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At least 307 records · Page 17Linked to original sources

[Enhanced apoptosis-inducing effect of etoposide on leukemic cell lines M-07e and TF-1 by the proteasome inhibitor Z-LLL-CHO].

Recent researches indicate that ubiquitin-protea some pathway plays an important role in apoptosis regulation. Proteasome inhibitors induce apoptosis in many kinds of neoplastic cells, thus provide a great opportunity for exploring synergy of proteasome inhibitors and other apoptosis-inducing agents. In this study, the effect of the proteasome inhibitor Z-LLL-CHO combined with etoposide (VP16) on leukemic cell lines M-07e and TF-1 was investigated by MTT assay, trypan blue exclusion, flow cytometry and Western blot. The results showed that the combination of Z-LLL-CHO and VP16 was much more effective than either agents alone in promoting cytotoxicity in both cell lines evaluated. Accumulation of cells in S + G2/M phase of the cell cycle was observed in the cells treated with VP16 and Z-LLL-CHO alone, while apparent increase of sub-G0/G1 fraction was detected in cells treated with combination of the agents. The cleavage of Bcl-2 into a shortened 22 kD fragment was detected in M-07e cells exposed to either agents alone, and the fraction of 22 kD fragment was increased in the cells treated with combination of the agents. In conclusion, the combination of Z-LLL-CHO and VP16 enhanced their individual cytotoxic effect by inducing apoptosis, in which increase of S + G2/M fraction in cell cycle as well as the enhanced cleavage of Bcl-2 are the possible mechanism of the additive effect on leukemic cells by Z-LLL-CHO and VP16.

Apoptosis↗

Investigations on the variability of four genetic serum protein markers (HP; TF, GC and PI subtypes) in Italy.

14 population samples from various Italian regions with a total of 2.577 unrelated male and female individuals were typed for four polymorphic serum protein polymorphisms: HP, and TF, GC and PI subtypes. The regional distribution of the allele frequencies of these four polymorphisms shows a considerable heterogeneity, which is for the most part statistically significant, thus indicating an obvious genetic variability of the population of the Italian Peninsula.

Alleles↗

[Rare electrophoretic variants of the proteins adenylate kinase 1, phosphoglucomutase 1 and 2, and transferrin (AK1, PGM1, PGM2, Tf) in two populations of French Guiana].

Two small populations of inner French Guiana were investigated for red cell enzymes and serum proteins. Rare variants were found in four systems (AK1, PGM1, PGM2, Tf). Similarities between some of these variants and those found in other Amerindian populations indicate that these genetic markers may be valuable in studies of Amerindians. A mutation rate has been estimated from the results.

Adenylate Kinase↗

Generation of free oxygen radicals from human polymorphonuclear granulocytes by cytokines from human mononuclear cells, treated with quartz dust DQ12 or coal mine dust TF-1--new aspects in pathogenesis of pneumoconiosis.

We report about the release of a soluble mediator(s) from cultured human monocytes/macrophages after exposure to quartz dust DQ12 or coal mine dust TF-1. This mediator(s) activates isolated human polymorphonuclear granulocytes (PMN) to generation of free oxygen radicals. The strong and long-lasting production of reactive oxygen species (ROS), especially of superoxide anion, was measured as lucigenin dependent chemiluminescence (CL). Studies of mediator exposed PMN with the NBT-test (nitroblue-tetrazolium test) also demonstrated the strong activation of PMN. Electromicroscopical studies of mediator exposed PMN showed strong chemotactic changes in a time dependent manner and suggested the release of lysosomal products. According to these properties we called the mediator(s) "granulocyte activating mediator(s)" (GRAM). Biochemical characterisation indicated a protein nature of GRAM. High pressure liquid chromatography (HPLC) gel-filtration suggested that two molecules or two fragments of one molecule with a m.w. of about 20 kda and just below 10 kda resp. were responsible for the observed effects. PMN are potent inflammatory cells, which are known to immigrate in the lung tissue, especially in the early phases of silicosis. ROS released by activated PMN can act tissue destroying, mutagenic and are probably involved in collagene synthesis by regulation of activity of prolylhydroxylase. Mediator induced release of ROS seems to be an important event in development of lung fibrosis and presents a new mechanism of quartz dust and coal mine dust fibrogenicity.

Biological Factors↗

Biodynamic effects of canopy loss in the TF-15 aircraft.

