[Chemotactic function of skin fibroblasts in patients with amyloidosis]. / Khemotaksicheskaia funktsiia fibroblastov kozhi u bol'nykh amiloidozom.

Chemotaxis of cultivated fibroblasts, obtained from patients with amyloidosis, chronic glomerulonephritis and healthy volunteers, was investigated. Fibroblast migration toward donor serum and serum from patients with amyloidosis was measured using Boyden chamber's technique. As "zero" chemoattractant Hank's solution was used. It was shown, that chemotactic index (CI) was independent from cell density. Significant CI depression of fibroblasts from patients with amyloidosis toward donor serum in contrast to fibroblasts from patients with chronic glomerulonephritis and healthy volunteers was shown. The depression of chemotactic function was the same with fibroblasts from patients with different variants of amyloidosis and different stages of amyloid nephropathy and was stable in several cell generations. The results obtained suggest the existence of primary hereditary variant (variants) of chemotactic function, which may lead to the development of amyloidosis in certain conditions.

[The chemotactic characteristics of the leukocytes and fibroblasts in amyloidosis]. / Osobennosti khemotaksisa leikotsitov i fibroblastov pri amiloidoze.

Altogether 44 patients with amyloidosis (7 with primary, 24 with secondary and 13 with hereditary associated with periodic disease) and different stages of renal impairment and 32 patients with chronic glomerulonephritis (CGN) (14 with the latent and 18 with the nephrotic form) were examined for chemotactic properties of peripheral blood leukocytes and skin fibroblasts in Boyden's chambers. Chemotaxis of leukocytes from patients with different clinical forms of amyloidosis was found to be decreased. That decrease manifested itself even at the proteinuric stage of renal impairment. Addition of autologous serum brought about another decrease of the chemotactic response of leukocytes. There was a lowering of chemotaxis of cultivated skin fibroblasts from amyloidosis patients, which remained unchanged on repeated cell passages. Chemotactic activity of cultivated fibroblasts from CGN patients did not differ from that of healthy persons' fibroblasts and embryonal fibroblast strain. Possible causes of the alterations revealed are discussed.

[Sensitivity of human lymphocytes to antiproliferative effects of glucocorticoids and effectiveness of reception]. / Chuvstvitel'nost' limfotsitov cheloveka k antiproliferativnomu deistviiu gliukokortikoidov i éffektivnost' retseptsii.

The relation between the type of lymphocyte dexamethasone sensitivity in vitro of 9 healthy donors and their corticosteroid receptor characteristics was tested. It was found that in the high sensitivity group the effectiveness of corticosteroid reception (ratio of quantity of glucocorticoid receptors and constant of dissociation (Bm/Kd) was significantly higher than in the group of low sensitivity. Thus, genetically related parameters of binding of glucocorticoid hormones to its receptors play a great role in lymphocyte glucocorticoid sensitivity of inhibition of mitogen stimulation.

[Cellular glucocorticoid reception in man and differences in type of reaction to stress]. / Kletochnaia retseptsiia gliukokortikoidov u cheloveka i razlichiia v tipe reagirovaniia na stress.

Three groups of individuals were investigated, which differed in constitution and reaction to stress. Group I comprised randomly selected individuals. Groups II and III were formed of highly qualified athletes, weight lifters and marathoners who matched those from Group I. Studies of the hormonal profile revealed significant differences in the baseline cortisol levels between Groups II and III. Evaluation of parameters of glucocorticoid reception by cultured individuals' fibroblasts also showed significant differences between Groups II and III. Employment of complex quantitative characteristics of potential cell sensitivity to the effect of physiological glucocorticoid concentrations, and of the resting biological effect of this hormone, characterising the efficacy of glucocorticoid reception in postreceptor and glucocorticoid-dependent processes in somatic cells, allowed for adequate qualitative evaluation of glucocorticoid-dependent reactions to stress on the cellular level which is indicative of the stress reaction type of the organism as a whole. Thus, genetically determined variability of cellular parameters was first revealed, the parameters being directly related to the ontogenetic formation of the stress reaction type. It is biologically understandable that this variability correlates with human resistance to long-term psychosomatic stress.

[Combined effect of heat shock and glucocorticoid hormones on cultured mammalian cells]. / Kombinirovannoe deistvie teplovogo shoka i gliukokortikoidnykh gormonov na kul'tiviruemye kletki mlekopitaiushchikh.

The combined effect of heat shock and glucocorticoid hormone (dexamethasone--DM) on plasmacytoma culture cells has been investigated. Fibroblasts and splenocytes were used as control cell types. Heat shock failed to induce the main hsp68 in plasmacytoma cells, however, the rate of synthesis of a constitutive protein (c-hsp70) increased significantly. In general, plasmacytoma cells exhibit hyperthermosensitivity as compared to control. DM treatment before heat shock did not protect plasmacytoma cells against heat damage. Moreover, if DM was present in culture medium for 3 days before heat shock, the synthesis of c-hsp70 was not increased. Heat-shock treatment leads to some decrease in the number of intact glucocorticoid hormone gc-receptors and binding sites in the nucleus. However, the preserved number of intact receptors after heat shock is quite enough for the realization of all glucocorticoid hormone effects. Interestingly, DM itself inhibits the proliferation of plasmacytoma cells. Furthermore, the combined action of heat shock and DM leads to more pronounced inhibition of plasmacytoma cells, depending on the DM doze and the time of heat shock treatment. The role of increased expression of c-myc gene, characteristic for plasmacytoma cells, in all the phenomena observed is discussed.

