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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 289 records · Page 16Linked to original sources
PubMed1990

Cellular uptake and relative efficiency in cell inactivation by photoactivated sulfonated meso-tetraphenylporphines.

The cellular uptake, relative fluorescence quantum yields and photosensitizing efficiencies of meso-tetraphenylporphines sulfonated to different degrees (TPPSn) have been investigated using the human carcinoma cell line NHIK 3025. The efficiencies of these dyes in photoinactivation of cells were highly dependent on the number of sulfonate groups on the derivatives. These differences in phototoxicity were primarily due to different abilities to be taken up by cells, but were also dependent upon the cellular localization of the dyes. TPPS1 and TPPS2a were more efficiently taken up by the cells than TPPS2o and TPPS4. Plasma membrane associated TPPS4 was less efficient in cell inactivation per quantum of fluorescence emitted than intracellularly located dye. This was also to some extent the case for TPPS1 but not for TPPS2a and TPPS2o. The results presented here indicate that TPPS2a and TPPS1 are the most promising of the TPPSns for possible future use in photodynamic therapy.

Cell Survival↗
PubMed1989

[Genetic variation and genetic diseases].

Detailed knowledge of the genetic make-up of individuals, revealed by examination of their DNA, is emerging as a significant component in medical diagnosis. Sometimes direct examination of DNA can determine whether a mutant gene is present or not. In other instances the genetic constitution of an individual can be inferred by use of genetic markers known to be close to the gene. The applications of this new level of knowledge are far reaching, extending to disease predisposition to several illness and responses to infectious agents. The use of DNA polymorphisms associated with linked DNA segments should permit diagnosis of hitherto undetectable disease states and also chromosomal localization of the loci responsible. The eventual isolation of the gene itself should lead to a better understanding of the molecular basis of inherited disease.

Chromosome Mapping↗
PubMed1989

[Genetics and coronary heart disease].

The article reviews some of the evidence that genetic factors are important in the etiology of coronary heart disease (CHD). Having a first degree relative with CHD at a relatively young age is in itself a risk factor that may not be reflected in increased lipid levels. Several genetic polymorphisms are associated with risk factor level and/or CHD, and genes have a significant effect on the level of several risk or "anti-risk" factors. Lp(a) lipoprotein, which exhibits a definite association with CHD, is under strict genetic control. A high level of Lp(a) lipoprotein does not in itself result in increased lipid levels, and it is therefore necessary to conduct specific tests with regard to this important genetic risk factor. DNA variation at several apolipoprotein loci has been examined and several associations with risk factor levels have been reported. Present knowledge of genetic predisposition to CHD should be utilized in predictive genetic testing to prevent disease, preferably within a framework of family-oriented preventive medicine.

Coronary Disease↗
PubMed1989

Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill.

The tetrazolium salt (MTT) method involving conversion of MTT to coloured formazan by cells serving as indirect measurements of cell growth/cell kill has been reported by several groups, although technical problems have been encountered. The present investigation was undertaken in order to delineate what laboratory variables have direct influence on the sensitivity and reproducibility of the method. The pH of the extraction buffer was of the utmost importance, since it was demonstrated that a pH greater than 5 would give rise to false signals. Furthermore, modifying the composition of the extraction buffer, all formazan dye grains were solubilised, totally. A direct comparison with published methods demonstrated that only the modified method would yield 100% higher signals without increasing the background. In contrast to previous reports, it was shown that phenol red does not interfere with the measurements and no washing steps are required since all ingredients can be added subsequently. Serum proteins at concentrations up to 25% have no influence on the result. All samples can be measured in an ELISA scanner at 570 nm with little intra-assay variation.

Animals↗
PubMed1989

Intracellular localization of photosensitizers.

The intracellular localization of photosensitizers can be studied by different methods. One method involves homogenization of the cells followed by differential ultracentrifugation which leads to fractions enriched in nuclear, mitochondrial, and microsomal material as well as a supernatant fraction. More detailed information can be obtained by electron microscopy of cells exposed to light in the presence of photosensitizers. This method is based on the assumption that damage is primarily induced at intracellular sites where the concentration of photosensitizer is high. By irradiating the cells at 6 degrees C, where biochemical reactions are slow, and then incubating them for different times at 37 degrees C, it is possible to follow the development of damage. The amount of photosensitized damage to enzymes or cell functions whose localization in the cells is known gives information about the intracellular localization of the sensitizer. Fluorescence microscopy is the most direct method and is widely applicable because most photosensitizers fluoresce. Lipophilic dyes generally localize in membrane structures. In future more attention should be paid to the localization of dyes in lysosomes, as suggested by early reports. Mitochondria, the endoplasmic reticulum and nuclear membrane are other important loci for intracellular localization of sensitizers.

Animals↗
PubMed1989

Genetic and environmental contributions to the covariance between occupational status, educational attainment, and IQ: a study of twins.

Scores of occupational status, educational attainment, and IQ were obtained for 507 monozygotic and 575 dizygotic male twin pairs born 1931-1935 and 1944-1960. A multivariate genetic analysis with statistics from different cohorts showed heterogeneity between cohorts, and analyses were performed in four separate cohorts. The only set of results which departed clearly from the rest was found for the group born 1931-1935, where the ratio of environmental to genetic effects exceeded those of the other groups. Typical heritability values in the three youngest groups (weighted means) were .43, .51, and .66 for occupation, education, and IQ, respectively. The values in the oldest group were .16, .10, and .37, but this sample is small and the estimates are unstable. Genetic variance influencing educational attainment also contributed approximately one-fourth of the genetic variance for occupational status and nearly half the genetic variance for IQ. The values for the between-families variances (reflecting family environment and assortative mating) varied from 2 to 35% in the three youngest groups but were higher for education (62%) and IQ (45%) in the oldest groups. All the between-families variance was common to all three variables. For educational attainment and IQ, the bulk of this between-families variance is probably genetic variance due to assortative mating. The common-factor environmental within-family variances were generally small, and the specific estimates seemed to contain mainly measurement error.

