctx- in their diagnostic value: only 55% of strains having gene ctxAB were found to be epidemically dangerous, i.e. 45% of strains capable of causing the disease were not detected. On the basis of the results obtained in this investigation cholera eltor bacteriophages ctx+ and ctx- were recommended for introduction into practical use, while further production of cholera diagnostic monophages X[symbol: see text]-3, 4, 5 was recommended to be stopped.     

Seed banks, salmon, and sleeping genes: effective population size in semelparous, age-structured species with fluctuating abundance

Previous studies reached contrasting conclusions regarding how fluctuations in abundance affect Ne in semelparous species with variable age at maturity: that Ne is determined by the arithmetic mean N among the T years within a generation (Ne approximately = T(N)t; monocarpic plants with seed banks) or the harmonic mean (Ne approximately T[symbol: see text]; Pacific salmon). I show that these conclusions arise from different model assumptions rather than inherent differences between the species. Sequentially applying standard, discrete-generation formulas for inbreeding Ne to a series of nominal generations accurately predicts the multigenerational rate of increase in inbreeding. Variability in mean realized reproductive success across years (kt) is the most important factor determining Ne and Ne/N. When abundance is driven by random variation in kt, Ne < or = T[symbol: see text] < T(N)t. With random variation in Nt and constant per capita seed production (C), variation in kt is low and Ne approximately T[symbol: see text]; however, if C varies among years, Ne can be closer to T[symbol: see text]. Because population regulation affects the genetic contribution of entire cohorts of monocarpic perennials, Ne for these species may be more closely approximated by T[symbol: see text] than by T(N)t. With density-dependent compensation, Cov(kt, Nt) < 0, and Ne is further reduced because relatively few breeders make a disproportionate contribution to the next generation.     

Are membrane enzymes regulated by the viscosity of the membrane environment?

We have examined the idea that membrane enzymes are regulated by the viscosity of surrounding lipids using data compiled from the literature for the effect of the change in membrane viscosity ([symbol: see text]) at the gel- to liquid-crystal-phase transition on the activities of several enzymes. The analysis was not extended explicitly to the problem of viscosity-dependent regulation of membrane enzymes in liquid-crystalline lipids because of the absence of exact data for values of [symbol: see text] in liquid-crystalline phases of variable composition. For most membrane enzymes studied, energies of activation are discontinuous, while kcat is continuous, at the main-phase transition. We consider that the energy of activation contains terms related to the height of the chemical barrier to reaction and terms due to the mechanical properties of the bilayer, such as the work of expansion during the catalytic cycle and the temperature dependence of [symbol: see text]. We find that the differences in energies of activation, above and below the break points in Arrhenius plots, are orders of magnitude larger than can be accounted for by the above mechanical factors. Thus, discontinuities in energies of activation at the phase transition appear to reflect changes in the chemical barrier to reaction, which is independent of [symbol: see text]. The theorectical analysis indicates too that values of [symbol: see text] for bilayers in the liquid-crystalline phase would have to be several orders of magnitude larger than those for gel phases in order to provide a basis for viscosity-dependent regulation of membrane enzymes in liquid-crystalline phases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.     

CO2.- radical induced cleavage of disulfide bonds in proteins. A gamma-ray and pulse radiolysis mechanistic investigation

Disulfide bond reduction by the CO2.- radical was investigated in aponeocarzinostatin, aporiboflavin-binding protein, and bovine immunoglobulin. Protein-bound cysteine free thiols were formed under gamma-ray irradiation in the course of a pH-dependent and protein concentration dependent chain reaction. The chain efficiency increased upon acidification of the medium, with an apparent pKa around 5, and decreased abruptly below pH 3.6. It decreased also at neutral pH as cysteine accumulated. From pulse radiolysis analysis, CO2.- proved able to induce rapid one-electron oxidation of thiols and of tyrosine phenolic groups in addition to one-electron donation to exposed disulfide bonds. The bulk rate constant of CO2.- uptake by the native proteins was 5- to 10-fold faster at pH 3 than at pH 8, and the protonated form of the disulfide radical anion, [symbol: see text], appeared to be the major protein radical species formed under acidic conditions. The main decay path of [symbol: see text] consisted of the rapid formation of a thiyl radical intermediate [symbol: see text] in equilibrium with the closed, cyclic form. The thiyl radical was subsequently reduced to the sulfhydryl level [symbol: see text] on reaction with formate, generating 1 mol of the CO2.- radical, thus propagating the chain reaction. The disulfide radical anion [symbol: see text] at pH 8 decayed through competing intramolecular and/or intermolecular routes including disproportionation, protein-protein cross-linking, electron transfer with tyrosine residues, and reaction with sulfhydryl groups in prereduced systems. Disproportionation and cross-linking were observed with the riboflavin-binding protein solely. Formation of the disulfide radical cation [symbol: see text], phenoxyl radical Tyr-O. disproportionation, and phenoxyl radical induced oxidation of preformed thiol groups should also be taken into consideration to explain the fate of the oxygen-centered phenoxyl radical.     