In-flight canopy loss in high-speed fighter or trainer aircraft poses serious aeromedical problems for the crew-members. To assess these problems in the TF-15, a series of canopy-off tests were conducted. Preliminary phases of the test consisted of a taxi and a flight test up to 485 knots with pilot in the front seat and an instrumented dummy in the back seat. Upon evaluation of these results, a taxi phase and a flight phase were conducted with a pilot in the front seat and a live subject in the back seat. Maximum air-speed attained was 410 knots. The front crewmember experienced no serious control or medical problems during all phases. The back crewmember did experience problems such as loss of communications, loss of vision, helmet lift, high frequency head buffet, and exhalation difficulties. Airspeed, seat height, and body position had the greatest effect on the severity of the windblast. Angle of bank, angle of attack, and acceleration had little effect. The aft crewmember was able to significantly decrease windblast effects by leaning forward and pulling his head and helmet forward and down with his hand.

Aerospace Medicine↗

[Serum markers in Portugal: C3, Gc, Hp and Tf].

The phenotypes C3, Gc, Hp and Tf were determined in 426, 1000, 1000 and 426, respectively, unrelated individuals living in Portugal. The calculated gene frequencies are: C3S = 0.7981, C3F = 0.2019; Gc1 = 0.715, Gc2 = 0.285; Hp1 = 0.430, Hp2 = 0.570; TfC = 1,000.

Alpha-Globulins↗

Serum protein polymorphisms Hp, Tf, Gc, Gm, Inv and Pt in Bantu speaking South African Negroids.

Frequencies for the genetic polymorphisms of the serum proteins Hp, Tf, Gc, Gm, Inv and Pt are presented for 7 ethnically defined Negroid sub-samples (total n = 918--977, depending on genetic marker system) from South Africa. The results are discussed in terms of previous findings and of factors assumed to have an influence on the distribution of the particular genetic markers. The present report on the Pt ("post transferrin" approximately C3) polymorphism represents the first report on the genetic variation of the corresponding beta1A-globulin fraction within African Negroids (PtA = 0.009, PtB = 0.966, PtC = 0.025).

Black People↗

Population genetic studies of PI, Tf, Gc and PGM1 subtypes among various caste groups in North India.

Approximately 500 blood samples from various endogamous groups in north India have been subjected to isoelectric focusing to reveal genetic variation at the PI, Tf, Gc and PGM1 loci. The average heterozygosity per locus varies from 40% to 60% and the gene frequency data reflects considerable variation among the caste groups studied. The Nei genetic distances calculated from the 4 loci demonstrate that Khatri, Arora and Rajput are strongly clustered together and genetically they are closer to Brahmin than to Vaish and Scheduled Castes. Vaish emerge as a unique group showing maximum genetic distances with all other caste groups. The comparison of the present populations with our own data from two south Indian populations indicates that the tribal population of Soliga is distinct from the non-tribal populations, but the non-tribal south Indian series clusters closely with the main caste populations in north India.

Gene Frequency↗

[Population genetics of taiga hunters and reindeer breeders in central Siberia. The biochemical markers of genes Hp, Tf, Gc, A1b, GLO1, PGM1, AcP and EsD].

Biochemical markers of gene systems Alb, Tf, Gc, Hp, GLO1, PGM1, EsD, AcP were analysed in the native population of Evenc national region. It is shown that native population of Central Siberia, in spite of its mongoloid racial type, posseses the complex of gene frequencies for protein loci studied which is not typical for mongoloids. The complex may be called "central-siberian" and its origin may be connected with the process of adaptation to environment of the Central Siberian geographical region. The system of gene markers analysed may be considered as a sensitive one in the studies of processes of gene adaptation to the local environmental factors and, in this connection, being perspective in these studies among native population of Siberia.

Animals↗

Serum protein polymorphisms (HP, TF-, GC- and PI subtypes) in two mountain communities of Sierra de Gredos (central Spain).

The genetic variation of four highly polymorphic serum proteins, haptoglobin (HP), transferrin (TF), group-specific component (GC) and alpha-1-antitrypsin (PI) was examined in two representative samples of the autochthonous populations living on either slope of Sierra de Gredos in central Spain. The genetic markers studied do not provide any evidence that the mountain chain has contributed to the maintenance of a genetic differentiation between the two populations. The allele frequency distributions in these Gredos samples are discussed in relation to the variability of these markers in the Iberian Peninsula populations.

Alleles↗

Transcription factor (TF) IIB and TFIIA can independently increase the affinity of the TATA-binding protein for DNA.

