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Biomedical subjects

G Link

Publications and source records attributed to G Link.

At least 73 records · Page 4Linked to original sources
PubMed1992

5'-upstream cis-elements and binding factor(s) potentially involved in light-regulated expression of a Brassica napus rbcS gene.

The 5'-upstream region of a Brassica napus rbcS gene contains sequence elements that resemble the cis-regulatory elements described for other species. In band shift competition assays using whole-cell extracts and sets of deletion fragments we could assign protein binding to a region located 110-130 base pairs upstream of the transcription start site. DNase I protection experiments showed that the binding region is non-contiguous and reveals symmetry. On the non-coding strand, the sequence contains 5'-CAC-3' and 5'-GTGG-3' elements which together resemble the contiguous G-box core motif, CACGTGG, of other rbcS genes. The DNA-protein interaction was more efficient with extracts from light-grown than with those from dark-grown seedlings, indicating the possible involvement of light-regulated factors(s).

Amino Acid Sequence↗
PubMed1992

The transport of thiamine, riboflavin and pyridoxal 5'-phosphate by human placenta.

In the present examination the concentrations of thiamine, riboflavin and pyridoxal 5'-phosphate in blood plasma of pregnant women and venous and arterial cord plasma were determined. In maternal plasma the concentration was 4.5 nmol/l (thiamine), 22.2 nmol/l (PLP), 8.7 nmol/l (free riboflavin) and 84.5 nmol/l (FAD + FMN). In venous cord plasma the concentration was 45.9 nmol/l (thiamine), 112.1 nmol/l (PLP), 40.6 nmol/l (free riboflavin) and 49.1 nmol/l (FAD + FMN). Therefore the gradients of concentration between maternal plasma and venous cord plasma were 1:10 for thiamine, 1:4.7 for free riboflavin and 1:5 for PLP. For the coenzyme forms of vitamin B2 the maternal circulation showed the higher concentration (1.7:1). Therefore an active transplacentar transport mechanism was assumed. The vitamin concentrations in cord arteria were significantly lower than that in cord vene, indicating a massive retention by the fetus.

Adolescent↗
PubMed1992

Deferoxamine-induced iron mobilization and redistribution of myocardial iron in cultured rat heart cells: studies of the chelatable iron pool by electron microscopy and Mössbauer spectroscopy.

Iron mobilization by deferoxamine from iron-loaded rat heart cells in culture was studied by electron microscopy and Mössbauer spectroscopy to identify the chelatable iron pool. Studies in which iron 59 was used have shown a diminishing response to deferoxamine with increasing time intervals, which suggests a gradual transit from a more available to a less available storage iron compartment. Mössbauer spectroscopy showed that practically all iron mobilized by deferoxamine was derived from the small (less than 3.0 nm) recently acquired iron particles, which supports the "last-in, first-out" principle. Quantitation of cytosolic ferritin iron particles has shown a highly reproducible increase in cytosolic ferritin iron after deferoxamine treatment. This intracellular redistribution of iron stores is explained either by a reduced transfer of cytosolic ferritin into siderosomes or, more likely, by increased mobilization of membrane-bound iron deposits from insoluble polynuclear iron complexes in siderosomes and their subsequent incorporation into cytosolic ferritin. Thus the protective effect of deferoxamine on iron-loaded heart cells may be twofold: (1) net removal of excess iron by the formation of a stable complex of iron with deferoxamine and its secretion into the extracellular environment and (2) a shift of solubilized iron from membrane-bound deposits into the cytosol where iron is detoxified by its incorporation into the hollow shell of the ferritin protein.

Animals↗
PubMed1991

The chloroplast transcription apparatus from mustard (Sinapis alba L.). Evidence for three different transcription factors which resemble bacterial sigma factors.

A chloroplast protein fraction with sigma-like activity [Bülow, S. & Link, G. (1988) Plant Mol. Biol. 10, 349-357], was further purified and characterized. Chromatography on heparin-Sepharose, DEAE-Sepharose and Sephacryl S-300 led to the separation of three sigma-like factors (SLF) polypeptides with Mr 67,000 (SLF67), 52,000 (SLF52) and 29,000 (SLF29). None of these polypeptides bind to DNA itself, but each one confers enhanced binding and transcriptional activity when added to Escherichia coli RNA-polymerase core enzyme and DNA fragments carrying a chloroplast promoter. SLF67, SLF52, and SLF29 differ in their ionic-strength requirements for activity. They each mediate the binding to promoters of the chloroplast genes psbA, trnQ, and rps16, with different efficiencies. It is suggested that chloroplast transcription in vivo might be controlled at least in part by these functionally distinct factors.

