[The availability and quality of the ambulatory polyclinic care].

The article deals with the results of the study of complex of medical demographic and social economic indicators of Nizhny Novgorod oblast during 1989-2010. The results are as follows. The policlinics' net reduced by 2.25 times, including by 10.6 times in rural area and by 12.6 times of ambulatories of community hospitals. The indicators of physicians' supply of oblast population decreased too especially in urban area. The annual number of visits to physicians per capita decreased by 1.36 times. The number of calls of out-patients to physicians of emergency medical care increased by 1.5 times. The morbidity with temporarily disability and primary registration as a disabled person decreased by 1.45 times, including able-bodied citizen by 1.54 times. In Nizhny Novgorod oblast, the rate of decrease of indicators of primary disability during 2006-2009 overpassed the corresponding federal indicators by 1.45 times. The population mortality increased by 1.43 times. The accessibility and quality of ambulatory polyclinic care significantly impacts on the levels of mortality and social security of population and can be used as an indicator of social risks in the region.

[Changes in rheological blood properties in patients with lupus nephritis and IgA-nephropathy].

AIM: To compare changes of hemorheological parameters in patients with lupus nephritis (LN) and IgA-nephropathy (IgA-N). MATERIAL AND METHODS: Kinetics of spontaneous aggregation, disaggregation of red cells in shearing flow, red cell deformability were studied in 73 patients with LN including 6 patients with active LN with nephrotic syndrome, 38 patients with active LN with urinary syndrome, 29 with inactive LN; in 24 patients with a hematuric form of IgA-nephritis (IgA-N); in 24 healthy volunteers (controls). RESULTS: Patients with LN and a hematuric form of IgA-H were found to have disorders of microrheological blood characteristics (accelerated formation of erythrocytic aggregates -EA of high density) depending on the form and activity of the disease. All LN and IgA-N patients exhibited increased time of "coin columbs" formation and accelerated aggregation. The largest EA were detected in IgA-H patients. Flow deformation ability of the red cells was poor in all the examinees. LN patients showed a positive correlation between maximal EA size and hematuria severity even in cases of trace proteinuria. A correlation was demonstrated in IgA-N patients between IgA level and EA density, between inhibition of GFR and erythrocytic deformability index. CONCLUSION: The above findings show deteriorated process of aggregation-disaggregation resultant from deterioration of red cell physical properties. Severity of hemorheological disorders depends on LN activity. Hematuria associated with increased size of EA is an important marker of the disease activity Hemorheological disorders in patients with active LN and IgA-N are an additional pathogenetic component of hematuria.

[The gastrointestinal stromal tumor of the stomach in child: characteristic of diagnostics].

The observation of stromal gastric tumor of 12 years old girl has been investigated. The diagnostics was carried out on tumor biopsy taken by a laparoscopy. An evident edema of stroma caused "pseudo-papillary" organization of epithelioid cell neoplasm prevented the right diagnosis established only by immunohistochemical staining of CD117 and CD34 markers. The absence of mutations in C-kit and PGFRA genes uncovered by molecular-genetic analysis is typical for stromal gastric tumors in child. The next gastric resection allowed to estimate tumor appearance and localization, histological organization, and to repeat immunohistochemical studying. This observation confirmed the correctness of diagnosis and established high level of Ki67 proliferative activity (12-15%) determined prescriptions of target medicamental therapy.

[A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit].

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.

[Significance of the markers of endothelial dysfunction and hemorheological disorders for assessing the activity and prognosis of chronic glomerulonephritis].

