Rapid change in the dynamics of antibody-forming cells under the influence of a single injection of various anthracyclines

The dynamics of the titers and number of the antibody forming cells was studied within 26 hours after a single injection of anthracycline to immunized animals at various phases of the immune response. The specificity of the "rapid" effect of anthracyclines suggests that the low differentiated precursors of the antibody forming cells are the main target for the rubomycin effect and the immune competent cells in the state of multiplication and differentiation under the effect of the antigen are the main target for the carminomycin effect. The study was performed with noninbred mice immunized with sheep red cells.     

Instrumental behavior in the activation or blockade of the neostriatum muscarinic receptors

In four dogs, microinjections of carbacholine enhanced the tonic component and inhibited the physical component of the instrumental defence reflex, put in order the posture, and increased its components' amplitude. Microinjections of raclopride yielded a similar though a less obvious result. Differentiation stimuli provided the greatest effect of both substances. A sharp improvement occurred in differentiation of sound signals. Microinjections of pyrenzepine yielded an opposite result. The data obtained are explained proceeding from the idea of a presence of the neostriatum's two efferent outputs exerting opposite effects on their targets, and the role of muscarine and dopamine receptors in their triggering and blockade.     

Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.     

Search for osteoarthritis genetic markers in women with undifferentiated connective tissue dysplasia

We conducted an association study of ten polymorphisms in six candidate genes of OA (rs1799750 (MMP1), rs35068180 (MMP3), rs2252070 (MMP13), rs63118460 and rs2276455 (COL2A1), rs143383 (GDF5), rs1544410, rs7975232, rs731236, and rs2228570 (VDR)) with the development of osteoarthritis (OA) in 333 women taking into account the localization of the pathological process, the age of disease manifestation, and ethnicity and investigated the presence of signs of undifferentiated connective tissue dysplasia (UCTD). On the basis of clinical and genetic data, we revealed statistically significant models to predict the development of osteoarthritis of various localizations (knee, hip, and generalized forms).     

Radiosensitivity of pluripotent stem cells detectable by cloning in the spleen of irradiated mice

It was shown that the dose--effect curves describing the radiosensitivity of CFUc of the bone marrow irradiated in vitro (0.04-3.7 Gy) and treated with normal rabbit serum (NRS) and anti-mouse-brain serum (AMBS) has two differently sloping portions indicating that two CFUc populations differing in radiosensitivity are present in the bone marrow. D0 was 0.93 Gy after irradiation with doses of 0.04-0.75 Gy and treatment with NRS, and 0.33 Gy after incubation of the bone marrow with AMBS. The addition of thymus cells "straightened" the dose--effect curve for the bone marrow treated with AMBS: in this case D0 was 1.81 Gy exceeding considerably the values of D0 for intact bone marrow. The CFUc population is suggested to be heterogeneous in radiosensitivity.     

Morphological criteria of early embryonal histogenesis exemplified by the development of the auxiliary ocular apparatus in humans]

In 50 human embryos at the age of 21 days--12 weeks of development, including the stages X-XXIII and beginning of the fetal period according to Carnegie's classification, spatial-temporal regularities on rearrangement of cellular material in the mesenchymal derivatives of the ocular auxiliary apparatus have been investigated. The main attention has been paid to ascertain the moments, when the first signs of differences appear in the previously homogenous cellular material of the differentiating mesenchyme around the ocular cup and in the eyelids, taking into account appearance of derivates in the ocular auxiliary apparatus: sclera, oculomotor muscles, stroma of the lacrimal gland, cartilagenous laminae in the eyelids and in the orbicular muscle. Regularities of cytochemical differentiation of the mesenchyme and its derivatives have been studied, taking into account the organ's changing topography. Morphometrical investigations of cells in the anlages mentioned are expanded and correlated with the time of their cytochemical differentiation. Correlation of the morphometrical and cytochemical data with the histological investigations has been performed.     

Comparative study of the antibacterial activity of aminoglycoside antibiotics and their combinations with carbenicillin against Pseudomonas aeruginosa

Antibacterial activity of 7 aminoglycoside antibiotics and combinations of tobramycin or gentamicin with carbenicillin was studied with respect to 33 clinical strains of Ps. aeruginosa. Tobramycin, sisomicin, gentamicin and amicacin showed high levels of antibacterial activity. Tobramycin and sisomicin were 3-4 and 2 times more effective than gentamicin. 100 per cent of the Ps. aeruginosa isolates was sensitive to tobramycin and amicacin. The number of the isolates sensitive to sisomicin and gentamicin amounted to 97 and 94 per cent respectively. The respective numbers for streptomycin and kanamycin were 32 and 11 per cent. No monomycin sensitive isolates were detected. Combination of tobramycin or gentamicin with carbenicillin increased the antibacterial activity of the aminoglycoside antibiotics by 2-16 times and that of carbenicillin by 2-32 times. The synergistic effect of gentamicin or tobramycin with carbenicilin was observed with respect to 50 and 58 per cent of the isolates respectively. No antagonistic effect was detected on the combined use of the antibiotics. The majority of the isolates (96 per cent) were sensitive to combinations of carbenicillin in a concentration of 50 micrograms/ml with tobramycin or gentamicin in concentrations of 0.15 or 0.3 micrograms/ml respectively.     

Role of intralaminar thalamic nuclei in strengthening inhibition induced by stimulation of the caudate nucleus

The influence of preliminary subthreshold activation of thalamic intralaminary nuclei on achievement of instrumental reflex and on inhibitory effects, caused by stimulation of the caudate nucleus head, were studied in chronic experiments on 5 dogs with a model of instrumental defensive conditioned reflexes, providing for maintainance of a given posture. It was shown that the preceding high-frequency electrostimulation of intralaminary nuclei activates motor components of the instrumental response (shortened latency, EMG and mechanogram of the response, increased amplitude of instrumental response) and significantly lowers threshold strength of the current, necessary for obtaining "caudate pause". The greatest increase in inhibitory influences, caused by stimulation of the caudate nucleus head, was observed when thalamic stimulation preceded stimulations, localized in the dorsolateral segment of the caudate nucleus head. The obtained data are discussed in aspect of Buchwald et al. hypothesis on the existence of "caudate loop".     

The effect of electrostimulation of the caudate nucleus and somatosensory cortex on defensive instrumental reactions in dogs]

It has been shown that the effect of stimulation of the caudate nucleus head in the contralateral hemisphere differs at different stages of achievement of a defensive instrumental habit in dogs. Stimulation preceding the action of the conditioned signal or delivered simultaneously with the beginning of the latter did not change the criteria for the achievement of successive programs of the instrumental defensive reaction. Stimulation of the same areas in the last phase of the instrumental response, as a rule, lead to the cessation of instrumental movement. A conclusion has been drawn that in a defensive situation the inhibitory influence of the caudate nucleus on instrumental behaviour of intact dogs is not so sharply expressed as in experiments with alimentary reinforcement. In dogs with a preliminary ablation of the CI and CII cortical zones of the contralateral hemisphere, stimulation of the caudate nucleus head was attended with a sharp drop in every criterion of the instrumental defensive reactions.     

Antiviral action of carminomycin and some of its derivatives]

Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use.