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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 235 records · Page 13Linked to original sources
PubMed1993

Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and myocardial infarction.

Male (n = 185) and female (n = 49) survivors of myocardial infarction (MI) below 56 and 61 years of age, respectively, were compared to 366 controls with respect to distribution of genotypes in an insertion/deletion (ID) polymorphism at the angiotensin I-converting enzyme (ACE) locus. The frequency of the DD genotype (homozygosity for the deletion allele) was significantly lower among male patients than controls (22.7% versus 34.9%, p = 0.011). In a "low-risk" group, defined as having less than the sex-specific, age-adjusted median values of body mass index (BMI) and apolipoprotein B (apoB), respectively, and absence of treatment with lipid-lowering drugs, the prevalence of the DD genotype was not statistically different between male patients and controls. In a male "high-risk" group (those individuals who had not been defined as "low-risk" subjects), the prevalence of the DD genotype was 20.9% in patients and 38.3% in controls (p = 0.002). In women, no significant differences in genotype frequencies between patients and controls were found in the whole sample or in any subgroup. These results appear to be at variance with data reported recently by Cambien et al. (1992). The difference may be due to chance, undetected selection biases, different gene-environment interactions between Norway and France or Ireland, or to preferential loss of DD individuals in our male "high-risk" group.

Apolipoproteins B↗
PubMed1993

Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and parental history of myocardial infarction.

One hundred and eighty-one male and 48 female myocardial infarction (MI) survivors and 172 male and 194 female controls were studied with respect to a possible association between premature parental MI (before age 61 years in mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). In the total series, the frequency of premature parental MI was 14% in the DD (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion (I) allele) genotypic group. In all males (male MI survivors and male controls combined), and in the total series, there was a significant excess of DD individuals as compared to II individuals among those with a parental history of premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families.

Alleles↗
PubMed1993

Normal genetic variation at the low density lipoprotein receptor (LDLR) locus influences cholesterol levels in children.

The population of Czechoslovakia is at high risk of premature atherosclerosis. Normal DNA polymorphism at the low density lipoprotein receptor (LDLR) locus detectable with the restriction enzyme PvuII was analyzed in Czech children with a high or a low concentration of total serum cholesterol. The PvuII restriction site was found significantly more often in the low cholesterol group than in the high cholesterol group. Thus, normal genetic variation at the LDLR locus contributes to the population variation in cholesterol in children in the population studied.

Apolipoproteins B↗
PubMed1993

Oxygen uptake during recovery from intense intermittent running and prolonged walking.

The purpose of this study was to compare recovery energy expenditure following three exercise conditions varying widely in intensity and duration. Subjects were five well-trained female distance runners whose mean age and VO2 max +/- 1 SD were 22.4 +/- 1.6 yr and 61.8 +/- 7.3 ml/kg-1/min-1, respectively. Exercise sessions consisted of walking for 2 h at 24.5% of VO2max, running continuously for 10 min at 81.1% of VO2max, and exercising intermittently with 2 min runs at 89.2% VO2max alternated with 2 min walks at 93.8 m/min-1. VO2 was determined continuously with open circuit spirometry during 1 h of exercise recovery. Total recovery VO2 (L) was taken as the sum of the 60 1-minute values. After walking, VO2 reached baseline values at 40 min of recovery while VO2 remained elevated at 1 h for both the continuous and intermittent exercise. The total VO2 (L) in recovery was significantly greater (p < 0.05) for both continuous (19.09 +/- 1.2 VO2) and intermittent (22.4 +/- 1.5 L) running than walking (17.4 +/- 0.7 L) and intermittent exercise recovery VO2 was significantly greater than for continuous running (p < 0.05). It was concluded that high intensity exercise, either intermittent or continuous, increases recovery VO2 (L) more than prolonged low intensity exercise. Furthermore, the total exercise VO2 explains a large portion of the variance in recovery VO2.

Adult↗
PubMed1993

Potentiation of photodynamic therapy by mitomycin C in cultured human colon adenocarcinoma cells.