AIM: to define the clinical value of changes in blood rheological properties and renal endothelial function in patients with hematuric and nephritic forms of chronic glomerulonephritis (CGN) and to ascertain whether the indices under study can be applied to assess the activity (progression) of nephritis and used as a prognostic criteria. SUBJECTS AND METHODS: Sixty-one patients, including 30 with hematuric nephritis (Group 1) and 31 with nephrotic nephritis (Group 2), were examined. A control group consisted of 12 healthy individuals. The rheological properties of blood, such as its viscosity; kinetics of spontaneous aggregation and disaggregation of red blood cells in shear flow; their deformability; urinary excretion of functionally active von Willebrandt factor (WF), a plasminogen activator inhibitor type 1 (PAl-1); urine total fibrinolytic activity (UTFA), activity of urinary urokinase-type plasminogen activator (UPA) were studied. RESULTS: The patients with CGN were found to have signs of impaired blood rheological properties (increased viscosity, an accelerated rapid phase of erythrocyte aggregation, increased strength of erythrocyte aggregates) and vascular endothelial dysfunction in the microcirculatory bed, among other factors, increased urinary excretion of functionally active WF, PA-1, which correlated with the activity of CGN. Data were obtained on the negative impact of the level of urinary PAl-1 excretion, red blood cell aggregation on the prognosis of CGN regardless of its form, the markers of endothelial damage/activation. Low urokinase activity and decreased red blood cell deformability in parallel with higher diurnal proteinuria are of poor prognostic value for hematuric nephritis. CONCLUSION: The findings illustrate two ways of the involvement of the endothelium in the mechanisms contributing to the development of tubular interstitial fibrosis, namely: endothelial dysfunction and as a substrate that links the processes of immune inflammation, hemorheology, and fibrinolysis/proteolysis in the kidney. The regularities revealed by clinical and laboratory comparison suggest that the indices under study may be used to determine the prognosis of the disease and may serve as a basis for the application of treatments aimed at correcting the detected disorders.

[The morphology and differential diagnosis of neuroglial heterotopias and related tumors].

The paper reviews the data available in the literature and a clinicomorphological analysis of 15 cases of neuroglial heteropias and related tumors retrieved from the joint databases of Sikl's Department of Pathology, Pilsen, Czech Republic, and the Department of Pathology, Petrov Oncology Institute, with emphasis on the histological, immunohistochemical and ultrastructural features, as well as differential diagnosis.

[Small-cell variant of renal oncocytoma].

Renal oncocytoma is a distinct benign tumor accounting for approximately 3-5% of all renal tumors. This neoplasm is easily recognizable in its classic form: there are polygonal cells with abundant granular eosinophilic cytoplasm filled with mitochondria. The tumor cells are arranged in nests and tubular pattern. Here, 1 case of renal oncocytoma with a domination of small cells is reported (the so-called "oncoblasts") arising in elderly woman. These small cells have scant cytoplasm, dense hyperchromatic nuclei, and a high nuclear/cytoplasmic ratio. The term "small-cell variant of renal oncocytoma" was proposed for these cases. The unusual extensive small-cell component of the tumor may represent a potential diagnostic pitfall for primary or metastatic malignant small cell tumors.

[Mucinous tubular and spindle-cell carcinoma of the kidney].

4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of the kidney were studied. The patients' age was 43 to 87 years. Microscopically, this tumor comprised two major cell populations. One of them involved spindle cells with a sparse cytoplasm, which were arranged in the fascicular pattern, often resembling low-grade smooth muscle tumors. The other population was small cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic activity was low. Only one tumor had both cell components. The other three tumors were represented by the second type cells. Immunohistochemical staining with avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA, and CD10. All cases were stained positively with antibodies to the cytokeratins AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney should be differentiated from angiomyolipoma with the preponderance of a leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma, and renal cell carcinoma with sarcomatoid differentiation.

[Organization of municipal medical-and-social rehabilitation of the invalids of able-bodied age-veterans of armed conflicts].

A territorial model of the organization of medical-and-social rehabilitation of labor-liable-age invalids was studied basing on the results of the experiment which enabled to test in practice the system of rehabilitation, ensuring step-by-step persistent successive complex rehabilitation process with an individual approach to each invalid according to his or her health, personality, labor ability, social environment. The efficacy of this treatment was higher than executing separate medical and professional rehabilitation of invalids.

Ca2+/Mg(2+)-dependent endonuclease activation is an early event in VP-16-induced apoptosis of human breast cancer MCF7 cells in vitro.

Apoptosis is now recognized as one of the major processes regulating the size of cell populations. However, despite intensive investigations the biochemical and enzymological mechanisms involved in apoptosis remain unclear. In the present study we demonstrate activation of a Ca2+/Mg(2+)-dependent endonuclease during VP-16-induced apoptosis in MCF7 cells. Nuclease activation occurred prior to the appearance of internucleosomal DNA fragmentation, suggesting that this activation may be an early and possibly critical step in drug-induced apoptosis. Analysis of the internucleosomal DNA fragments showed that they contained phosphorylated 5'-ends, indicating that they were produced by a Ca2+/Mg(2+)-dependent endonuclease.