Temperature dependence of the dissociation rate constants for 8 S, 4 S, and meroreceptor forms of the estrogen receptor from rat uterus

Conversion of a steroid receptor complex from the 8 S to the 4S form results in new interactions between the steroid and the receptor and/or formation of new intra-protein bonds within the receptor molecule itself. These bonds must be broken before the steroid is released. In order to localize these newly formed interactions, the dissociation kinetics of meroreceptors derived from 4 S and 8 S (molybdate-stabilized) receptor complexes were examined. At temperatures between 6 and 30 degrees C, no differences in the rates of dissociation were observed for the meroreceptors derived from the two forms of estrogen receptor, whereas approximately a twofold difference in dissociation rates for 4 S intact receptor versus 8 S intact receptor was detected. These findings indicate that the new interactions accompanying this conversion are likely to occur in regions of the receptor molecule other than the C-terminal portion of the steroid-binding site. The thermodynamic parameters of the dissociation reaction for the intact 4 S, and 8 S, and meroreceptor forms, respectively were: delta H [symbol; see text] = 26.2 +/- 1.3, 19.7 +/- 1.7, and 23.2 +/- 1.0 kcal/mol; +T delta S [symbol; see text] = 9.4 +/- 1.2, 3.2 +/- 1.7 and 6.6 +/- 0.9 kcal/mol (at 25 degrees C); and delta G [symbol; see text] = 16.8 +/- 2.5, 16.5 +/- 3.4, and 16.7 +/- 1.9 kcal/mol. As is the case for other steroid receptors, an increase in the enthalpy of steroid-receptor interaction after this conversion reflects the stability of the 4 S estrogen receptor complex.     

Effect of melanins from black yeast fungi on cultured human cells. I. Proliferation of keratinocytes and fibroblasts

Results of screening of the influence exerted by yeast black melanin on the proliferation of human skin keratinocytes and embryonic fibroblasts are presented. The optimal concentration of the investigated melanins was found to be within 0.005 and 0.0001 mg/ml. 17 samples of DHN-melanin from black yeast and 2 commercial samples of [symbol: see text]OPA-melanin (natural and synthetic) were investigated. It was established that keratinocyte proliferation was inhibited by 3 black yeast melanin samples; the influence of other 14 samples was the same as in the control. Keratinocyte proliferation was stimulated only by a commercial sample of natural [symbol: see text]OPA-melanin at concentration 0.005 mg/ml. The synthetic melanin at concentrations 0.005 and 0.001 mg/ml inhibited keratinocyte proliferation. Of the 17 investigated black yeast melanin samples, only one sample stimulated fibroblast proliferation at concentration 0.005 mg/ml. Three other samples inhibited the proliferation; of these one sample did it at all used concentrations, and two samples at concentration 0.0001 mg/ml. The rest 13 samples of black yeast DHN-melanins and the synthetic [symbol: see text]OPA-melanin did not differ in either action from the control.     

Premature condensation of sperm chromosomes in human oocytes fertilized in vitro

Analysis of the frequency of oocytes containing premature condensed sperm chromosomes depending on clinical and embryological parameters has been carried out. It was shown that this frequency comes to 11.6% during in vitro fertilization and depends on morpho-functional characteristics of acnipo[symbol: see text] oocytes.     

Immunoprophylaxis of acute respiratory diseases with bacterial multicomponent vaccine VP-4 in children at preschool institutions

The prophylactic action of polycomponent vaccine B[symbol: see text]-4, prepared from the antigens of opportunistic bacteria, on morbidity rate in acute respiratory diseases (ARD) of bacterial and mixed (bacterial and viral) etiology in 121 children aged 2-5 years, attending pre-school institutions was evaluated. For comparison, a group of 118 children of the same age from the same institutions was formed. The vaccine was introduced after the schedule consisting of 3 intranasal and 6-9 oral administrations made at intervals of 3-4 days. The duration of the course of immunization was 26 +/- 4 days. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity was evaluated by the number of ARD cases and their duration per child. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity lasted 14 months (the term of observation) after immunization and was manifested by a decrease in the number and duration of ARD cases after administration of the preparation, also in a group of highly susceptible children.     

