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Biomedical subjects

D Ivanov

Publications and source records attributed to D Ivanov.

At least 19 recordsLinked to original sources
PubMed2003

RFP2, c13ORF1, and FAM10A4 are the most likely tumor suppressor gene candidates for B-cell chronic lymphocytic leukemia.

Occurrence of 13q14 deletions between D13S273 and D13S25 in B-cell chronic lymphocytic leukemia (B-CLL) suggests that the region contains a tumor suppressor gene. We constructed a PAC/cosmid contig largely corresponding to a 380-kb 13q14 YAC insert that we found deleted in a high proportion of B-CLL patients. We found seven genes by exon trapping, cDNA screening and analysis/cDNA extension of known expressed sequence tags. One appeared to originate from another region of 13q. Recent publications have focused on two of the genes that most likely do not have a tumor suppressor role. This study evaluates the remaining four genes in the region by mutation scanning and theoretical analysis of putative encoded products. No mutations suggestive of a pathogenic effect were found. The 13q14 deletions may be a consequence of an inherent instability of the region, an idea supported by our finding of a considerable proportion of AluY repeats. Deletion of putative enhancer sequences and/or genes in the region may result in an inactivation of tumor suppression by a haploinsufficiency mechanism. We conclude that RFP2, c13ORF1, and a chromosome 13-specific ST13-like gene, FAM10A4, are the most likely candidates for such a type of B-CLL TSG.

B-Lymphocytes↗
PubMed2003

Lichens as biomonitors of uranium in the Balkan area.

The contribution of the conflict of 1999 to the environmental levels of uranium in the Balkan area was evaluated by means of lichens used as biomonitors. The average U concentration found in lichens in the present study was in line with the values reported for lichens from other countries and well below the levels found in lichens collected in areas with natural or anthropogenic sources of U. Measurement of isotopic ratios 235U/238U allowed to exclude the presence of depleted uranium. According to these results, we could not detect widespread environmental contamination by depleted uranium in the Balkan area.

Environmental Monitoring↗
PubMed2003

Chromosome 22q11 deletions, velo-cardio-facial syndrome and early-onset psychosis. Molecular genetic study.

BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with interstitial deletions of chromosome 22q11. About 30% of patients with VCFS have psychosis, and the rate of these deletions in schizophrenia has been reported to be about 1%. Even higher rates of VCFS deletions have been reported for childhood-onset schizophrenia. AIMS: To test the hypothesis that there is an increased rate of VCFS among patients with early-onset psychosis (age at onset <18 years). We screened 192 early-onset patients and 329 patients with adult-onset schizophrenia. METHOD: We genotyped the patients and 444 healthy controls for hemizygosity of five microsatellite markers and one single nucleotide polymorphism that map to the 22q11-deleted region. RESULTS: One patient had a VCFS deletion, confirmed with semi-quantitative polymerase chain reaction. None of the controls showed a pattern of genotypes consistent with hemizygosity. CONCLUSIONS: VCFS may be less frequent among patients with psychosis than previously suggested; this rate is not increased among early-onset patients.

Abnormalities, Multiple↗
PubMed2002

Topologically protected quantum bits using Josephson junction arrays.

All physical implementations of quantum bits (or qubits, the logical elements in a putative quantum computer) must overcome conflicting requirements: the qubits should be manipulable through external signals, while remaining isolated from their environment. Proposals based on quantum optics emphasize optimal isolation, while those following the solid-state route exploit the variability and scalability of nanoscale fabrication techniques. Recently, various designs using superconducting structures have been successfully tested for quantum coherent operation, however, the ultimate goal of reaching coherent evolution over thousands of elementary operations remains a formidable task. Protecting qubits from decoherence by exploiting topological stability is a qualitatively new proposal that holds promise for long decoherence times, but its physical implementation has remained unclear. Here we show how strongly correlated systems developing an isolated twofold degenerate quantum dimer liquid ground state can be used in the construction of topologically stable qubits; we discuss their implementation using Josephson junction arrays. Although the complexity of their architecture challenges the technology base available today, such topological qubits greatly benefit from their built-in fault-tolerance.

Journal Article↗
PubMed2001

The Mus cervicolor MuLV isolate M813 is highly fusogenic and induces a T-cell lymphoma associated with large multinucleated cells.

