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Biomedical subjects

P Georgiev

Publications and source records attributed to P Georgiev.

At least 37 records · Page 2Linked to original sources

hobo Induced rearrangements in the yellow locus influence the insulation effect of the gypsy su(Hw)-binding region in Drosophila melanogaster.

The su(Hw) protein is responsible for the insulation mediated by the su(Hw)-binding region present in the gypsy retrotransposon. In the y2 mutant, su(Hw) protein partially inhibits yellow transcription by repressing the function of transcriptional enhancers located distally from the yellow promoter with respect to gypsy. y2 mutation derivatives have been induced by the insertion of two hobo copies on the both sides of gypsy: into the yellow intron and into the 5' regulatory region upstream of the wing and body enhancers. The hobo elements have the same structure and orientation, opposite to the direction of yellow transcription. In the sequence context, where two copies of hobo are separated by the su(Hw)-binding region, hobo-dependent rearrangements are frequently associated with duplications of the region between the hobo elements. Duplication of the su(Hw)-binding region strongly inhibits the insulation of the yellow promoter separated from the body and wing enhancers by gypsy. These results provide a better insight into mechanisms by which the su(Hw)-binding region affects the enhancer function.

Animals↗

P-Element insertion at the polyhomeotic gene leads to formation of a novel chimeric protein that negatively regulates yellow gene expression in P-element-induced alleles of Drosophila melanogaster.

Polyhomeotic is a member of the Polycomb group (Pc-G) of homeotic repressors. The proteins encoded by the Pc-G genes form repressive complexes on the polycomb group response element sites. The phP1 mutation was induced by insertion of a 1.2-kb P element into the 5' transcribed nontranslated region of the proximal polyhomeotic gene. The phP1 allele confers no mutant phenotype, but represses transcription of P-element-induced alleles at the yellow locus. The phP1 allele encodes a chimeric P-PH protein, consisting of the DNA-binding domain of the P element and the PH protein lacking 12 amino-terminal amino acids. The P-PH, Polycomb (PC), and Posterior sex combs (PSC) proteins were immunohistochemically detected on polytene chromosomes in the regions of P-element insertions.

Animals↗

Effects of indomethacin on lipopolysaccharide-induced plasma PGE2 concentrations and clinical pathological disorders in experimental endotoxemia.

The effects of indomethacin, a cyclooxygenase inhibitor, upon plasma concentrations of prostaglandin E2 (PGE2), the febrile response, and metabolic and hematological alterations induced by lipopolysaccharide (LPS) were studied. Experimental endotoxemia was provoked via i.p. injection of 1.0 mg E coli LPS/kg in rats (group A). Indomethacin was introduced/os (2.5 mg/kg) 30 min prior to LPS challenge (group B). Pretreatment with this medication completely inhibited the hyperthermic response to LPS and eliminated the LPS-induced non-specific symptoms of anorexia, adipsia, reduced locomotory activity and gastrointestinal troubles. Plasma PGE2 concentrations increased as early as the 2nd h after the LPS challenge but were blocked when endotoxin application was preceded by indomethacin treatment. Indomethacin did not significantly influence hematological parameters. The dynamics of hematocrit and erythrocyte counts were similar in both groups with a decrease up to the 2nd h followed by an increase to maximum at post-treatment day 3. Pretreatment with indomethacin did not influence the endotoxin-induced leukopenia observed at the 2nd h or the accompanying neutropenia and left shift. Cyclooxygenase inhibition affected total protein concentrations; they were decreased in the early hours of the study (hours 4-6) in both groups. The later tendency towards increase in total protein concentrations was more expressed in animals from group B. Changes in blood glucose were characterized by a permanent tendency towards decrease after hour 2 of LPS challenge up to day 6 (group A). In group B, a similar tendency was observed, but glucose concentrations decreased between hours 2-6 and then returned to initial values.

Administration, Oral↗

A new family of genes which, when mutated, suppress the inhibitory effect of the mod(mdg4)1u1 mutation on y2 expression in Drosophila melanogaster.

