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.     

The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.     

Humoral immune response in patients with bronchopulmanory infections to immunotherapy

The content of IgA, IgM, IgG and the level of specific antibodies in the blood serum of patients with bronchopulmonary diseases after a course of immunotherapy with polycomponent vaccine B[symbol: see text]-4 was studied. A rise in the concentration of IgM due to the synthesis of specific antibodies to Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae was found to occur. The examination of sick children revealed that a high proportion of them (54%) showed a pronounced decrease in the level of IgA. The use of the preparation made it possible to enhance the level of IgA.     

Dynamics of autoantibodies in elderly persons in the process of vaccination with Grippol and multicomponent vaccine VP-4

The dynamics of antibodies to organ specific and organ nonspecific antigens in the process of combined immunization with Grippol, an influenza polymer subunit vaccine and polycomponent vaccine VP-4 used for prophylaxis of acute respiratory infections, was under study. Persons aged 65 years and older were vaccinated. Grippol alone was introduced in a single subcutaneous injection into 92 persons and Grippol in combination with vaccine VP-4--to 103 persons. B[symbol: see text]-4 Vaccine was introduced intranasally and orally (6-8 doses). The administration of vaccine VP-4 was started simultaneously with vaccination with Grippol. Prior to immunization and 1 and 5 months later autoantibodies to the following antigens were detected: DNA (native and denaturated), collagen, elastin, myelin basic protein, microsomal fractions of kidneys, lungs, heart, liver, intestine, pituitary body, thyroid gland, pancreas, adrenal glands, ovaries, mucous and muscular layers of stomach. The number of persons with the level of antibodies at least to one of the antigens under study exceeding the normal values prior to vaccination varied from 19.4 +/- 8.6% to 41.5 +/- 7.7%, the average values of positive sera being 0.26 +/- 0.05 to 0.32 +/- 0.08 delta OD. One and 5 months after vaccination both values varied within the same limits in both groups. Immunization with Grippol as well as with its combination with vaccine VP-4 was found to increased spectrum of antibodies to tissue antigens and their increased content. The data give evidence that Grippol and vaccine Vp-4, introduced according to the immunization schedule used in these experiments, do not induce development of autoimmune processes.     

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.     

The effect of immunotherapy with the VP-4 multicomponent vaccine in children with frequent acute respiratory diseases and obstructive bronchitis

The results of prolonged observations on children with frequent acute respiratory diseases (ARD), subject to immunoprophylaxis with the use of polycomponent vaccine (VP-4), prepared from the antigens of opportunistic microorganisms, are presented. The vaccine was introduced to 30 children in 3 intranasal administrations and 6-8 oral administrations. The morbidity rate of the children was registered and their clinical status was evaluated for a year after the introduction of vaccine VP-4. As revealed in these observations, the frequency of ARD cases among the immunized children decreased 3 times or more in comparison with that among the same children, registered during a year prior to the introduction of the vaccine. In addition to a decrease in the frequency of ARD cases, a decrease in their duration and in the number of antibiotic administrations, as well as in the necessity of hospitalization, were also registered.     

Immune response following administration of multicomponent vaccine VP-4 in elderly patients

The dynamics of immunological characteristics after the administration of polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a risk group with respect to acute respiratory diseases and exacerbations of chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral administration of the vaccine induced immunological shifts in the systems of local and systemic immunity. The content of the populations of lymphocytes with markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable shifts in the system of local immunity were registered: the content of sIgA and IgA in the saliva greatly increased; in addition, an increase in the titers of antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli was observed in persons with initially low titers.     

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.     

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.     

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.     

The use of influenza vaccines and remantadine for protection against influenza in industrial enterprises

The effectiveness of inactivated and live influenza vaccines and remantidin was studied in persons with different annual morbidity rate in influenza and acute respiratory diseases (ARD). After three and more years of immunization with the inactivated vaccine the number of seroconversions to viruses A (H1N1) and A (H3N2) in vaccinees decreased, respectively, from 75.0 to 26.0% and from 79.3 to 38.8%, and after an interval of two years or the alternation of inactivated and live vaccines the number of seroconversions increased to 57.9-64.0%. The significant decrease of morbidity rate in influenza and ARD were observed only in persons, having had frequent ARD in their medical history and immunized with live and inactivated vaccines simultaneously or separately with the alternation of these vaccines every year (the effectiveness index being equal to 1.7-1.8). At the period of epidemic the controlled administration of remantadin to persons with contraindications to immunization ensured the decrease of morbidity rate in influenza 1.5-1.8 times; in vaccinees, highly susceptible to ARD, the administration of remantadin decreased morbidity rate 2.3 times.     