The effects of photodynamic therapy (PDT) alone and in combination with Mitomycin C (MMC) on WiDr cells, a human colon adenocarcinoma cell line, were investigated. The addition of MMC increased the cytotoxicity of PDT. The presence of MMC resulted in a reduction or a removal of the shoulder of the PDT survival curves as well as an increase in their slopes. Increasing with the concentrations of MMC from 0.01 to 0.025 micrograms/ml, the cytotoxic effects of the two treatments changed from additivity to supra-additivity as judged by comparing dose-response curves for each treatment alone with survival curves after combination therapy and by isobologram analysis. The cytotoxicity of MMC could also be enhanced by a practically nontoxic treatment of PDT (8% cell inactivation). The cytotoxicities of MMC and PDT in combination were found to be dependent on the sequence of the two treatments. When MMC (> or = 0.02 micrograms/ml) and Photofrin II were given simultaneously for 16 h and then followed by irradiation, the combination was found to be more effective than when MMC was given to the cells immediately after PDT and kept in the medium for 16 h. Possible mechanisms of the combination effects of PDT and MMC are discussed briefly.

Adenocarcinoma↗
PubMed1993

Screening for point mutations by semi-automated DNA sequencing using sequenase and magnetic beads.

We have established an improved method for detecting point mutations by semi-automated DNA sequencing of PCR fragments generated from genomic DNA. The method employs magnetic beads to create immobilized single-stranded DNA templates, and the sequencing reaction is performed with Sequenase. This method is superior to sequencing with Taq DNA polymerase because the uniform peak height with Sequenase makes heterozygosity easily detectable as double peaks that are half the normal height. Detection of heterozygosity by this method is illustrated by sequencing a 180-bp fragment of the human apolipoprotein B gene. This fragment contains codon 3500, where a point mutation (3500CGG-->CAG) is found in subjects with the autosomal dominant disease familial defective apolipoprotein B. The nonuniform peak height with Taq DNA polymerase makes it more difficult to detect heterozygosity. This is also illustrated by sequencing a 278-bp fragment of the low-density lipoprotein receptor gene.

Apolipoproteins B↗
PubMed1992

Does Lp(a) lipoprotein inhibit the fibrinolytic system?

Lp(a) lipoprotein contains a unique apolipoprotein, apolipoprotein (a), that has a striking homology with plasminogen. This homology has brought forward speculations as to an inhibitory effect of Lp(a) lipoproteins on fibrinolysis. The present investigation was undertaken to study the influence of Lp(a) lipoprotein on the fibrinolytic system. In an in vitro model, we have studied the influence of purified Lp(a) lipoprotein on plasminogen activation by tissue plasminogen activator (t-PA) in the presence of soluble fibrin. Increasing concentrations of Lp(a) lipoprotein (0-32 mg/dl) did not inhibit plasminogen activation by t-PA in the presence of thrombin or bathroxobin digested fibrinogen. When purified Lp(a) lipoprotein was added to whole blood, the degree of fibrin degradation obtained following standardized coagulation, as evaluated by the generation of D-dimer, was not reduced. D-dimer levels in plasma and in serum after standardized coagulation, as well as conventional parameters for evaluation of the fibrinolytic system, were determined in 10 individuals with high and 10 individuals with low levels of Lp(a) lipoprotein. No differences in the fibrinolytic parameters were observed between the groups. Thus, we found no evidence that Lp(a) lipoprotein interferes with the fibrinolytic process in the present experiments.

Amino Acid Sequence↗
PubMed1992

Effect of mitomycin C on the uptake of photofrin II in a human colon adenocarcinoma cell line.

Flow cytometry (FCM) was used to investigate the effect of mitomycin C (MC) on the cellular uptake of Photofrin II (PII) in a cultured human colon adenocarcinoma cell line (WiDr). The surface area of the cells increased as they passed through the cell cycle from G0/G1 to G2/M phase. MC retarded the cells in G2/M phase and enhanced the surface area of the cells. A 1.3-2.3-fold increase in the cell surface area and a 1.3-2.7-fold increase in the cellular uptake of PII in the tumor cells was observed after 2 h-8 h incubation with MC. Within each sample, an almost linear relationship between the intensity of PII fluorescence in the cells and the surface area of the cells was found. However, for the cells incubated with MC the surface area was not the only determinant of PII uptake. Effects of MC on the cell cycle, the cell surface area and the permeability of the cell membrane are suggested as possible reasons for the increase of cellular uptake of PII in the tumor cells.

Adenocarcinoma↗
PubMed1992

The unpolymerized form of tubulin is the target for microtubule inhibition by photoactivated tetra(4-sulfonatophenyl)porphine.