Evaluation of methodology for detection of genetic bottlenecks: inferences from temporally replicated lake trout populations

Statistical methods have been proposed to detect recent bottlenecks on the basis of genetic characterizations of natural populations. In the absence of direct estimates of contemporary or historical population numbers, we tested the indirect M-ratio method based on microsatellite motif size frequency profiles using three historical and three contemporary Great Lakes populations of Salvelinus namaysuch for which severe reductions in population numbers are documented. Simulations employing plausible ranges of empirical population parameter values were used to explore bottleneck likelihood surfaces. We show that single values of the M-ratio are not sufficient to unambiguously infer a bottleneck without knowledge of mutation rates and effective population size (i.e., 4Ne mu or [symbol: see text]). Inferences of the degree of population bottleneck would be best supported if analyses were conducted across plausible ranges of [symbol: see text] and by qualitative comparisons among population samples.     

Trans-Theta Logistics: A New Family of Population Growth Sigmoid Functions

Sigmoid functions have been applied in many areas to model self limited population growth. The most popular functions; General Logistic (GL), General von Bertalanffy (GV), and Gompertz (G), comprise a family of functions called Theta Logistic ([Formula: see text] L). Previously, we introduced a simple model of tumor cell population dynamics which provided a unifying foundation for these functions. In the model the total population (N) is divided into reproducing (P) and non-reproducing/quiescent (Q) sub-populations. The modes of the rate of change of ratio P/N was shown to produce GL, GV or G growth. We now generalize the population dynamics model and extend the possible modes of the P/N rate of change. We produce a new family of sigmoid growth functions, Trans-General Logistic (TGL), Trans-General von Bertalanffy (TGV) and Trans-Gompertz (TG)), which as a group we have named Trans-Theta Logistic (T [Formula: see text] L) since they exist when the [Formula: see text] L are translated from a two parameter into a three parameter phase space. Additionally, the model produces a new trigonometric based sigmoid (TS). The [Formula: see text] L sigmoids have an inflection point size fixed by a single parameter and an inflection age fixed by both of the defining parameters. T [Formula: see text] L and TS sigmoids have an inflection point size defined by two parameters in bounding relationships and inflection point age defined by three parameters (two bounded). While the Theta Logistic sigmoids provided flexibility in defining the inflection point size, the Trans-Theta Logistic sigmoids provide flexibility in defining the inflection point size and age. By matching the slopes at the inflection points we compare the range of values of inflection point age for T [Formula: see text] L versus [Formula: see text] L for model growth curves.     

Haemolytic anaemia in Basenji dogs. 2. Partial deficiency of erythrocyte pyruvate kinase (PK; EC 2.7.1.40) in heterozygous carriers

Congenital nonspherocytic haemolytic anaemia (HA) in dogs of the Basenji breed is inherited as a simple, autosomal recessive trait. Previous results of pyruvate kinase (PK) assays suggest a causal relationship between the anaemia and PK deficiency in erythrocytes. In the present investigation assays of this enzyme have been performed on haemolysates from 45 Basenji dogs, comprising 3 anaemic and 42 non-anaemic individuals of which 13 were known heterozygotes. The PK activity in haemolysates from the 42 non-anaemic dogs exhibited a bimodal distribution corresponding to the genotypic classes: heterozygotes and normal homozygotes. The results indicate that heterozygotes have a partial, detectable enzyme deficiency, not reflected in clinical disease, and thus give evidence of a gene dosage effect in agreement with observations in man. The proposed genotypes PK PK, PK pk and pk pk refer to normal homozygotes, heterozygotes, and anaemic individuals, respectively. The findings strengthen the genetic hypothesis of recessiveness of the anaemia by direct detection of heterozygosity of parents of affected individuals. Moreover, the results are of value in comparative studies and they have practical application in connection with eradication programmes.     

