[A complicated case of calcium urolithiasis in a carrier of SLC7A9 gene mutation responsible for cystinuria].

The article describes a clinical case of kidney stone disease (KSD) in a child of 4 y.o. with calcium urolithiasis. Analysis of chemical content of the kidney stones revealed their calcium-oxalate composition. According to the results of clinical exome sequencing the patient found to be a heterozygous carrier of a pathogenic variant c.695A>G (p.Tyr232Cys) in the gene SLC7A9, attributable for an autosomal recessive form of cystinuria type B. Because of the uroliths calcium composition the patient was also genotyped for SNPs in 15 genes involved in calcium metabolism. Polymorphisms associated with increased risk of calcium urolithiasis were found in 8 of 15 tested genes. The findings could explain clinical features of the patient.

[Molecular and genetic technologies for the diagnosis of monogenic forms of urinary stone disease: clinical cases].

Kidney stone disease (KSD) is an actual problem of modern health care. By now, more than 80 monogenic forms of urolithiasis have been described. To diagnose such forms of KSD different molecular genetic technologies are used. In the current article 5 clinical cases of KSD among the patients aged 1-9 years old are presented. All of them underwent comprehensive instrumental, clinical, laboratory and molecular genetic investigations. DNA analysis was carried out by Next Generation Sequencing method (NGS) (target NGS-panels and Whole Exome Sequencing). In all cases the molecular genetic cause of the disease was found - idiopathic infantile hypercalcemia type 1 (gene CYP24A1 - 3 cases) and cystinuria (gene SLC7A9 - 2 case). Several unknown genetic variants were found in CYP24A1 (c.1379G>T, c.1156A>T, c.1286T>C) and SLC7A9 (c.920T>A). The importance of genetic testing and the role of genetic counseling for patients with KSD were shown.

[Genetic aspects of primary hyperoxaluria: diagnostics and treatment].

Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.

[Genetic aspects of primary hyperoxaluria: epidemiology, ethiology, pathogenesis, and clinical signs of the disorder].

Primary hyperoxaluria is a group of rare inherited diseases characterized by impaired oxalate metabolism with the early manifestation of urolithiasis and the development of the chronic kidney disease. The mutations in the AGXT, GRHPR, HOGA1 genes are attributable for different types of primary hyperoxaluria leading to the dysfunction of specific enzymes involved in the oxalate metabolism. The article summary the current data on the epidemiology, genetic and biochemical aspects of pathogenesis of the primary hyperoxaluria types 1-3. The variety of clinical signs and disease severity depend on the type of hyperoxaluria.

[Genetic factors for monogenic forms of calcium urolithiasis].

The article presents pooled results of domestic and international studies investigating genetic aspects of urolithiasis associated with impaired calcium metabolism. The review highlights the importance of early and accurate diagnosis of hereditary diseases associated with kidney stone formation. Of more than 80 currently known monogenic forms of urolithiasis, the authors provide the list of the most significant forms. Using such molecular genetic methods as NGS (next generation sequencing) allows accurate detection of the genetic cause of the disease, develop an individual approach the patients management and timely prevention of the disease among the relatives of the proband.

[Genetic aspects of urolithiasis].

The article presents summarized results of domestic and international studies of the genetic aspects of urolithiasis. The presented evidence suggests the importance of early and accurate molecular genetic diagnostics of hereditary diseases associated with stone formation for timely treatment and prevention for patients' relatives. Also provided are examples of using molecular genetic diagnostics in urologist's practice for monogenic and multifactorial diseases associated with stone formation. Taken together, these results show that using modern post-genomic technologies for assessing the risk of hereditary predisposition to urolithiasis is justified.

[Organization of genetic service in multiprofile hospitals].

The necessity to organize genetic service for patients and their relatives in multiprofile hospitals is discussed. Analysis of long-term experience of the Medical Genetic Department at the First Moscow Medical University yielded main characteristics to be used for the organization of medical genetic service at such hospitals based at independent divisions. Such services ensure more efficacious care than those at the regional level.

[Effect of electromagnetic irradiation of the millimetric range on hemodynamics in patients with arterial hypertension]. / Vliianie élektromagnitnogo izlucheniia millimetrovogo diapazona na gemodinamiky u bol'nykh arterial'noi gipertoniei.

The study of efficacy of combined therapy including exposure to millimetric electromagnetic radiation (MER) in hypertensive patients has found a corrective hemodynamic effect of such treatment which appeared more potent than pharmacotherapy alone or combinations with sinusoidal modulated currents and placebo electromagnetic radiation. In hypokinetic and eukinetic types of hemodynamics MER raises cardiac output, lowers peripheral vascular resistance; in the hyperkinetic type there was a fall in the stroke and cardiac indices, compensatory rise of vascular resistance. The above changes in the course of treatment result in decline of both systolic and diastolic pressure and conversion of "extreme" types of hemodynamics in eukinetic in 11% patients. In hypertensive patients with eukinetic and hyperkinetic type of hemodynamics the best hemodynamic efficacy was achieved in combined therapy with 5.6 mm radiation.

[Ito's hypomelanosis]. / Gipomelanoz Ito.

A severe form of hypomelanosis of Ito in two-year-old white girl is reported. The disease was revealed as fetal microcephalia and epileptic seizures. Peripheral blood lymphocyte karyotype was normal. Brain MRI revealed absence of clear delineation between cortical grey matter and brain white matter. The literary review with emphasis of the neurological manifestations is presented.

