PubMed Health⌕ Search

Biomedical subjects

M Hedman

Publications and source records attributed to M Hedman.

At least 19 recordsLinked to original sources
PubMed2006

A microarray system for genotyping 150 single nucleotide polymorphisms in the coding region of human mitochondrial DNA.

We established a genotyping system for a panel of 150 SNPs in the coding regions of mitochondrial DNA based on multiplex tag-array minisequencing. We show the feasibility of this system for simultaneous identification of individuals and prediction of the geographical origin of the mitochondrial DNA population lineage of the sample donors by genotyping the panel of SNPs in 265 samples representing nine different populations from Africa, Europe, and Asia. Nearly 40,000 genotypes were produced in the study, with an overall genotyping success rate of 95% and accuracy close to 100%. The gene diversity value of the panel of 150 SNPs was 0.991, compared to 0.995 for sequencing 500 nucleotides of the hypervariable regions I and II of mtDNA. For 17 individuals with identical sequences in the hypervariable regions of mtDNA, our panel of SNPs increased the power of discrimination. We observed 144 haplotypes that correspond to previously determined mitochondrial "haplogroups," and they allowed prediction of the origin of the maternal population lineage of 97% of the analyzed samples.

Asian People↗
PubMed2006

The association of CTLA-4 and HLA class II autoimmune risk genotype with regulatory T cell marker expression in 5-year-old children.

Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance by suppression of autoreactive lymphocytes that have avoided thymic depletion. The defective function of Treg cells has recently attracted attention in autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and multiple sclerosis. Susceptibility to these diseases is associated with specific human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms. This study aimed to investigate the relationship between HLA class II and CTLA +49 A/G polymorphisms associated with susceptibility to T1D and the number and characteristics of Treg cells in children. Samples from 47 5-year-old children who participated in the All Babies in South-east Sweden (ABIS) follow-up study were grouped according to the presence of the T1D risk-associated HLA genotype (DQA1*0501-DQB1*0201, DQA1*0301-DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (P = 0.03) and CD4+ CD25high cells (P = 0.06) expressing intracellular CTLA-4 were detected in samples from children with CTLA-4 +49GG compared to children with the +49AA genotype. Similarly, lower percentages of CD4+ (P = 0.002) and CD4+ CD25high (P = 0.002) cells expressing CTLA-4 were observed in children positive for HLA DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 (P = 0.04 for CD4+ and P = 0.02 for CD4+ CD25high) risk haplotypes when compared to children without these alleles. The percentage of CD25high cells among CD4+ cells was correlated inversely with CTLA-4 mRNA expression in PBMC (r = -0.56, P = 0.03). Decreased levels of CTLA-4 in CD4+ and CD4+ CD25high cells in individuals with CTLA-4 and HLA class II alleles associated with T1D may contribute to the initiation and/or progression of autoimmune response.

Antigens, CD↗
PubMed2005

Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries.

This study was performed to evaluate angiogenic responses of angiopoietin-1 (Ang1) in vivo after adenovirus-mediated gene transfer in the periadventitial space of the rabbit carotid arteries using a collar technique. Adenoviruses encoding LacZ and vascular endothelial growth factor (VEGF) receptor-1-Ig fusion protein (VEGF-R1-Ig) adenoviruses were used as controls. Increased neovessel formation was seen in adventitia of the Ang1 transduced arteries 7 days after the gene transfer. Neovessels in the Ang1 transduced arteries were large in size and well perfused. Ang1 binds to Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domain) receptors, which were expressed in the endothelium of the neovessels. When VEGF-R1-Ig was used with Ang1, it resulted in a decrease in the number of neovessels, which implies that VEGF-A or some other VEGF-R1 ligand(s) play a crucial role in angiogenesis occurring in response to Ang1. There were no significant differences in the total number of capillaries in the adventitia of the VEGF-R1-Ig transduced arteries as compared to LacZ controls. Neointima formation was not increased in the Ang1 transduced arteries as compared to the controls. We conclude that in the periadventitial space Ang1 shows angiogenic activity and is a potentially useful factor for the induction of therapeutic vascular growth in vivo.

Adenoviridae↗
PubMed2004

Analysis of 16 Y STR loci in the Finnish population reveals a local reduction in the diversity of male lineages.