Relationships between basic life history parameters and population size

We consider an ideal population with a stable age composition changing according Lotka equation. Additional assumptions are made concerning the constancy of population size, independence of specific mortality rate on age, and linear dependence of female fecundity on its weight. A relationship has been obtained [formula: see text] where N0 is initial numbers of a generation, N[alpha, omega] is total numbers of the mature part of the population, w[alpha, omega] is a mean weight of a mature individual, s is sex ratio, c is specific fecundity (per unit of weight) and l0 is the probability of larval surviving. The growth of an individual is described by the Bertalanffy function. Methods of calculation of life history parameters are discussed. A method is proposed to calculate the age of maturity (alpha) and at the end (omega) of the reproduction period as first and second inflection points of the growth rate curve. Based upon data on development of 27 populations of several species of fishes of inland waters of Russia the following relationship have been obtained: [formula: see text] for populations with [formula: see text] < or = 100 g, [formula: see text] for populations with [formula: see text] > 100 g, and [formula: see text] for all populations.     

New tandem-repeating peptide structures in polysialoglycoproteins from the unfertilized eggs of kokanee salmon

New polysialoglycoproteins, designated PSGP(On), were isolated from the fertilized and unfertilized eggs of the kokanee salmon, Oncorhynchus nerka adonis. The polysialylglycan chains consisting of alpha-2,8-linked O-acetylated poly(N-glycolylneuraminyl) chains have recently been characterized. We have now determined the complete amino acid sequence of the tandem-repeating units of PSGP(On) from the unfertilized eggs of kokanee salmon and found that the following two distinct forms are present in PSGP(On) in almost identical amounts: [formula: see text] and [formula: see text] where * denotes the O-glycosylation site and mean value of m, n = about 20. Upon fertilization these high-molecular-weight forms of PSGP(On) were proteolytically cleaved to the corresponding repeating units, low-molecular-weight PSGP(On), by the action of a specific protease (PSGPase) at the position two residues set C-terminally to the Pro residue and N-terminally to the Asp residue, i.e. -Pro-Ser-Xaa-Asp-: [formula: see text] and [formula: see text].     

Modelling transmission of vector-borne pathogens shows complex dynamics when vector feeding sites are limited

The relationship between species richness and the prevalence of vector-borne disease has been widely studied with a range of outcomes. Increasing the number of host species for a pathogen may decrease infection prevalence (dilution effect), increase it (amplification), or have no effect. We derive a general model, and a specific implementation, which show that when the number of vector feeding sites on each host is limiting, the effects on pathogen dynamics of host population size are more complex than previously thought. The model examines vector-borne disease in the presence of different host species that are either competent or incompetent (i.e. that cannot transmit the pathogen to vectors) as reservoirs for the pathogen. With a single host species present, the basic reproduction ratio R(0) is a non-monotonic function of the population size of host individuals (H), i.e. a value [Formula: see text] exists that maximises R(0). Surprisingly, if [Formula: see text] a reduction in host population size may actually increase R(0). Extending this model to a two-host species system, incompetent individuals from the second host species can alter the value of [Formula: see text] which may reverse the effect on pathogen prevalence of host population reduction. We argue that when vector-feeding sites on hosts are limiting, the net effect of increasing host diversity might not be correctly predicted using simple frequency-dependent epidemiological models.     

Multicomponent vaccine VP-4 in the therapy of allergic diseases

In the present study the results of the polycomponent vaccine B[symbol: see text]-4 use for the therapy of patients with bronchial asthma (BA) and latex allergy were generalized. The vaccine was introduced by the nasal-subcutaneous or nasal-oral administration simultaneously with the basic therapy. Te studies were conducted first on limited groups of patients, then in the course of the State Trial with the use of placebo control. Excellent and good effect lasting for 1 year and over was registered in 36 patients (66.7%) out of 54 BA patients receiving the vaccine by the intranasal-subcutaneous method. Immunotherapy produced no positive effect in 13 patients (24.1%). Out of 35 examined patients receiving the vaccine by the intranasal oral method, excellent and good effect was registered in 26 patients (74.2%). No effect was registered in 4 patients (11.4%). In the group of 28 patients receiving placebo simultaneously with the basic therapy positive dynamics in the course of the disease was observed only in 3 patients. Treatment with polycomponent vaccine B[symbol: see text]-4 led to a prolonged (to a year and more) decrease in the frequency and severity of exacerbations, contributed to the prolongation of remissions and to a decrease in the amount of administered medicinal preparations, especially systemic corticosteroids. Immunotherapy ensured the correction of the content of lymphocyte subpopulations with markers CD3, CD4, CD72 and a rise in the titers of antibodies to antigens contained in the preparation. The use of therapeutic polycomponent vaccine B[symbol: see text]-4 for the treatment of patients with latex allergy ensured the state of prolonged remission in this group of patients. On the basis of our investigations we believe that the use of the therapeutic polycomponent vaccine B[symbol: see text]-4 may be included into the basis therapy of allergic diseases.