Tracking T-cell immune reconstitution after TCRαß/CD19-depleted hematopoietic cells transplantation in children.

αßT-cell-depleted allogeneic hematopoietic cell transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαß-/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of αßT-cell counts 2 months after transplantation is based on only several hundred rapidly expanded clones originating from non-depleted graft cells. In further months, frequency of these hyperexpanded clones declines, and after 1 year the observed T-cell counts and TCRß diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCRß diversity at day 60 observed for some of the patients is determined by recipient T cells and intrathymic progenitors that survived conditioning regimen. Our results indicate that further efforts on optimization of TCRαß-/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation.

[The new technologies of kinesiotherapy for the rehabilitation of the patients suffering from the post-stroke locomotor disorders].

This paper was designed to report the results of the application of two therapeutic modalities for the rehabilitation of 44 patients presenting with post-stroke locomotor disorders in the form of spastic hemiparesis. The patients allocated to the main group were treated with the use of the new kinesiotherapeutic methods including cryomassage and the Armeo robotic complex. The patients of the control group had to perform traditional therapeutic physical exercises in combination with classical massage and remedial gymnastics. It is concluded that the application of the combination of the modern kinesiotherapeutic factors exerting the positive corrective influence on different aspects of the locomotor deficiency in the upper extremities and the psychoemotional status of the patients has advantages over traditional physical exercise therapy in terms of clinical efficiency because it enhances the rehabilitative potential for these patients with serious locomotor problems.

Collision Cross Sections for O + Ar(+) Collisions in the Energy Range 0.03-500 eV.

The interatomic potentials of the a(2)Π and b(2)Π states of the OAr(+) molecule are calculated using the relativistic complete-active space Hartree-Fock method followed by a multireference configuration interaction calculation with an aug-cc-pwCVNZ-DK basis sets where N is 4 and 5. The calculations were followed by an extrapolation to the complete basis set limit. An avoided crossing between the two potential energy curves is found at an internuclear separation of 5.75 bohr (3.04 Å). As the transition probability between the curves is negligible in the relative collision energy range 0.03-500 eV of interest here, collisions on the lower adiabatic a(2)Π potential may be treated without reference to the upper state. For low energies and orbital angular momentum quantum numbers, the one-dimensional radial Schrödinger equation is solved numerically using a Numerov algorithm method to determine the phase shift. The semiclassical JWKB approximation was employed for relative energies greater than 5 eV and orbital angular quantum numbers higher than 500. Differential, integral, transport (diffusion), and viscosity cross sections for elastic collisions of oxygen atoms with argon ions are calculated for the first time for the range of relative collision energies studied. The calculated cross sections are expected to be of utility in the fields of nanotechnology and arc welding. The combination of an Ar(+)((2)P) ion and a O((3)P) atom gives rise to a total of 12 different molecular electronic states that are all coupled by spin-orbit interactions. Potential energy curves for all 12 states are computed at the complete active space self-consistent field (CASSCF) level and scattering calculations performed. The results are compared with those obtained using just the lowest potential energy curve.

[Dynamics of the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis under effect of contrast massage].

The objective of the present work was to study the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis before and after a course of contrast massage. Three types of functional changes in the microcirulation system were distinguished based on the results of laser-assisted Doppler flowmetry. All of them were characterized by high coefficients of correlation with the results of dopplerometry of uterine blood flow and underwent dynamic changes in the course of the treatment. The study has demonstrated the high therapeutic effectiveness of the contrast massage technique as a tool for inducing hemodynamic changes in the small pelvis basin in the women suffering from chronic endometritis.

Equal impact of diffusion and DNA binding rates on the potential spatial distribution of nuclear factor κB transcription factor inside the nucleus.

There are two physical processes that influence the spatial distribution of transcription factor molecules entering the nucleus of a eukaryotic cell, the binding to genomic DNA and the diffusion throughout the nuclear volume. Comparison of the DNA-protein association rate constant and the protein diffusion constant may determine which one is the limiting factor. If the process is diffusion-limited, transcription factor molecules are captured by DNA before their even distribution in the nuclear volume. Otherwise, if the reaction rate is limiting, these molecules diffuse evenly and then find their binding sites. Using well-studied human NF-κB dimer as an example, we calculated its diffusion constant using the Debye-Smoluchowski equation. The value of diffusion constant was about 10(-15) cm(3)/s, and it was comparable to the NF-κB association rate constant for DNA binding known from previous studies. Thus, both diffusion and DNA binding play an equally important role in NF-κB spatial distribution. The importance of genome 3D-structure in gene expression regulation and possible dependence of gene expression on the local concentration of open chromatin can be hypothesized from our theoretical estimate.