Internucleosomal chromatin degradation in myeloma and B-hybridoma cell cultures.

The activity of Ca/Mg-dependent endonuclease (CME) is strongly inhibited in myeloma X-63.Ag8.653 and B-hybridoma MLC-1c as compared with mouse splenocytes. Nevertheless, pronounced internucleosomal chromatin degradation occurs in both cell lines during long-term cultivation without passing. In isolated cell nuclei of X-63 the activation of CME, which precedes chromatin fragmentation in vivo and loss of cell viability, is revealed. The time-course of CME activation is opposite to cell proliferation and is not accompanied by alterations in enzyme quantity. The results suggest that cell death of X-63 and MLC-1c occurs via apoptosis, and involves the mechanisms controlling the activation and/or interaction of CME with chromatin.

The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine.

The purpose of this study was to develop a multitarget, multicolor fluorescence in situ hybridization (FISH) assay for the detection of urothelial carcinoma (UC) in urine specimens. Urinary cells obtained from voided urine specimens of 21 patients with UC and 9 normal donors were analyzed with nine different centromere enumeration probes and a single locus-specific indicator probe to determine an optimal set of FISH probes for UC detection. The four probes with the greatest sensitivity for UC detection were then labeled with a unique fluorophore and combined into a single probe set. The probes with the greatest combined sensitivity for UC detection were CEP3, CEP7, CEP17, and the 9p21 (P16) LSI. This probe set was used to evaluate urine specimens acquired from 179 patients for prospective testing (46 with biopsy-proven UC). FISH slides were evaluated by scanning the slide for cells with nuclear features suggestive of malignancy and assessing the FISH signal pattern of these cells for polysomy (ie, gains of two or more different chromosomes). A receiver operator characteristic curve revealed that a cutoff of 5 cells with polysomy as the positive criterion for cancer resulted in an overall sensitivity of 84.2% for patients with biopsy-proven UC and a specificity of 91.8% among patients with genitourinary disorders but no evidence of UC. This study demonstrates that a multitarget, multicolor FISH assay containing centromeric probes to chromosomes 3, 7, and 17 and a locus-specific probe to band 9p21 has high sensitivity and specificity for the detection of UC in voided urine specimens.

Mechanisms of induction of apoptotic DNA fragmentation.

PURPOSE: Despite its common use as an indicator of apoptosis, little is known about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells. This review discusses the pathways of chromatin fragmentation, and the role of both nucleases and chromatin structure in this process. DEFINITIONS: DNA fragmentation linked to apoptosis is a combination of cleavage events excising both large DNA fragments within the range 0.4-1.0 Mbp and 50 kbp followed by random cuts within internucleosomal regions (i.e. DNA laddering). The first two cleavage steps can be detected in virtually all apoptotic cells, but DNA laddering is not ubiquitously observed. Endonucleases that mediate this cleavage of chromatin may be classified by substrate specificity, mode of DNA cleavage and their cofactor requirements. CONCLUSIONS: Three major pathways of DNA fragmentation are proposed and discussed: (1) upregulation of endonucleases, (2) their intranuclear/intracellular redistribution and (3) primary changes of chromatin structure.

Abortive apoptosis as an initiator of chromosomal translocations.

Apoptosis is a well-recognized regulator of a cell populations size and structure. Irreversible stages of apoptosis lead to activation of different enzymatic cascades, changes in cell morphology and DNA fragmentation. However, little is known about nuclear events which accompany the initial stages of apoptosis. These events are connected with introduction of limited amounts of double strand breaks into genomic DNA, some of which may be subsequently rejoined. We hypothesize here that the initial stages of apoptotic DNA fragmentation may be reversible and connected with the initiation of recombinational events and certain chromosomal translocations. The factors influencing apoptosis reversibility and cell survival after delivery of apoptotic stimuli may provide new insights into mechanisms of lymphocyte development and tumorigenesis.