We analysed samples of 400 Finnish males using nine Y-chromosomal short tandem repeat (STR) loci (minimal haplotype); for 200 of these subjects an additional seven Y-chromosomal STR loci were used. The geographical distribution of the observed haplotypes was determined from 200 individuals of known paternal origin within Finland. The observed number of alleles varied from 2 to 13 alleles per locus. A total of 146 minimal haplotypes were identified in our population sample. Interestingly, 90 (22.5%) individuals shared an identical haplotype. This haplotype was extremely frequent in the northern and eastern subpopulations of Savo, Pohjanmaa and Karjala (53, 42 and 37%, respectively). With the seven additional loci analysed in the sample of 200 individuals, 120 haplotypes were identified, and individuals sharing the most common haplotype decreased to 13.0%. However, in comparison to other European populations, the Finnish population showed decreased genetic diversity (GD) when the number of different minimal haplotypes in the population was divided by the sample size (36.5% in Finns versus 83.7% on average). Our results strongly support the earlier hypothesis of individual isolated Y-chromosomal lineages and population substructuring in Finland. For paternity testing, power of exclusion was 92% using minimal haplotype data, but including the seven additional loci this value increased to 97%.

Adult↗
PubMed2004

Evaluation of gastrointestinal cancer tissues as a source of genetic information for forensic investigations by using STRs.

Malignant tissue samples may sometimes be the only source of biological material for forensic investigations, including identification of individuals or paternity testing. However, in use of such samples, uncertainties due to microsatellite instability (MSI) and loss of heterozygosity (LOH) often associated with neoplasias may be encountered. In this study, we have analysed the applicability of autosomal tetranucleotide short tandem repeat (STR) markers, which are routinely used in forensic analysis, to gain genetic information. MSI and LOH were analysed in 41 surgically removed gastrointestinal cancer specimens and the adjascent non-cancerous tissue marginals. The cancer specimens showed great variability in their genetic phenotypes due to MSI or LOH, with only 32% being microsatellite-stable. Of the 15 autosomal STR loci analysed, only TH01 had no MSI-type alteration in these samples. The loci most frequently affected by MSI were D8S1179, D21S11, D18S51 and D19S433 (MSI in 15-17% of cases). LOH-type alterations were observed at all of the loci, including the amelogenin locus used for sex determination. The highest LOH frequency was found at locus D18S51 (27%). The genetic alterations at the marker loci may indicate false homozygosity or heterozygosity, and false gender may result from erroneous deduction of DNA profiles. Therefore, typing of autosomal STRs from malignant tissues in forensic settings warrants careful interpretation of MSI and LOH results together with microscopic analysis of a tissue specimen. Results by two commercially available and widely used forensic DNA profiling kits used here were comparable.

Aged↗
PubMed2001

Forensic osteological investigations in Kosovo.

A team of Finnish forensic experts performed investigations of alleged mass graves in Kosovo under the mandate of the European Union (EU). Human skeletal remains from two locations were examined. The remains contained three almost complete skeletons, and individual bones and bone fragments, part of which were burned. Injuries, pathological changes, and findings for identification purposes were examined and documented using standard methods of forensic pathology and osteology. Gunshot injuries were found in some cases, but reliable determination of the cause and manner of death was not possible. A discrepancy arose between the number of victims reported in information received from the presiding district court, and results of the investigations. The estimation of the minimum number of victims was mostly acquired by DNA analysis.

Age Determination by Skeleton↗
PubMed2000

Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome, as revealed by direct observation in father/son pairs.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

Adolescent↗
PubMed2000

Gene therapy for the treatment of peripheral vascular disease and coronary artery disease.

Owing to the easy accessibility and general importance of the vascular system, cardiovascular diseases, including postangioplasty and graft restenosis, have become one of the new areas for gene therapy and molecular medicine. Promising therapeutic effects have been obtained in animal models of vascular diseases and restenosis with the transfer of genes for vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), thymidine kinase, p53, retinoblastoma, bcl-x, tissue inhibitor of metalloproteinase (TIMP), hepatic growth factor (HGF) and nitric oxide synthase (NOS). Also, growth arrest homeobox gene and antisense oligonucleotides or antibodies against transcription factors or cell cycle regulatory proteins have produced beneficial therapeutic effects. However, further developments in gene delivery techniques and vectors are needed before the full therapeutic effects of gene therapy in vascular diseases can be obtained.