M813 is a type-C murine leukemia virus (MuLV) isolated from the Asian rodent Mus cervicolor. We have recently demonstrated that M813 defines a distinct MuLV receptor interference group. Here we show that M813 rapidly induces fusion of MuLV-expressing fibroblasts from "without," with syncytia being observed within 1 h after exposure to virus. Infection of fibroblasts with MuLV from all tested receptor-interference groups imparts susceptibility to M813-induced fusion, provided the cells also express the M813 receptor. Syncytium induction is also observed in vivo; mice infected with M813 develop a peripheral T-cell lymphoma, which is associated with large multinucleated cells of macrophage origin. A recombinant Moloney MuLV/M813 chimeric virus demonstrated that syncytium induction is a function of the Env SU protein. We postulate that the highly fusogenic property of M813 is attributable to either its unique receptor usage or sequences in the proline-rich domain of the Env protein.

Animals↗
PubMed2001

Expression of cell adhesion molecule T-cadherin in the human vasculature.

Alterations in expression of surface adhesion molecules on resident vascular and blood-derived cells play a fundamental role in the pathogenesis of cardiovascular disease. Smooth muscle cells (SMCs) have been shown to express T-cadherin (T-cad), an unusual GPI-anchored member of the cadherin family of adhesion molecules. Particular relevance for T-cad in cardiovascular tissues is indicated by our present screen (immunoblotting) of human tissues and organs whereby highest expression of T-cad was found in aorta, carotid, iliac and renal arteries and heart. To explore the (patho)physiological role for T-cad in the vasculature we performed an immunohistochemical analysis of T-cad expression in normal human aorta and atherosclerotic lesions of varying severity. T-cad was present both in the intima and media and was expressed in endothelial cells (ECs), SMCs and pericytes, but not in monocytes/macrophages, foam cells and lymphocytes. In the adventitia T-cad was present in the wall of vasa vasorum and was expressed in ECs, SMCs and pericytes. T-cad was differentially expressed in SMCs from distinct vascular layers of normal aorta (for example, high in the subendothelial (proteoglycan) layer of the intima, low in the musculoelastic intimal layer and in the media), as well as at different stages of lesion progression. In SMCs there was an apparent inverse relationship between the intensities of T-cad and smooth muscle alpha-actin expression, this being most prominent in lesions. The findings suggest a phenotype-associated expression of T-cad which may be relevant to control of the normal vascular architecture and its remodelling during atherogenesis.

Aorta↗
PubMed2001

Induction of vascular endothelial growth factor by nitric oxide in cultured human articular chondrocytes.

We investigated the role of nitric oxide (NO) in the control of vascular endothelial growth factor A (VEGF) gene expression in cultured human articular chondrocytes. Cell treatment with the NO-generating compound nitrosoglutathione (GSNO) caused a significant accumulation of 4.4 kb VEGF mRNA, a major VEGF mRNA isoform expressing in chondrocytes. This is the first demonstration that NO can induce VEGF mRNA expression in chondrocytes. VEGF mRNA level was not affected in cells exposed to dibutyryl cGMP, a non-hydrolyzable analog of cGMP, suggesting that the cGMP system is not involved in NO-dependent transcriptional activation of VEGF gene. The GSNO-stimulated induction of VEGF mRNA was slightly attenuated by MAP protein kinase inhibitors PD98058 and SB203580, but was completely blocked in cells incubated with GSNO in the presence of catalase and superoxide dismutase, enzymes scavenging reactive oxygen species (ROS), or in the presence of thiol-containing antioxidants, N-acetyl cysteine and reduced glutathione. These results suggest that in articular chondrocytes the GSNO-induced VEGF gene transcriptional activation is dependent on endogenous ROS production and oxidative thiol modifications.

Antioxidants↗
PubMed2001

Preparation, physicochemical characterization and pharmacological study of novel ruthenium(III) complexes with imidazole and benzimidazole derivatives.

Complex compounds of ruthenium(III) with 1,2-dimethylimidazole (CAS 1739-84-0), 2-phenylimidazole (CAS 670-96-2) and 2-aminobenzimidazole (CAS 934-32-7) were prepared and were characterised by physicochemical methods. Coordination sites were determined. The complexes were tested for cytotoxic activity using MTT (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye-reduction assay and the values LD50 were evaluated.

Animals↗
PubMed2001

Mus cervicolor murine leukemia virus isolate M813 belongs to a unique receptor interference group.

Murine leukemia virus (MuLV) M813 was originally isolated from the Southeast Asian rodent Mus cervicolor. As with the ecotropic MuLVs derived from Mus musculus, its host range is limited to rodent cells. Earlier studies have mapped its receptor to chromosome 2, but it has not been established whether M813 shares a common receptor with any other MuLVs. In this study, we have performed interference assays with M813 and viruses from four interference groups of MuLV. The infection efficiency of M813 was not compromised in cells expressing any one of the other MuLVs, demonstrating that M813 must use a distinct receptor for cell entry. The entire M813 env coding region was molecularly cloned. Sequence analysis revealed high similarity with other MuLVs but with a unique receptor-binding domain. Substitution of M813 env sequences in Moloney MuLV resulted in a replication-competent virus with a host range and interference profile similar to those of the biological clone M813. M813 thus defines a novel receptor interference group of type C MuLVs.