Several porphyrins, including tetra(4-sulfonatophenyl)porphine, sensitize cells to photoinactivation. The treatment leads to an accumulation of cells in mitosis, directly or indirectly due to a perturbation of the mitotic spindle. The present work relates to the target for this mode of action. Cells incubated with tetra(4-sulfonatophenyl)porphine were exposed to light and the microtubules were quantified 30 min after light exposure. The amount of microtubules decreased with increasing fluences. The reduction in the amount of microtubules after light exposure was enhanced by prior treatment with nocodazole (1 microgram/ml for 20 min) or low temperature (1 degree C for 60 min). When nocodazole was combined with the photochemical treatment the extent of the inhibition of microtubule formation was dose-dependent only for the lowest fluences applied. Additional light exposure did not further reduce the amount of microtubules 30 min after light exposure. The results presented indicate that the unpolymerized fraction of tubulin is the target for photochemical inhibition of microtubule formation.

Fluorescent Antibody Technique↗
PubMed1992

Synergistic effects of photoactivated tetra(4-sulfonatophenyl)porphine and nocodazole on microtubule assembly, accumulation of cells in mitosis and cell survival.

Human carcinoma cells of the line NHIK 3025 were incubated with meso-tetra(4-sulfonatophenyl)porphine (TPPS4) for 18 h and exposed to light in the absence or presence of nocodazole. Nocodazole (1 microgram ml-1) was applied to the cells 15 min prior to light exposure and washed off the cells immediately afterwards. The presence of nocodazole during photoactivation of TPPS4-loaded cells leads to a significantly reduced ability of tubulin to repolymerize after withdrawal of nocodazole, an increased accumulation of the cells in mitosis with a larger fraction in c-metaphase and a higher yield of photoactivated cells. A higher proportion of the cells accumulating in mitosis 6-12 h after exposure to light is unable to form colonies when exposed to light in the presence of nocodazole than in its absence. The present results are consistent with a specific TPPS4-induced photodamage to the unpolymerized form of the microtubule components.

Carcinoma in Situ↗
PubMed1992

Long-term effect of lovastatin alone and in combination with cholestyramine on lipoprotein (a) level in familial hypercholesterolemic subjects.

We have determined the effect of lovastatin alone or in combination with cholestyramine on lipoprotein (a) [Lp(a)] levels in 59 heterozygotes for familial hypercholesterolemia (FH) treated for 33.8 (+/- 6.1) months. The median pretrial Lp(a) value was 10.2 mg/100 ml, which is twice the median value in healthy people examined at the Institute of Medical Genetics, University of Oslo. The median Lp(a) level was insignificantly reduced by 10.3% during the first 20 weeks when the subjects were on a standardized medication of increasing doses of lovastatin and cholestyramine. The first 20 weeks were followed by usual care treatment period, and a further decrease in Lp(a) level to 16.2% (P = 0.0012) was observed at the end of the study. Comparison between the 20 subjects on lovastatin monotherapy and the 31 subjects on the combined therapy of lovastatin and cholestyramine, revealed that the subjects on monotherapy had a median reduction of 20.1%, and the subjects on the combined therapy had a reduction of 15.4%. Thus, it appears that the reduction in Lp(a) level could be ascribed to lovastatin alone.

Adolescent↗
PubMed1992

Genetic and environmental effects on type A scores in monozygotic twin families.

Monozygotic (MZ) twin pairs with spouses and children, altogether 787 subjects, completed the Jenkins Activity Survey (JAS). The observed correlations for the various sets of relationships fitted well with biometric models including only parameters for additive genetic effects and, for Type A and Job Involvement, assortative mating. There was no evidence of effects of the family environment (cultural transmission) or genetic dominance (nonadditivity). For all but the Hard Driving and Competitive scale, there was evidence of effects of sex-specific genes. The heritability estimates were, for males and females, respectively, .33 and .39 for Type A, .36 and .48 for Job Involvement, .20 and .52 for Speed and Impatience, and .13 (both sexes) for Hard Driving and Competitive. The estimates given here are deflated by measurement errors and should probably be corrected by multiplying by values in the neighborhood of 1.3. Even after correction, the results suggest that individual differences for Type A and related traits depend more on nonfamilial environment than on genes.

Adult↗
PubMed1992

Cytotoxicity and cytokinetic effects of mitomycin C and/or photochemotherapy in a human colon adenocarcinoma cell line.