Journal Article↗
PubMed1995

Chronic hepatitis C in alcoholic patients: prevalence, genotypes, and correlation to liver disease.

BACKGROUND: Only one-fifth of chronic alcoholic patients develop chronic liver disease in spite of continuous alcohol abuse. Hepatitis C has been proposed to be one of several suggested factors contributing to the development of liver disease. METHODS: In 201 consecutive chronic alcoholic patients admitted to the hospital for detoxification, antibodies to hepatitis C virus (HCV) were determined, using second-generation enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) tests. Sera from patients with antibodies were tested with polymerase chain reaction (PCR) to detect HCV RNA and subsequently genotyped. RESULTS: Twenty-nine patients (14%) were positive in the ELISA and RIBA tests. HCV RNA was detected in 23 of the 29 (79%); 21 could be genotyped. Previous intravenous drug abuse was present in 18 of 29 (58%) in the positive group versus 3 of 172 (2%) in the negative group (p < 0.001), whereas the prevalence of previous blood transfusions did not differ between the groups. In one-third of the positive cases no obvious route of transmission was found. On the basis of clinical and biochemical variables and, if available, histology, altogether 6 of 29 (21%) HCV-positive patients were classified as having severe liver disease as compared with 12 of 172 (7%) HCV-negative patients (p < 0.05). HCV-positive patients with liver disease were younger than HCV-negative patients with liver disease (p < 0.05). CONCLUSIONS: Hepatitis C virus infection is common among chronic alcoholic patients in Stockholm, especially among patients with a history of intravenous drug abuse. To confirm ongoing infection, detection of HCV RNA is necessary. This infection seems to be a factor contributing to the development of liver disease in alcoholic patients.

Adult↗
PubMed1988

Endocrine, seminal and peripheral effects of depot medroxyprogesterone acetate and testosterone enanthate in men.

Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Blood and tissue steroid levels and their interrelationship in men with pathological conditions of the reproductive organs.

We have investigated the interrelationship of the levels of 10 steroids in peripheral venous, spermatic arterial and spermatic venous blood, and in tissue specimens from the epididymis, vas deferens and testis from 8 patients who underwent orchidectomy for pathological conditions of the reproductive organs. The steroids analyzed by radioimmunoassay were: pregnenolone (5-P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OH-P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and the sulpho-conjugated forms (-S) of 5-P, DHEA, T and DHT. The quantitatively major steroids in peripheral venous blood were, in order of magnitude, DHEA-S, 5-P-S, DHT-S, T-S and T. No difference was observed between the levels of any of the steroids measured in peripheral venous and spermatic arterial blood. With the exception of DHEA-S and DHT-S, the levels of all steroids in spermatic venous blood were substantially higher than in peripheral venous blood (P less than 0.001). No correlation was found between steroid levels in spermatic venous and peripheral venous blood. Steroid concentrations in tissue from the epididymis, vas deferens and testis were markedly higher than in peripheral venous blood (P less than 0.01 to P less than 0.001), except for the levels of DHEA-S which were about equal in the various blood and tissue specimens. Tissue to blood ratios varied from approximately 2.0 to 500 according to the steroid in question. The peripheral blood levels of 5-P-S, DHEA-S and DHT-S were substantially higher than respective unconjugated steroid levels (P less than 0.001); the ratios (sulpho-conjugated to unconjugated) were approximately 17, 215 and 30, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Effect of vasectomy on the steroid profile of human seminal plasma.

The effect of vasectomy on the steroid profile of seminal plasma was studied in 19 healthy men at 4-monthly intervals during a 2-year post-vasectomy period. The steroids analyzed by radioimmunoassays were: androstenedione (A), testosterone (T), dihydrotestosterone (DHT), oestradiol (E2) and the sulphoconjugated forms of pregnenolone (delta 5P-S), dehydroepiandrosterone (DHEA-S), testosterone (T-S), dihydrotestosterone (DHT-S), oestrone (E1-S) and oestradiol (E2-S). The quantitatively most important steroids present in the seminal plasma were DHEA-S, delta 5P-S and DHT-S. Vasectomy resulted in a significant but non-progressive reduction in DHT (40%) and T (23%) levels. The levels of E2, delta 5P-S and DHT-S also exhibited a smaller reduction following vasectomy. No significant changes were observed in the levels of the other steroids studied. The results are interpreted as suggesting that under normal conditions the bulk of the steroids present in the ejaculate is contributed by the accessory reproductive organs. In addition, a significant part of the DHT and T reach the ejaculate together with the sperm directly from the testis and/or epididymis. It is suggested that the normal steroid levels in seminal plasma established in this investigation could serve as reference values in the hormonal evaluation of male infertility.

