Biomedical subjects

S V Ivanov

Publications and source records attributed to S V Ivanov.

At least 19 recordsLinked to original sources

PubMed2006

Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13.

DEC1/STRA13 is a bHLH type transcriptional regulator involved with immune regulation, hypoxia response and carcinogenesis. We recently demonstrated that STRA13 interacts with STAT3 in the transcriptional activation of STAT-dependent promoters. Here, we pursue STRA13 involvement in the JAK/STAT pathway by studying its role in STAT1 expression. First, we showed that VHL deficiency or HIF-1 activation resulted in the repression of endogenous STAT1 mediated by STRA13. We then characterized the STAT1 proximal promoter to assess its response to STRA13 by transient coexpression in a luciferase reporter assay. Using sequential truncation and site-directed mutagenesis of the STAT1 promoter with STRA13 deletion constructs, we showed that the STRA13 C-terminal trans-activation domain, which is known to bind HDAC1, mostly determines the repressive activity. Involvement of HDAC activity in STAT1 regulation was validated by TSA inhibition and chromatin immunoprecipitation (ChIP) assay. Thus, we demonstrate that STRA13-mediated repression of STAT1 transcription utilizes an HDAC1-dependent mechanism. Furthermore, we show that targets of unphosphorylated STAT1, such as antigen presenting genes and CASP1, are also repressed by hypoxia possibly through the same STRA13-mediated mechanism. Thus, the newly discovered link between HIF-1 and STAT1 reveals a previously unknown role of STRA13 in hypoxia and carcinogenesis.

Amino Acid Motifs↗

PubMed2005

Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins.

STRA13 is a hypoxia-inducible bHLH transcription factor implicated in the pVHL/HIF, TGF-beta, and Jak/STAT pathways. To further characterize the STRA13 protein-interacting network and mechanisms of STRA13-dependent transcription, we utilized yeast two-hybrid screening. Here we report on STRA13 interaction with the cell cycle-associated transcription factor MSP58. We demonstrated that the basic domain of STRA13 and the FHA domain of MSP58 are essential for this association. We performed phospho-peptide mapping of both MSP58 and STRA13 and showed that their association was modulated by the STRA13 phosphorylation status. STRA13/MSP58 complex formation protected both proteins from the proteasome-mediated degradation, extending their half-lives considerably. STRA13 and MSP58 synergistically co-operated in the STRA13 promoter-driven transcription repression. Both proteins were co-localized in the nucleus and showed transcript accumulation during the S phase of the cell cycle. Thus, we characterize a novel STRA13-associated transcription repression complex and provide a link between cell cycle regulation and STRA13 activity.

Alternative Splicing↗

PubMed2004

STRA13 interacts with STAT3 and modulates transcription of STAT3-dependent targets.

STRA13 is a pVHL-dependent bHLH transcription factor up-regulated on the mRNA level in multiple cancer cell lines and implicated recently in the regulation of immune cell homeostasis and autoimmunity. In searching for STRA13-interacting proteins with oncogenic potential by the yeast two-hybrid screening, we identified STAT3 beta as a STRA13-binding partner. We showed that STRA13 binds predominantly to phosphorylated (active) STAT3 alpha and beta isoforms via its HLH and C-terminal regions. We also found that STRA13 was able to activate transcription from STAT-dependent cis-elements. Expression of endogenous STRA13 was shown to be cytokine-inducible, consistent with STRA13 involvement in STAT-dependent transcription regulation. We demonstrated that the STAT3-regulated promoter of the pro-apoptotic Fas gene was activated upon STRA13 over-expression and that co-expression of STRA13 with STAT3 beta or STAT3 alpha modulated the transcriptional outcome. Forced expression of STRA13 induced apoptosis, in agreement with the STRA13 activation effect on the Fas promoter. Simultaneous expression of STRA13 and STAT3 beta resulted in alleviation of the STRA13 pro-apoptotic effect. Thus, for the first time, we identify STRA13 as a STAT3 partner and provide a consistent line of evidence for STRA13 involvement into regulation of apoptosis via the STAT pathways.

Amino Acid Sequence↗

PubMed2004

Mie resonances, infrared emission, and the band gap of InN.

Mie resonances due to scattering or absorption of light in InN-containing clusters of metallic In may have been erroneously interpreted as the infrared band gap absorption in tens of papers. Here we show by direct thermally detected optical absorption measurements that the true band gap of InN is markedly wider than the currently accepted 0.7 eV. Microcathodoluminescence studies complemented by the imaging of metallic In have shown that bright infrared emission at 0.7-0.8 eV arises in a close vicinity of In inclusions and is likely associated with surface states at the metal/InN interfaces.

Journal Article↗

PubMed2004

[Effectiveness of collagen plasty in complex treatment of localized pyopneumothorax].

