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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 253 records · Page 14Linked to original sources

No effect of a Taq1 polymorphism in DNA at the endothelin I (EDN1) locus on normal blood pressure level or variability.

Endothelin is a peptide reported to be one of the most potent vasoconstrictors known. Presumably, endothelin could play a role in the physiological regulation of blood pressure in healthy or hypertensive people. We have studied a normal restriction fragment length polymorphism (RFLP) at the endothelin-I (EDN1) locus detected with the restriction enzyme TaqI. In three different series comprising 166, 120 and 207 unrelated individuals, we found no evidence for association between genotype in this polymorphism and level of systolic or diastolic blood pressure. In two series of 156 and 117 monozygotic (MZ) twin pairs, respectively, there was no difference between genotypes in within-pair variation in systolic or diastolic blood pressure. Thus neither "level gene" nor "variability gene" effects of normal genes at the EDN1 locus could be detected with the polymorphism analyzed, in healthy population samples.

Adult↗

Action spectra of phthalocyanines with respect to photosensitization of cells.

Human carcinoma cells (NHIK 3025 cells) and Chinese hamster cells (V79 cells) were incubated with AlPcS1, AlPcS2 and AlPcS4, phthalocyanines with different lipophilicity but with similar photochemical properties when in monomeric solutions. The absorption- and fluorescence spectra of the dyes in the cells were recorded as well as their action spectra with respect to sensitizing cells to photoinactivation. These spectra show that under the present conditions AlPcS1 is strongly aggregated in both cell lines; AlPcS2 is aggregated in V79 cells but much less so in NHIK 3025 cells. A main finding is that the shapes of the action spectra are similar to that of the fluorescence excitation spectra, but not to the absorption spectra, indicating that the photosensitizing effects of the dyes are mainly due to their monomeric fraction in the cells. AlPcS2 and AlPcS4 localize intracellularly mainly in lysosomes while AlPcS1 was found to be more diffusely distributed in cells. As measured per quantum of fluorescence emitted, AlPcS1 and AlPcS2 are more efficient sensitizers than AlPcS4. The difference in efficiency between AlPcS2 and AlPcS4 is supposedly due to a different localization pattern on the suborganelle level.

Animals↗

Retention and phototoxicity of tetra(4-sulfonatophenyl)porphine in cultivated human cells. The effect of fractionation of light.

Human cervix carcinoma cells of the line NHIK 3025 were incubated for 18 h with tetra(4-sulfonatophenyl)porphine (TPPS4) and further incubated for 1-29 h in sensitizer free medium before exposure to light. After 1 h in sensitizer free medium only a 20% further loss of TPPS4 was observed within the next 28 h. During the time in sensitizer free medium, each TPPS4 molecule became more efficient in sensitizing single cells to photoinactivation. This enhanced photosensitizing efficiency of TPPS4 correlated well with the enhanced fluorescence yield of TPPS4. In some experiments the cells were exposed to a light dose inactivating 10% of the cells after incubation for 1 h in sensitizer free medium and a second graded light dose given 4-28 h later. Exposure of the cells to the first light dose led to loss of 60% of TPPS4 from the cells. Despite the significant loss of sensitizer from the cells the fluorescence yield of TPPS4 from each cell was found to increase (e.g. by 100% 4 h after light exposure). The enhanced fluorescence yield of cell bound TPPS4 was followed by a 1.6-2.5-fold increase in sensitivity of each cell to second light dose. Thus, a small light dose increased the photosensitivity of TPPS4-loaded NHIK 3025 cells for several hours after the first light exposure. The advantageous effect of light fractionation was reduced by a significantly enhanced loss of sensitizer induced by the first light exposure. The optimal time between the two fractions of light seems to be 30-90 min.

Humans↗

Mitotic inhibition by phenylporphines and tetrasulfonated aluminium phthalocyanine in combination with light.

This work relates to studies on modes of phototoxicity by tetrasulfonated aluminium phthalocyanine (AlPcS4), tetrahydroxy- and monosulfonated meso-tetraphenylporphines (3-THPP and TPPS1) on culture cells. Toxicity at moderate light exposures appears to be related to inhibition of microtubule function. Treatment of human cervix carcinoma cells of the line NHIK 3025 incubated for 18 h with the sensitizers and exposed to light inhibits multiplication for the first hours after light exposure, a significant fraction of the cells accumulating in mitosis. For the first hours after treatment, the mitotic cells were always mainly found in metaphase; generally seen as c-metaphases and three-group metaphases. During this time, anaphase and telophase cells were absent or greatly reduced in number. Indirect immunofluorescence staining of beta-tubulin showed that the spindle apparatus of mitotic cells was perturbed in all cases. The accumulation in mitosis was more extensive after treatment with AlPcS4 and light than after treatment with 3-THPP or TPPS1 and light. This may be related to the great difference in the lipophilic properties of these sensitizers; i.e. AlPcS4 being highly water soluble while TPPS1 and 3-THPP are lipophilic sensitizers. The lipophilicity of several sensitizers has been measured by two different methods, the partition between an aqueous and a lipophilic phase (Triton X-114) and the binding strength to a reverse phase column. The results show that the measured relative lipophilicity of the sensitizers may be influenced by the method of analysis.

