[Irreversible electroporation in locally advanced pancreatic cancer]. / Neobratimaya elektroporatsiya pri mestno-rasprostranennoi adenokartsinome podzheludochnoi zhelezy.

OBJECTIVE: To determine the feasibility of irreversible electroporation (IRE) for locally advanced pancreatic adenocarcinoma. MATERIAL AND METHODS: Twenty-three patients underwent IRE after chemotherapy for locally advanced pancreatic cancer between 2015 and 2022. IRE was performed during laparotomy as a rule (n=22). In one case, IRE was combined with palliative pancretoduodenectomy. Nineteen (86.3%) patients received adjuvant chemotherapy after the procedure. The follow-up examination included contrast-enhanced CT/MRI of the abdomen, chest X-ray or CT, analysis of CA 19-9 marker one month after surgery and then every three months. RESULTS: Complications after IRE developed in 5 (21.7%) patients. Three patients (13.0%) had arrhythmia, two (8.7%) ones had pancreatic necrosis. A 90-day mortality after the procedure was 4.3% (n=1), the cause was pancreatic necrosis. According to intraoperative data and the first examination (CT/MRI), the entire tumor infiltrate was treated in 21 (91.3%) cases. Median follow-up was 19 months. Median period until local recurrence was 15 months. Isolated local recurrence was observed in 7 patients. Of these, 3 ones underwent radiotherapy, one patient underwent repeated IRE. Distant metastases were found in 11 patients; systemic therapy was restarted. Median time to progression was 7 months after IRE and 14 months after initiation of chemotherapy. The median overall survival was 16 months after electroporation and 25 months after chemotherapy. CONCLUSION: Irreversible electroporation may be useful in carefully selected patients with unresectable locally advanced pancreatic adenocarcinoma after successful induction chemotherapy. This procedure provides local control, but the impact on long-term outcomes and feasibility of routine use should be analyzed in randomized trials.

Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk.

The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.

[Resection of liver segments VII-VIII: is right hepatic vein reconstruction advisable?] / Rezektsiya VII­VIII segmentov pecheni: est' li tselesoobraznost' rekonstruktsii pravoi pechenochnoi veny?

OBJECTIVE: To improve the treatment outcomes in patients with primary and metastatic liver tumors localized in segments VII-VIII involving the right hepatic vein and its branches. MATERIAL AND METHODS: There were 16 surgical interventions including resection of liver segment VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction. All procedures were carried out at the Department of Liver and Pancreatic Tumors of the Blokhin National Medical Cancer Research Center for the period 2016-2020. The cause of surgery was colorectal cancer liver metastases in 8 patients, hepatocellular carcinoma in 2 cases, angiomyolipoma in 1 case and metastases of uterine cancer in 1 patient. Minor liver resection was additionally performed in 5 cases. RESULTS: Median surgery time was 150 (80-220) min, intraoperative blood loss - 400 (100-2000) ml. Afferent blood flow was blocked in 4 patients for 14 (12-25) min. None patient had intraoperative signs of impaired venous outflow. Biliary fistula in postoperative period occurred in 1 patient. No complications were noted in other cases. Median postoperative hospital-stay was 13 (9-19) days. There were no specific complications in long-term postoperative period that could be associated with venous outflow blockade through the right hepatic vein. CONCLUSION: Existing vessels and intrahepatic collaterals de novo can provide adequate venous outflow into the middle hepatic vein and short hepatic veins during resection of liver segments VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction and the absence of inferior right hepatic vein.

NF-κB-dependent DNA damage-signaling differentially regulates DNA double-strand break repair mechanisms in immature and mature human hematopoietic cells.