Optimizing reactive responses to outbreaks of immunizing infections: balancing case management and vaccination

For vaccine-preventable infections, immunization generally needs to be supplemented by palliative care of individuals missed by the vaccination. Costs and availability of vaccine doses and palliative care vary by disease and by region. In many situations, resources for delivery of palliative care are independent of resources required for vaccination; however we also need to consider the conservative scenario where there is some trade-off between efforts, which is of potential relevance for resource-poor settings. We formulate an SEIR model that includes those two control strategies - vaccination and palliative care. We consider their relative merit and optimal allocation in the context of a highly efficacious vaccine, and under the assumption that palliative care may reduce transmission. We investigate the utility of a range of mixed or pure strategies that can be implemented after an epidemic has started, and look for rule-of-thumb principles of how best to reduce the burden of disease during an acute outbreak over a spectrum of vaccine-preventable infections. Intuitively, we expect the best strategy to initially focus on vaccination, and enhanced palliative care after the infection has peaked, but a number of plausible realistic constraints for control result in important qualifications on the intervention strategy. The time in the epidemic when one should switch strategy depends sensitively on the relative cost of vaccine to palliative care, the available budget, and [Formula: see text]. Crucially, outbreak response vaccination may be more effective in managing low-[Formula: see text] diseases, while high [Formula: see text] scenarios enhance the importance of routine vaccination and case management.     

Assessment of the prophylactic effectiveness of an inactivated influenza vaccine by immunizing schoolchildren in the springtime

To evaluate the prophylactic effectiveness of influenza inactivated chromatographic vaccine, limited epidemiological observations were made on school children aged 11-14 years in Leningrad, in the autumn of 1981 and the spring of 1982. For immunization, made in a single administration, the vaccine composed of A (H3N2) + +A (H1N1) and containing 3.0-3.4 micrograms of hemagglutinin of each component per 0.2 ml of the preparation was used. Altogether 6928 schoolchildren were under observation; of these, 3686 children were immunized and 3242 children received placebo. The results of questioning and the analysis of morbidity rate among the schoolchildren, both immunized and receiving placebo, showed the safety and low reactogenicity of the vaccine irrespective of the time of the immunization campaign. The immunogenic potency of the preparation, as indicated by all observation results, proved to be higher in spring, than in autumn. The data thus obtained indicate that children immunized in spring were better protected and retained a higher level of protection within 12 months after immunization. The shift of the time of the immunization campaign from autumn to spring increased the immune layer in the groups of children by 16.5%. In 10 months after spring immunization the morbidity rate in influenza and acute respiratory diseases among the vaccinees was found to decrease 1.7 times.     

The in vitro and in vivo resistance of synthetic enkephalin analogs to three enkephalin-hydrolyzing enzymes

The magnitude of the in vitro and in vivo resistance of 3 synthetic enkephalin analogs, [D-Ala2,Met5]-enkephalin (DAME), [D-Ala2,Met5]-enkephalinamide (DAME-NH2) and [D-Ala2,D-Met5]enkephalin (DADME), to 3 enkephalin-hydrolyzing enzymes, amastatin-sensitive aminopeptidase (AsA), phosphoramidon-sensitive endopeptidase-24.11 (PsE) and captopril-sensitive dipeptidyl carboxypeptidase I (CsD), was estimated by comparing the potency of enkephalins in the absence of the peptidase inhibitor (PI) with that in the presence of the PI. The enhancement of the potency of enkephalins in the isolated mouse vas deferens preparation by 3 PIs, amastatin, phosphoramidon, and captopril, indicated that the resistance of enkephalins to AsA, PsE, or CsD was DADME [symbol: see text] DAME-NH2 [symbol: see text] DAME > [Met5]-enkephalin (ME), DADME > DAME-NH2 > DAME [symbol: see text] ME, or DADME [symbol: see text] DAME-NH2 > DAME > ME, respectively. Additionally, the data obtained by the s.c. administration of enkephalin analogs to 10-day-old rats with or without PI, showed that PsE played the most important role in the inactivation of both DAME and DAME-NH2. In addition to PsE, both AsA and CsD, or AsA alone, played the significant role in the inactivation of DAME, or DAME-NH2, respectively. In the inactivation of DADME, AsA alone played the significant role. These results showed that the 3 peptidases all played important roles in the inactivation of enkephalins, and therefore only an analog like DADME, which was quite resistant to the 3 enzymes, was able to produce the effect without PIs after its systemic administration. Since even DADME was not completely resistant to the 3 enzymes; however, its potency was further increased by pretreatment of infant rats with the PIs.     

