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Biomedical subjects

L Beckman

Publications and source records attributed to L Beckman.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Hereditary hemochromatosis. Genetic findings result in new therapeutic possibilities].

Hereditary haemochromatosis is a well-known disease characterised by abnormally high iron absorption and a variety of clinical manifestations. As it's expression is dependent on such factors as gender and diet, it has often been difficult to diagnose before the onset of damage to different organs. However, since the recent discovery of the gene for hereditary hemochromatosis, early detection and treatment of the disease has become possible.

Gene Frequency↗
PubMed1997

Interferon-alpha and p53 alleles involved in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma, which is very frequent in southern China, has in previous investigations been found to be associated with a number of risk factors, including a disease susceptibility gene linked to the HLA-region, p53 alleles and deletions of the chromosome 9p21-22 region, which includes the IFNA and p16 loci. We have therefore studied 64 patients (54 males and 10 females) with nasopharyngeal carcinoma and 99 healthy controls from the Guizhou province in southern China with respect to association with the SspI polymorphism at the IFNA17 locus, and the possible interaction between IFNA17 and p53 alleles in the etiology of nasopharyngeal carcinoma. The frequency of the SspI A1 allele was much higher (P < 10(-10)) in Chinese patients and controls than in a previously reported study of Swedes. Among the patients there was a significant increase in the frequencies of the SspI A2 allele (P = 0.011) and SspI 2-2 genotype with an OR (odds ratio) of 2.76, 95% CI = 1.13-6.73 in relation to the SspI 1-1 type. When combinations of SspI and the p53 codon 72 (BstUI) genotypes were studied a highly significant risk figure was found for the SspI 2-2/BstUI 1-1 (pro/pro) combination (OR = 8.2, 95% CI = 2.2-30.0). No other combinations showed significant risk figures. There was no significant interaction between the SspI 2-2 and BstUI 1-1 types indicating that IFN-alpha and p53 genotypes behave as independent risk factors. Since IFN-alpha is located close to the tumor suppressor gene p16, and intronic p53-haplotypes show stronger association with nasopharynx cancer than the codon 72-polymorphism, both associations may be due to linkage disequilibrium with adjacent genes influencing cell-cycle control.

Alleles↗
PubMed1996

Genetic markers associated with high versus low performance on episodic memory tasks.

Associations were studied between six serum protein polymorphisms (C3, BF, HP, ORM, TF, and GC) and high versus low scoring on episodic memory tasks in an attempt to identify QTL (quantitative trait loci) contributing to the heritability of this quantitative trait. Since a highly significant sex difference (p = .00002) was found with respect to the distribution of high and low scoring, with men showing a poorer performance, associations were studied separately for males and females. In females significant differences (p < .05) between the high and the low groups were found in four of six marker systems (C3, HP, TF, and CG), whereas in males a significant difference was found only in the HP system. Significant differences from population frequencies were also found more frequently in females than in males. The strongest marker associations were found with complement C3 and the acute-phase reactant HP, which suggests that immune response factors may be of importance in preserving episodic memory function. The overall results appear to indicate that episodic memory is a multifactorial and heritable quantitative trait where sex is an important determinant.

Adult↗
PubMed1996

p53 polymorphisms and haplotypes in breast cancer.

Three polymorphisms in the human tumor suppressor gene p53 (BstUI and MspI RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patients with breast cancer and controls. A significant increase in the codon 72 BstUI A1 (pro) allele frequency (P = 0.016) and of individuals carrying the pro allele (pro/pro and pro/arg) (OR, 1.47; P = 0.01 4; 95 % CI, 1.08-2.00) was observed in breast cancer. This increase was most pronounced in highly differentiated breast cancer. Significant associations were found only in BstUI and haplotypes containing this polymorphism, which indicates that the codon 72 pro allele may be functionally involved in low malignancy breast cancer. The distributions of genotypic combinations in breast cancer patients and controls were significantly different (P = 0.005). Two BstUI-16 bp-MspI combinations were significantly overrepresented; 2-1, 1-1, 2-2 (OR, 1.61; 95% CI, 1.13-2.30) and 1-1, 2-1, 2-1 (OR, 2.94; 95% CI, 1.37-6.27).

Adult↗
PubMed1996

Transferrin C3 offers protection against smoking-associated lung cancer?

