Angiotensin-converting enzyme genotype and encephalopathy in Chernobyl cleanup workers.

BACKGROUND AND PURPOSE: To identify, using a genetic model, a key role for the renin-angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. METHODS: Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. RESULTS: Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). CONCLUSIONS: These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group.

[Chromosomal aberrations and parameters of oxidative stress in Chernobyl clean-up workers in a remote period after ionizing radiation]. / Khromosomnye aberratsii i pokazateli okislitel'nogo stressa u likvidatorov posledstvii avarii na Chernobyl'skoi AES v otdalennom periode posle deistviia ioniziruiushchei radiatsii.

This investigation was performed to test a supposition about the influence of disturbances in antioxidative system on cytogenetical parameters in Chernobyl' clean-up workers. It was shown that some cytogenetical parameters straightly correlated with the parameters of oxidative stress, while other cytogenetical parameters show just reverse correlations. Apparently, these relationships are not of cause-and-effect type, but they reflect a complex processes occurring in humans for a long period after radiation exposure.

[Some complexities in evaluating radiation-induced mutagenic effects in man]. / O nekotorykh slozhnostiakh v otsenke radiatsionno-indutsirovannykh mutagennykh éffektov u cheloveka.

Chromosomal aberrations in somatic cells (circulating lymphocytes) have been investigated in a remote period in different groups of people who suffered from radiation accidents. The chromosomal radiation markers were found even decades after irradiation. The question about the necessity of registration of non-classical mutagenic effects after human irradiation is raised.

[ A long-term changes of macro- and microelement balance in blood serum, its ultrafiltrates and hairs after exposure to low doses of ionizing radiation]. / Izmenenie makro- i mikroélementnogo balansa v syvorotke krovi, ee ul'trafil'trate i volosakh v otdalennye sroki posle vozdeistviia malykh doz ioniziruiushchei radiatsii.

Using inductively coupled plasma atomic emission spectrometry, we examined the level of Al, Cd, Co, Cu, Fe, Mg, Mo, P, Pb, S, and Zn in blood serum, its ultrafiltrates, and hairs of liquidators of the Chernobyl Nuclear Power Plant accident who were working in the disaster region in 1986-1987. Studies continued over a period of time provided evidence for a distinct change in the balance of macroelements and trace elements in the studied biological substrates of irradiated individuals. An increase in the level of copper in the ultrafiltrate and a marked decrease in the content of zinc in the ultrafiltrate are viewed as key factors in the generation of a response to low doses of ionizing radiation. Concerning the content of iron in hairs, we demonstrate its accelerated removal from the body of liquidators. The altered balance of biotic macroelements, phosphorus, and sulfur remained unchanged when these characteristics were studied as a function of time. We found changes in the ratios of divalent cations, magnesium and zinc, in the ultrafiltrates. The magnesium concentration in the studied biological substrates was the most stable characteristic after irradiation. The level of toxic trace elements (lead, cadmium, and aluminum) did not exceed physiologically acceptable levels, while their content in hairs may be a biological indicator of their accumulation in the body.

[The number of nucleoli in peripheral blood lymphocytes of the Chernobyl accident liquidators]. / Issledovanie kolichestva iadryshek v iadrakh limfotsitov perifericheskoi krovi u likvidatorov posledstvii avarii na ChAES.

The number of nucleoli in lymphocyte nuclei was compared in the peripheral blood of the Chernobyl liquidators and non-irradiated persons (control). The former was significantly distinguished from the latter (p < 0.01) by the parameter "the number of nucleoli in lymphocytes", mean numbers of nucleoli per nucleus in these being 1.18 and 1.12, respectively. The increased number of nucleoli in lymphocytes of the Chernobyl liquidators may be associated with cytogenetic radiation effects.

[Nuclei with protrusions--"tailed" nuclei--and radiation cytogenetic markers in a lymphocyte culture after x-ray irradiation]. / Iadra s protruziiami--"khvostatye" iadra i radiatsionnye tsitogeneticheskie markery v kul'ture limfotsitov posle rentgenovskogo oblucheniia.

Frequency of the appearance of binuclear cells with nuclei having outgrowth into the cytoplasmic space and arise after first mitosis in human lymphocyte culture is linear-square dependent on the X-irradiation at doses from 0.0 to 4.0 Gy. Positive correlation between frequency of cells with "tailed" nuclei and frequency of metaphases of first mitosis having dicentrics and rings was established. Apparently, formation such "tailed" nuclei is connected with dicentrics and rings.

Tailed nuclei and dicentric chromosomes in irradiated subjects.

A study of peripheral blood smears from irradiated Chernobyl liquidators and other subjects has shown nuclei of some lymphocytes to have a protrusion into the cytoplasm. Such abnormal nuclei are called "tailed" nuclei (TN). Sixteen main morphologic types, observed in human peripheral blood lymphocytes, are described. The frequency of appearance of lymphocytes with TN in a group of Chernobyl liquidators was significantly higher than in control groups (p < 0.001, in all cases). A positive correlation was found between the TN frequency in lymphocytes and dicentric chromosomes in lymphocytes cultured to metaphase (p < 0.001). Elevated frequencies of dicentrics, higher than 0.1%, were found in 17 out of 22 subjects in whom the frequency of lymphocytes with TN was 0.8% and more. Abnormalities of the TN type in lymphocytes are likely to result from breakdown of chromosome bridges formed by dicentrics. The TN can be considered as a possible marker of irradiation and, therefore, their detailed study is important.