Immunological effectiveness of a booster inoculation against measles in children remaining seronegative after vaccination

Booster immunization against measles with a highly immunogenic vaccine leads to the development of prolonged postvaccinal immunity lasting at least 6-7 years (the term of observation) in the groups of children found to be seronegative after the titration of their blood sera with 1 hemagglutinating unit (HAU) of the antigen. The booster immunization of children in whose blood sera the minimal concentrations of antibodies can be determined in the presence of 1 HAU of the antigen (seronegative in the presence of 4 HAU) is less effective. The serological checks of immunized children entering preschool institutions and the primary grades at schools and the subsequent booster immunization of children found to be seronegative will lead to a further decrease in measles morbidity.     

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

Background:

The multicomponent serogroup B meningococcal (4CMenB) vaccine induces antibodies against indicator strains of serogroup B meningococcus under various schedules. We investigated the persistence of antibodies in 5-year-old children 18–20 months after their last dose (at about 3.5 years of age).

Methods:

We assessed 5-year-old children who received the 4CMenB vaccine or a recombinant protein vaccine in a previous randomized trial. We also recruited 50 vaccine-naive 5-year-olds and administered 2 doses of 4CMenB to each child. We measured serum bactericidal antibody titres against 4 indicator strains of serogroup B meningococcus matched to each individual vaccine component and against 4 mismatched strains.

Results:

Of those who received the 4CMenB vaccine at 2, 4, 6, 12 and 40 months (n = 16), the percentage with protective antibody titres (≥ 1:4) at 60 months ranged from 44% to 88% against matched strains and from 13% to 81% against mismatched strains. Loss of protective titres was also observed for those who received the 4CMenB vaccine at 12, 40 and 42 months (n = 5) (80%–100% against matched strains, 60%–100% against mismatched strains) or at 40 and 42 months (n = 29) (31%–100% against matched strains, 41%–81% against mismatched strains). Administering the 4CMenB vaccine to 5-year-old children yielded protective titres against matched strains in 92%–100% and against mismatched strains in 59%–100%. The majority of these children reported injection-site pain (40/50 [80%] after dose 1, 39/46 [85%] after dose 2) and erythema (47/50 [94%] and 40/46 [87%], respectively); rates of fever were low (5/50 [10%] and 2/46 [4%], respectively).

Interpretation:

Waning of immunity by 5 years of age occurred after receipt of the 4CMenB vaccine in infancy, even with an additional booster at 40 months. The 4CMenB vaccine is immunogenic and was fairly well tolerated by 5-year-old children, although injection-site pain was noteworthy. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01027351","term_id":"NCT01027351"}}NCT01027351The multicomponent serogroup B meningococcal (4CMenB) vaccine is licensed in the European Union, Australia and Canada to prevent serogroup B meningococcal disease. It was developed using “reverse vaccinology,” in which candidate antigens were identified by interrogating the whole meningococcal genome.¹ The 4CMenB vaccine consists of 3 surface proteins (factor H binding protein [fHbp], Neisseria adhesin A [NadA] and Neisseria heparin-binding antigen [NHBA]), along with a fourth component, the outer membrane vesicle, which acts as both antigen and adjuvant.¹Group B meningococcal disease is a potentially devastating condition, with an average case fatality rate of 5.2% (data for England and Wales²), and over a third of survivors are left with measurable functional deficits.³ The incidence of laboratory-confirmed cases is about 1 per 100 000 population in England⁴ and 0.33 per 100 000 population in Canada.⁵ The recommendation of the United Kingdom Joint Committee on Vaccination and Immunisation that the 4CMenB vaccine be introduced into the routine UK immunization schedule should, if implemented, lead to a reduction in this morbidity and mortality.⁶ Data on the persistence of antibody responses following infant or toddler immunization, and after subsequent boosting, remain limited yet will be important for guiding implementation of this recommendation.We present here the results of a follow-on study investigating the persistence of antibodies 18–20 months after the last dose in 5-year-old children previously immunized under a variety of schedules with 4CMenB vaccine or another investigational vaccine (recombinant protein serogroup B meningococcal [rMenB] vaccine), which lacks the outer membrane vesicle component of the 4CMenB vaccine. Since the original infant study,⁷ 4CMenB vaccine has emerged as the preferred vaccine, because addition of the outer membrane vesicle component improves the breadth of strain coverage;⁸ however, the extension study continued follow-up for all of the original children, and all results are therefore presented here.     

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)