Search PubMed⌕ Search

Biomedical subjects

O Georgiev

Publications and source records attributed to O Georgiev.

65 records · Page 4Linked to original sources

[Changes in the lungs in progressive systemic scleroderma].

In 24 patients with progressive systemic scleroderma the respiratory disturbances, X-ray, scintigraphic and clinical deviations as well as the statistical correlations between them are described. The functional examination of respiration revealed lowered diffusion capacity, restrictive type of ventilatory failure and hypoxemia as the most frequent disturbances. The functional examination of respiration is correlated with the X-ray changes in the lungs in these patients.

Acid-Base Equilibrium↗

A novel expression assay to study transcriptional activators.

A novel assay to study transcriptional regulation in vivo designated trans-activation-dependent replication (TDR) assay is based on the modulation of a simian virus 40 (SV40)-derived replication system. A mixture of four plasmids (pPARA + pCIS + pTRANS + pREF) is co-transfected into vertebrate cells. After appropriate incubation, the replication of the pPARA plasmid (containing an SV40 origin of replication) is measured with a simple enzymatic test. We demonstrate that the level of replication is dependent on the differential trans-activation of the reporter pCIS (in which SV40 T-antigen is brought under control of the desired promoter) by the specific regulator protein encoded by the pTRANS plasmid. Three advantages make this assay a convenient tool for the systematic analysis of trans-activation in vivo: (1) remarkable sensitivity (higher than conventional assays); (2) rapid sample processing combined with a built-in standard (pREF-plasmid); (3) avoidance of expensive reagents such as freshly radiolabelled probes. We present the application of the TDR assay to the analysis of deletion mutants of the glucocorticoid receptor (GR) and other, GR-based chimeric trans-activators. The results demonstrate that the properties of protein domains are not always additive in a particular chimaera. Further application possibilities of the TDR assay are also discussed.

Animals↗

[Dynamic changes in the functional respiratory indices in chronic obstructive lung disease].

The basic functional respiratory indices were followed up in 50 patients suffering from various forms of chronic obstructive pulmonary disease before and after treatment. A decrease of the dynamic indices followed up was found: inspiration indices--FEV 1% (forced expiratory volume), FVC% (forced vital capacity), FEV 1/FVC%, FEV 1/VC%; flow indices--MEF 25% (maximal expiratory flow), MEF 50% MEF 75%, PEF% (peak expiratory flow), MEF/FVC%, MMEF 25-70% (maximal mean expiratory flow). A decrease of vital capacity and of diffusion capacity was also found. The ratio RV/TLC% (residual volume/total lung capacity) was increased and a general hyperventilation was established. Moderate hypoxemia and lowered saturation by normocapnia and normal pH were also established. The control examinations after treatment showed improvement of all indices followed up.

Blood Gas Analysis↗

[Favorable therapeutic results in a patient with alcoholic cardiopathy].

A case of a 52-year-old man with alcoholic myocardiopathy with significant enlargement of the heart and heart failure is described. After a long treatment, improvement of the pump and contractile functions of the myocardium was achieved. The case indicates that significant improvement could be achieved by a long treatment and prompt discontinuance of alcohol abuse.

Cardiomyopathy, Alcoholic↗

The conserved CAAGAAAGA spacer sequence is an essential element for the formation of 3' termini of the sea urchin H3 histone mRNA by RNA processing.

Analysis of cDNA sequences obtained from the small nuclear RNA U7 has previously suggested specific contacts, by base pairing, between the conserved stem-loop structure and CAAGAAAGA sequence of the histone pre-mRNA and the 5'-terminal sequence of the U7 RNA during RNA processing. In order to test some aspects of the model we have created a series of linker scan, deletion and insertion mutants of the 3' terminus of a sea urchin H3 histone gene and have injected mutant DNAs or in vitro synthesized precursors into frog oocyte nuclei for interpretation. We find that, in addition to the stem-loop structure of the mRNA, the CAAGAAAGA spacer transcript within the histone pre-mRNA is required absolutely for RNA processing, as predicted from our model. Spacer sequences immediately downstream of the CAAGAAAGA motif are not complementary to U7 RNA. Nevertheless, they are necessary for obtaining a maximal rate of RNA processing, as is the ACCA sequence coding for the 3' terminus of the mature mRNA. An increase of distance between the mRNA palindrome and the CAAGAAAGA by as little as six nucleotides abolishes all processing. It may, therefore, be useful to regard both these sequence motifs as part of one and the same RNA processing signal with narrowly defined topologies. Interestingly, U7 RNA-dependent 3' processing of histone pre-mRNA can occur in RNA injection experiments only when the in vitro synthesized pre-mRNA contains sequence extensions well beyond the region of sequence complementarities to the U7 RNA. In addition to directing 3' processing the terminal mRNA sequences may have a role in histone mRNA stabilization in the cytoplasmic compartment.

Animals↗

Stimulation of sea urchin H2B histone gene transcription by a chromatin-associated protein fraction depends on gene sequences downstream of the transcription start site.

We isolated a chromosomal protein fraction derived from chromatin of sea urchin embryos which specifically stimulated the expression of the histone H2B gene by a factor of 5- to 10-fold when the complete sea urchin histone gene repeat h22 was injected in Xenopus laevis oocyte nuclei. Gene manipulation experiments revealed the existence of two different target sites in the H2B gene which appear to mediate the response to injection of the stimulatory sea urchin chromatin-associated proteins; both are located downstream of the transcription initiation site. The first sequence element which is shown to be implicated is within, or at least includes, the H2B 5' untranslated leader sequence between nucleotides 11 and 76. The second element resides within an H2B DNA segment located near the 3' end of the gene, extending from 90 base pairs upstream of the mRNA 3' terminus to 140 base pairs in the spacer sequences downstream.

Animals↗

Processing and nucleo-cytoplasmic transport of histone gene transcripts.

Precursors of Xenopus and sea urchin histone mRNAs were synthesized in vitro with the SP6 transcription system, and their maturation and nucleo-cytoplasmic transport was studied by frog oocyte injection. 3' processing is most rapid for homologous histone messenger sequences and does not require either genuine 5' or specific 3' ends of the precursor, but capping of the 5' terminus strongly influences the efficiency of 3' processing. No generation of 5' histone mRNA ends can be detected when precursors containing 5' spacer sequence extensions are injected into the oocyte nucleus. This finding may have some implications for the question whether histone gene transcription could be polycistronic. Using a novel oocyte technique, we have separated nuclei from cytoplasm and have studied the time course of exit of the processed RNA from the oocyte nucleus into the cytoplasm. The results suggest that RNA maturation and nucleo-cytoplasmic transport are not temporally coupled processes.

Animals↗

Relaxed mutant of Saccharomyces cerevisiae: proper maturation of ribosomal RNA in absence of protein synthesis.

We have characterized a relaxed yeast mutant, S. cerevisiae SY15, isolated by mutagenesis with ethylmethanesulfonate of strain A364A. Starvation for a required amino acid or treatment with cycloheximide blocks protein synthesis in both parental and mutant strains, while the synthesis of total RNA is inhibited by 72% in A364A and 23% in SY15 cells. In the absence of protein synthesis, the transcription of 37S primary precursor to rRNA is not inhibited in the SY15 mutant, and the rRNA transcripts are correctly processed, although at a reduced rate, and are almost free of ribosomal proteins. The relaxed phenotype in yeast is accompanied by alteration in the regulation of rRNA biosynthesis at transcriptional and posttranscriptional levels.

Base Sequence↗