In previous investigations increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects, including cancer. In this investigation transferrin C (TF C) subtypes were studied in lung cancer patients and controls from the Stockholm area in central Sweden. There was a significant difference between patients and controls with respect to the distribution of TF C alleles and genotypes, which was mainly due to a low frequency of the TF C3 allele among the patients (P = 3 x 10(-6). However, in adenocarcinoma the frequency of TF C3 types was almost identical to that among the controls, whereas in the smoking-related (squamous and small cell) tumor types the TF C3 frequency was remarkably low (OR = 0.03, 95% CI = 0.00-0.22). Thus individuals with the TF C3 variant appear to enjoy an almost complete protection against smoking-related lung cancer. The frequency of individuals carrying the protective TF C3 variant is approximately 17% in central Sweden and 25% in Finland, which has the highest TF C3 frequency found so far. The mechanism behind the observed association, which appears to be independent of iron binding and body iron stores, remains to be elucidated.

Adenocarcinoma↗
PubMed1996

Polymorphism in the interferon-alpha gene family.

A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases "nested" PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-alpha 1 and interferon-alpha 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines.

Base Sequence↗
PubMed1995

Listening and learning from women about mifepristone: implications for counseling and health education.

The careful, reflective, and honest way in which the women in the study analyzed, questioned, and explored the benefits and disadvantages of a mifepristone abortion compared with vacuum aspiration yielded an extensive list of information needed by women to make informed choices as well as an understanding of the diverse social contexts in which choices are made. Needed information identified by this study included technical information about the drugs themselves and their mechanisms of action, roles and responsibilities of health personnel, and descriptions of other women's experiences with mifepristone. A multiplicity of factors entered the decision-making process, demonstrating at the same time a complexity and flexibility of thought. In their hypothetical evaluation of mifepristone, women weighed such factors as experience with childbirth, spontaneous abortion and vacuum aspiration, specific issues for teenagers, lack of a support system, experience with herbal emenagogues and nonprescription drugs intended as abortifacients, and the relative dependence on health care providers. Social, personal, and cultural factors entered into women's interpretation of the different options. These socio-cultural contexts can profoundly influence decisions and potentially affect clinical outcomes. If health care professionals are not proactive, do not fully provide answers to questions (even if unasked), and fail to probe for specific life circumstances, then poor choices and poor outcomes may follow with long term negative consequences for clients.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents, Steroidal↗
PubMed1995

P53 germ line haplotypes associated with increased risk for colorectal cancer.

Three p53 DNA polymorphisms (BstU I and Msp I restriction fragment length polymorphisms (RFLPs) in exon 4 and intron 6 respectively, and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patients with colorectal cancer and compared with patients with ulcerative colitis and healthy controls. There were only minor differences between patients with ulcerative colitis and controls, the only significant difference was observed in the distribution of BstU I-Msp I haplotypes. When single polymorphisms were studied, a significantly lower frequency of the 16 bp duplication was found in patients with colorectal cancer. The protective effect of the 16 bp duplication was more pronounced in haplotype combinations with the BstU I A1 and Msp I A1 alleles, whereas these alleles in combination with the 16 bp A1 allele (no duplication) were associated with an increased risk for colorectal cancer. The genotypic combination BstU I 2-1, 16 bp 1-I, Msp I 2-1 was found in 8.4% of cases among patients with colorectal cancer and 0.5% of cases in the controls (odds ratio = 18.8). The extended haplotype responsible for the high cancer risk of this genotype appears to be BstU I A1-16 bp A1-Msp I A1. The results of this study indicate that the haplotype approach to the identification of p53 germ line alleles associated with increased susceptibility to cancer is far more powerful than the analysis of single polymorphisms, since the capacity to identify germ line alleles predisposing to cancer should increase with the number of polymorphic sites included in the analysis.

Alleles↗
PubMed1995

P53 polymorphisms and haplotypes in lung cancer.