3T3 Cells↗
PubMed2001

[Laparoscopic resection of the rectum].

Improving the laparoscopic equipments and the techniques have spreaded the repertoire of the laparoscopic procedures. In the beginning, it was performed the laparoscopic-assisted resection of the rectum, and later was performed the entire laparoscopic procedures on the colon. It had presented a patient, 71 years old man with diagnosis of the adenocarcinoma recti. After preoperately prepare carried out the laparoscopic procedure with T-T anastomosis by EEA stapler. We presented the first case of the laparoscopical performed resection of the rectum with desire to show possibilities and advantages of the laparoscopic surgery in the relation with conventional surgery and with hope that this techniques would be found the application in our land.

Adenocarcinoma↗
PubMed2000

Domains in the SPT5 protein that modulate its transcriptional regulatory properties.

SPT5 and its binding partner SPT4 regulate transcriptional elongation by RNA polymerase II. SPT4 and SPT5 are involved in both 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB)-mediated transcriptional inhibition and the activation of transcriptional elongation by the human immunodeficiency virus type 1 (HIV-1) Tat protein. Recent data suggest that P-TEFb, which is composed of CDK9 and cyclin T1, is also critical in regulating transcriptional elongation by SPT4 and SPT5. In this study, we analyze the domains of SPT5 that regulate transcriptional elongation in the presence of either DRB or the HIV-1 Tat protein. We demonstrate that SPT5 domains that bind SPT4 and RNA polymerase II, in addition to a region in the C terminus of SPT5 that contains multiple heptad repeats and is designated CTR1, are critical for in vitro transcriptional repression by DRB and activation by the Tat protein. Furthermore, the SPT5 CTR1 domain is a substrate for P-TEFb phosphorylation. These results suggest that C-terminal repeats in SPT5, like those in the RNA polymerase II C-terminal domain, are sites for P-TEFb phosphorylation and function in modulating its transcriptional elongation properties.

Amino Acid Sequence↗
PubMed1999

Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation.

Tat activates transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by increasing the processivity of RNA polymerase II. Recently, it has been demonstrated that the cellular kinase CDK9 and its binding partner cyclin T1 are involved in regulating transcriptional elongation and tat-activation. Cyclin T1, CDK9 and Tat bind as a complex to elements in TAR RNA that are required for tat-activation. Here, we used cyclin T1 mutants to define domains in this protein that bind to both CDK9 and Tat and are involved in stimulating tat-activation. The region of cyclin T1 extending from amino acid residues 1 to 263 is necessary for complex formation with Tat bound to TAR RNA and for stimulation of tat-activation in murine cells that are normally poorly responsive to the actions of Tat. In contrast, a smaller region of cyclin T1 was required to bind to CDK9 and stimulate its kinase activity. Recombinant cyclin T1 and CDK9 stimulated both basal and tat-induced in vitro transcriptional elongation from the HIV-1 LTR. The effects of Tat on transcriptional elongation may be mediated by its ability to increase CDK9 phosphorylation of the RNA polymerase II C-terminal domain. These results demonstrate that cyclin T1 interactions with Tat and TAR RNA are critical for activation of HIV-1 gene expression.

Cyclin T↗
PubMed1999

Role of the human and murine cyclin T proteins in regulating HIV-1 tat-activation.

Human cyclin T1 markedly stimulates tat-activation in rodent cells which are normally poorly responsive to the effects of Tat. This result suggests that there are likely to be critical differences in the murine and human cyclin T1 proteins. Here, we analyzed the role of the murine and human cyclin T1 proteins in addition to the human cyclin T2a and T2b proteins on regulating tat-activation. Only the human cyclin T1 protein efficiently formed a complex with Tat bound to TAR RNA. This difference in function was due to the presence of a cysteine residue in human cyclin T1 at position 261 rather than a tyrosine or asparagine residue which are found in the murine cyclin T1 protein and the human cyclin T2a and T2b proteins, respectively. A mouse cyclin T1 protein containing a substitution of tyrosine residue 261 with a cysteine residue, was able to interact with Tat and stimulate tat-transactivation in rodent cells. Likewise, substitution of a cysteine residue for an asparagine residue at position 260 of the cyclin T2a and T2b proteins also resulted in their ability to interact with Tat and stimulate tat-activation in rodent cells. The data indicate that a specific residue in the cyclin T proteins is required for their in vitro interaction with Tat and their ability to stimulate in vivo tat-activation.