The work is based on an analysis of results of treatment of 25 patients with localized pleuro-pulmonary cavities by the methods of minor surgery. During abscessoscopy collagen was placed on the wound surface, the surface was filled with fibronectin and followed by active aspiration within 12-24 hours. In 20 (80%) patients the lung was expanded earlier. Five patients had no effect.

Collagen↗

PubMed2004

[Personality disorders in postoperative period of coronary artery bypass graft surgery].

Personality disorders (PD) are recognized among key maladaptive factors in postoperative period of coronary artery bypass surgery (CABS). However studies on PD among CABS patients are predominantly under psychological approach and information on clinical features is very limited. A present investigation aimed at assessing clinical features and prognostic value of PD in late post operative period of CABS (from 1 to 3 years). Using psychiatric, cardiological and psychological methods, 48 patients (42 male, mean age 61.3 +/- 8.2 years) with diagnosis of PD and favorable cardiological status after CABS have been assessed. PD in post operative period is an important predictor of unfavorable social and occupational outcome of CABS. Three types of clinical course of PD were singled out: 1) hypohondric personality development; 2) "second life" personality development; 3) "denial of illness" reactions. Pronounced maladaptation was observed in type 1, most severe one--in type 2 and minimal maladaptation or its absence--in type 3. These types were differentiated by different repertoires of psychological defense mechanisms (PMD): type 1 was characterized by a limited number of them with a drift to mature mechanisms; PD of type 2 are featured by a narrow and rigid repertoire of defenses with predomination of immature mechanisms and in type 3 a maximum number of PMD with balanced involvement of mature and immature mechanisms was observed.

Adaptation, Psychological↗

PubMed2003

[Spectrum of therapeutic efficacy and safety of Lorafen (lorazepam) use for anxiety disorders].

Presented here, are the results of 4-weeks lorafen monotherapy in 31 in-patients of psychiatric and cardio-surgical clinics divided, respectively, into 2 groups: 16 patients with chronic anxiety disorders and 15--with acute developed before an coronary artery bypass surgery in ischemic heart disease. A dynamics of the patients' state was evaluated with Hamilton Rating Scale for Anxiety and the Hospital Anxiety and Depression Scale. Lorafen proved to be highly effective, with percentage of responders being about 77% (24 patients out of 31). Therapeutically effective dosage was 3.7 +/- 1.1 mg daily for chronic anxiety disorders and 2.1 +/- 0.6 mg--for situation-induced anxiety. Lorafen was shown to be tolerable and safety.

Adolescent↗

PubMed2003

[Pyrazidol in the treatment of depression in patients with ischemic heart disease].

AIM: To study efficacy and safety of pirazidol administration in depressive patients with ischemic heart disease (IHD). MATERIAL AND METHODS: Pirazidol was given in a dose 0.15-0.3 g/day for 4 weeks to 30 IHD patients aged 21-65 years. 21 of them had nosogenic depression, 9 patients had dysthymia. The efficacy of the antidepressive action was assessed by the Hamilton scale. RESULTS: The trend to a decrease in Hamilton scale scores was manifest by the end of the treatment week 2. To the end of the study the overall score median lowered from 17 to 9, most of the patients had the score sum under 11. Side effects were insignificant. In pirazidol combination with beta-blockers, blockers of calcium channels, antiaggregant, diuretic drugs, nitrates and other cardio- and angiotropic drugs unfavorable interactions were not registered. CONCLUSION: Pirazidol can be effectively used in the treatment of psychosomatic disorders in patients with cardiovascular diseases.

Adult↗

PubMed2002

Differential display analysis of gene expression in yeast.

RNA differential display (DD) is a powerful and straightforward method that employs random reverse-transcription polymerase chain reaction amplification of mRNA species with electrophoresis for comparative analysis of two or more transcriptomes. The small yeast genome represents a convenient model for studying basic functions of the eukaryotic genome and simultaneously provides valuable information towards further refinement of this technique. Several examples discussed below illustrate how DD coupled with classical yeast genetic approaches may be used for studying transcriptionally regulated genetic systems.

Blotting, Northern↗

PubMed2002

[Visceral neuroses: clinical approaches to the problem].

Visceral neuroses are regarded as psychosomatic pathology represented by functional symptom complexes common for both psychic (personality, psychopathologic disorders of anxietyphobic, affective, hypochondriac spectrum) and somatic pathology. Two hundreds fourteen patients: 67 with hyperventilation syndrome (HVS), 77 with Da Costa syndrome (DCS), 70 with irritable bowl syndrome (IBS) have been studied. The study suggest that visceral neuroses represent a group of independent diseases. In contrast to converse neuroses, a topical projection (respiratory, cardiovascular system, gastrointestinal tract, etc.) of visceral neuroses reflects not only a psychosomatic disorder's specificity but also the course and prognosis regularities inherent to them. HVS course is wavy with periodic exacerbations and incomplete remissions, DCS one is phased (remissive), IBS is chronic without distinct phases and intervals. HVS and DCS are comorbid to milder psychic (personality and anxiety phobic disorders) and somatic pathology. IBS is associated with not only more severe mental disorders (overvalued, hypochondriac, affective) but also with chronic somatic diseases (alimentary system).