[Morphological anomalies in "tailed" lymphocyte nuclei and their connection with dicentric chromosomes in irradiated patients]. / Morfologicheskie anomalii iader tipa "khvostov" v limfotsitakh i ikh sviaz' s ditsentricheskimi khormosomami u obluchennykh patsientov.

Lymphocyte nuclei with a narrow outgrowth into the cytoplasm ("tail") were detected on peripheral blood smears of patients exposed to ionizing radiation during the clean up after the Chernobyl meltdown (liquidators). On average, lymphocytes with tailed nuclei occurred at a frequency of 0.43% and 0.15% in exposed patients (n = 101) and healthy donors (n = 50), respectively; the difference between the samples was significant, P < 0.001. The coefficient of correlation between frequencies of lymphocytes with tailed nuclei and those with dicentric chromosomes was 0.74 (n = 27, P < 0.001). The frequency of lymphocytes with dicentric chromosomes was increased in 9 out of 10 patients, in which lymphocytes with tailed nuclei occurred at a frequency larger than 0.8%. A double-color FISH was used to localize centromeric (not more than two signals) and telomeric (not more than one signal) regions in nuclear tails. Abnormal tailed lymphocyte nuclei were assumed to result from breaking the chromosome bridges formed by the dicentric chromosomes.

[The psychological sequelae of the accident]. / Psikhologicheskie posledstviia avarii.

The psychological status of rescuers of consequences of Chernobyl's disaster, having planned stationary examination and treatment of common somatic diseases, has been examined. The age of men represented the study group was 35-54 years old. The next methodics have been used: questionnaire MMPI (adapted by L. N.Sobchik), the method of colour choice (adapted version of Liusher's test) and questionnaire of Spilberger-Khanin. The results of medical-psychological examination showed the development in rescuers of common dysadaptation and stress state, characterized by depressive-hypochondriac state with high anxiety. The course of psychotherapeutic activities made possible to improve essentially the psychological status of the patients.

[The status of the gastric and duodenal mucosa, biopsied from those who worked in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station, in an organotypic tissue culture]. / Sostoianie slizistoi obolochki zheludka i dvenadtsatipertsnoi kishki likvidatorov posledstvii avarii na Chernobyl'skoi AES v organotipicheskoi kul'ture tkani.

Biopsies of stomach and duodenum different regions mucosa obtained from patients with gastroduodenitis (liquidators of consequences of accident in Chernobyl nuclear station--LCA CNS-- and control patients) were studied cultured in vitro. The following are the differences found. Mononuclear cells, differentiating into macrophages were exposed from control biopsies. Mononuclear cells exposed from LCA CNS biopsies formed rosette-like accumulations after mitotic dividing on a distance from the explant. Part of cells within the rosettes acquired processes and formed syncytial structure.

[The course of duodenal peptic ulcer in the participants in the cleanup of the aftereffects of the accident at the Chernobyl Atomic Electric Power Station]. / Techenie iazvennoi bolezni dvenadtsatiperstnoi kishki u uchastnikov likvidatsii posledstvii avarii na Chernobyl'skoi AES.

80 liquidators of Chernobyl disaster with aggravation of duodenal ulcer were examined, as well as a control group of 70 patients. In the group of liquidators some characteristic features were disclosed, namely peculiarities in the state of abdominal mucosa and clinical course of the disease. These data were obtained in the results of hematological, immunological and biochemical researches.

[An attempt at a polythetic classification of a group of clean up team workers after the Chernobyl AES accident]. / Popytka politeticheskoi klassifikatsii gruppy likvidatorov avarii na Chernobyl'skoi AES.

Using the complex statistics methods with due regard for the time lapsed from the moment of exposure to ionizing radiation, multifactors of the accident and the number of studies, the manifestations of the radiation effect (within the dose range from 0.1 to 0.5 Gy) on certain functional systems in a group of Chernobyl A.P.S. accident liquidators.

[Evaluation of the effectiveness of treating breast cancer metastases to the bones by the "no-pain index"]. / Otsenka po "bezbolevomu indeksu" éffektivnosti lecheniia metastazov raka molochnoi zhelezy v kosti.

The results of evaluation of treatment of 98 breast cancer patients with bone metastases are presented. Metastases appeared 6 months -- 15 years after treatment; on the average, they appeared 20.2 months after treatment. Patients received complex therapy -- radiation and medication. The results of treatment were assessed on the basis of subjective (abatement or cessation of pain) and objective (bone reparation) criteria. Objective effect was observed in 4%, subjective one -- in 68.3% of cases. Apart from survival time and remission, the results of treatment were evaluated on the basis of the duration of painless period expressed by means of "no-pain index" -- the ratio of the painless period duration to survival time which elapsed since skeletal metastasis detection, multiplied by 100. The study showed that complex therapy has a considerable palliative effect in some cases -- abatement or cessation of pain for over 54--60% of the survival time of patients.