Adult↗
PubMed1983

Lack of effect of vasectomy on peripheral gonadotrophin and steroid levels.

In order to re-assess the possible hormonal consequences of male sterilization, the peripheral plasma levels of lutropin (LH) follitropin (FSH), and dihydrotestosterone sulphate (DHT-S) were measured in a group of 20 healthy men at weekly intervals in the month before and at bimonthly intervals up to 2 years after vasectomy. In addition, the levels of 14 steroids of gonadal and/or adrenal origin were measured before, and then every second month (12 subjects) or every sixth month (8 subjects) following vasectomy. No significant alterations were observed in the levels of any of the hormones studied. The results are interpreted as indicating that in the first 2 years following vasectomy in men there is no consistent or progressive change in the peripheral plasma levels of gonadotrophins or in a variety of steroids of testicular and/or adrenocortical origin.

Adult↗
PubMed1982

Intratesticular and plasma steroid profiles in fertile and infertile men.

In 24 apparently healthy men who requested sterilization by vasectomy, we have measured the intratesticular and peripheral plasma levels of 9 unconjugated and 5 sulphoconjugated steroids. These steroid levels were then compared with those found in a group of 18 men, admitted to the hospital with complaints of infertility. With the exception of higher dihydrotestosterone levels in the infertile group, no differences were found between the two groups with regard to the peripheral plasma levels of the unconjugated or sulphoconjugated steroids studied. On the other hand, the intratesticular levels of cortisol, pregnenolone, androstenedione, dihydrotestosterone, pregnenolone sulphate and testosterone sulphate (but not those of testosterone) were significantly diminished in the infertile group. With the exception of dehydroepiandrosterone levels in the fertile group, and dehydroepiandrosterone sulphate and dihydrotestosterone sulphate in the infertile group, the intratesticular steroid levels were uncorrelated with the plasma levels. The data are interpreted as suggesting that a) male infertility may be associated with intratesticular alterations of steroid metabolism which are not reflected by the peripheral steroid levels; b) the plasma and intratesticular levels of testosterone are not sensitive enough indices for the endocrine evaluation of male infertility; c) the role of the sulphoconjugated forms of steroids in the maintenance of male fertility deserves further investigation.

Adult↗
PubMed1981

A study of the short-time variation and interrelationship of plasma hormone levels reflecting pituitary, adrenocortical and testicular function in fertile men.

Using radioimmunoassay method, we have estimated the levels of cortisol (C), pregnenolone (delta 5P), 17-hydroxypregnenolone (17-OH-delta 5P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OH-P), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) in peripheral plasma samples collected at short-time (15 min) intervals from 10 fertile men, during two 4-h periods (06.00 to 10.00 and 18.00 to 22.00). In addition, the levels of biologically active luteinizing hormone (LH) were measured by an in vitro bioassay method in 9 of the subjects. The levels of all steroids studied exhibited diurnal variation with higher levels during the morning and lower levels during the evening period. The cortisol and the delta 5-steroid levels also exhibited individual short-term episodic spikes during the 2 periods. No short-term variation was observed in the levels of 17-OH-P, A, T and DHT. Statistically significant correlations were found between the levels of C and those of the delta 5-steroids and A in most of the subjects. No correlation was found between the above steroid levels and those of 17-OH-P, T and DHT. Also the LH levels exhibited episodic spikes of 60 to 90 min duration, but no diurnal variation. When the LH levels were related to those of T found in the same samples or in samples withdrawn 15 to 810 min afterwards, a significant positive correlation was found on repeated occasions in 5 of the 9 subjects. No systematic negative correlation was found when the T levels were related to those of LH in the same sequential fashion. Whereas the positive correlations found between LH and T levels in some of the subjects might suggest that physiological changes in peripheral LH levels are instrumental in regulating T-secretion, the rather consistent lack of significant negative correlation between T and LH levels seems to favour the view that the release of LH is not modulated by peripheral testosterone levels alone.

Adrenal Cortex Hormones↗