Effect of 1,2-dimethylhydrazine on the level of specific binding and ligand affinity to the estradiol receptor in the cytosol of uterine tissue in CBA mice

1,2-dimethylhydrazine (DMH) inducing uterine sarcomas in CBA mice was studied for its prolonged effect on the level of specific binding and affinity to the estradiol receptors in cytosol fraction of CBA mice uterine tissue. It is shown that the dissociation constant 3H-estradiol-17 beta with a receptor protein in the cytosol of uterine tissue of DMH treated mice was slightly higher than in control mice. The theoretical number of the ligand binding sites with receptor protein and the level of free binding sites of estrogen receptors were higher in DMH-treated animals than in control mice during the whole period of observation.     

Modifying effect of ascorbic acid and sodium ascorbate on uterine carcomogenesis induced by 1,2-dimethylhydrazine in CBA mice

Administration of ascorbic acid (0.3% in drinking water) inhibited the promoting effect of estradiol dipropionate on the 1,2-dimethylhydrazine-induced uterine sarcomogenesis in CBA mice. However administration of sodium ascorbate intensified the promoting effect of estradiol on the uterine sarcomogenesis, as evidenced by the shortening of the periods of tumour incidence.     

Testosterone stimulation of the growth of a human osteogenic sarcoma strain transplanted into athymic rats

Intraperitoneal testosterone administration stimulated the growth of subcutaneously transplanted cell line of human osteogenic sarcoma in nude rats but did not provoke tumour metastasizing to other organs and tissues. The specific connection of androgens with receptor proteins in the cytosol fraction was not found in the studied osteogenic sarcomas, whereas cytoplasmic estrogen receptors were revealed in all tumours. It is supposed that the mechanism of the stimulating effect of androgens on the tumour growth is mediated through other biologic systems being not related to androgen receptors.     

Interaction of the ligand molecules with the membrane receptors of tumor cells

The mechanism of the ligand molecule interaction with cell membrane receptors is considered. The equation is obtained which describes dynamics of change in the number of ligand-receptor complexes on membranes with their constant internalization. It is shown that the in vivo internalization leads to saturation of the cell surface with the ligand-receptor complexes, the ligand concentrations being less than Kd. Theoretical conclusions are compared with the experimental data.     

Different populations of inositol 1,4,5-trisphosphate receptors expressed in the bovine adrenal cortex

The inositol 1,4,5-trisphosphate (InsP3) receptor forms a tetrameric channel responsible for the release of Ca2+ from intracellular stores. In the present study we showed that the experimental approach used to separate bound and free ligands may discriminate between two populations of InsP3 binding sites in bovine adrenal cortex microsomes. A large population of low affinity sites and a small population of high affinity sites were detected with centrifugation and filtration approaches, respectively. Both populations were found in the supernatant and the cytoskeleton fractions of Triton X-100 solubilized microsomes. After treatment of microsomes with thimerosal, an alkylating reagent known to increase InsP3 receptor affinity, the filtration and the centrifugation approaches yielded identical results. With selective anti-InsP3 receptor antibodies, we showed that types 1, 2 and 3 InsP3 receptors are present in intact microsomes and in the cytoskeleton fraction. Binding studies on immunoprecipitated receptors revealed that anti-type 1 antibody recognizes a large population of low affinity sites whereas anti-type 2 antibody recognizes a small population of high affinity sites. Our results indicate that the three types of InsP3 receptors are expressed at different levels in the bovine adrenal cortex. The presence of different types of InsP3 receptors with different ligand binding affinities and their association with the cytoskeleton offer a convenient way for the cell to simultaneously regulate its intracellular Ca2+ concentration and reorganize the spatial distribution of its Ca2+ stores.     

Receptors for calcitonin gene-related peptide,adrenomedullin, and amylin: the contributions of novel receptor-activity-modifying proteins

The discovery of receptor-activity-modifying proteins (RAMP) revealed a new principle for the function of G protein-coupled receptors. The initially orphan calcitonin receptor-like receptor (CRLR) was identified as a CGRP receptor when coexpressed with RAMP1. The same receptor is specific for adrenomedullin (ADM) in the presence of RAMP2. Calcitonin receptors (CTR) with 60% homology to the CRLR predominantly recognize calcitonin in the absence of RAMP. An amylin/CGRP receptor was recognized when a calcitonin receptor (CTR) was coexpressed with RAMP1. In the presence of RAMP3, the CTR only interacts with amylin. Noncovalent association of the RAMP with the CRLR or the CTR reveals heterodimeric RAMP/receptor complexes at the cell surface. Thus, two Class II G protein-coupled receptors, the CRLR and CTR, associate with three RAMP to form high affinity receptors for CGRP, ADM, or amylin. Here, the molecular composition and the functional properties of these receptors is reviewed.     