Carcinoma in Situ↗

Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.

Absolute linkage between the gene, on chromosome 19, for the calcium release channel (CRC) of the sarcoplasmic reticulum in skeletal muscle and malignant hyperthermia (MH) has been reported by other workers. In the present study of three Swedish Families informative with respect to this linkage relationship, definite recombinants were found in two families. We conclude that mutations in other genes than the CRC gene can cause the clinical picture of MH. Accordingly, MH appears to be genetically heterogeneous.

Alleles↗

The epidemiology of pregnancy complications and outcome in a Norwegian twin population.

OBJECTIVE: To measure the contribution of genetic factors to selected pregnancy complications, including miscarriage, twinning, hypertension-toxemia, and nausea-vomiting. METHODS: Information on 22,241 pregnancies of 8675 female twins or spouses of male twins was obtained by questionnaire from members of the population-based Norwegian Twin Panel. Comparisons of observed tetrachoric correlations were used to assess the importance of genetic influences on the variables examined. RESULTS: Pregnancy history information was provided by both members of 830 monozygotic and 902 dizygotic female twin pairs and by the spouses of both members of 459 monozygotic and 464 dizygotic male twin pairs. The incidence of twin pregnancy in general, and of opposite-sexed twins in particular, found among dizygotic twin women was nearly twice that observed for any other group. Monozygotic female twin pairs were more concordant than dizygotic female twin pairs for the occurrence of miscarriage, nausea or vomiting during pregnancy, and hypertension or overt toxemia. A similar pattern of twin similarity was observed for the use of certain medications during pregnancy including vitamins, aspirin, and nausea medication. CONCLUSIONS: Maternal genetic factors make an important contribution to a predisposition for dizygotic twinning, contribute to the risk of miscarriage, and appear to determine, in part, whether a woman experiences nausea-vomiting or hypertension-toxemia during pregnancy. In addition, health-seeking behaviors of women during pregnancy, as reflected by the use of several classes of medication, appear to be influenced somewhat by genetic factors.

Female↗

Sustained induction of egr-1 by v-src correlates with a lack of fos-mediated repression of the egr-1 promoter.

Serum stimulation of quiescent fibroblasts leads to a transient induction of the transcription factor egr-1. However, the induction of egr-1 by v-src was found to be sustained rather than transient. The proto-oncogene fos has been reported to be co-regulated with egr-1 and to repress serum-induced egr-1 expression. We found that c-fos prevents v-src-induced gene expression regulated by the egr-1 promoter. Thus, the sustained induction of egr-1 by v-src could be explained by a lack of c-fos induction by v-src. Consistent with this hypothesis, egr-1 and c-fos were co-induced by serum, but not by v-src, in Balb/c 3T3 cells; v-src did not induce c-fos expression in these cells. We propose that sustained expression of egr-1 induced by v-src in Balb/c 3T3 cells is due to a lack of c-fos down-regulation of egr-1.

3T3 Cells↗

Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE: To compare the serum concentrations of lipoproteins and apolipoproteins in insulin dependent diabetic patients with and without microalbuminuria. DESIGN: Cross sectional study. SETTING: Paediatric and medical outpatient clinic at a university hospital. PATIENTS: 76 insulin dependent diabetic patients: 41 with microalbuminuria (20 males, 21 females) and 35 controls without microalbuminuria (18 males, 17 females). The two groups were similar with respect to age, duration of disease, and haemoglobin A1c concentrations before the study. MAIN OUTCOME MEASURES: Serum concentrations of Lp(a) lipoprotein, total cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I, A-II, and B. RESULTS: Median serum Lp(a) lipoprotein concentration was 10.0 mg/100 ml in the microalbuminuric group and 4.9 mg/100 ml in the control group (p = 0.007). 17 (41%) of the microalbuminuric patients and five (14%) of the control patients had Lp(a) lipoprotein values above the upper quartile of a normal population. Median serum triglycerides concentrations in the microalbuminuric and control groups were 1.15 mmol/l and 0.88 mmol/l respectively (p = 0.03). Median very low density lipoprotein cholesterol concentration was 0.52 mmol/l in the microalbuminuric group and 0.40 mmol/l in the control group (p = 0.03). No significant differences in serum concentrations of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, or apolipoproteins A-I, A-II, and B were found between the groups. CONCLUSIONS: Serum concentrations of Lp(a) lipoprotein are twice as high in insulin dependent diabetic patients with microalbuminuria as in those without microalbuminuria. Increased concentrations of Lp(a) lipoprotein might partly explain the increased morbidity and mortality from cardiovascular disease observed among patients with diabetic nephropathy.

