[Significance of surfactant proteins in the diagnosis of therapeutic diseases].

The lung provides not only respiration, but also the functioning of innate immunity mechanisms. The hydrophilic proteins SP-A and SP-D are responsible for the regulation of the latter. In the literature, there is evidence for elevated serum SP-A and SP-D levels in respiratory diseases accompanied by enhanced mucosal inflammation of the lung or its parenchymal injury and their association with age and cardiovascular diseases has been recently found. Studies of the efficiency of using SP-A and SP-D as specific markers for inflammatory lung diseases are presently worthwhile.

Polymorphism of genes associated with infectious lung diseases in Northern Asian populations and in patients with community-acquired pneumonia.

The innate immune system is the first to respond to invading pathogens. It is responsible for invader recognition, immune-cell recruitment, adaptive-immunity activation, and regulation of inflammation intensity. Previously, two single-nucleotide polymorphisms of innate-immunity genes - rs5743708 (Arg753Gln) of the TLR2 gene and rs8177374 (Ser180Leu) of the TIRAP gene - have been shown to be associated with both pneumonia and tuberculosis in humans, but the data are contradictory among different ethnic groups. It has also been reported that rs10902158 at the PKP3-SIGGIR-TMEM16J genetic locus belongs to a haplotype race-specifically associated with tuberculosis. Meanwhile, a gradient of its frequency is observed in Asia. The aim of this work was to assess the effect of selection for the genotypes of the above-mentioned SNPs on the gene pools of populations living in harsh climatic conditions that contribute to the development of infectious lung diseases. We estimated the prevalence of these variants in white and Asian (Chukchis and Yakuts) population samples from Northern Asia and among patients with community-acquired pneumonia (CAP). Carriage of the rs5743708 A allele was found to predispose to severe CAP (odds ratio 2.77, p = 0.021), whereas the GG/CT genotype of rs5743708/rs8177374 proved to be protective against it (odds ratio 0.478, p = 0.022) in white patients. No association of rs10902158 with CAP (total or severe) was found among whites. Stratification of CAP by causative pathogen may help eliminate the current discrepancies between different studies. No significant difference in rs5743708 or rs8177374 was found between adolescent and long-lived white samples. Carriage of the alleles studied is probably not associated with predisposition to longevity among whites in Siberia. Both white and Asian populations studied were different from Western European and East Asian populations in the variants' prevalence. The frequency of the rs8177374 T (Ser180Leu) variant was significantly higher in the Chukchi sample (p = 0, χ2 = 63.22) relative to the East Asian populations. This result may confirm the hypothesis about the selection of this allele in the course of human migration into areas with unfavorable climatic conditions.

[Clinical and genetic features in patients with asthma and their relatives].

A familial survey was conducted in 81 probands who were diagnosed as having bronchial asthma (BA) and their 183 first-, second-, and third-degree relatives (a study group). A control group comprised 263 apparently healthy individuals. The familial accumulation of BA was ascertained in the families of probands with this condition. Autosomal dominant inheritance of BA was established. The heterozygous variant of the macrophage-colony-stimulating factor receptor (MCSFR) gene genotype chi-fms may be considered as one of the genetic predictors of BA. The homozygous genotype in a rare allele of the MCSFR gene may be also a predictor of BA.

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance]. / Deletsionnyi polimorfizm 11-go introna gena c-fms cheloveka: chastoty allelei v nekotorykh populiatsiiakh Rossii i vozmozhnaia funktsional'naia znachimost'.

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

[Nonspecific lung diseases among the population of Western Siberia]. / Nespetsificheskie zabolevaniia legkikh u zhitelei Zapadnoi Sibiri.

Epidemiological surveys conducted in the city of Novosibirsk and the Novosibirsk region in 1980-1986, revealed a high though unequal prevalence of nonspecific pulmonary diseases among different age, sex and occupational groups of the urban and rural population. Chronic bronchitis ranked first in the structure of chronic nonspecific pulmonary diseases. ARVI and recurrent acute pneumonia, unfavorable working conditions and harmful habits influenced the development of chronic bronchitis. The introduction of a 5-group system of dynamic dispensary observation was conductive to a 2.5-3-fold decrease in temporary disability caused by diseases of the respiratory organs preventing a considerable economic loss.

[The specific features of TNF-alpha gene polymorphism in asthmatic patients and their relatives].

The polymorphism of the TNF A gene was studied in 89 asthmatic patients and their 162 relatives in order to estimate the contribution of this candidate gene to the predisposition to the development of asthma and allergic diseases. A control group comprised 258 individuals without bronchopulmonary pathology The polymerase chain reaction was used to study the 308 G/A polymorphism of the TNF A gene. The findings suggest that the asthmatic patients and their relatives have no association of the polymorphism of the TNF A gene in position 308 with their predisposition to the disease. Analysis of the distribution of the frequencies of alleles and genotypes among their probands, relatives, and the control group revealed no statistically significant differences between the groups.

[Organization of detection of patients with nonspecific diseases of the lung and their ambulatory care]. / Organizatsiia vyiavleniia bol'nykh nespetsificheskimi zabolevaniiami legkikh i dinamicheskogo dispansernogo nabliudeniia za nimi.

The rate of nonspecific diseases of the lungs among urban and rural population of the Novosibirsk Region was studied by using two-stage screening. It was shown that the number of tuberculous patients per 100,000 adults in the Region as a whole was in 1985-1987 the following: 860.0-1497.0 persons with chronic bronchitis and 170.0-187.0 persons with bronchial asthma. An increase in the number of the persons with chronic bronchitis and bronchial asthma among the inhabitants of both Novosibirsk and the Region was stated. On the basis of these data a scheme for differential dispensary observation was developed. The scheme includes combined prophylactic and treatment programs. The developed organizational grounds for the prophylaxis, early detection and treatment promoted a decrease in primary invalidism due to nonspecific respiratory diseases among the inhabitants of Novosibirsk from 2.2 per 10,000 workers in 1985 to 1.6 in 1987. The respective figures for the inhabitants of the Region were 4.7 and 3.9.