Absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome]

The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment.     

Radiosensitivity of chromosomes in lymphocytes from Down's syndrome patients

A study was made of the yield of chromosome aberrations in gamma-irradiated G0 peripheral blood lymphocytes from 6 patients with different forms of Down's syndrome. The doses used were from 0.25 to 3.0 Gy. Seven healthy donors of different age made the control group. There was a significant increase in the yield of chromosome exchanges in lymphocytes from all the patients as compared to control. The spontaneous level of chromosome aberrations and the frequency of radiation-induced fragments did not differ from the control values. The yield of exchanges in diploid and trisomic cells from patients with the mosaic form of Down's syndrome did not change significantly as the time of cultivation was raised. The origin of DNA repair defects leading to the increased chromosome radiosensitivity in Down's syndrome is discussed.     

Changes in lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity in the course of muscle alteration]

Changes of outflux, extractability and activity of lactate dehydrogenase (LDG) and glucose-6-phosphate dehydrogenase (G-6PhDG) of muscles under the action of heating (at 32--44 degrees for 15 min) and urea (1 M during 10 min, 30 min, 2 hr. and 9 hr.) on the skeletal muscles of R. temporaria L. were studied. Under the thermal action not accompanied by contracture and fall of the excitability (32--36 degrees), the increase of outflux of LDG out of muscles into surrounding solutions is observed. G-6-PhDG in the external medium under any heating action was not revealed. Extractibility of LDG and G-6-PhDG did not change. Under the thermal action accompanied by the fall of excitability and by the contracture, along with the prolong increase of outflux of LDG, a decrease of extractability of LDG takes place. The decrease of G-6-PhDG is set at 42 degrees. Under the alteration of muscles by urea in the period of the temporary fall of excitability and contracture (10 and 30 min) an increase of the outflux of LDG out of muscles is observed. G-6PhDG in the surrounding medium was not revealed up to 9 hr. of incubation of muscle. In the period of the recovery of the excitability and relaxation of muscles (2hr.) the outflux of LDG approaches the control level. During the temporary loss and recovery of excitability, the extractability of LDG and G-6-PhDG does not change. In the period of irreversible contracture and loss of the excitability (6--10 hr.) a sharp increase of outflux of LDG out of muscles takes place. The extractability of the examined enzymes, especially of LDG, decreases.     

Changes in lactate dehydrogenase isoenzyme patterns of human lymphocytes before and after blast formation

The lactate dehydrogenase isoenzyme pattern of human lymphocitic cells has been determined in several people before and after stimulation by mitogenic lectins at different times after the start of the culture. A very significant change take place in the LDH 5 which can reach a greater concentration towards the other isoenzymes at the 72 h from the mitogenic stimulus, even if it starts from a smaller concentration.     

Bleomycin-induced chromosomal aberrations in Down's syndrome lymphocytes

Blood samples from 4 Down's syndrome (DS) patients with a 47,XY,21 + karyotype and from 4 normal male probands were cultured for 72 h in the presence of BrdU and lymphocytes analysed at their first mitosis for chromosomal aberrations. The frequencies of spontaneous aberrations and the proportions of cells in the first or later mitoses in culture were not different between the groups. Treatment with various doses of bleomycin in vitro resulted in similar delays in cell development for both DS and normal lymphocytes and dose-dependent increases in the incidence of chromosome-type aberrations. However, the induction of both dicentric aberrations and acentric fragments was significantly enhanced in DS cells relative to cells of normal karyotype.     

Regulation of the expression of lactate dehydrogenase isozymes in human lymphocytes

Mitogen activation of human peripheral lymphocytes leads to a switch in the isozymes of LDH; resting cells contain low activities of only the B₄ and B₃A forms, whereas activated cells contain high activities of the A₄ and A₃B forms. B₄ LDH is not altered in activated cells. In this study we show that the appearance of the A subunits occurs concomitantly with a several fold increase in the steady state levels of LDH-A mRNA. Responses in LDH-A mRNA are observed within 12 hrs of activation, and are, thus, associated with the G0/G1 transition or with early G1 (Marjanovicet al. Exp. Cell Res. (1991) 193: 425–431). Maximal expression of LDH-A mRNA requires both phorbol ester and concanavalin A, implying a complex regulatory pathway involving cascade systems activated through both the antigen receptor (TR) and protein kinase C.     