Adult↗

PubMed2002

[Schizophrenia and schizophrenia spectrum disorders in general hospital].

The prevalence and clinical presentation of schizophrenia and schizophrenia spectrum disorders in general hospitals were studied. The disease incidence rate was estimated at 3.1% that was 3 times higher than that in general population. Slow-progredient (latent) schizophrenia with comorbid functional visceral disorders ("organoneurotic" schizophrenia) occurs most frequently. Once manifested, the latter was associated with somatoform disorders during the disease course and developed concomitantly with neurotic and overvalued hypochondria symptoms. The authors suggest that several variants of complex relations between the endogeneous disease (schizophrenia) severity and functional somatic disorders. Slow-progredient (latent) disease reveals an affinity to a number of somatic disorders associated with neurotic and overvalued hypochondria. In more severe disease forms combination of endogenous process with somatoform disorders is accompanied by development of hypochondria with stable algias. In progressive (paranoid) schizophrenia, association with somatoform disorders occurs only at the initial stage of the process. Somatic sensations trigger formation of delusion symptom complexes of cathestesic delusion type.

Adult↗

PubMed2001

Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway.

In this study, we focus on different modes of regulation of STRA13, a human ortholog of the mouse basic helix-loop-helix transcriptional factor, previously identified by us as a new von Hippel-Lindau tumor suppressor gene (VHL) target. The gene was overexpressed in VHL-deficient cell lines and tumors, specifically clear cell renal carcinomas and hemangioblastomas. Introduction of wild type VHL transgene into clear cell renal carcinoma restored low level expression of STRA13. Overexpression was also detected in many common malignancies with an intact VHL gene, suggesting the existence of another, VHL-independent pathway of STRA13 regulation. Similar to many other von Hippel-Lindau tumor-suppressor protein (pVHL) targets, the expression of STRA13 on the mRNA level was hypoxia-sensitive, indicating oxygen-dependent regulation of the gene, presumably through the pVHL/hypoxia-inducible factor 1 (HIF-1) pathway. The yeast two-hybrid screening revealed interaction of the STRA13 protein with the human ubiquitin-conjugating enzyme (UBC9) protein, the specificity of which was confirmed in mammalian cells. By adding the proteasome inhibitor acetyl-leucinyl-leucinyl-norleucinal, we demonstrated that the 26 S proteasome pathway regulates the stability of pSTRA13. Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. Hypoxia treatment of mammalian cells transiently expressing STRA13 protein showed that stability of pSTRA13 is not affected by hypoxia or VHL. Thus, STRA13, a new pVHL target, is regulated in cells on multiple levels. We propose that STRA13 may play a critical role in carcinogenesis, since it is a potent transcriptional regulator, abundant in a variety of common tumors.

Basic Helix-Loop-Helix Proteins↗

PubMed2001

The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity.

Examination of patients with various forms of anxiety and phobic disorders (according to DSM-4 criteria) demonstrated a considerable shortening of enkephalin half-life and reduced total enkephalinase activity in the blood during generalized anxiety, but not during panic disorders and agoraphobia. This was probably related to low blood concentration of endogenous inhibitors of enkephalin-degrading enzymes in patients with generalized anxiety disorders. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which attenuates behavioral anxiety reactions and does not cause side effects typical of most anxiolytics, dose-dependently inhibited enzymatic hydrolysis of plasma enkephalin (IC50 15 microM). Selank was more potent than peptidase inhibitors bacitracin and puromycin in inhibiting enkephalinases. These results suggest that high efficiency of Selank in the therapy of anxiety and phobic disorders, including generalized anxiety, is due to its ability to inhibit enkephalin hydrolysis.

Anti-Anxiety Agents↗

PubMed2000

Mesenchymal-epithelial transition in the developing metanephric kidney: gene expression study by differential display.