Site-specific differential effects of once-yearly zoledronic acid on the hip assessed with quantitative computed tomography: results from the HORIZON Pivotal Fracture Trial.

UNLABELLED: We used new approaches to the analysis of diagnostic scans to detect changes in bone density in different regions of the hip after 3 years of treatment with the zoledronic acid. We showed that the drug significantly increases hip bone density compared to placebo at regions where hip fractures usually occur. INTRODUCTION: This study aims to identify whether treatment with zoledronic acid exerts site-specific differential effects on volumetric bone mineral density (vBMD) at the hip. METHODS: We analysed quantitative computed tomography scans of the hip obtained at baseline and 36 months in 179 women participating in the HORIZON Pivotal Fracture Trial. Cortical, trabecular and integral BMDs were determined at three main regions of interest-the femoral neck (FN), trochanter (TR) and total hip (TH)-and several sub-regions of interest, namely the proximal, middle, distal, anterior, posterior, inferomedial and superolateral FN, and the middle and distal TR. RESULTS: Volumetric BMD increased significantly (p < 0.05) from baseline with zoledronic acid compared to placebo. Trabecular vBMD increased as follows: FN, 5.4 %; FN sub-regions, 6.0 % (proximal), 4.4 % (middle), 5.6 % (distal), 7.5 % (anterior), 7.0 % (superolateral) and 5.4 % (posterior); TR, 6.5 % and TH, 5.7 %. Cortical vBMD increased as follows: FN sub-regions, 5.0 % (proximal FN) and 2.3 % (anterior); TR, 4.6 %; middle TR, 2.7 % and TH, 3.8 %. CONCLUSIONS: The effects on vBMD of annual infusion of 5 mg of zoledronic acid are site-specific and dominated by trabecular changes.

High-resolution crystal structure of the isolated ribosomal L1 stalk.

The crystal structure of the isolated full-length ribosomal L1 stalk, consisting of Thermus thermophilus ribosomal protein L1 in complex with a specific 80-nucleotide fragment of 23S rRNA, has been solved for the first time at high resolution. The structure revealed details of protein-RNA interactions in the L1 stalk. Analysis of the crystal packing enabled the identification of sticky sites on the protein and the 23S rRNA which may be important for ribosome assembly and function. The structure was used to model different conformational states of the ribosome. This approach provides an insight into the roles of domain II of L1 and helix 78 of rRNA in ribosome function.

Purification and functional analysis of recombinant Acholeplasma laidlawii histone-like HU protein.

HU is a most abundant DNA-binding protein in bacteria. This protein is conserved either in its heterodimeric form or in one of its homodimeric forms in all bacteria, in plant chloroplasts, and in some viruses. HU protein non-specifically binds and bends DNA as a hetero- or homodimer and can participate in DNA supercoiling and DNA condensation. It also takes part in some DNA functions such as replication, recombination, and repair. HU does not recognize any specific sequences but shows some specificity to cruciform DNA and to repair intermediates, e.g., nick, gap, bulge, 3'-overhang, etc. To understand the features of HU binding to DNA and repair intermediates, a fast and easy HU proteins purification procedure is required. Here we report overproduction and purification of the HU homodimers. The method of HU purification allows obtaining a pure recombinant non-tagged protein cloned in Escherichia coli. We applied this method for purification of Acholeplasma laidlawii HU and demonstrated that this protein possesses a DNA-binding activity and is free of contaminating nuclease activity. Besides that we have shown that expression of A. laidlawii ihf_hu gene in a slow-growing hupAB E. coli strain restores the wild-type growth indicating that aclHU can perform the basic functions of E. coli HU in vivo.

[Permissible degree of reduction of diet caloricity for obese patients]. / Dopustimaia stepen' reduktsii kaloriinosti ratsiona dlia tuchnykh bol'nykh.

A study was made of the effects of diets with varying degree of caloricity reduction at the expense of the decreased content of carbohydrates and fat (1200, 600, 300 kcal and calorie-free "zero" diet) on some indicators of lipid, carbohydrate, protein and mineral metabolism comparatively to the patients' clinical status. A group of patients receiving the diet with a caloricity of 1800 kcal served as control. It was shown that the diet with an average reduction of caloricity (1200 kcal) may be applied to the treatment of obese patients for a long period of time both on in- and outpatient basis. The decrease permissible and such a diet may be indicated for a short period of time (1-1 1/2) months), diets with extremely reduced caloricity (300 kcal, "zero" diet) is not advisable), since such diets exert an adverse action on metabolic processes in the body.