The suppressor of Hairy-wing [su(Hw)] protein inhibits the function of transcriptional enhancers located distal to the promoter with respect to the location of su(Hw)-binding sites (insulation). Mutations in the modifier of mdg4 [mod(mdg4)] interfere with insulation and enhance the effect of the su(Hw)-binding region inserted in the y2 mutation by inhibiting the function of regulatory elements located on both sides of the su(Hw)-binding region. From P-M hybrid dysgenic crosses, 21 mutations that suppress the negative effect of the mod(mdg4)1u1 mutation on the y2 allele were obtained among 47,000 flies scored. These Su(mg) mutations have a dominant suppressor effect and map to at least 13 different loci. Some of Su(mg) mutations also suppress the effect of mod(mdg4)1u1 on two other gypsy-induced mutations, scD1 and ct6. Most of Su(mg) mutations do not affect the viability or fertility of homozygous flies. We speculate that the Su(mg) genes represent a new family of redundant regulatory genes in Drosophila melanogaster.

Animals↗

Insertions of hybrid P elements in the yellow gene of Drosophila cause a large variety of mutant phenotypes.

A series of yellow mutations associated with a great variety of tissue-specific phenotypes were obtained from several highly unstable Drosophila melanogaster strains carrying the gypsy-induced y2 allele. These mutations are caused by insertion of additional DNA sequences of variable size 69 bp upstream of the yellow transcription start site. These sequences are flanked by identical copies of a deleted 1.2-kb P element arranged in the same or inverted orientation. The central part of the inserted element consists of genomic sequences originating from different regions of the X chromosome. The mutant phenotype caused by these chimeric elements depends on the nature of the sequences present either in the P element or in the central part of the insertion, suggesting that these sequences are able to affect expression of the yellow gene. In addition, sequences present in the central region of the insertions strongly modify the effects of the gypsy-bound suppressor of Hairy-wing [su(Hw)] and modifier of mdg4 [mod(mdg4)] proteins on yellow transcription. Analyses of these mutations give new insights into the mechanisms by which su (Hw) and mod(mdg4) affect enhancer function.

Alleles↗

Phenotypic reversion of the gypsy-induced mutation scD1 of Drosophila melanogaster by replicative transposition of a sc enhancer to the yellow gene and by mutations in the enhancer of yellow and zeste loci.

Both mutations of Drosophila melanogaster in the y2scD1 strain are caused by the insertion of gypsy, but the scD1 mutation contains, in addition, an insertion of the jockey mobile element at a distance of 1.8 kb from gypsy. The su(Hw)-binding region in the copy of gypsy in scD1 inhibits scute expression in several specific areas of the epithelium, and in particular, blocks the formation of anterior notopleural (ANP) bristles. The y2 reversions y+2MC and y2#+9 restore the formation of ANP bristles. Molecular analysis revealed that both revertants were induced by transposition into the gypsy element at the yellow locus of jockey and an adjacent 1.8-kb region of the scute gene which contains an enhancer responsible for the development of ANP bristles. The duplicated enhancer is not insulated by the su(Hw)-binding region and can interact with the scute promoter in spite of the presence of two other promoters between them. Hypomorphic mutation in the e(y)2 gene and zOp6 allele partially inhibit ANP bristle formation in flies with y+2MC and y2+9 mutations. In addition, we found that mutations in the e(y)1, e(y)3 and zeste genes may interfere with transcriptional insulation by the su(Hw)-binding region in the scD1 allele.

Alleles↗

Interactions between cut wing mutations and mutations in zeste, and the enhancer of yellow and Polycomb group genes of Drosophila melanogaster.

The phenotypic expression of several mutations in the cut locus of Drosophila melanogaster is modified by mutations in the zeste, e(y)2 and e(y)3 genes and in some genes of the Polycomb group. All tested sensitive cut mutations have a partially inactivated cut wing enhancer. e(y)3u1, Zv77h and Su(z)2(5) mutations enhance, while e(y)2u1, ZOp6, PSC1, Su(z)301, Su(z)302 and ScmD1 mutations suppress the ct mutant phenotype. The results are discussed in terms of the role of long-distance interactions and DNA compaction in transcriptional control of the cut locus.

Animals↗

Interaction between mutations in the suppressor of Hairy wing and modifier of mdg4 genes of Drosophila melanogaster affecting the phenotype of gypsy-induced mutations.

