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Biomedical subjects

V Gudnason

Publications and source records attributed to V Gudnason.

42 records · Page 3Linked to original sources

Polymorphism of the c-Ha-ras-1 proto-oncogene in sporadic and familial breast cancer.

Two studies on breast cancer patients are described. Our aim was to examine whether the combined frequency of rare c-Ha-ras-1 alleles in cancer patients was raised. Firstly, the c-Ha-ras-1 locus in 56 breast cancer patients and 48 controls was examined for restriction fragment length polymorphism (RFLP) by Southern blot analysis of leukocyte DNA. Four predominant allelic fragments were found in both groups together with a variety of rare alleles. The 2 groups did not differ significantly in overall distribution of c-Ha-ras-1 alleles. Rare alleles combined were about as frequent in cases (7.1%) as in controls (6.3%). Secondly, 53 members of 3 families having a high incidence of breast cancer were c-Ha-ras-1 genotyped. None of 10 affected members was found to carry a rare c-Ha-ras-1 allele. The only c-Ha-ras-1 allele common to 11 affected members was a 6.8-kb allele which is found in 72% of the controls. Furthermore, this allele was found with equal frequency in affected and non-affected family members.

Adult↗

A study of familial hypercholesterolaemia in Iceland using RFLPs.

We have studied 17 unrelated families from Iceland who have familial hypercholesterolaemia (FH), using three different restriction fragment length polymorphisms (RFLPs) of the LDL receptor gene. In one family FH was caused by a 2 kb deletion in the LDL receptor gene in the region of exons 9 to 10. The PvuII (intron 15), NcoI (exon 18), and ApaLI (intron 15) RFLPs were used to determine the haplotypes associated with the defective LDL receptor gene in Iceland. Genotypes were determined in 77 subjects from these 17 families, both FH and non-FH. A rare new NcoI RFLP was detected in three subjects. Among the patients, at least four different haplotypes were observed indicating that FH in Iceland is caused by at least four different mutations and is a heterogeneous disease, even in the small, geographically isolated population of Iceland.

Adult↗

Specific polypeptide differences in normal versus malignant human breast tissues by two-dimensional electrophoresis.

Postmitochondrial and cytosolic polypeptides were extracted from human breast tumors and non-malignant breast tissue and analyzed using high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Approximately 800-1000 postmitochondrial and 600-800 silver stained cytosolic polypeptides were detected over the pH range of 4.8 to 7.5 and molecular weight range of 18-120 kDa. The 2D-PAGE patterns of polypeptides from normal and malignant tissue were very similar, although both qualitative and quantitative polypeptide differences were noted. Six cytosolic polypeptides (pI/molecular weight X 10(-3) 5.20/80 kDa, 5.75/43, 6.25/40, 5.43/35, 5.45/34.5, 5.50/34 and 6.15/24 were expressed only in malignant tissues. One constitutive polypeptide, 7.25/52, was not detected in any of the malignant tissue samples. Quantitatively, marked differences in spot density were noted in polypeptides localized mainly in the molecular weight ranges of 22-40 kDa and pI ranges of 5.65-7.00. A general increase in polypeptide expression was noted in malignant tissues as compared to normal. Twenty-two polypeptides were significantly and consistently increased in tumor samples while only one polypeptide was decreased. One polypeptide, p24 (6.15/24) was expressed in greatest concentrations in tumors which also expressed the greatest estrogen receptor content. Expression of p24 was markedly reduced in normal tissue and malignant tissues expressing low levels of estrogen and progesterone receptors.

Biomarkers, Tumor↗

Catabolite repressive effects of 5-thio-D-glucose on Saccharomyces cerevisiae.

The effect of the glucose analogue 5-thio-D-glucose (5TG) on the yeast Saccharomyces cerevisiae was studied. Derepression of mitochondrial respiratory chain cytochromes, alcohol dehydrogenase (isoenzyme II), NADH dehydrogenase and maltase was inhibited by 0.5-2 mM-5TG. Growth rate was only slightly affected. Ethanol was efficiently produced with 2 mM-5TG in medium initially containing 0.25% glucose. Mutants resistant to the growth inhibitory effects of 5TG on glycerol medium showed resistance to the catabolite repressing effects of glucose. Other mutants, known to be catabolite repression resistant, showed resistance to 5TG. The analogue seems to inhibit derepression of glucose repressible enzymes with greater potency than glucose itself.

Cytochromes↗

Suppression of temperature sensitive mutations in oncogene-related CDC genes in Saccharomyces cerevisiae by catabolite repression resistance and cytoplasmic petite mutations.

The "start" cell division control genes CDC36 and CDC28 have been reported to contain a certain sequence homology to tissue oncogenes (ets and some protein kinase encoding oncogenes respectively). Here we report that temperature sensitive mutations in these genes are suppressed in cytoplasmic "petite" mutants and catabolite repression resistant mutants.

Genes, Fungal↗

Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue.

Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions used were cytosol, mitochondria and microsomes. A comparison of two methods for detecting HK activity was made, yielding different results regarding HK II and HK III. A method based on the ability of NADPH to fluoresce in UV gave a constant pattern of HK isoenzymes. In non-pathological breast tissue, only HK I was seen, i.e. in the cytosol and the microsomal fractions. HK I was also seen in all fractions of the cancers, but another more anodal band of HK I, as well as HK II and HK III, consistently appeared in the cytosol fractions. The more commonly used staining technique with tetrazolium dye revealed HK II in 45% and HK III in 50% of the samples. The pattern of HK isoenzymes in the cancers was the same irrespective of estrogen and progesterone cytosolic receptor contents and the histology of the tumors. The fluorescence method is, therefore, much more sensitive than the tetrazolium technique for detecting HK activity after electrophoresis and could explain difference in results obtained by various laboratories.

Breast↗