Chloroplasts↗
PubMed1991

Iron mobilization from myocardial cells by 3-hydroxypyridin-4-one chelators: studies in rat heart cells in culture.

The ability of 3-hydroxypyridin-4-ones (CP), a family of bidentate orally effective iron chelators, to remove iron and to prevent iron-induced lipid peroxidation was studied in beating rat myocardial cells in culture. The iron (III) binding constant (log beta 3) of all CP compounds is 36, but their lipophilicity may be modified by altering the length of the R2 substituent on the ring nitrogen. There was a direct relation between lipid solubility and chelating efficiency. Although at high concentrations all CP compounds were more effective in iron mobilization than deferoxamine, the opposite was true for low concentrations. Further studies with 1,2-diethyl-3-hydroxypyridin-4-one (CP94), the most effective CP compound, have shown that iron mobilization is completed within 6 hours, that effective mobilization requires a drug: iron molar ratio exceeding 3:1 permitting the formation of a hexadentate complex, and that the beneficial effects of iron mobilization are manifested in a marked reduction in membrane lipid peroxidation as indicated by cellular malonaldehyde content. Our study represents the first demonstration of a direct interaction between myocardial cells and an orally effective iron chelator, and underlines the need for high molar concentrations for achieving an optimal therapeutic effect.

Animals↗
PubMed1991

RNA-protein interactions at transcript 3' ends and evidence for trnK-psbA cotranscription in mustard chloroplasts.

In vitro transcripts from the 3' flanking regions of mustard chloroplast genes were tested for protein binding in a chloroplast extract. Efficient and sequence-specific RNA-protein interaction was detected with transcripts of the genes trnK, rps16 and trnH, but not with the 3' terminal region of trnQ RNA. The transacting component required for specific complex formation is probably a single 54 kDa polypeptide. The protein-binding region of the rps16 3' terminal region was mapped and compared with that of the trnK transcript determined previously. Both regions reveal a conserved 7-mer UUUAUCU followed by a stretch of U residues. Deletion of the trnK 3' U cluster resulted in more than 80% reduction in the binding activity, and after deletion of both the U stretch and the 7-mer motif no binding at all was detectable. RNase protection experiments indicate that the protein-binding regions of both the rps16 and trnK transcripts correlate with the positions of in vivo 3' ends, suggesting an essential role for the 54 kDa binding protein in RNA 3' end formation. In the case of the trnK gene, evidence was obtained for read-through transcripts that extend into the psbA coding region, thus pointing to the possibility of trnK-psbA cotranscription.

Base Sequence↗
PubMed1991

Long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Zidovudine Epidemiology Study Group.

An epidemiologic study was initiated in 1987 to evaluate the long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Data from 886 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and CD4+ lymphocyte count less than 0.25 x 10(9)/L are reported. Eighteen-month survival was 67% for the cohort. Pretreatment factors associated with increased survival time included index diagnosis of AIDS-related complex, hematocrit of 0.35 or greater, CD4+ lymphocyte count of 0.15 x 10(9)/L or greater, high functional status, and time from diagnosis of AIDS to treatment of less than 60 days. By proportional hazards analysis, development of serious anemia was the most significant factor associated with early death. Receiving zidovudine for a high proportion of time significantly improved chances of survival even if anemia developed. Serious leukopenia occurring in 37% and serious anemia occurring in 32% of patients. Nonhematologic adverse events were uncommon and no previously unreported adverse events were seen.

Adult↗
PubMed1991

Immunological analysis of cloned Schistosoma mansoni antigens Sm31 and Sm32 with sera of schistosomiasis patients.

Two immunogenic proteins, Sm31 and Sm32, originating from the gut of Schistosoma mansoni were evaluated for their potential as recombinant immunodiagnostic reagents. Sm31 and Sm32 cDNA fragments were cloned and expressed in Escherichia coli as polypeptides fused to RNA polymerase of bacteriophage MS2. The recombinant proteins were tested in enzyme-linked immunosorbent assays (ELISA) with paired sera of 182 persons from Mali with S. mansoni and S. haematobium infections collected before and one year after treatment with praziquantel. Pretreatment sera of the study population gave a strong antibody response to Sm31 and Sm32 in immunoblots of total worm extract with the sera. The sensitivities of both western blotting (86%) and ELISA (75%) using Sm31 and Sm32 fusion proteins compared well with a single egg count (84%). Chemotherapy resulted in an overall decline of egg counts. Posttreatment sera gave significantly lower reactivities than the pretreatment sera. Our results demonstrate the feasibility of detecting circulating antibodies with recombinant antigens in schistosomiasis.