[Interstrain differences in cellular glucocorticoid reception in mice and the degree of suppression of normal killer activity during immobilization stress]. / Mezhlineinye razlichiia v kletochnoi retseptsii gliukokortikoidov u myshei i stepen' podavleniia aktivnosti normal'nykh killerov pri immobilizatsionnom stresse.

The correlation between the level of stress-induced natural killer (NK) depression and glucocorticoid binding to specific spleen cell receptors and hormonal profile in inbred mouse strains (CBA, BALB/c, C57BL/c, A/Sn) has been investigated. Stable interstrain differences in stress-induced natural killer activity and glucocorticoid receptor binding (Bm and Kd) have been revealed. It was demonstrated that the mechanism of NK activity depression during stress consists in genetically determined potential sensitivity of lymphoid cells to physiological fluctuations of glucocorticoid levels. This made it possible to identify stress-resistant and stress-sensitive mouse strains.

[Determination of the amount of somatic cell glucocorticoid receptors as one of the prospective approaches to the individual prognosis of glucocorticosteroid therapy]. / Opredelenie kolichestva gliukokortikoidnykh retseptorov somaticheskikh kletok--odin iz perspektivnykh podkhodov k individual'nomu prognozirovaniiu gliukokortikosteroidnoi terapii.

The authors discuss the importance of the content of receptors to glucocorticosteroid hormones in somatic cells to predict the effectiveness of glucocorticosteroid therapy. Prognostically important is the detection of a relatively low amount of receptors in cells when administration of corticosteroids at high doses might be most probably ineffective. Any human somatic cells are representative (with respect to the receptor content) for other cell types therefore investigation of the number of glucocorticoid receptors in lymphocytes (the quickest result) or in skin biopsy specimens (less traumatic for a patient) seems most effective.

[Glucocorticoid receptors in normal human lymphocytes]. / Retseptory k gliukokorticoidam v normal'nykh limfotsitakh cheloveka.

Glucocorticoid (GC) receptors were studied in intact lymphocytes from 11 donors. GC binding parameters were found to be highly reproducible in repeated experiments with lymphocytes. It was shown that GC receptors in donors' lymphocytes could be distributed into two different classes similarly to the pattern seen in skin fibroblasts. Human lymphocytes are an adequate object for studying genetically determined variability of GC receptors and its clinical importance.

[Cellular DNA repair, proliferative activity and biochemical characteristics in the human premature aging syndrome (progeria)]. / Reparatsiia DNK, proliferativnaia aktivnost' i biokhimicheskie osobennosti kletok pri sindrome prezhdevremennogo stareniia (progeriia).

Fibroblasts of a patient with the Hutchinson-Gilford progeria show a decreased proliferative activity in culture and run through no more than 19 subcultivations. Progeria cells rejoin gamma-induced single strand DNA breaks to the same extent and with the same rate as do normal cells. Spontaneous and induced by X-ray chromosome aberration frequency in progeria cells does not differ from that in normal cells. The activity of DNA-polymerases alpha, beta and gamma in different way depends on culture conditions in progeria and normal cells, but no expressed deficiency of these enzymes was found in progeria cells. The activity of easy-soluble arginine-specific proteases in progeria fibroblasts is sharply decreased, and sensitivity of proteins in these cells to trypsin-catalyzed hydrolysis is significantly increased compared to that of normal cells. Defect in the turnover of intracellular proteins is considered to be a reason of a rapid accumulation of altered proteins in cycling cells and a possible reason of accelerated ageing of progeria cells in vitro.

[Microinjection of non-histone chromatin protein derived from mouse spleen into L cells]. / Mikroinbektsiia negistonovogo belka khromatina selezenki myshi v L-kletki.

Non-histone protein selectively released from mouse spleen nuclei by mild hydrolysis with micrococcal nuclease or DNase I was introduced into L cells by the microinjection method. It is shown that this protein selectively accumulates in cell nuclei. Analysis of the mitotic cells after microinjection of 125I labeled protein demonstrated its location in chromosomes of L cells.

[Use of polyethylene glycol for the microinjection of exogenous protein into cultured murine cells]. / Ispol'zovanie poliétilenglikolia dlia mikroin"ektsii ékzogennogo belka v kul'tiviruemye kletki myshi.

Polyethylene glycol was applied to microinject two exogenous proteins: bovine serum albumin and non-histone protein derived from mouse spleen chromatin, into the mouse L-cells. The effectiveness of fusion of mammal (human, in the given case) erythrocytes in which hemoglobin is substituted for the protein under study was shown to be higher than when Sendai virus was used. The microinjected proteins preserve their specificity to subcellular structures.