Hematopoietic stem and progenitor cells (HSPC), that is, the cell population giving rise not only to all mature hematopoietic lineages but also the presumed target for leukemic transformation, can transmit (adverse) genetic events, such as are acquired from chemotherapy or ionizing radiation. Data on the repair of DNA double-strand-breaks (DSB) and its accuracy in HSPC are scarce, in part contradictory, and mostly obtained in murine models. We explored the activity, quality and molecular components of DSB repair in human HSPC as compared with mature peripheral blood lymphocytes (PBL). To consider chemotherapy/radiation-induced compensatory proliferation, we established cycling HSPC cultures. Comparison of pathway-specific repair activities using reporter systems revealed that HSPC were severely compromised in non-homologous end joining and homologous recombination but not microhomology-mediated end joining. We observed a more pronounced radiation-induced accumulation of nuclear 53BP1 in HSPC relative to PBL, despite evidence for comparable DSB formation from cytogenetic analysis and γH2AX signal quantification, supporting differential pathway usage. Functional screening excluded a major influence of phosphatidylinositol-3-OH-kinase (ATM/ATR/DNA-PK)- and p53-signaling as well as chromatin remodeling. We identified diminished NF-κB signaling as the molecular component underlying the observed differences between HSPC and PBL, limiting the expression of DSB repair genes and bearing the risk of an inaccurate repair.

Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions.

The risk of radiation exposure during embryonic development is still a major problem in radiotoxicology. In this study we investigated the response of the murine embryonic stem cell (mESC) line D3 to two radiation qualities: sparsely ionizing X-rays and densely ionizing carbon ions. We analyzed clonogenic cell survival, proliferation, induction of chromosome aberrations as well as the capability of cells to differentiate to beating cardiomyocytes up to 3 days after exposure. Our results show that, for all endpoints investigated, carbon ions are more effective than X-rays at the same radiation dose. Additionally, in long term studies (≥8 days post-irradiation) chromosomal damage and the pluripotency state were investigated. These studies reveal that pluripotency markers are present in the progeny of cells surviving the exposure to both radiation types. However, only in the progeny of X-ray exposed cells the aberration frequency was comparable to that of the control population, while the progeny of carbon ion irradiated cells harbored significantly more aberrations than the control, generally translocations. We conclude that cells surviving the radiation exposure maintain pluripotency but may carry stable chromosomal rearrangements after densely ionizing radiation.

[Molecular karyotyping of eukaryotic microorganisms].

In many fungi and protists small size and weak morphological differentiation of chromosomes embarrass the study of karyotypes using microscopical tools. Molecular karyotyping based on the fractionation of intact chromosomal DNAs by pulsed field gel electrophoresis (PFGE) provides an alternative approach to the analysis of chromosomal sets in such organisms. To assign the bands observed in PFGE gel to the individual chromosomes the following methods of chromosome identification are applied: densitometric analysis of the bands; Southern hybridization with chromosome- and telomere-specific probes, which often is combined with comparative karyotyping of a series of strains with pronounced size polymorphism of chromosomes; comparison of the patterns of restriction fragments of chromosomal DNAs fractioned by KARD 2-D PFGE; comparison with the strains with well-studied interchromosomal rearrangements. Besides estimation of the number and the size of chromosomes, molecular karyotyping allows assessment of haploid genome size and ploidy level, study of genome dynamics, identification of chromosomal rearrangements and associated chromosomal polymorphism. The analysis of karyotype and dynamics of the genomes is important for the study of intra- and interspecial variability, investigation of the chromosome evolution in closely related species and elaboration of the models of speciation. The comparison of molecular karyotypes among isolates of different origin is of great practical importance for clinical diagnostics and for agricultural microbiology. In this review we discuss: 1) the methods of karyotyping and their application to the analysis of chromosomal sets in eukaryotic microorganisms; 2) the specificity of the methods used for extraction and fractionation of intact chromosomal DNAs; 3) the reasons for difficulties in interpretation of molecular karyotypes and the ways of their overcoming; 4) fields of application of molecular karyotyping; 5) the definition of "molecular karyotype" formulated in accordance with modern methodological requirements.

[Pulsed field gel electrophoresis: theory, instruments and applications].

Pulsed Field Gel Electrophoresis (PFGE) is a powerful technique for the fractionation of high molecular weight DNAs ranging from 10 kb to 10 Mb in size. PFGE separates DNA molecules in agarose gel by subjecting them to electric fields that alternate ("pulsate") in two directions. This technology plays a key role in the modern genomics as it allows manipulations of the DNA of whole chromosomes or their large fragments. In this review we discuss: 1) the theory behind PFGE, 2) different instruments based on the principle of pulsed field, their advantages and limitations, 3) factors affecting the mobility of DNA in PFGE gels, 4) practical applications of the technique.