The developing metanephric kidney is a convenient model to study molecular events associated with epithelial cell differentiation. To determine the genes involved in the defining event of this process, namely, the conversion of metanephric mesenchyme to the epithelium of the nephron, we applied differential display (DD) techniques. Explants of rat metanephric mesenchymes were induced to condense ex vivo with fibroblast growth factor 2 (FGF2) or to form tubules with FGF2 and conditioned medium (CM) from a cell line (RUB1) of ureteric bud, the renal inductive tissue. Three time points (6, 24, and 72 h) were chosen to track the dynamics of gene expression during morphogenesis. Seventy-two up- or down-regulated mRNAs were identified, including 36 novel sequences and those of cell cycle regulatory proteins (TGF-beta2, Cyclin D1, p57Kip2), transcription factors (beta-catenin, Sox11, DP1), signaling proteins (SH3-domain binding protein, G-protein-coupled receptor, Ser-Thr protein kinase), cell adhesion molecules (syndecan-4, integrin-beta1), and also gene33, H19, SM20, IGFBP5, MAMA receptor, lectin, keratin, beta-tubulin, calreticulin, GRP78, ERp72, MnSoD, thioredoxin, and others. Some have previously been associated with kidney development and serve as good controls for expected changes, while most have not been linked with kidney epithelial cell differentiation. Using thin sections of embryonic kidney and labeled antisense RNA probes, we applied RNA hybridization to confirm the results of DD and related the expression of these genes to specific cell lineages of the developing kidney. These results provide a window into the events that mediate this critical differentiation process and suggest that a limited number of interrelated events direct the epithelial conversion of metanephric mesenchyme. genesis 27:22-31, 2000. Published 2000 Wiley-Liss, Inc.

Animals↗

PubMed2000

[Differentiated types of chronic agoraphobia].

The study included 60 patients aged 18-65 years with anxious-phobic disorder (APD)--agoraphobia with and without panic disorders. Diagnosis of the disease was performed according to ICD-10. It was established that dynamics and outcome of APD with stable agoraphobia depend on some comorbid psychic disorders (neurotic, nonpsychotic affective, personality disorders, slow-progredient schizophrenia). Influence of such disorders on APD depends on level of realization of the comorbid correlations: symptomatic (nondelirious hypochondria) and intersyndromal ones (affective and personal disorders as well as slow-progredient schizophrenia). Typology of APD with stable agoraphobia is proposed, that is determined by comorbid correlations with the phenomena of nondelirious (overvaluable or neurotic) hypochondria. Agoraphobia, comorbid with the phenomena of overvaluable hypochondria, is characterized by isolated phobic avoidance (1-2 situations), lack of the signs of progredience of psychopathologic disorders and relatively favourable outcome (lack of the cases of invalidism, decrease of a professional status in 8% of the patients). Agoraphobia, comorbid with the phenomena of neurotic hypochondria, is characterized by total phobic avoidance, syndromal comorbidity with polymorphic and generalized somatophormic disorders, depressive disorders syndromally completed, slow-progredient schizophrenia and less favourable outcome (avoidance behaviour of severe degrees was found in 57% of the patients, including 18% of patients disabled due to mental disease).

Adolescent↗

PubMed2000

[The use of late temporary bronchial occlusion in the combined treatment of patients with acute suppurative lung abscesses].

The article presents results of late temporary occlusion of bronchi for prevention of chronicalization of the inflammatory process in 34 patients with acute purulent abscesses of the lungs. Formation of the dry residual cavity with the diameter of 2 cm and more was taken as an indication for such intervention. As a result of the treatment complete recovery was noted in 18 patients (52.9%), the state of 13 patients (38.2%) was improved, 3 patients (8.8%) had no effect. It was found that late temporary occlusion of the bronchi in combination with transdrainage vacuum aspiration made the effectiveness of conservative therapy for lung abscesses higher and reliably increased the amount of completely recovered patients.

Acute Disease↗

PubMed2000

Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples.

The human RON gene (MST1R) maps to 3p21.3, a region frequently altered in lung cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK) closely related to MET, whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progression of lung cancer. We first determined the exon-intron structure of the gene by direct sequencing of RON cosmid DNA and PCR products containing intronic sequences, and then developed primers suitable for mutation analysis by the single-strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, all but the first one small (average size: 170 bp), a feature shared with other RTK genes. We performed SSCP analysis of RON in small and non-small cell lung cancer samples, upon detection of its expression in a sample of lung cancer cell lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several single nucleotide polymorphisms were also found. The panel of intron-anchored primers developed in this work will be useful for mutation analysis of the RON gene in different types of human tumors.

Animals↗

PubMed2000

[Sulpiride treatment of irritable colon syndrome].

A blind placebo-controlled randomized trial was made of efficiency and safety of sulpirid compared to basic treatment in irritable colon syndrome (ICS). 40 patients over 18 years with ICS were randomized into two groups. Group 1 patients received sulpirid monotherapy (200-450 mg/day). Group 2 received basic therapy (combined treatment with spasmolytic, bacterial and cholagogic drugs). The treatment took 6 weeks. It was proved that sulpirid is more effective in ICS as it reduced the syndrome by 85% (basic therapy by 10%), relieved abdominalgia, anxiety, depression, corrected stool. As to disbacteriosis, sulpirid effect was weak. Tolerance of treatment in both groups was good. Side effects developed in 15% of group 1 patients and were easily corrected by lowering of the daily dose.

Adolescent↗