An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 codon 72 polymorphism and lung cancer has previously been reported by Kawajiri et al. A reanalysis of the data by Kawajiri et al. revealed no significant difference between patients and controls with respect to allele frequencies, and the increased frequency of BstU I 1-1 homozygotes was mostly ascribable to a deviation from the Hardy-Weinberg equilibrium. In an attempt to replicate the results by Kawajiri et al. we have studied three p53 polymorphisms (BstU I and Msp I RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotypes in Swedish lung cancer patients and controls. The results concerning the codon 72 polymorphism were largely negative. Thus there was no significant association between lung cancer and the BstU I 1-1 type, and only a marginal difference (P = 0.044) with respect to the BstU I allele frequency when lung cancer patients were compared with patients with chronic obstructive pulmonary disease (COPD). However, when the analysis was based on haplotype frequencies larger differences appeared and it was found that only BstU I 1 (pro) alleles linked to 16 bp 1 alleles were associated with lung cancer. Pro alleles linked to the 16 bp duplication appeared instead to confer some protection against cancer. Thus the codon 72 alleles need not be functionally involved in lung cancer, but may rather be markers in linkage disequilibrium with other cancer susceptibility sites on p53.

Alleles↗
PubMed1995

Genes and languages in Europe: an analysis of mitochondrial lineages.

When mitochondrial DNA sequence variation is analyzed from a sample of 637 individuals in 14 European populations, most populations show little differentiation with respect to each other. However, the Saami distinguish themselves by a comparatively large amount of sequence difference when compared with the other populations, by a different distribution of sequence diversity within the population, and by the occurrence of particular sequence motifs. Thus, the Saami seem to have a long history distinct from other European populations. Linguistic affiliations are not reflected in the patterns of relationships of mitochondrial lineages in European populations, whereas prior studies of nuclear gene frequencies have shown a correlation between genetic and linguistic evolution. It is argued that this apparent contradiction is attributable to the fact that genetic lineages and gene frequencies reflect different time perspectives on population history, the latter being more in concordance with linguistic evolution.

Base Sequence↗
PubMed1995

Synergistic interaction between ORM1 and C3 types in disease associations.

In previous studies of orosomucoid (ORM) types and disease the ORM1 1 type has been found to be associated with sarcoidosis and other immunogenetic diseases, and the ORM 1 2 type with different types of carcinomas. We report significant associations between ORM1 and C3 types in sarcoidosis and breast cancer, but not in healthy individuals. The ORM1 1 and C3S variants in combination increased the risk of sarcoidosis, and the ORM1 2 and C3F variants together gave an increased risk of breast cancer. A probable mechanism may be that the ORM1 and C3 molecules modify the immune response by interacting with the lymphoid cell surface.

Alleles↗
PubMed1994

Geographical distribution of TTR met30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate.

The first Swedish case of familial amyloidotic polyneuropathy (FAP) was published in 1965. The same transthyretin (TTR met30) mutation as that seen in Japanese, Portuguese, and other populations was also found in Swedish FAP patients. More than 350 patients with clinical manifestations of FAP have been diagnosed in northern Sweden, most of them originating from the areas around Skellefteå and Piteå. The mean age of onset is 56 years, much later than in patients from Japan and Portugal. To estimate the frequency of the TTR met30 mutation in the counties of Västerbotten and Norrbotten, sera from 1276 persons aged 24 to 65 years, randomly sampled from a health programme (MONICA), were screened with the monoclonal antibody FD6. In 19 persons, 13 females and six males, a positive reaction was seen in an Elisa test using this antibody. DNA analysis confirmed the TTR met30 mutation and showed that 18 were heterozygous and one homozygous for this mutation. Other mutations were not looked for in this study. The mean TTR met30 carrier frequency in the area was 1.5% ranging from 0.0 to 8.3% in 23 subpopulations. There was a notable discrepancy between the regional distribution of the TTR met30 allele and the morbidity rate for FAP. The estimated number of TTR met30 gene carriers in a total population of 500,000 in the area is approximately 7500. The penetrance of the TTR met30 mutation shows considerable variation between families, and the overall diagnostic (predictive) value in this population is as low as around 2%.

Adult↗
PubMed1992

Idiopathic hemochromatosis and chromosomal damage.

Spontaneous and radiation-induced chromosome damage in cultured lymphocytes was examined in a pilot study of 11 patients with idiopathic hemochromatosis and matched controls. Increased frequencies of chromosome breaks were found in the patients, both spontaneously and after exposure to ionizing radiation, but the differences between patients and controls were not statistically significant (p greater than 0.05) when individual data were analyzed. When pooled (group) data for patients and controls were compared, significant increases in spontaneous and radiation-induced chromosome breaks were found among the patients. The results suggest that iron overload may lead to chromosome damage in idiopathic hemochromatosis.