[Inhomogeneity of control samples as the reason for additional variations in the spontaneous level of chromosome aberrations in a human lymphocyte culture]. / Neodnorodnost' kontrol'nykh vyborok kak prichina dopolnitel'nykh variatsii spontannogo urovnia khromosomnykh aberatsii v kul'ture limfotsitov cheloveka.

The results of population cytogenetic studies performed by a standard technique in one laboratory during 1987-1992 are summarized. Variations in the rate of spontaneous chromosomal aberrations were found in lymphocyte culture derived from individuals employed in the nonindustrial sphere and in the administrative sector of the chemical industry. The proportion of cells with chromosomal aberrations is 1.56 +/- 0.10% in the first group and 2.78 +/- 0.15% in the second one. The ratio of types of aberration is similar in both groups. No differences were observed in the rate of spontaneous chromosomal aberrations as related to the extent of chemical pollution of place of residence.

[Cytogenetic screening of workers of rubber manufacturing industry]. / Tsitogeneticheskoe obsledovanie rabochikh proizvodstva reziny.

Cytogenetic analysis of lymphocytes was performed in 36 preparatory workers engaged into rubber shoes and general mechanical rubber goods production. Preparatory workers and management staff had the same chromosomal aberrations frequency. Although chromosomal aberrations frequency in employees of the enterprise appeared to be twice as much as that for general population, which proves hazardous factors of rubber production to afflict genofond of employees.

[Comparison of the cytogenetic effects of cyclophosphamide on monkey lymphocytes in vivo and in vitro]. / Sravnenie tsitogeneticheskikh éffektov pri deistvii tsiklofosfamida na limfotsity obez'ian in vivo i in vitro.

The comparative in vivo and in vitro study of chromosomal aberrations and SCE induced by cyclophosphamide (CP) in macaca rhesus lymphocytes was performed. The dose of mutagenic exposure for quantitative estimation of effects was determined as a product of concentration of alkylating CP metabolites on the exposure time. The mutagenic effect caused by the same doses of CP (CP metabolites) appeared similar in vivo and in vitro. This suggests that the results obtained in adequate in vitro mutagen-testing experiments may be quantitatively extrapolated for the in vivo conditions.

Cytogenetic effects of cyclophosphamide on human lymphocytes in vivo and in vitro.

A comparative study of cytogenetic effects in human lymphocytes caused in vivo by cyclophosphamide (CP) after intravenous injection and in vitro by exposure of plasma of the same patients was carried out. It was found that the frequency of induced chromosome aberrations (CA) and sister-chromatid exchanges (SCE) increased linearly for SCE and exponentially for CA within the 'dose' of alkylating activity of CP metabolites. Parameters of 'cytogenetic effect-dose' in vivo and in vitro coincided. The intensity of cytogenetic effects varied between individuals.

[Induction of chromosome aberrations in human lymphocytes by cyclophosphamide action in vivo and in vitro]. / Induktsiia khromosomnykh aberratsii v limfotsitakh cheloveka pri deistvii tsiklofosfamida in vivo i in vitro.

The dose dependences of chromosome aberrations rate were investigated in lymphocytes of oncological patients after cyclophosphamide (CP) administration. It was shown that the rate of chromosome aberrations and the number of disruptions per cell in vivo and in vitro increases exponentially with the dose. At the same time, the parameters of regression equations coincide. This evidences that CP has the similar effect in vivo and in vitro.

[Principles of cytogenetic examination for detecting occupational hazards]. / Printsipy tsitogeneticheskogo obsledovaniia dlia vyiavleniia professional'nykh vrednostei.

The main principles are stated of carrying out a cytogenetic examination of human populations on the basis of critical analysis of data from literature and the authors' own experience in this field. The method for estimation of sister chromatid exchanges is shown expedient to be used together with the chromosome aberration analysis in carrying out cytogenetic examinations. Statistically ascertained approaches are adduced to select the necessary amount of persons examined in groups and the number of cells for analysis when using methods for estimation of sister chromatid exchanges and chromosome aberrations.

Alterations in the baseline sister-chromatid exchange frequency in human lymphocyte culture following a number of cell divisions.

A significant decrease in the baseline of sister-chromatid exchanges (SCEs) was observed in cultured human lymphocytes, if 5-bromodeoxyuridine (BrdU) was added after 60 h of culture, and the cells were harvested at least 24-30 h after BrdU exposure. This decrease is supposed to occur if at least one cell division takes place before the addition of BrdU. For cytogenetic monitoring of mutagenic environmental factors, using human lymphocyte cultures, it is assumed that two time periods are sufficient for comparison.

[Frequency of sister chromatid exchanges in oncological patients during treatment with cyclophosphane]. / Chastota sestrinskikh khromatidnykh obmenov u onkologicheskikh bol'nykh v protsesse lecheniia tsiklofosfanom.

The sister chromatid exchange (SCE) level in patients with cancer of lungs before treatment did not differ from the mean number of SCE in healthy donors. In the process of a cyclophosphane treatment the SCE frequency in the patient lymphocyte culture increased with the drug doses of 4 and 5 g. Analysis of the ratio of cells in mitoses I, II and III revealed no differences in the cell cycle rate for groups of healthy donors, patients before the treatment, and treated patients.