[Specificity of fragmentation of DNA from pBR322 plasmid by Ca,Mg-dependent endonuclease from cell nuclei of human lymphocytes]. / Spetsifichnost' fragmentatsii DNK plazmidy pBR322 Ca/Mg-zavisimoi éndonukleazoi kletochnykh iader limfotsitov cheloveka.

Fragmentation of the plasmid pBR322 DNA by a purified preparation of Ca/Mg-dependent endonuclease has been studied. It was shown that on the first steps of reaction the double-stranded cuts are introduced into the superhelical DNA independent of singlestranded ones. The doublestranded cuts are introduced into superhelical and linear DNA in 12 sites enriched with GC-pairs, 9 of them include pentanucleotide CGCGG(CCGCC) that is functionally significant. Relaxation of the plasmid DNA by topoisomerase I blocks the sitespecific action of the enzyme. Ca/Mg-dependent endonuclease is concluded to be topologically dependent enzyme, possibly, participating in the recombination processes.

[Ca/Mg-dependent endonuclease as a probe for detecting chromatin changes in lymphocytes in chronic lymphoid leukemia]. / Ca/Mg-zavisimaia éndonukleaza kak zond dlia vyiavleniia izmenenii khromatina limfotsitov pri khronicheskom limfoleikoze.

Chromatin fragmentation of bovine peripheral blood lymphocytes from normal animals and the ones suffering from chronic lympholeucosis (CLL) by DNase I, micrococcal nuclease and purified Ca/Mg-dependent endonuclease from nuclei of human splenocytes was studied. The lymphocytes chromatin from CLL animals was shown to be more resistant to nucleases, than the one from normal animals. It was found that difference between fragmentation of chromatin samples from normal and CLL bovines was more dramatic when Ca/Mg- dependent endonuclease was used versus traditionally exploited DNase I and micrococcal nuclease. The data suggest that purified Ca/Mg-dependent endonuclease can be a useful enzymatic probe for detection of lymphocytes chromatin changes during CLL.

[The action of high-molecular linear polymers on the circulatory system]. / Vozdeistvie vysokomolekuliarnykh lineinykh polimerov na sistemu krovoobrashcheniia.

An analysis of the hemodynamic consequences of the injections of long linear polymers with high molecular weight is introduced. These injections lead to an increase of the cardiac output, to a decrease of the blood pressure, and hence cause a reduction of the resistance to blood flow. It follows that such kind of polymers is able to normalize hemodynamics under some pathophysiological conditions, e.g., during experimental atherosclerosis, ischemic state, hemorrhagic shock. An addition of drag-reducing polymers into the blood system is associated with a modification of the blood flow microstructure itself.

[Vergina-like strains of tick-borne encephalitis in Russia]. / Verginapodobnye shtammy virusa kleshchevogo éntsefalita v Rossii.

The Greek strain Vergina representing an individual third serotype of tick-borne encephalitis (TBE) virus has been compared with 13 TBE strains isolated on the territory of Russia and Central Asia (in Kirghizia). A kit of deoxyoligonucleotide probes complementary to genome sites of Neudorfle strain of the TBE Central European subtype (protein C and prM genes) and of strain Sofyin of the Eastern subtype (protein E, C, M, prM, ns 1, ns 2b, ns 4b genes) was used in molecular hybridization of nucleic acids. Vergina strain was referred to the genetic variant VI prevalent in the western part of the East European plain, in Udmurtia, in the Altai mountains, and in West Siberia. By its antigenic properties Vergina strain is most close to strain Yar-90 isolated in the Yaroslavl district from Ixodes persulcatus ticks.

[Morphological characteristics of the capillary network in the rat brain in experimental DOCA-salt and renal hypertension]. / Nekotorye morfologicheskie osobennosti kapilliarnoi seti golovnogo mozga krys s DOKA-solevoi i pochechnoi éksperimental'noi gipertenziei.

The capillary network of nuclei n. reticularis pontis caudalis and n. ventralis thalami of the brain of the normal rats and animals with DOCA-salt and renal forms of experimental hypertension have been studied. It is shown that in 91 92% of the visual fields the number of capillary fragments is statistically significantly decreased as compared to the controls. 8-9% of the visual fields did not show statistically significant difference from the normal as to the density of the capillaries.