Cells, Cultured↗
PubMed1992

DNA polymorphism of alkaline phosphatase isozyme genes: linkage disequilibria between placental and germ-cell alkaline phosphatase alleles.

The use of human placental alkaline phosphatase (PLAP) cDNA as a probe allows the detection and identification of restriction DNA fragments derived from three homologous genes, i.e., intestinal alkaline phosphatase (AP), germ-cell AP (GCAP), and PLAP. In previous RFLP studies we have reported linkage disequilibria between an RsaI and two PstI (a and b) polymorphic restriction sites and electrophoretic types of PLAP. In this report we present evidence that, in spite of the strong correlation with PLAP types, PstI(b) is an RFLP of GCAP. The data indicate close linkage between the PLAP and GCAP loci.

Alkaline Phosphatase↗
PubMed1991

Is the genotoxic effect of arsenic mediated by oxygen free radicals?

Previous investigations have shown that trivalent arsenic is inducing chromosomal aberrations and sister chromatid exchanges (SCEs). In a search for the genotoxic mechanism we have studied the effects of the oxygen-radical-scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) on arsenic-induced SCEs in cultured human lymphocytes. The results indicate that SOD and possibly also CAT have a protective effect against arsenic-induced DNA damage. Arsenic, which is emitted in environmental pollutions e.g. from smelters and coal-fired power plants, appears to be underestimated as environmental mutagen and potential synergist to ionizing radiation.

Arsenic↗
PubMed1991

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase. RFLP haplotypes and correlation with electrophoretic types.

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase (PLAP) was discovered in a study of a Finnish population sample and designated PstI(b)1 or Pst(b)2 depending on the presence or absence of the cleavage site. The frequency of the PstI(b)2 allele was 0.24. This allele showed a positive (p = 3 x 10(-6) association with the electrophoretic allele 2(F) and a negative association (2 x 10(-7) with the electrophoretic allele 1(S). The previously described PstI RFLP [PstI(a)] was also found to be associated with electrophoretic types; the PstI(a)1 allele (presence of site) was associated with the electrophoretic type 2 (p = 0.023). Haplotype frequencies and disequilibria were calculated between PstI(a), PstI(b) and RsaI RFLPs. A complete disequilibrium (p = 1 x 10(-6) was found between PstI(a) and RsaI, whereas there was no significant disequilibrium between PstI(b) and RsaI. There was no strict correlation between the distances between the RFLP loci and the degree of linkage disequilibrium. The allele controlling the electrophoretic variant PLAP 18 (D) was found in polymorphic frequency (0.024) in the Finnish population.

Alkaline Phosphatase↗
PubMed1991

Population studies in northern Sweden. XVII. Estimates of Finnish and Saamish influence.

The North-Swedish population is a mixture of Finnish, Saamish and Central-Swedish ethnic groups. We have studied the Finnish and Saamish admixture by means of genetic markers in 23 North-Swedish subpopulations. The Finnish influence was estimated using the transferrin genes B0-1, DCHI and C3 and the enzyme gene SOD1*2, and markers for Saamish influence were the blood group gene ABO*A2, the serum group gene GC*1F and the enzyme gene 6PGD*C. In the subpopulations the Finnish influence (admixture) varied between 0 and 84% and the Saamish influence between 0 and 34%. The Saamish influence was strongest in the western and northern parts of the area. In the northern part of the area, between 1/4 and 1/3 of the gene pool of the present-day population may be Saamish in origin. The Finnish influence was strongest in the northern and northeastern parts of the area. In the subpopulations along the Finnish border, between 60 and 80% of the gene pool may be Finnish in origin. Significant correlations were found between the Saamish marker genes and between the Finnish marker genes. Due to geographical overlapping of Finnish and Saamish influence, significant correlations were also found between Finnish and Saamish marker genes. The geographical pictures of Saamish and Finnish influence in northern Sweden showed a fair agreement with the expectations derived from historical knowledge. Although a substantial part of the genetic heterogeneity of the North-Swedish population is ethnic in origin, it is obvious that founder effect and genetic drift also have played an important role.

Ethnicity↗