Cell cycle arrest and aberration yield in normal human fibroblasts. II: Effects of 11 MeV u-1 C ions and 9.9 MeV u-1 Ni ions.

PURPOSE: To investigate further the relationship between high linear energy transfer (LET) induced cell cycle arrests and the yield of chromosome aberrations observable in normal human fibroblasts at the first post-irradiation mitosis. MATERIALS AND METHODS: Normal human fibroblasts (AG01,522C) were exposed in G0/G1 to either 11 MeV u(-1) C ions (LET = 153.5 keV microm(-1)) or 9.9 MeV u(-1) Ni ions (LET = 2,455 keV microm(-1)), subcultured in medium containing 5-Bromo-2'-deoxyuridine (BrdU) and at multiple time-points post-irradiation the yield of chromosomal damage, the mitotic index and the cumulative BrdU-labelling index were determined. Furthermore, a mathematical approach was used to analyse the entire cell population. RESULTS: Following high LET exposure normal fibroblasts suffer a transient delay into S-phase and into mitosis as well as a prolonged, probably permanent cell cycle arrest in the initial G0/G1-phase. Cells that reach the first mitosis at early times carried less aberrations than those collected at later times indicating a relationship between cell cycle delay and the number of aberrations. However, with respect to the whole cell population, only a few aberrant fibroblasts are able to progress to the first mitosis. For all endpoints studied the relative biological effectiveness (RBE) of C ions is in the range of 2 - 4, while for Ni ions RBE < 1 is estimated. In contrast, when compared on a per particle basis Ni ions with the higher ionization density were found to be more effective. CONCLUSIONS: Detailed analysis of the data demonstrates that the number of fibroblasts at risk for neoplastic transformation is significantly reduced by a chronic cell cycle arrest in the initial G0/G1-phase and, for the first time, the LET-dependence of this effect has been shown.

Prediction of dose response for radiation induced exchange aberrations taking cell cycle delays into account.

Chromosomal aberrations (CAs) are regarded as one of the most sensitive biological indicators of genetic alterations. The aberration frequency is routinely determined in the first metaphase. Yet, the data interpretation can be complicated due to radiation induced mitotic delays. To investigate the effect of delays on CA frequency in the first mitosis, human lymphocytes were irradiated with X rays and Giemsa detectable CAs were measured at different sampling times. Besides, a computer simulation was performed reproducing the main effects under investigation, that is, CA induction and cell progression through the mitotic cycle. The CA formation model takes into account the structural organisation of interphase chromosomes in a lymphocyte nucleus, DNA double-strand break (DSB) induction and their rejoining/misrejoining. Lymphocyte transition through the cell cycle was simulated by a Monte Carlo technique. The delay was proposed to result from DNA DSBs. The predicted ratios of first/second/third cycle metaphases agree with the experimental data for control and irradiated samples. Both experimental and calculated CA frequencies in the first mitosis were nearly time-independent. This was proposed to result from de-synchronisation of the lymphocyte population.

Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes.

Chromosome damage and the spectrum of aberrations induced by low doses of gamma-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm) in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose-effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena.

[Cytogenetic effects of low dose radiation with different LET in human peripheral blood lymphocytes and possible mechanisms of their realization].

The induction of chromosome damage by the exposure to low doses of gamma-(60)Co and accelerated carbon ions 12C in peripheral blood lymphocytes of different donors was investigated. The complex nonlinear dose-effect dependence at the range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type aberration, which is typical to those spontaneously generated in the cell and believed not to be induced by the irradiation of unstimulated lymphocytes according to the classical theory of aberration formation. With the increasing dose the frequency of the aberrations decreases significantly, in some cases up to the control level. At the doses over 50-70 cGy the dose-effect curve becomes linear. The possible role of the oxidative stress, caused by radiation-induced increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon of hypersensitivity (HS) at low doses is discussed as well as cytoprotective mechanisms causing the increased radioresistance at higher doses.

[Induction of chromosome aberrations and micronuclei in human peripheral blood lymphocytes at low dose of radiation].