Achievement↗
PubMed1989

Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. Cellular uptake studies.

Cellular uptake of aluminum phthalocyanine sulfonated to different degree was studied by means of fluorescence measurements and HPLC chromatography. These results were correlated to the lipophilic property of each drug measured as the distribution of the drug between a lipophilic phase (Triton X-114) and an aqueous phase. All the sulfonated aluminum phthalocyanines were taken up into cells to a higher extent than porphyrins of a similar lipophilicity. The cellular uptake of monosulfonated aluminum phthalocyanine was 10-fold higher than the cellular uptake of tetrasulfonated aluminum phthalocyanine and at least 50% higher than tetra(3-hydroxy-phenyl)porphin which is so far the porphyrin shown to be taken up into cells to the highest extent.

Cells, Cultured↗
PubMed1989

DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels.

Cholesteryl ester transfer protein (CETP) is a protein involved in "reverse cholesterol transport" and it could play an important role in facilitating the removal of cholesteryl esters from peripheral tissues for transport to the liver or for transfer of cholesterol between plasma lipoprotein particles. Both functions may be relevant to susceptibility or resistance to atherosclerotic disease. We have studied 149 and 146 unrelated persons, respectively, for the A and B polymorphism at the CETP locus detectable with the restriction enzyme TaqI. The B system is by far the more polymorphic. A search for association with risk or "anti-risk" factor levels was conducted with the following quantitative parameters: total cholesterol, HDL cholesterol, triglycerides, apolipoprotein AI (apoA-I), apolipoprotein B (apoB) and Lp(a) lipoprotein levels. Highly significant differences in apoA-I concentration were found between the two categories of homozygotes in the B polymorphism. The association observed remained significant after multiplying the p value by the number of quantitative parameters used for the association tests. There was a dosage effect on the apoA-I level of genes in the B polymorphism. We conclude that the associations observed are likely to reflect true biological phenomena. The effect of CETP genes appeared to be limited to non-smokers.

Adult↗
PubMed1989

Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level.

Subjects drawn from a population-based register were studied with respect to lipid level association. The association of isoforms of apolipoprotein E (apoE) with lipid level in the general population was found to be limited to people with one particular genotype at the low density lipoprotein receptor (LDLR) locus. The results presented in this paper suggest that functional LDLR variants enhance or limit the effect of isoforms of apoE. The association between apoE4 and serum total and LDL cholesterol level may be mediated through the LDL (apoB100, apoE) receptor to a greater extent than previously thought.

Age Factors↗
PubMed1989

"Variability gene" effect of cholesteryl ester transfer protein (CETP) genes.

Cholesteryl ester transfer protein (CETP) may have important roles in transfer of lipids from cells to serum lipoproteins or between circulating lipoprotein particles. Restriction fragment length polymorphisms (RFLPs) in DNA at the CETP locus have been detected. In the present study we have used RFLPs detectable with the restriction enzyme TaqI to examine if CETP influences serum lipid variability (as opposed to absolute lipid levels). We have compared within-pair difference in serum lipid and apolipoprotein levels in monozygotic twin pairs of various genotypes in the B polymorphism at the CETP locus and uncovered significant differences between genotypes. We conclude that the CETP locus has "variability genes" (as opposed to "level genes") with respect to total and LDL cholesterol variability. A person's total genetic risk for coronary heart disease may depend on his or her combination of "level genes" and "variability genes". The method of analysis applied may be the best available for the study of gene - environment interaction.

Apolipoproteins↗
PubMed1989

DNA polymorphisms at fibrinogen loci and plasma fibrinogen concentration.

Associations have been reported between restriction fragment length polymorphisms (RFLPs) at fibrinogen loci and plasma fibrinogen concentration, in a British study. We have examined a series of unrelated Norwegians. We found no association between plasma fibrinogen concentration and any genotype in either of two fibrinogen polymorphisms examined (one at the alpha-fibrinogen locus, the other at the beta-fibrinogen locus). We have also examined monozygotic twins and evaluated heritability of fibrinogen level by the intraclass correlation coefficient. We arrived at an unimpressive estimate of heritability. With such a low level of heritability, it would have been surprising if we had found an association with a single gene marker in a relatively limited series of people. The reason for the discrepancy between the British and the Norwegian study is unknown. Great care has to be exercised in interpreting disease associations, since with DNA variations being examined at an increasing number of "candidate loci", the risk of finding spurious associations increases with the number of analyses conducted.

Adult↗
PubMed1989

Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. A study on the relative efficiencies of photoinactivation.

The cellular photosensitivity caused by aluminum phthalocyanines sulfonated to different degrees (AlPcSn) has been investigated. The phototoxic effect increased with decreasing number of sulfonate groups on the macrocycle, with the exception of AlPcS1 which was less phototoxic than AlPcS2 but more phototoxic than AlPcS3 and AlPcS4. The tendency of the AlPcSns to aggregate in our cellular system increased with increasing lipophilicity of the sensitizers. The aggregates had little or no photosensitizing activity. The low efficiency of cell inactivation caused by AlPcS1 can be explained by the highly aggregated state of this sensitizer in the cells. AlPcS2 and AlPcS3 induced a lower degree of cell inactivation per fluorescing quantum and per quantum absorbed by monomeric species than did AlPcS2 and AlPcS1. AlPcS4 and AlPcS3 are therefore suggested to be in different intracellular locations than AlPcS2 and AlPcS1.

Cells, Cultured↗