[Specific and nonspecific cytolysis reactions in rheumatic patients with a low degree of activity in the process of combined treatment by a high-protein diet and drug preparations]. / Izuchenie reaktsii spetsificheskogo i nespetsificheskogo tsitoliza u bol'nykh revmatizmom s maloi stepen'iu aktivnosti v protesse kompleksnogo lecheniia vysokobelkovoi dietoi i medikamentoznymi preparatami.

Effect of therapy including high-protein diet and hormones on specific and nonspecific cytolysis was studied in patients with torpid and latent-running recurrent rheumatic carditis. The number of HeLa cells on which specific antigens (cardiac tissue extract, collagen, group C streptococcal nucleoproteid) were adsorbed significantly decreased on addition to the test target sensitized lymphocytes from the patients examined. As a result of therapy most patients showed the reduced activity of supernatants obtained from peripheral blood lymphocyte cultures that were incubated with specific antigens.

[Parameters of polynuclear cell activity in torpid and latent recurrent rheumocarditis in the process of treatment with a high-protein diet and drug preparations]. / Nekotorye parametry aktivnosti polinuklearov u bol'nykh vialo i latentno tekushchim vozvratnym revmokarditom v protsesse lecheniia vysokobelkovoi dietoi i medikamentoznymi preparatami.

The in vitro test of direct granulation of basophils affected by specific antigens (cardial tissue, acid-soluble fraction of collagen, streptococcal allergens) was investigated in the course of treating 41 patients (29 women and 12 men aged from 20 to 50 years) suffering from a little active rheumatic fever. The patients received a complex of therapeutic measures including high-protein diet (130-140 g protein) and drugs (1.5-2.0 g acetylsalicylic acid and 15 mg of prednisolone a day). As a result of the treatment all the patients improved and demonstrated pain relief in the heart region, reduced palpitation, abatement of general weakness and fatigue. At the same time there was a decrease in the reactivity of basophilic leukocytes, shown by less number of degranulated cells in vitro, activated with specific antigens.

[Effect of diet therapy on the immunological indices in rheumatism]. / Vliianie dietoterapii na nekotorye immunologicheskie pokazateli u bol'nykh revmatizmom.

Rheumatic patients with torpid and latent course of the process were kept on a protein-rich diet (up to 140.0 g of protein). The effect of the diet on the organism was appraised by the peripheral blood lymphocytes blast-transformation reaction, as the one most comprehensively reflecting the immunological status of the individual. The patients were examined in dynamics, on admission to and at the time of discharge from the clinic. The data thus obtained suggest that the protein-rich diet tends to bring down the number of activated cells in in vitro cultures.

[Flagellar antigens of E. coli serologically interrlelated to H40, 41 and H41, 42, 43 flagellar antigens of Citrobacter. New H-antigeny E. coli i Citrobacter]. / Zhgutikovye antigeny E. coli, serologicheski vzaimosviazannye so zhgutikovymi antigenami Citrobacter H40, 41 i H41, 42, 43. Novye H-antigeny E. coli i Citrobacter.

The authors confirmed the reference of the test strains H13 (P6c) and H22 (A231a) of the international collection of E. coli to Citrobacter; their antigenic formula was established. As shown, strains P6c possessed a variety of the H-antigen which was not described in Citrobacter earlier, designated as H41a, 97. Three types of flagellar antigens characterized by the presence of an interrelationship with the partial factor H41 of the flagellar Citrobacter antigens were revealed in E. coli; the partial composition of H-antigenic components common for E. coli and Citrobacter was studied. Two of three new varieties of the E. coli H-antigen revealed was characterized by a cross correlation and a relation to the standard H19 E. coli antigen. The strain with the third variety of the H-antigen was capable of forming the H-antigenic mutants which acquired the antigenic component identical to the standard H16 E. coli antigen. E. coli strain is recommended for the replacement of the strain P6c in the International collection of E. coli.

[Influence of an anti-atherosclerotic diet containing a protein enricher on the clinico-biochemical indices of patients with ischemic heart disease]. / Vliianie protivoateroskleroticheskoi diety, soderzhashchei belkovyi obogatitel', na kliniko-biokhimicheskie pokazateli bol'nykh ishemicheskoi bolezn'iu serdtsa.

Observations covered two groups of patients with ischemic heart disease (IHD). The first, control group (50 patients) received a course of treatment with antiatherosclerotic diet, while the second (50) was kept on a curative diet that included a protein enrichment agent. It was found that the patients of the lastly named group demonstrated, along with an improved general condition and diminution of basic clinical manifestation of IHD, a more noticeable fall of all the lipid fractions and also a more distinct and significant reduction of an elevated permeability of the capillaries to protein. The results obtained justify recommending inclusion of the protein enrichment agent in the diet of patients with IHD, to increase the biological value of the ration and the effect of the ongoing dietotherapy.