Molecular hybridization of native and modified subunits of lactate dehydrogenase isoenzymes and aldolase A in rats]

Experimental conditions for the molecular hybridization in vitro between iodine and native subunits of isoenzymes 1 and 5 of lactate dehydrogenase (LDH) are described. It is also shown that the covalently fixed on the polyacrylamide beads rat J125 labelled LDH-5 and J125 labelled aldolase A, under conditions of complete dissociation of the quaternary structure of these enzymes, only one of the four subunits remain bound with the beads. Subunit of LDH-5, which is covalently bound with the polyacrylamide beads, is capable to hybridize (reassociated) with 3 native subunits. In addition, the immobilized LDH-5 subunits and aldolase A are capable to hybridize with J125 labelled subunits of these enzymes. Thus, when thyrosine, lysine and N-terminal amino acids are modified, subunits of LDH-5 and aldolase A retain their capacity to restore their quaternary structures.     

Use of differences in substrate inhibition for determination of the interrelationship between molar fractions of lactate dehydrogenase subunits]

A kinetic method of estimating the ratio of mole quota of H and M human lactate dehydrogenase (LDG) subunits is proposed, based on changes in substrate inhibition of LDG isoenzymes with lactate. Stability of kinetic constants for a long period of time is demonstrated. The dependency of activities ratio under low and high substrate concentration on the contribution of mole quota of LDG M subunits is studied. The correlation of experimental and theoretical values is shown to be: r=0.998 p less than 0.001. A comparison is carried out of the content of LDG subunits molar quotas in artificial mixtures with electrophoretic experimental data, a good coinsidence of these values being registered. The informative importance of the method described with standard methods of the estimation of LDG isoenzyme systems is discussed. No effect of components of human diploid cells homogenate and an insignificant effect of blood serum components on kinetic constants of LDG isoenzymes is registered. A dependency of variation coefficients on the enzyme activity is studied, minimal omegan value being 0.6%. The applicability of the method described for the calculation of quantitative content of both LDG subunits in natural objects (blood serum, diploid cell homogenate etc.) is demonstrated.     

Effects of bleomycin on Down's syndrome lymphocytes in culture

Blood lymphocytes from 3 Down's syndrome (DS) and 3 age- and sex-matched normal probands were studied for the induction of chromosomal aberrations and sister-chromatid exchange (SCEs). Treatment with bleomycin (30 and 60 ng) at the initiation of culture showed a dose-dependent increase in the incidence of dicentric and ring chromosome aberrations. In contrast, the cells which were treated for the last 24 h in culture with bleomycin did not show an increase in chromosome-type aberrations. The proportion of metaphases in M1, M2, and M3 in cultures was not different between DS and normal cells. Sister-chromatid exchange frequency did not show significant changes between DS and normal individuals.     

Changes in the lactate dehydrogenase isoenzyme spectrum during T-lymphocyte differentiation

The pattern of lactate dehydrogenase isoenzyme spectrum changes on different stages of T-lymphocyte differentiation was studied An enriched population of stem cells has LDH-5, 4 and 3 isoenzymes, and much less LDH-2 activity. The isoenzyme pattern of thymic cell precursors consists of LDH-5, 4, 3 and 2. All the five LDH isoenzymes were found in cortical thymocytes. Medullary thymocytes reveal LDH-5, 4 and 3 isoenzymes. T-lymphocytes of peripheral lymphoid organs contain mainly LDH-5 and in a lesser degree LDH-4 activity.     

Malate dehydrogenase and lactate dehydrogenase in the serum of hyperthyroxinemic and hypothyroid rats]

In serum of hyperthyroxinemic and hypothyreotic rats the activities of MDH and LDH were investigated. In both groups the level of MDH was significantly elevated in comparison with control animals. The activity of LDH did not show any significant alterations.     

Changes in the liver lactate dehydrogenase isozyme profile after induced glycogenolysis

Summary Treatment with cystamine, phlorrhizin or nicotinic acid, which induced liver glycogenolysis, resulted in the increase of liver lactate dehydrogenase activity. This increase was counteracted by the administration of cycloheximide or actinomycin D and coincided with the increase of isozymes 4 and 3 and the decrease of isozyme 5. The enhancement of liver lactate dehydrogenase activity and the changes observed in the isozyme profile were similar to those observed after starvation. These results suggest that the changes in the lactate dehydrogenase isozyme profile found after cystamine, phlorrhizin or nicotinic acid administration may be related to the glycogenolysic effect of these compounds. These result in an adaptation of the liver lactate dehydrogenase to gluconeogenesis.     

Minutiae of skin ridges in Down's syndrome]

Minutiae of the epidermal ridges were examined in 16 children with Down's syndrome and 50 children without genetic and familial abnormalities. Minutiae in standard areas on the hand palms (according to Grzeszyk's concept) were examined. Comparative analysis confirmed by the statistical analysis showed significant differences in the incidence of particular minutiae types on the hand palms of children with Down's syndrome and control group.