Reversibility of structural changes in chromatin of interphase nuclei of peripheral blood lymphocytes of patients with Down's syndrome under the influence of healthy human serum

A luminescence-microscopic investigation of short-term human cell cultures stained with Acridine Orange showed that the melting curve of the cell chromatin DNA in the region from 78 to 85°C depends on changing external environmental conditions, i.e., on the composition of the blood serum.Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 878–879, July, 1976.     

Lymphocyte interphase chromatin in healthy subjects, patients with Down''s syndrome, and their parents and sibs.

A study of the interphase chromatin structure of lymphocytes in healthy subjects, patients with Down's syndrome, and their parents and sibs was carried out by AO labelled fluorometry using our modification of DNP cell thermal denaturation. Analysis by the Sperry Univac 90/30-B computer showed that in 40% of healthy subjects the lymphocyte chromatin melting profiles had a regularly repeated curve with six (seven) maxima at definite temperatures. In the remaining 60% some regularly repeated deviations were present and were correlated with the sex of the subject examined. There were five subgroups in the female group and seven subgroups in the male group. In 97% of patients with Down's syndrome the lymphocyte chromatin melting profiles gave curves with three maxima at temperatures of 65, 85, and 92 degrees C (+/- 2 degrees). Maxima at 78 and 45 degrees C were absent. In 80% of the mothers of probands with Down's syndrome and in 30% of female sibships, lymphocyte melting profiles also produced curves with three maxima: 65, 85, and 92 degrees C (+/- 2 degrees). In view of the fact that similar changes were observed in mothers and female sibs only, we propose that some women may have genotypical peculiarities which may possibly contribute to the origin of this chromosome pathology.     

Analysis of the modified structural state of the chromatin in Down's syndrome

The relationship between optical density (=260 nm) of the nuclear chromatin of normal human lymphocytes and lymphocytes from patients with Down's syndrome and temperature was studied. Lymphocyte nuclei from healthy donors were characterized by the presence of a low-temperature (about 70°C) absorption maximum which was absent in nuclei of lymphocytes from patients with Down's syndrome. Analysis of this relationship for particular regions of the nucleus showed the existence of at least two types of regions—those with a low-temperature absorption maximum and those without. For Down's syndrome, the content of regions of the latter type in the lymphocyte nuclei was found to be greater than normal.Laboratory of Molecular Biology, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR S. S. Debov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 471–473, April, 1978.     

Effect of levamisole on the cytotoxic activity of normal lymphocytes in tissue culture

Preliminary incubation of normal nonimmune splenic lymphocytes from C57BL/6j and BALB/c mice for 45 min at 37°C with levamisole (1·10^–4 to 1·10^–5 M) followed by washing potentiated the cytotoxic effect against allogeneic target cells (L cells). When lymphocytes and levamisole were added to the culture of target cells simultaneously no cytotoxic effec occurred.Laboratory of Clinical Immunology, Oncologic Scientific Center, Academy of Medical Sciences of the USSR. All-Union Center for the Study of Antirheumatic Agents, Institute of Rheumatism, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Trapeznikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol 88, No. 11, pp. 581–582, November, 1979.     

Effect of cultivation temperature on blast transformation of lymphocytes from people of different ages

The effect of the cultivation temperature on blast transformation of lymphocytes from persons aged 20–35 and 90–102 years induced by phytohemagglutinin was studied. Cultivation at 39°C was found to increase, but at 41°C to reduce sharply the index of blast transformation compared with the control (37°C). The effect of cultivation temperature on the blast-transformation process has certain features which depend on the donors' age.Institute of Gerontology, Academy of Medical Sciences of the USSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR D. F. Chebotarev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 470–472, April, 1977.     

Effect of autologous serum on the state of the interphase chromatin of the lymphocytes in Down's syndrome

A luminescence microscopic study of a short-term culture of human lymphocytes with the aid of acridine orange showed that the modified state of the interphase chromatin in patients with Down's syndrome can be partly restored to normal by incubating the patient's lymphocytes with healthy human serum. These results suggest that the component inhibiting chromatin activation is absent or qualitatively changed in the serum of patients with Down's syndrome. The incomplete restoration of the ability of the chromatin to fix the dye points to irreversible changes in the structure of the chromatin itself, in the direction of condensation.Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR S. S. Debov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 10, pp. 97–99, October, 1974.     