The suppressor of Hairy-wing [su(Hw)] protein mediates the mutagenic effect of the gypsy retrotransposon by repressing the function of transcriptional enhancers located distally from the promoter with respect to the position of the su(Hw)-binding region. Mutations in a second gene, modifier of mdg4, also affect the gypsy-induced phenotype. Two major effects of the mod(mdg4)1u1 mutation can be distinguished: the interference with insulation by the su(Hw)-binding region and direct inhibition of gene expression that is not dependent on the su(Hw)-binding region position. The mod(mdg4)1u1 mutation partially suppresses ct6, scD1 and Hw1 mutations, possibly by interfering with the insulation effect of the su(Hw)-binding region. An example of the second effect of mod(mdg4)1u1 is a complete inactivation of yellow expression in combination with the y2 allele. Phenotypic analyses of flies with combinations of mod(mdg4)1u1 and different su(Hw) mutations, or with constructions carrying deletions of the acidic domains of the su(Hw) protein, suggest that the carboxy-terminal acidic domain is important for direct inhibition of yellow transcription in bristles, while the amino-terminal acidic domain is more essential for insulation.

Animals↗

Eradication of poliomyelitis in Bulgaria--problem encountered.

The authors analyze the effectiveness of the National Vaccination Programme with regard to poliomyelitis eradication in Bulgaria and the difficulties encountered in the 1980s and at the beginning of the 1990s. An account is presented on the eradication achieved, interrupted by an outbreak of 46 cases in 1991. The critical analysis points out the negative influence of several factors, disrupted by the failure in 1991. Based on these fact conclusions are drawn on a prolongation of the period needed to achieve the Eradication Programme goal. The main reasons for the delay are as follows: the intensive migration process, the existence of small non-immunized groups of population (gipsy population) as well as some shortcomings in the organization of the health services. According to the authors, stricter epidemiologic supervision is imperative for the country as well as coordination of similar approach to the problem in countries of the region.

Adolescent↗

[The preparation of materials and the isolation of human genomic DNA for analysis].

The work reviews the usual and most convenient human samples (blood cells, fibroblasts, etc.) for extraction of DNA, storage conditions, DNA extraction approaches, and the criteria for assessment of quality and suitability of the extracted DNA for subsequent analysis. The aim of this work is to make professionals from different laboratory disciplines aware of the basic approaches to DNA sampling and storage in order to promote their further involvement in diagnostics and research based on DNA technology.

DNA↗

[Puerperal streptococcal sepsis].

A series of 8 cases of puerperal sepsis caused by beta-haemolytic Streptococcus from group A is analysed, including two cases of death--of a mother and her newborn. Among the women in seven cases serotype 2 of beta-haemolytic Streptococcus from group A has been identified. The cases have been observed in the Delivery department as a result of the existing favorable conditions for the transmission of the infection. Most probably among these conditions are the negligence of the sterility of the obstetric service from the moment of admission in the ward as well as the possibility for personal contacts among the patients after delivery. The late diagnosis (after two cases of death--of a newborn and a mother) can be attributed to the atypical clinical course of the disease as well as to the negligence of the existing relatively simple methods for early diagnosis. Among the mothers in two of the cases after radical surgical treatment combined with antibiotics and in all the others--after the application of high doses of antibiotics alone, the septic conditions has been overcome. The authors stress on the existing possibilities for the development of streptococcal sepsis in the era of the effective treatment of infections caused by this agent with antibiotics and once more underline the role of the penicillins in cases of septic streptococcal infections.

Acute Disease↗

Super-unstable mutations associated with P-M hybrid dysgenesis in Drosophila melanogaster.

Super-unstable mutations occasionally appear either in natural populations of Drosophila melanogaster or in P-M hybrid dysgenesis. We found that they may be reproducibly obtained with a high frequency from crosses between males from the pi 2 strain and females from the waG* strain or its derivatives. Super-unstable mutations in the ocelliless, singed, white, yellow and other loci have been obtained. Each super-unstable mutation gives rise to a large family of new super-unstable mutations with a wide range of phenotypic expression. Mutations with the same phenotype often differ in the specificity of their potential for further mutation. As a rule, a super-unstable mutation is associated with a specific reversible mutation and paired alleles are formed in this way. Other mutations are usually irreversible, but new mutations of these may also form paired alleles. Active transposase encoded by transposable P elements is necessary to maintain super-instability. Finally, some preliminary molecular data are discussed which suggest that this type of super-instability is a result of interaction between P elements and a novel mobile element, designated as X.

ATP-Binding Cassette Transporters↗

Genes involved in the development of bristles and hairs in Drosophila melanogaster.

Mutations in three loci influencing the development of bristles and hairs were detected in experiments with strains containing either a mobilized Stalker or a mobilized P-element. The mutations in two genes, suppressor of scute and putative microchaete, modify phenotypic expression of mutations in the scute locus. In particular, su(sc) mutations suppress the sc-phenotype in the scutellum and enhance the Hw-phenotype in the thorax. Mutations in the third gene, pseudoscute, lead to reduction of all bristles and hairs. The latter locus seems to control the development of bristles independently of the achaete-scute complex control.