Animals↗
PubMed1999

Training astronauts using three-dimensional visualisations of the International Space Station.

Recent advances in personal computer technology have led to the development of relatively low-cost software to generate high-resolution three-dimensional images. The capability both to rotate and zoom in on these images superposed on appropriate background images enables high-quality movies to be created. These developments have been used to produce realistic simulations of the International Space Station on CD-ROM. This product is described and its potentialities demonstrated. With successive launches, the ISS is gradually built up, and visualised over a rotating Earth against the star background. It is anticipated that this product's capability will be useful when training astronauts to carry out EVAs around the ISS. Simulations inside the ISS are also very realistic. These should prove invaluable when familiarising the ISS crew with their future workplace and home. Operating procedures can be taught and perfected. "What if" scenario models can be explored and this facility should be useful when training the crew to deal with emergency situations which might arise. This CD-ROM product will also be used to make the general public more aware of, and hence enthusiastic about, the International Space Station programme.

Astronauts↗
PubMed1998

Isolation and characterization of [3H]fucose-labeled glycoproteins from the serum of normal rats and rats bearing Zajdela hepatoma.

Specific [3H]fucose-labeled glycoproteins were found in the serum of rats bearing Zajdela hepatoma, which possess different isoelectric points in comparison with serum glycoproteins from normal rats. The electrophoretic profile of the serum glycoproteins is significantly altered. There is approximately a 2.5 times increase of [3H]fucose incorporation into serum glycoproteins from rats with an ascitic form of hepatoma, compared with normal rats and to animals bearing a solid form of the tumor (which have a considerably greater survival). Serum fucoproteins identical for the two forms of hepatoma were isolated, as well as glycoproteins strongly specific for each of the forms.

Animals↗
PubMed1998

Synthesis, toxicological, pharmacological assessment, and in vitro bronchodilating activity of some 7-theophyllinylacetyloxyglycols.

The synthesis of four ester derivatives of 7-theophylline-acetic acid and glycols by DCC/DMAP-mediated esterification under mild conditions was studied. The structures of the synthesized compounds were proved by microanalyses, UV-, IR-, and 1H-NMR data. Acute toxicity assessment of the compounds in mice showed that compounds 2a-d are less toxic than aminophylline. It was shown by in vivo experiments that 2a-d had depressive action on CNS (increasing of hexobarbital sleeping time and decreasing of spontaneous locomotor activity), and they did not influence to a statistically significant extent the normal 24 hour diuresis of rats (except 2c). The results of cardiovascular screening in rats show that compounds 2a and 2c decreased the heart rate of rats. A pharmacological study of the in vitro broncholytic effect (IC50 and pD2 values) of the derivatives and aminophylline showed that 2c exhibited good broncholytic effect in vitro especially in acetylcholine and serotonin induced guinea pig tracheal contraction. It was demonstrated that compounds 2b,c exerted a stronger inhibitory effect on the enzymic activity of phosphodiesterase in concentration 2 x 10(-3) M than aminophylline.

Animals↗
PubMed1997

Purification of a Tat-associated kinase reveals a TFIIH complex that modulates HIV-1 transcription.

The Tat protein is a transcriptional activator which is required for efficient human immunodeficiency virus 1 (HIV-1) gene expression Tat stimulates HIV-1 transcriptional elongation by increasing the processivity of RNA polymerase II. To address whether Tat-mediated effects on HIV-1 gene expression are due to modulation in the phosphorylation of the RNA polymerase II C-terminal domain (CTD), we developed a purification protocol to identify cellular kinases that are capable of binding to Tat and hyperphosphorylating the RNA polymerase II CTD. A 600 kDa protein complex with these properties was isolated, and specific components were identified using peptide microsequence analysis. This analysis indicated that proteins comprising the multi-subunit TFIIH complex, in addition to several novel factors, were associated with Tat using both in vitro and in vivo analysis. The Tat-associated kinase bound to the activation domain of Tat, and its ability to hyperphosphorylate RNA polymerase II was markedly stimulated by Tat. Furthermore, the addition of the Tat-associated kinase to in vitro transcription assays stimulated the ability of Tat to activate HIV-1 transcription. These results define a cellular kinase complex whose activity is modulated by Tat to result in activation of HIV-1 trancription.

Cyclin-Dependent Kinases↗