Polymorphism of C-heterochromatin regions in chromosomes of different lines of mice

The C-heterochromatin regions were studied in the chromosomes of mice of lines C3HA and CBA and of mice homozygous for chromosomal translocations T6T6 and T1IEM. Preparations of metaphase chromosomes were obtained from bone marrow cells by Ford's method. The pericentromeric heterochromatin was revealed by the method of Arrighi and Hsu. Different chromosomes in the karyotypes of mice of different lines were found to contain different quantities of pericentromeric heterochromatin. Polymorphism of the C-heterochromatin regions is observed not only in mice of different lines, but also in different individuals belonging to the same line.Department of Embryology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 8, pp. 106–108, August, 1974.     

Thermosensitivity of specific transplantation antigens of the tumor cell membrane

A study of tumor specific transplantation antigen (TSTA) on the cell membrane of SV40-induced tumors and spontaneous hepatomas of inbred Syrian hamsters and also of monkey cells infected in vitro with tsA-mutants of SV40 virus demonstrated its high temperature sensitivity. Heating the cells to 56°C for 30–60 min led to the total loss of their immunogenic activity. Moreover, in animals immunized by tumor cells heated to 56°C, stimulation of growth of the test tumor cells was regularly observed.Laboratory of Immunology of Tumors, Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 351–353, March, 1978.     

Structure of interphase chromatin in patients with Down's syndrome and their mothers

Features of an altered structure of the interphase chromatin characteristic of their affected children were found in mothers of children with Down's syndrome by luminescence microscopy of short-term cultures of lymphocytes stained with acridine orange. Abnormalities similar to the changes found in their mothers also were found in girl sibs. The results suggest that there is a certain population of women whose genotype is such that it favors the appearance of this type of chromosome pathology. Since the altered structural organization of the chromatin was found only in the mothers and girl sibs, it seems likely that these features of the genotype are inheritable and are linked with genes (or particular regions of chromatin) limited by sex.Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 353–355, March, 1977.     

Effect of hyperthermia on spermatogenesis in mice and the role of heat training in adaptation of the sex cells to high temperatures

Keeping sexually mature albino mice in a hot and humid chamber at a temperature of 43°C and a relative humidity of 65% for a single exposure causes destruction of the spermatogenic epithelium, as reflected in degeneration and desquamation of the sex cells in 55% of the seminiferous tubules. Preliminary heat training for 10 days increased the physiological degeneration of the spermatogenic cells in only 16% of seminiferous tubules. This could be evidence of adaptation of the sex cells to the action of high temperatures.Department of Histology and Embryology, Smolensk Medical Institute. Laboratory of Growth and Development, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1489–1491, December, 1976.     

Relationship between frequency and amplitude of myocardial contractions in rats adapted to heat

After preliminary adaptation of rats to heat (for 3 h daily at 35°C for 1 month) the amplitude of contractions of the isolated papillary muscles from the left ventricle at 28°C at high frequency was higher than in control animals. This difference persisted at 36°C and disappeared at 25°C. It is postulated that adaptation to heat leaves a definite structural imprint in heart muscle cells.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Institute of Physiology and Experimental Pathology of the Arid Zone, Academy of Sciences of the Turkmenian USSR, Ashkhabad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1168–1170, October, 1976.     

Role of the adhesive lymphocyte population in areactivity to hepatoma 22a

The role of the adhesive fraction of T lymphocytes in areactivity of mice to hepatoma 22a was studied. Experiments showed that removal of the adhesive fraction from a suspension of spleen cells enriched with T lymphocytes potentiates cellular immunity in mice tolerant to hepatoma.Research Laboratory of Experimental Immunobiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 336–338, September, 1979.     

Mechanisms of reversibility of the stathmokinetic reaction induced by suboptimal temperatures

Autoradiographic studies using [³H]leucine showed that the reversibility of the stathmokinetic reaction induced by a suboptimal temperature (21°C) does not require additional protein synthesis and, consequently, is not connected with the formation of new microtubules. Normalization of the mitotic regime was delayed in the presence of copper ions, which prevent polymerization of the microtubules. These data suggested that repolymerization of subunits of microtubules is the principal method of restoring mitosis after exposure to a suboptimal temperature.Laboratory of Cytology, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Transiated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 205–207, February, 1978.     

Effect of folic acid and methotrexate on reproduction of Rauscher leukemia virus

Folic acid was found to stimulate and its structural analog methotrexate was found to inhibit the reproduction of an oncogenic RNA-containing virus in tissue culture.D. I. Ivanovskii Institute of Virology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. M. Zhdanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 7, pp. 85–86, July, 1974.     