Animals↗

Chemotherapy of human cystic echinococcosis: comparative efficacy of mebendazole and albendazole.

The relative efficacy of mebendazole (MEB) and albendazole (ALB) was tested by treating 51 patients with single, multiple and multi-organ hydatid cysts; 28 patients were treated with MEB, 50-70 mg kg-1 body weight daily for six to 24 months, and 23 with ALB, 10 mg kg-1 body weight daily in four courses of 30 days with 15-day intervals between courses. The therapeutic effect during the follow-up was assessed by ultrasonography, computerized tomography and chest X-ray. The criteria used when assessing the results were: 'success', evidence of effect on all cysts; 'partial success', evidence of effect on some of the cysts; and 'no success', no changes in cyst morphology. Treatment with MEB was successful in eight cases (28.6%), partially successful in eight (28.6%) and unsuccessful in 12 (42.8%). Treatment with ALB was successful in 10 cases (43.5%), partially successful in 10 (43.5%) and unsuccessful in three (13.0%).

Abdomen↗

Factors influencing the response to chemotherapy in human cystic echinococcosis.

As the effectiveness of mebendazole and albendazole in patients with echinococcosis has been found to vary, we investigated some of the factors likely to be responsible. A total of 79 patients who were treated with mebendazole (44 patients) or albendazole (35 patients) were included in the study. Evaluation of the treatment results was based on the changes in cyst morphology, as evidenced by the results of X-ray radiography, sonography, and computed tomography, and on analysis of the findings in relation to parasitic and drug factors. The response of cysts according to their site did not vary much, with the exception of the poor response of bone cysts. A more important factor seems to be cyst size, since the treatment was more efficacious against smaller and younger cysts. The presence of daughter cysts should be regarded as an unfavourable factor for treatment response. Cyst multiplicity did not present insurmountable difficulties, provided the cysts were small and a prolonged course of therapy was undergone. The choice of drug used for the therapy was important, with the results supporting the advantage of albendazole. In planning the chemotherapy of hydatid disease, factors such as cyst condition and drug used should therefore be taken into consideration.

Adolescent↗

[The differentiation of cirrhotic from malignant ascites by ultrasonic tomography of the gallbladder].

99 patients with ascites (60 patients with liver cirrhosis and 39 patients with peritoneal carcinosis) were examined by ultrasound tomography of the gall bladder. In most of the cirrhotic patients a thick gall bladder wall was found (7.7 +/- 3.4 mm) often with a three-layer structure. The gall bladder wall of the patients with peritoneal carcinosis was most often not thickened (2.5 +/- 1.6 mm). The difference is statistically significant (p less than 0.1). Thickening of the gall bladder wall was found in both groups of patients by a decreased serum albumin level. The ultrasound tomography of the gall bladder could help in the differentiation of cirrhotic from malignant ascites, especially in combination with determination of the serum albumin level.

Adult↗

[Present-day indications for laparoscopy].

Laparoscopy is an useful endoscopic method. It retains its deserved priority in the examination of the peritoneum and the differential diagnosis of ascites. In the focal and diffuse diseases of the parenchymal organs (liver, spleen) it complements the imaging methods (ultrasound tomography, computed tomography) especially in the cases when their potentialities are limited by the character of the pathologic process.

Adult↗

[Mechanisms of the lactogenic action of thyroid hormones and nonspecific resistance in ruminants].

Studied was the effect of thyroid hormones on the nonspecific resistance and the milk productivity of ruminant animals in the conditions of hypodynamia and in various functional conditions of the thyroid gland. Both the removal of the thyroid gland (thyroidectomy) and the hypofunction of the gland (as induced by ammonium perchlorate at 10 mg/kg body mass) were accompanied by the drop of the indices characterizing the nonspecific resistance of the animals as well as their milk productivity. The immobilization of lactating ruminant animals (hypodynamia) had a negative impact on the milk producing process, enhanced the incretion of ACTH, lowered the release of thyroid hormones (T3, T4, FT4) and decreased milk productivity, deteriorating the biologic properties of colostrum. The thyroid gland and its hormones (T4, T3) were shown to have a positive effect on milk secretion, raising the activity of the enzyme adenylate cyclase and the amount of the cyclic 3.5 cyclic adenosine monophosphate (cAMP) in the parenchymal tissue of the mammary gland.

Animals↗