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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 631 records · Page 35Linked to original sources
PubMedDate not supplied

Role of endosomes in gene transfection mediated by photochemical internalisation (PCI).

BACKGROUND: Most non-viral gene therapy vectors deliver transgenes into cells through the endocytic pathway. Lack of escape from endocytic vesicles in many cases constitutes a major barrier for delivery of the functional gene. We have developed a new technology named photochemical internalisation (PCI) to achieve light-inducible cytosolic delivery of the transgene. The technology is based on a photochemical treatment employing photosensitisers localised in endocytic vesicles. In this work mechanisms involved in PCI-mediated transfection (photochemical transfection) were studied. METHODS: Human melanoma or colon carcinoma cells were pre-incubated with the photosensitiser aluminium phthalocyanine disulfonate (AlPcS2a) followed by treatment with plasmid encoding enhanced green fluorescent protein (EGFP) complexed with poly-L-lysine, N-(1-(2,3-dioleoxyloxy)propyl)-N,N,N,-trimethylammonium-methyl-sulfate (DOTAP) or polyethylenimine (PEI) and light exposure. The expression of the EGFP-gene was scored by fluorescence microscopy and flow cytometry. RESULTS: The photochemical treatment using light doses corresponding to D50 substantially improves the efficiency of transfection mediated by poly-L-lysine and PEI, but not by DOTAP. The treatment does not enhance the delivery of the plasmid complex across the plasma membrane, since the amount of internalised plasmid is similar for irradiated and non-irradiated cells. Light-inducible transfection occurs only under temperature conditions allowing endocytic uptake and is not improved by chloroquine or ammonium chloride, but is inhibited by bafilomycin A1 (agents that increase vesicular pH and interfere with the endocytic transport). CONCLUSIONS: Photochemical transfection occurs through endocytosis, followed by cytosolic release of the transfecting DNA from photochemically permeabilised endocytic vesicles. Release of plasmid from early endosomes seems to be of importance in photochemical transfection, although a role of later endocytic vesicles can, however, not be ruled out.

Ammonium Chloride↗
PubMedDate not supplied

Study of the amniotic fluid from smokers and non-smokers in the Ames test.

Amniotic fluid from smokers and non-smokers was tested by the Salmonella/mammalian microsome test. Concentrated amniotic fluid from heavy smokers at term showed an increase in the number of revertants with increasing exposure to tar. However, some of the non-smokers had a higher number of revertants than the smokers. No significant differences were found between second-trimester samples from smokers and non-smokers, but the limited volumes available at this stage of pregnancy may be a source of error.

Adult↗
PubMedDate not supplied

Mutagenic effect of amniotic fluid from smoking women at term.

Concentrated term amniotic fluid samples from 44 women smokers and 44 controls were investigated with respect to mutagenic effect in the Salmonella/mammalian-microsome mutagenicity test, using tester strains TA98 and TA100. Tests with freeze-dried specimens of term amniotic fluid showed increases in the number of revertant colonies over background values, regardless of smoking status. However, samples from heavy smokers produced a higher number of revertants than did samples from nonsmokers in several experiments with tester strain TA98. The increase was statistically significant, using either total tar content or number of cigarettes smoked to identify heavy smokers. Experimental series with tester strain TA100 also resulted in higher group means for heavy smokers than for nonsmokers, but the difference was not statistically significant with the concentrations used in this assay. We conclude that heavy smokers may expose their unborn children to mutagenic substances.

Amniotic Fluid↗
PubMedDate not supplied

Education policy and the heritability of educational attainment.