Dimethylaminochalcone,an indicator of structural changes in theE. coli cell membrane produced by Ca++ cations and tris buffer

An attempt was made to find hypothetical structural changes in the cell membrane ofEscherichia coli under the influence of Ca⁺⁺ cations with the aid of the uncharged fluorescent proble 4-dimethylaminochalcone (DMC). Effects of Tris buffer (0.01 M) at 0°C and of other agents, namely Mg⁺⁺ cations and EDTA, also were tested for comparison. Treatment of theE. coli cells with Ca⁺⁺ cations was shown to cause structural changes in the surface of the cell membrane which differed from the changes produced by treatment with Tris buffer at 0°C, Mg⁺⁺ cations, and EDTA. DMC can be used with success as an indicator of structural changes in biomembranes.Laboratory of Molecular Microbiology, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. M. Zhdanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp 65–68, July, 1979.     

Lymphocyte response in the early period after heart transplantation

The quantitative and qualitative composition of the leukocytes and dehydrogenase activity of the lymphocytes were determined in blood entering and leaving the transplanted heart at different times after grafting in dogs. A decrease in the lymphocyte count in blood flowing from the grafted heart was found, on account of retention of the lymphocytes in the graft; the activities of the mitochondrial dehydrogenases also were reversed as the result of contact of the lymphocytes with the foreign antigens of the transplanted heart. It is suggested that the mechanism of reversal is connected with the functions of the lymphocytes as immunocompetent cells.A. N. Bakulev Institute of Cardiovascular Surgery, Academy of Medical Sciences of the USSR, Moscow. Institute of Experimental Surgery, Slovak Academy of Sciences, Bratislava, Czechoslovakia. (Presented by Academician of the Academy of Medical Sciences of the USSR, P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 704–708, June, 1978.     

Antibody-stimulating factor secreted by spleen cells in vitro

The intensity of antibody formation in irradiated syngeneic recipients was studied in relation to its restoration by various cell suspensions. A lymphocyte suspension free of macrophages restored the ability of the irradiated recipients to respond to sheep's red blood cells only weakly. Addition of peritoneal or splenic macrophages to the lymphocytes led to a sharp increase in plaque formation. The same response was produced by injecting a suspension of spleen cells incubated beforehand in vitro for 3 h at 37°C into the recipients. After incubation of the spleen cell suspension in this way in the absence of antigen, a factor capable of sharply increasing antibody formation in irradiated recipients on restoration of their immune response by injection of donors' lymphocytes was secreted into the medium. The antibody-stimulating factor was not produced after incubation of lymphocytes for the same times. It is suggested that the antibody-stimulating factor appearing in the medium during culture of spleen cells in vitro in the absence of antigen is formed by cells of the mononuclear phagocytic system.Laboratory of Physiology and Regulation of Immunity, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 183–186, August, 1979.     

Metabolic changes in the lymphocytes of newborn rats in asphyxia

Hydrocortisone and cocarboxylase injected into newborn rats increased their chances of survival after asphyxia. Asphyxia was accompanied by increased succinate and dihydroorotate dehydrogenase activity in the lymphocytes, by lymphocytosis, and by an increase in the number of monocytes with hyperbasophilia of their cytoplasm in the blood and tissues. Hydrocortisone and cocarboxylase had a normalizing effect on these changes.Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 12, pp. 21–23, December, 1974.     

Transplacental carcinogenic action of p-hydroxyphenyllactic acid

Through the transplacental action of the tyrosine metabolite p-hydroxyphenyllactic acid, which has carcinogenic activity, on progeny of CC57BR and C57BL mice, malignant and benign neoplasms (leukemias, lymphosarcomas, adenomas and carcinomas of the lung, hepatomas, papillomas, carcinomas of the bladder, and other tumors) developed in 88 and 78% of cases respectively. The number of these neoplasms was significantly higher than in the control, they appeared sooner, and they were more malignant in character.Laboratory of Systemic Blood Diseases, Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 39–41, January, 1979.     

Adhesion of hematopoietic cells and lymphocytes to stromal mechanocytes in vitro

Adhesion of guinea pig bone marrow and spleen cells to stromal mechanocytes of medullary, splenic, and thymic origin, to peritoneal exudate fibroblasts, and also to macrophages was studied in monolayer cultures. Primary cultures and subcultures of fibroblasts were able to bind hematopoietic cells and lymphocytes, and this property was independent of the origin of the mechanocytes. Hematopoietic cells were much less adherent to macrophages. Adhesion of cells to mechanocytes is determined by the number of adhesion sites present on the surface of the fibroblasts. There are significantly more of these sites for adhesion of myeloid cells on the surface of stromal mechanocytes than for adhesion of lymphocytes.Laboratory of Immunomorphology, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. Department of Medical Biophysics, Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Vershilov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 703–704, December, 1979.