The chromosome damage induced by the doses of y-irradiation 6)Co in peripheral blood lymphocytes was studied using different cytogenetic assays. Isolated lymphocytes were exposed to 0.01-1.0 Gy, stimulated by PHA, and analysed for chromosome aberrations at 48 h postirradiation by metaphase method, at 49 h--by the anaphase method, at 58 h by micronucleus assay with cytochalasin B and, additionally, micronuclei were counted at 48 h on the slides prepared for the metaphase analysis without cytochalasin B. Despite of the quantitative differences in the amount of chromosome damage revealed by different methods all of them demonstrated complex nonlinear dose dependence of the frequency of aberrant cells and aberrations. At the dose range from 0.01 Gy to 0.05-0.07 Gy the cells had the highest radiosensitivity mainly due to chromatid-type aberration induction. With dose increasing the frequency of the aberrant cells and aberrations decreased significantly (in some cases to the control level). At the doses up to 0.5-0.7 Gy the dose-effect curves have become linear with the decreased slope compare to initial one (by factor of 5 to 10 for different criteria) reflecting the higher radioresistance of cells. These data confirm the idea that the direct linear extrapolation of high dose effect to low dose range--the procedure routinelly used to estimate genetic risk of low dose irradiation--cannot be effective and may lead to underestimation of chromosome damage produced by low radiation doses. Preferences and disadvantages of used cytogenetic assays and possible mechanisms of low ionising radiation doses action were discussed.

[Atherosclerotic lesion of the vessels in systemic lupus erythematosus in males: relations with concentration of C-reactive protein].

AIM: To elicit prevalence of clinical and subclinical manifestations of atherosclerosis in men with systemic lupus erythematosus (SLE), to assess correlation between vascular atherosclerosis, risk factors and concentration of C-reactive protein (CRP). MATERIAL AND METHODS: Analysis of conventional and disease-related factors of risk, ultrasonic scanning of the carotid arteries, high-performance enzyme immunoassay for CRP were made in 37 patients (mean age 36.9 +/- 10.7 years, duration of the disease 130.2 +/- 108.2 months). RESULTS: Clinical symptoms of atherosclerosis were seen in 35% patients. By thickness of the intimamedia complex (IMC), the patients were divided into 2 groups. Group 1 consisted of 21 patients with vascular atherosclerosis (IMC > 0.9 mm), group 2--of 16 patients with IMC < 0.9 mm. Mean age, age of the disease onset, body mass index were greater in group 1. A mean CRP concentration in patients with athrosclerosis was significantly higher than in the group without vascular atherosclerosis (p = 0.004). CONCLUSION: SLE men comprise a group of high atherosclerosis risk. An elevated CRP level is associated with thicker IMC.

Correlation between mitotic delay and aberration burden, and their role for the analysis of chromosomal damage.

The aim was to investigate further the relationship between radiation-induced mitotic delay and the expression of chromosome damage in V79 cells. Recently published data on the time-course of chromosome aberrations in V79 first-cycle metaphases after exposure to 10.4 MeV u(-1) Ar ions (LET = 1226 keV microm(-1)) were supplemented and reanalysed. A statistical analysis of the distribution of aberrations among cells was performed. Furthermore, cells were grouped into subpopulations carrying 0, 1 -2, 3-4, 5- 6 and 7 or more aberrations. Then, based on the mitotic index, the flux of each subgroup through the first mitosis was determined and the average entrance time to mitosis was estimated. For comparison, the flux of aberrant V79 cells generated by X-irradiation was analysed. Analysis of the Ar ion data revealed that the flux of each subpopulation through the first mitosis is strongly affected by its aberration burden, i.e. a positive correlation between the mitotic delay and the number of aberrations carried by a cell was observed. The distribution of aberrations among cells could be well described by Neyman-type A statistics; the corresponding fit parameters also reflect the damage-dependent mitotic delay. Interestingly, comparison of the flux of Ar ion and X-ray-irradiated V79 cells through mitosis revealed (1) that a direct correlation exists between the number of aberrations carried by a cell and its average entrance time to mitosis, and (2) that this effect is independent of the linear energy transfer. The role of these observations for radiation cytogenetics is discussed.

Chromosome aberration yields and apoptosis in human lymphocytes irradiated with Fe-ions of differing LET.