Many workers assume that genetically determined differences in intellectual ability will be influenced little by changes in educational policy or other environmental interventions. Others, however, have suggested that increasing equality of educational opportunity will lead to an increase in the heritability of educational attainment. The resolution of this issue has been delayed until now because of the extremely large sample sizes which would be required. Education data on twins and their parents, from the Norwegian twin panel, provide a unique opportunity to determine the impact on the heritability of educational attainment of the more liberal social and educational policies introduced in Norway after the Second World War. As reported here, for individuals born before 1940 there is a strong effect of family background on educational attainment, accounting for 47% of the variance, though genetic factors account for an additional 41% of the variance. For females born after 1940 and before 1961, the relative importance of genetic (38-45%) and familial environmental (41-50%) differences changes very little. For males born during the same period, the broad heritability of educational attainment has increased substantially (67-74%), and the environmental impact of family background has correspondingly decreased (8-10%). For males, at least, having well-educated parents no longer predicts educational success, as measured by duration of education, independent of the individual's own innate abilities.

Achievement↗
PubMedDate not supplied

Detailed mapping of the phosphomannomutase 2 (PMM2) gene and mutation detection enable improved analysis for Scandinavian CDG type I families.

The gene for carbohydrate-deficient glycoprotein syndrome type I (CDG1) has previously been localised by us close to marker D16S406 in chromosome region 16p13.2-3. We also presented data indicating a strong founder mutation associated with a specific haplotype in CDG I patients from western Scandinavia. The phosphomannomutase 2 (PMM2) gene was recently put forward as a likely CDG1 candidate gene. We have now shown that the specific haplotype is associated with the PMM2 mutation 357C > A. Using data from radiation hybrid panel we have refined the position of the PMM2 gene to very close to marker D16S3020 in the interval between D16S406 and AFM282ze1 on the distal side and D16S3087 on the proximal side. Due to the severity of the disease many families request prenatal diagnostic services for CDG I. In the meantime, until the mutation spectrum is fully examined, we propose the combined use of mutation analysis and linkage analysis with polymorphic markers as diagnostic tools for Scandinavian CDG I families requesting prenatal diagnosis. Using this strategy we have to date successfully performed 15 prenatal diagnoses for CDG I.

Base Sequence↗
PubMedDate not supplied

Ag(c): recognition by a monoclonal antibody.

A monoclonal antibody directed against human apolipoprotein B, which was previously shown in family studies to detect allelic variations (J Biol Chem 1984; 259:6423-6430), has now been identified with the Ag(c) factor. This identification allows the location of the Ag system on the structural gene for apolipoprotein B and on the short arm of human chromosome 2. The epitope corresponding to Ag(c) is located within the amino acid sequence common to apolipoproteins B-100 and B-48. Since a single molecule of apolipoprotein B-100 is present on human LDL, individual LDL possesses either the epitope corresponding to Ag(c) or that corresponding to Ag(g). These studies on allelic variation among human apolipoprotein B species parallel similar studies in animals in which a relationship to atherosclerosis was found.

Alleles↗
PubMedDate not supplied

The price of silence.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMedDate not supplied

Predictive genetic testing to control coronary heart disease and hyperlipidemia.

The contribution of genes to the etiology of coronary heart disease (CHD) is highly significant even when monogenic hyperlipidemias are excluded. Previous studies in the area of quantitative genetics and of disease or risk factor association with random genetic markers have, in recent years, been supplemented with studies focused on "candidate genes"--genes whose products are known or suspected to be involved in the atherogenic process, the thrombogenic process, lipid metabolism, or apolipoprotein (apo) structure or function. In 1974, the candidate gene approach led to the detection of a strong association between genetically determined Lp(a) lipoprotein and premature CHD and, in 1976, also led to the detection, in several populations, of the association between lipid levels and genetic types in the normal low density lipoprotein (LDL) polymorphism referred to as the Ag(x) variation. Restriction fragment length polymorphisms in DNA have been uncovered in the genes for several functionally important proteins including apos. Some of these DNA variants have been reported to be associated with CHD or lipid level. Such variants should become useful tools in predictive genetic testing for CHD risk. Most studies on the genetics of risk factors have focused on risk factor level. Because an individual's propensity to develop atherosclerosis could depend not only on absolute lipid levels but also on lipid responses to atherogenic stimuli, we have developed a method to examine if "variability genes" exist. To detect the latter class of genes, we examine within-pair differences in quantitative parameters between monozygotic (MZ) twin pairs possessing and MZ twin pairs lacking the gene under study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