Adolescent↗
PubMed1990

In vitro transcription and DNA binding characteristics of chloroplast and etioplast extracts from mustard (Sinapis alba) indicate differential usage of the psbA promoter.

The psbA gene which is differentially expressed in vivo in chloroplasts and etioplasts has an unusual promoter, containing both prokaryotic-type '-35' and '-10' elements and a sequence motif that resembles the nuclear TATA box. Single base pair substitutions were introduced into the mustard psbA promoter and the mutants were tested in transcription and DNA binding experiments, using extracts from either chloroplasts or etioplasts. Positions within the '-35' region appear to play an essential role in the chloroplast but not in the etioplast system. Altering the first or second position of the 'TATA box'-like region led to decreased psbA in vitro transcription in either plastid extract. These two mutations, however, did not affect binding of extracts to the (linear) psbA promoter fragment in gel retardation assays. Fragments carrying two other plastid promoters effectively competed psbA promoter binding of the etioplast extract, but more weakly that of the chloroplast extract. Lambda exonuclease mapping shows that the 5' border of the binding region is more upstream with the etioplast than with the chloroplast system, whereas the 3' border appears to be the same. Hence, protein(s) of the two plastid types seem to interact differently with the mustard psbA promoter in vitro and perhaps also in vivo.

Base Sequence↗
PubMed1990

The chloroplast psbK operon from mustard (Sinapis alba L.): multiple transcripts during seedling development and evidence for divergent overlapping transcription.

The mustard chloroplasts genes psbK and psbI are co-transcribed, giving rise to precursor transcripts of several size classes, which are processed to the monocistronic mature RNAs. The psbK and psbI coding regions are flanked by the two tRNA genes trnS-GCU and trnQ-UUG on the opposite DNA strand. Transcript mapping indicates that the (primary) psbK-psbI transcript overlaps the complete trnS-GCU and trnQ-UUG transcripts. The transcription start site of the psbK operon appears to overlap that of the rps16 gene. During seedling development, the psbK and psbI precursors and mature transcripts all become detectable between 30 and 48 h after sowing and then remain at constant levels without much difference either in light or in darkness.

Base Sequence↗
PubMed1990

Iron chelation.

Adequate iron chelation in thalassaemia has resulted in a striking improvement in survival, with a reduction of cardiac mortality at age 15 years from 14-3%, and a predicted survival at age 36 years of 85%. Long term desferrioxamine (DF) therapy in thalassaemic children should be started between 2-4 years of age. In addition to daily 8-12 h subcutaneous infusions, intermittent high dose (9-16 g) i.v. supplementation over 24-48 h may be given on the occasion of blood transfusions. In established myocardiopathy continuous i.v. DF infusion at 100-125 mg/kg/d may result in improved myocardial function. In addition, there is considerable current interest in the use of DF in conditions unrelated to iron overload by preventing the formation of free-radicals in inflammatory reactions, or by S-phase inhibition of cell proliferation. Although at present highly experimental, this novel approach may have important implications for the management of patients with inflammatory conditions and perhaps in the control of protozoal infections. Over the last decade several hundred candidate compounds have been studied in cell cultures and in animal models and a number of orally effective iron chelators have been identified, all of which are superior to DF in their in vivo iron chelating effect. Although we do not yet have a new drug which is immediately available for replacing DF in clinical practice, significant progress has already been made, and some of the most promising candidate drugs are currently undergoing extensive toxicity tests in anticipation of their development for large-scale clinical use.

Administration, Oral↗
PubMed1989

Interaction of a 3' RNA region of the mustard trnK gene with chloroplast proteins.

The 3' flanking region of the chloroplast trnK gene for tRNALys of mustard contains a palindromic sequence previously implicated with transcription termination and/or processing of the precursor RNA. Here we have investigated whether RNA sequences from the trnK 3' region are capable of interacting with chloroplast proteins in vitro. We find specific binding to an RNA region which is located further downstream from the palindromic sequence. The approximate length and position of this 3' binding region is reflected by a 41 nt spanning RNA segment which is protected against RNase T1 digestion by chloroplast protein(s). Competition experiments and sequence analyses suggest that U residues play an essential role in the RNA-protein interaction. Only a small number of proteins, possibly one single species, is in contact with the trnK 3' RNA.

Base Sequence↗