Effect of tilorone on the immunological indices of guinea pigs with synestrol-induced glandular hyperplasia of the endometrium

The immune system state was studied before and after administration of tilorone (an immunologic adjuvant) to guinea pigs with synestrol-induced glandular hyperplasia of endometrium. The total amount of T- and B-lymphocytes. T-lymphocytes with receptors to the Fc-fragment of IgM and IgG, the content of immune complexes were determined. Immune and nonimmune adherence of neutrophils was investigated as well. It was established that the total amount of T-lymphocytes decreased and the quantity of T-lymphocytes and immune complexes increased with the development of glandular hyperplasia of the endometrium. The tilorone administration normalized the structure of endometrium and T-lymphocyte immune controlling system.     

Steroid hormone receptors in malignant mammary gland tumors in dogs

The content of estrogen (ER) and progesteron receptors (PR) were studied as related to histological type, the degree of malignancy and growth rate of spontaneous canine mammary carcinomas. No correlation was found between the ER and PR amount, histological type and degree of malignancy. Inverse correlation was detected between ER and PR and the growth rate. These results correspond to those obtained for human mammary tumours. Therefore canine mammary carcinomas can be considered as an adequate model for experimental therapy of this type of tumours.     

Synthesis and Biophysical Study of Disassembling Nanohybrid Bioconjugates with a Cubic Octasilsesquioxane Core

Polyhedral oligosilsesquioxanes (POSS) have recently attracted attention as scaffolds for the synthesis of multivalent bioconjugates. The synthesis of glycosyl‐octasilsesquioxanes (glyco‐POSS) using a copper(I)‐catalyzed azide‐alkyne 1,3‐dipolar cycloaddition approach is reported. The problems associated with the use of bases or aqueous media in their preparation are investigated and a comprehensive study of the multivalent interaction between the mannosyl‐octasilsesquioxanes and a model lectin, concanavalin A (Con A), using an array of complementary biophysical techniques is presented. The possibility to modulate the half‐life of POSS conjugates in aqueous solution and the low toxicity of their constituent monomeric organosilanes offers an advantage over other scaffolds in vivo, preventing bioaccumulation and saturation of complementary receptors (lectins). Despite the hydrolysis in water, the octamannosyl‐POSS studied shows a 50‐fold higher binding affinity to Con A than methyl α‐D ‐mannopyranoside. These experiments suggest that the novel glyco‐POSS are attractive compounds for in vivo applications that require multivalent display of glycans.     

Proliferative activity of the uterine epithelium and mesenchymal elements in CBA-strain mice administered 1,2-dimethylhydrazine and estradiol dipropionate

Difference have been demonstrated in proliferative responses of epithelial and mesenchymal cells in the uterus of CBA mice under administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) and estradiol dipropionate (EP) separately and in combination (DMH+EP). The proliferative pool (Pc) of uterine glands epithelium increases under the effect of EP and decreases under the effect of both DMH and DMH+EP. The proliferative pool of mesenchymal cells increases under the effect of DMH, EP, and DMH+EP 5 to 10 weeks after the beginning of their administration, then it decreases. But percentage of DNA synthesizing cells in the regions of hyperplasia and the tumour formation enhances significantly by the 15th to 20th weeks after the beginning of DMH+EP administration.     

Changes in the epidermal growth factor receptors in the liver cells of rats in N-nitrosodiethylamine-induced hepatic carcinogenesis

A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed.     

Electrochromism of interpolyelectrolyte poly(pyridinium) – Poly(styrene sulfonate) complexes

This paper represents a synthesis method of both soluble and insoluble interpolyelectrolyte complexes due to interaction of poly(4,4-(1,4-phenylene)bis(2,6-diphenylpyridinium) triflate) (PV) and sodium polystyrene sulfonate (PSS). Systematic evaluation of electrochromic properties of the both type complexes is given compared to the pristine electrochromic PV. The complexes composition and properties were studied as a function of polyanion and polycation concentrations and their ratios. It was demonstrated that non-stoichiometric insoluble complexes PV/PSS with an excess of PSS are formed in the initial mutual solvent DMF/H₂O 5/1. Films prepared from that mixtures exhibit slower response times and deteriorated electrochromic stability. Non-stoichiometric interpolymer complexes PV/PSS with an excess of PV remain soluble in the initial solvent. Corresponding films have a superior electrochromic contrast than films obtained from the solution of pristine PV under identical conditions. Thus, optimum mixture ratios were found to obtain soluble interpolymer complexes with the advanced properties that may open up new possibilities for making novel electrochromic devices.     

Role of protein receptors of Vitamin A in the mechanism of antitumor action of retinoids

Data on protein receptors of vitamin A participating in retinoid metabolism, storage, transport and action are presented. Information about cytosolic protein receptors of vitamin A exerting hormone-like action on the cell proliferation and differentiation is considered in detail. Data concerning the presence of protein receptors in normal and tumour tissues, correlation between protein receptors and biological retinoid effect are analyzed. A hypothetic model of the binding protein mode of action in target cells related to the action model of steroid hormones is described. The authors' own data on action of vitamin A and steroid hormones on the level of estrogen and progesterone receptors in the rate of mammary cancer are reviewed.     