The general transcription factors (TF) IIB and TFIIA are the first factors to associate with the TATA-binding protein (TBP) during formation of a transcription initiation complex on RNA polymerase II promoters. DNase I footprint titration was used to measure the effects of TFIIB and TFIIA on binding of TBP to a consensus TATA box. Under reaction conditions optimized for TBP-DNA complex formation, the presence of TFIIB increased affinity of TBP for the TATA box by 2.5-fold, while TFIIA had no effect. When TBP binding conditions were sub-optimal, both TFIIB and TFIIA independently increased TBP affinity by approximately 10-fold. Therefore both TFIIB and TFIIA have the intrinsic ability to directly increase the affinity of TBP for the TATA box. We suggest that this property of TFIIA and TFIIB may increase the range of conditions under which high affinity TBP-DNA interactions can occur and may therefore favor the formation of the preinitiation complex.

Base Sequence↗

Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling.

Peroxisome proliferators form a family of diverse xenobiotic compounds that includes hypolipidemic agents, herbicides, and plasticizers. These compounds activate transcription of a subset of nuclear genes including those encoding peroxisomal fatty acid beta-oxidation enzymes, whose elevated activities can lead to hepatocarcinogenesis. Induction of the genes encoding fatty acyl-CoA oxidase and hydratase-dehydrogenase, the first and second enzymes of the pathway, is mediated by peroxisome proliferator-activated nuclear receptors (PPARs) that bind to upstream responsive elements (PPREs) through heterodimerization with retinoid X receptors. We demonstrate that the chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), another member of the nuclear hormone receptor superfamily, binds to the hydratase-dehydrogenase PPRE in vitro and in vivo and antagonizes PPAR-dependent signaling. These data suggest that members of the COUP-TF family play a role in modulating receptor-mediated activation of peroxisome proliferator-responsive genes.

Animals↗

Induction of Sp1-p53 DNA-binding heterocomplexes during granulocyte/macrophage colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1.

The involvement of Sp1 in regulating cell proliferation in myeloid leukemia cells was determined by measuring the levels and DNA binding activity of Sp1 in TF-1 cells, a human erythroleukemia cell line dependent on granulocyte/macrophage colony-stimulating factor (GM-CSF) for viability and cell growth. DNA binding of Sp1 to a specific double-stranded oligodeoxynucleotide was increased markedly in a dose-dependent manner in proliferating cells in response to GM-CSF compared with growth-arrested or apoptotic cells. Competition experiments and mobility shift interference assays with antibodies against Sp1 as well as wild-type or mutant p53 indicated that GM-CSF-inducible DNA-binding complexes contained both Sp1 and p53 and that these heterocomplexes bound to both p53- and Sp1-binding sequences with high affinity. Immunoprecipitation of nuclear extracts with a p53 antibody indicated that Sp1 was associated as a heterocomplex with p53. Formation of this complex was dependent on the level of p53 since p53 was more abundant in proliferating cells and decreased upon induction of growth arrest and apoptosis by withdrawal of GM-CSF while Sp1 levels remained unchanged. These results suggest that the association of Sp1 with p53 may represent a novel mechanism of growth regulation in cytokine-dependent leukemia cells.

Apoptosis↗

A concurrent human herpesvirus-6 infection renders two human hematopoietic progenitor (TF-1 and KG-1) cell lines susceptible to human immunodeficiency virus type-1.

In human immunodeficiency virus type-1 (HIV-1) infected individuals, CD34+ hematopoietic stem/progenitor cells are profoundly impaired in their proliferation/differentiation capacities. The bulk of the available experimental evidence seems to indicate that hematopoietic progenitors are not susceptible to HIV-1 infection and their defects seem rather the consequence of direct or indirect negative influences of HIV-1-specific soluble proteins released by productively infected accessory cells. We have now shown that in the presence of a concurrent human herpesvirus-6 infection, two hematopoietic (TF-1 [erythromyeloid] and KG-1 [lymphomyeloid]) progenitor cell lines and human CD34+ hematopoietic progenitors isolated from the bone marrow of normal donors, became susceptible to HIV-1 infection and permissive to HIV-1 replication, although with a limited virus yield. These results suggest a further possible mechanism leading to hematopoietic derangement in HIV-1-infected subjects and may help to clarify the controversial issue of the susceptibility of human hematopoietic progenitors to HIV-1 infection.

Antibodies, Monoclonal↗