In the present paper the relationship between cell cycle delays induced by Fe-ions of differing LET and the aberration yield observable in human lymphocytes at mitosis was examined. Cells of the same donor were irradiated with 990 MeV/n Fe-ions (LET=155 keV/micrometers), 200 MeV/n Fe-ions (LET=440 keV/micrometers) and X-rays and aberrations were measured in first cycle mitoses harvested at different times after 48-84 h in culture and in prematurely condensed G2-cells (PCCs) collected at 48 h using calyculin A. Analysis of the time-course of chromosomal damage in first cycle metaphases revealed that the aberration frequency was similar after X-ray irradiation, but increased two and seven fold after exposure to 990 and 200 MeV/n Fe-ions, respectively. Consequently, RBEs derived from late sampling times were significantly higher than those obtained at early times. The PCC-data suggest that the delayed entry of heavily damaged cells into mitosis results especially from a prolonged arrest in G2. Preliminary data obtained for 4.1 MeV/n Cr-ions (LET=3160 keV/micrometers) revealed, that these delays are even more pronounced for low energy Fe-like particles. Additionally, for the different radiation qualities, BrdU-labeling indices and apoptotic indices were determined at several time-points. Only the exposure to low energy Fe-like particles affected the entry of lymphocytes into S-phase and generated a significant apoptotic response indicating that under this particular exposure condition a large proportion of heavily damaged cells is rapidly eliminated from the cell population. The significance of this observation for the estimation of the health risk associated with space radiation remains to be elucidated.

[The fine structure of chromatin in Paranosema grylli (Microsporida)].

Nucleosomes were found for the first time in the nuclear chromatin of Microsporida--organisms known among the smallest eukaryotes on Earth. Chromatin of Paranosema grylli sporoplasm was studied by Miller's technique. On low ionic-strength cell spreads, this chromatin was represented by 10 nm nucleosome filaments, 20 nm filaments, and "smooth" (nucleosome-free) filaments of 3-4 nm in diameter. Nucleosome filaments display structural heterogeneity seen as irregular arrangement of nucleosome particles along the filament length. Different nucleosome filaments show 13-30 nucleosomes per 1 microm with the length of linker DNA ranging from 10 to 45 nm. The present results suggest that microsporidian chromatin is weakly condensed. Only lower-order chromatin packaging levels displayed some structural peculiarities.

Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X-rays and 195 MeV u(-1) C ions.

PURPOSE: To examine the relationship between cell proliferation and the expression of chromosomal damage in normal human skin fibroblasts after X-ray and particle irradiation. MATERIALS AND METHODS: Confluent G0/G1 AG1522B cells were exposed to X-rays or 195MeV u(-1) C ions with a linear energy transfer of 16.6 keV microm(-1) in the dose range 1-4 Gy. Directly after irradiation, cells were reseeded at a low density in medium containing 5-bromo-2'-deoxyuridine. At multiple time points post-irradiation, the cumulative BrdU-labelling index, mitotic index and aberration frequency were measured. Based on these data, the total amount of damage induced within the entire cell population was estimated by means of mathematical analysis. RESULTS: Both types of radiation exposure exert a pronounced effect on the cell cycle progression of fibroblasts. They result in delayed entry of cells into S-phase and into the first mitosis, and cause a dramatic reduction in mitotic activity. Measurement of chromosomal damage in first-cycle cells at multiple time points post-irradiation shows that the frequencies of aberrant cells and aberrations increase with time up to twofold for the lower doses. However, for the higher doses, this effect is less pronounced or even disappears. When the data for the whole cell population are analysed, it becomes evident that only a few damaged fibroblasts can progress to the first mitosis, a response attributable at least in part to a long-term arrest of injured cells in the initial G0/G1-phase. As observed in other investigations, the effectiveness of 195 MeV u(-1) C ions was similar or slightly higher than X-rays for all endpoints studied leading to a relative biological effectiveness in the range 1.0-1.4. CONCLUSIONS: Cell cycle arrests affect the aberration yield observable in normal human fibroblasts at mitosis. The data obtained for the cell population as a whole reveal that injured cells are rapidly removed from the mitotically active population through a chronic cell cycle arrest, which is consistent with other studies that indicate that this response is a specific strategy of fibroblasts to minimize the fixation and propagation of genetic alterations.