Adolescent↗

Metaphase-specific phosphorylations weaken the association between chromosomal proteins HMG 14 and 17, and DNA.

The high-mobility-group proteins HMG 14 and 17 have been isolated from human cells arrested in metaphase. The affinity between an unphosphorylated and two phosphorylated forms of these proteins, and DNA has been investigated using columns of single-stranded and double-stranded DNA. It was shown that the most phosphorylated forms had much lower affinity for single-stranded and double-stranded DNA compared to the unphosphorylated form present in interphase cells. The results are in accordance with the view that HMG 14 and 17 may dissociate transiently from chromatin during mitosis.

Chromatography, Liquid↗

Lipoprotein(a) and atherosclerosis.

Lipoprotein(a) [Lp(a)], a lipoprotein variant, was relegated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been a tremendous upsurge of interest in Lp(a), primarily because of multidisciplinary efforts in structural and molecular biology. Findings emerging from these efforts include the following: Lp(a) represents a cholesteryl-ester, low-density-lipoprotein (LDL)-like particle with apolipoprotein (apo) B-100 linked to apo(a); apo(a) is a glycoprotein coded by a single gene locus on the long arm of chromosome 6, which has several alleles, accounting for its remarkable size polymorphism (300 to 800 kD); apo(a) size polymorphism relates to plasma levels and density distribution of Lp(a); apo(a) is strikingly similar to plasminogen; and in vitro, Lp(a), in appropriate levels, competes for some physiologic functions of plasminogen in the coagulation and fibrinolytic cascade and may thus be thrombogenic. The LDL-like properties of Lp(a) may also confer atherogenic potential, but the mechanisms underlying this atherogenicity remain to be defined. In epidemiologic studies, high plasma Lp(a) levels have been associated with an increased incidence of atherosclerotic cardiovascular disease, especially in patients less than 60 years of age. Moreover, Lp(a) has been found as an intact particle in the arterial intima, particularly in association with atherosclerotic plaque. This finding suggests that Lp(a) can transverse the endothelium, possibly by a non-receptor-mediated process, and, at the intimal level, acquire thrombogenic and atherogenic potentials. Current information justifies the need to determine plasma Lp(a) levels in patients with a history of atherosclerotic cardiovascular disease. Unfortunately, the available techniques need to be standardized. Apolipoprotein(a) exists in isoforms of different sizes, and the importance of determining apo(a) phenotypes in clinical practice remains to be established.

Arteriosclerosis↗

Mutagenicity study of urine from smoking and non-smoking road tanker drivers.

Urine from 32 road tanker drivers handling petrol, diesel, paraffin and white spirit was tested in the Salmonella/microsome mutagenicity system using tester strains TA98 anbd TA100. Urine samples were collected before and after tanking and were concentrated 250-fold on XAD-2 columns before testing. Controls were 33 office employees from the same plant. No effect on urinary mutagenicity of occupational exposure to petroleum products was found. Significant differences in mutagenic effect were demonstrated between smokers and non-smokers. Methodological experiments demonstrated a dose/response effect of smoking on urinary mutagenicity. A modified test using a preincubation period and an increased concentration of bacteria was more sensitive than the standard Ames test to mutagens from tobacco smoking.

Dose-Response Relationship, Drug↗

Pedigree analysis of Eysenck Personality Questionnaire (EPQ) scores in monozygotic (MZ) twin families.

MZ twins with spouses and children, altogether 811 subjects, completed the Eysenck Personality Questionnaire (EPQ). For extraversion (E), neuroticism (N), and lying (L), models including only additive genetic effects fitted well to the observed sex-specific correlations for the various sets of relationships. There was no evidence of sex differences for any parameter estimate for E, N, and L. The fit for E improved significantly after including dominance, and the fit for L improved significantly after including assortative mating. A model specifying genetic additive and dominance effects and assortative mating fitted well to the Psychoticism (P) data, but the fit improved significantly when a parameter for cultural transmission from fathers to daughters were included. Except for this, there was no evidence of cultural transmission for any scores. The heritabilities for the best-fitting models were .53 (E), .36 (N), .43 (L), and .39 (P). The latter includes almost only nonadditive, and no additive, variance, suggesting an overestimation of this effect due to random fluctuation or environmental sibling effect misinterpreted as dominance.

Adult↗

Transcobalamins in the etiology of neural tube defects.

In a sample of 79 pregnant women at risk offspring with neural tube defects (NTDs) and 158 controls, significantly increased median values were found for apo-transcobalamins I and II in amniotic fluid in the group at risk, thus confirming previous results. The findings may reflect a genetic disposition to NTDs associated with altered levels of apo-transcobalamins, and research on the etiology and mechanisms of NTDs should focus on these proteins.

Adult↗