1. The cytotoxicity and cytokinetic effects of Mitomycin C (MC) and/or photochemotherapy (PCT) in cultured human colon adenocarcinoma (WiDr) cells were investigated using colony formation to determine cell survival and DNA flow cytometry to analyze cell kinetics. 2. A low concentration of MC (0.01 micrograms/ml) caused accumulation of cells in late S and early G2 phase; higher concentrations (0.05-0.5 micrograms/ml) induced accumulation of the cells in mid and early S phase. 3. The effects of the lowest concentration of MC (0.01 micrograms/ml) were reversible upon removal of the drug, whereas a higher concentration of MC (0.1 micrograms/ml) resulted in a permanent inhibition of cell cycle progression. 4. The sensitivity of Photofrin II-loaded cells to PCT can be enhanced significantly by the addition of MC. 5. The MC-induced accumulation of the cells in S phase may be one reason for the increased cytotoxicity of PCT combined with MC. 6. The data suggest that MC may also inhibit repair of PCT-induced DNA damage.

Adenocarcinoma↗
PubMed1992

StyI polymorphism in an enhancer region of the second intron of the apolipoprotein B gene in hyper- and hypocholesterolemic subjects.

The regulation of the human apolipoprotein (apo) B gene that plays a crucial role in lipid metabolism is apparently very complex, with multiple cis- and trans-acting regulatory factors. One of these factors is an enhancer region in the second intron. In this region a point mutation at position + 722 has been found that is detectable by the restriction enzyme StyI. The report of Levy-Wilson et al. (1991) could suggest that the mutant allele (abolished StyI site) is associated with hypocholesterolemia. To investigate further the possible effect of this mutation on plasma cholesterol levels, we have compared the frequency of the mutant allele between 206 hypercholesterolemic Norwegian or Czech subjects on one hand, and 165 hypocholesterolemic Norwegian or Czech subjects on the other hand. No significant difference in frequency was found between the hypercholesterolemic and the hypocholesterolemic groups. This finding indicates either that the mutation at position + 722 does not affect the enhancer activity or that this in vitro enhancer activity is of little or no clinical significance. One of the Norwegian hypercholesterolemic subjects who was of Czech descent possessed the apoB 3500 mutation that leads to defective binding of low density lipoprotein (LDL) to the LDL receptors. Haplotype analysis of the apoB gene in her family showed that the mutation-bearing allele was identical to that reported in other countries, indicating a common gene source.

Adult↗
PubMed1992

A new polymorphism in exon 11 of the LDL receptor gene in healthy people and in familial hypercholesterolemia subjects.

We have screened exon 11 of the low density lipoprotein receptor (LDLR) gene from familial hypercholesterolemia (FH) heterozygotes for point mutations by using analysis of single strand conformation polymorphisms (SSCP). A variant pattern was observed in three out of 39 subjects. By DNA sequencing, this variant pattern was found to be due to a C-->T transition at nucleotide 1617 that affects the third base of codon 518. A PCR method was developed to screen FH heterozygotes and normal subjects for this mutation. The gene frequencies in FH heterozygotes and normal subjects were 4% and 4.5%, respectively. Thus, the mutation cannot be in linkage disequilibrium with a mutation that causes FH. Rather, the mutation may be a useful genetic marker at the LDLR locus. Haplotype analysis at the LDLR locus in two FH families where the proband possessed the mutation revealed that the mutation was on two different haplotypes. This finding is consistent with the mutation occurring at a mutational hot spot.

Base Sequence↗
PubMed1992

A 9.6 kilobase deletion in the low density lipoprotein receptor gene in Norwegian familial hypercholesterolemia subjects.

Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.

Adolescent↗
PubMed1992

Population variation and genetics of plasma homocyst(e)ine level.

A high level of plasma homocyst(e)ine (H(e)) has been reported to be an independent risk factor for coronary heart disease (CHD), at least in some populations. We have determined the H(e) concentration in the plasma of two series of Norwegians in order to establish a baseline for future analysis of people with CHD. The mean sex- and age-adjusted homocyst(e)ine level was 10.6 (range 4.84-29.88) in one series and 10.5 (range 3.76-40.57) in the other. The H(e) level appeared to be independent of other proven or potential risk factors or protective factors with respect to CHD. The intraclass correlation coefficient in monozygotic (MZ) twins is a (possibly inflated) estimate of heritability. We have examined two series of MZ twins. The intraclass correlation coefficient was significant in both series. In one series, the Pearson correlation coefficient was 0.53 and the Kendall correlation coefficient 0.38. In the other, the values were 0.56 and 0.46, respectively. We conclude that in the population examined, H(e) levels exhibit significant heritability.

Adult↗