Steroid hormone receptors and cellular proliferative activity following the short-term use of tamoxifen and chlorotrianisene in breast cancer

The content of estrogen receptors (ER), progesterone receptors (PR), the proliferative pool level in the tumour tissue were investigated in 6 patients with the disseminated breast tumour before and after 9-day treatment with tamoxifen and chlorotrianisene for intensification of the effect of cytostatic preparations. A significant increase of the DNA synthesis intensity and proliferative pool value is observed in ER+ tumours of 2 patients. An increase of the PR level in tumour biopsies was registered in 2 patients. A decrease of the ER+ level was detected in ER+ tumours in all three patients.     

Immunoregulatory lymphocytes and circulating immune complexes in gastric cancer

The characteristics of T-lymphocyte common population and their subpopulations, the level of circulating immune complexes and A, M, G immunoglobulins and the interaction between these items were studied in 75 patients with gastric cancer of clinical stages II-IV. The number of T mu-lymphocytes in patients with gastric cancer increased, that of T gamma-lowered. Correlation disturbances between these cells were observed. The level of circulating immune complexes and IgG increased. The disbalance as to immunoregulatory lymphocytes and its progress were followed by an increase in the content of circulating immune complexes.     

子宫颈神经内分泌小细胞癌胎盘转移的电镜观察

目的：观察子宫颈神经内分泌小细胞癌合并妊娠的胎盘超微结构.方法：利用透射电镜观察一例子宫颈神经内分泌小细胞癌合并妊娠的癌组织及胎盘超微结构.结果：在胎盘的合体滋养层内及绒毛间质均可见到癌细胞,有些癌细胞的胞质尚可见电子致密的神经内分泌颗粒.结论：电镜检查有助于证实宫颈神经内分泌小细胞癌的胎盘转移.     

The Fabrication of a Photoresponsive Molecularly Imprinted Polymer for the Photoregulated Uptake and Release of Caffeine

A photoresponsive molecularly imprinted polymer (MIP) material is successfully fabricated from an azobenzene‐based functional monomer, 4‐[(4‐methacryloyloxy)phenylazo]benzoic acid (MPABA), using caffeine as a molecular template. The trans–cis photoisomerization properties of MPABA are retained after incorporation into the rigid 3D crosslinked polymer matrix. Substrate affinity of the MIP receptor sites is photoswitchable. This can be attributed to the photoisomerization of azobenzene chromophores within the MIP receptors, resulting in the alteration of their geometry and the spatial arrangement of their binding functionalities. The favorable binding constant of the MIP receptors for caffeine is 5.48 × 10⁴ M ^–1 in dimethylsulfoxide. The density of the caffeine‐specific receptor sites in the MIP material is 0.95 μmol (g MIP)^–1. Upon irradiation at 365 nm, 58.3 % of receptor‐bound caffeine is released from the MIP material. Subsequent irradiation at 440 nm causes 96.4 % of the released caffeine to be rebound by the MIP material. This near‐quantitative uptake of the released caffeine is evidence of the reversibility of the receptor‐site configuration and substrate affinity during the photoswitching of the azobenzene chromophores. Although the photoregulated substrate release and uptake processes are generally repeatable, a gradual reduction in the extent of substrate release and rebinding is observed. This may be caused by the slow deformation of MIP receptors during the course of repetitive photoswitching. The results of this work demonstrate the potential of stimuli‐responsive MIP materials as smart chemicals and as drug‐delivery systems.     

Photosensitive properties of metal-containing polydisalicylidene azomethines

Photosensitive properties of new metal-containing polydisalicylidene azomethines were studied. It was shown that polymer properties are controlled by the nature of the metal atom (its electron affinity energy A _a and ionic radius r _i ) included in “nonclassical” polyconjugation. The photosensitivity S _0.1 of studied polymers is ～10⁵cm²/J, and the quantum yield of free-carrier photogeneration is η ≈ 0.10–0.15, which corresponds to the level of organometallic complexes that have found application in optoelectronics.     

钌络合物的非线性光学性质和与DNA结合的光谱研究

报导对一组[Ru(bpy)2L]2+络合物的光谱特性和非线性光学性质的研究。其中bpy=2,2-bipirdine,l=imidazo[f]1.10-phenanthroline(IP),or2-pheny-limidazo[f]1,10-phenanthline (PIP)or PIP的衍生物。采用时间分辨的ns激光对这组Ru络合物在含水溶液中和与DNA结合的发光特性进行研究。实验结果表明,当在L上结合不同电子施主或受主基时,对[Ru(bpy)2L]2+的MLCT的发光强度和寿命都有很大的影响,同样DNA的插入也对此有影响。采用四波混频方法对其非线性光学特性进行了测量,由此推算出三阶极化系数和分子的三阶超极化系数。并讨论了不同配体对三阶非线性光学系数的影响。