[The specific features of circadian blood pressure variations in patients with hypertensive disease in different types of weather]. / Osobennosti tsirkadiannykh ritmov arterial'nogo davleniia u bol'nykh gipertonicheskoi bolezn'iu pri razlichnykh tipakh pogody.

The specific features of circadian blood pressure (BP) variations were studied in 162 patients aged 20 to 60 years who had hypertensive disease (HD) in the warm period of a year in different types of weather. In accordance with the type of weather in which daily BP monitoring (DBPM) was performed, the examinees were divided into 2 groups: 1) those examined in droughty (anticyclonic) weather; 2) those examined in moist (cyclonic) weather, The groups were matched by the number (81) of patients, age, gender, duration of the disease, and office BP values. The mean BP during a day, daylight and night hours, the maximum and minimum BP during wake and sleep was significantly high in moist weather. Examining the magnitude of a nocturnal BP decrease indicated that in Group 1, its adequate decrease (the dipper daily curve) was recorded in 72.3% of the patients; inadequate BP decrease (the non-dipper daily curve) was in 24.2%; paradoxical nocturnal hypertension (night peaker) was seen in 1.8%. In Group 2, adequate and inadequate nocturnal BP decreases were observed in 44.4 and 41.3%, respectively; paradoxical nocturnal hypertension was in 7.7%. Statistical processing confirmed the validity of the findings. Moist (cyclonic) weather was ascertained to be marked by the changes in adequate circadian BP variations: a significant mean daily, maximum, and minimum systolic BP (SBP) and diastolic BP (DBP), as well as by the inadequate nocturnal lowering of SBP and DBP, which determines a poor prognosis and may serve as a basis for preventing HD complications in this period of a year.

Cytogenetic effects of densely ionising radiation in human lymphocytes: impact of cell cycle delays.

The classical cytogenetic assay to estimate the dose to which an individual has been exposed relies on the measurement of chromosome aberrations in lymphocytes at the first post-irradiation mitosis 48 h after in vitro stimulation. However, evidence is accumulating that this protocol results in an underestimation of the cytogenetic effects of high LET radiation due to a selective delay of damaged cells. To address this issue, human lymphocytes were irradiated with C-ions (25-mm extended Bragg peak, LET: 60-85 keV/ micro m) and aberrations were measured in cells reaching the first mitosis after 48, 60, 72 and 84 h and in G2-phase cells collected after 48 h by calyculin A induced premature chromosome condensation (PCC). The results were compared with recently published data on the effects of X-rays and 200 MeV/u Fe-ions (LET: 440 keV/ micro m) on lymphocytes of the same donor (Ritter et al., 2002a). The experiments show clearly that the aberration yield rises in first-generation metaphase (M1) with culture time and that this effect increases with LET. Obviously, severely damaged cells suffer a prolonged arrest in G2. The mitotic delay has a profound effect on the RBE: RBE values estimated from the PCC data were about two times higher than those obtained by conventional metaphase analysis at 48 h. Altogether, these observations argue against the use of single sampling times to quantify high LET induced chromosomal damage in metaphase cells.

[Clinical value of soluble adhesion molecules in systemic scleroderma]. / Klinicheskoe znachenie rastvorimykh molekul adgezii pri sistemnoi sklerodermii.

The aim of the trial was to study clinical significance of estimation of cell adhesion soluble molecules (CASM) in scleroderma systematica (SS). Quantitation of CASM VCAM-1, ICAM-1 and R-selectin was made with enzyme-immunoassay (R&D System kits, USA) in 38 patients with SS (11 with limited SS and 27 with diffuse SS). The levels of VCAM-1, ICAM-1 and R-selectin was elevated in 30 (79%), 17 (45%) and 20 (53%) patients, respectively. Mean values of VCAM-1 and ICAM-1 in patients were significantly higher than in healthy donors. R-selectin was also higher but insignificantly. A mean CASM level and a relative number of patients with elevated count of CASM in patients with diffuse and limited forms of SS did not differ. In 15 patients with active (progressive) course of the disease the level of VCAM-1 was significantly higher than in patients with chronic (non-progressive) course of SS while concentrations of ICAM-1 and R-selectine were almost the same. Thus, SS patients have elevated levels of CASM. CASM VCAM-1 concentration is the most sensitive marker of SS activity compared to other CASM.