PubMed Health⌕ Search

Biomedical subjects

Mette Madsen

Publications and source records attributed to Mette Madsen.

At least 37 records · Page 2Linked to original sources
PubMed2004

Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region.

CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163 truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies binding to SRCR domain 3 exhibited effective inhibition of ligand binding. Furthermore, analysis of purified native CD163 revealed that proteolytic cleavage in SRCR domain 3 inactivates ligand binding. Calcium protects against cleavage in this domain. Analysis of the calcium sensitivity of ligand binding to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes.

Animals↗
PubMed2004

Case-fatality rates for myocardial infarction declined in Denmark and Sweden during 1987-1999.

OBJECTIVE: To evaluate trends in prognosis after acute myocardial infarction (AMI) between Denmark and Sweden using routinely collected data and different case-fatality measures. STUDY DESIGN AND SETTING: We compared three case-fatality measures during 1987-1999 using national registries in Denmark and Sweden, and extended these measures with underlying deaths of ischemic heart disease and sudden deaths of unknown cause. RESULTS: Changed coding practice distorted trends of case fatality rates during the day of the event. In general, Denmark had higher case-fatality rates, but trends in hospital-based rates were very similar, except for men 35-64 years old; Denmark declined more steeply. Short- and long-term prognosis improved considerably: the odds ratios for case fatality during days 1-28 for 1999 vs. 1987 were 0.48 among men in Denmark (women 0.58) and 0.53 among men in Sweden (women 0.55) and the odds ratios for case fatality during days 29-365 for 1999 vs. 1987 were 0.56 among men in Denmark (women 0.65) and 0.66 among men in Sweden (women 0.67). CONCLUSION: Short- and long-term prognosis improved considerably during 1987-1999 in Denmark and Sweden. Case fatality during the day of the event is epidemiologically important, but less certain than case-fatality measures defined after the day of the event when comparing countries.

Adult↗
PubMed2004

Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice.

Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). To characterize the physiological role of IMP1, we generated IMP1-deficient mice carrying a gene trap insertion in the Imp1 gene. Imp1(-/-) mice were on average 40% smaller than wild-type and heterozygous sex-matched littermates. Growth retardation was apparent from E17.5 and remained permanent into adult life. Moreover, Imp1(-/-) mice exhibited high perinatal mortality, and only 50% were alive 3 days after birth. In contrast to most other organs, intestinal epithelial cells continue to express IMP1 postnatally, and Imp1(-/-) mice exhibited impaired development of the intestine, with small and misshapen villi and twisted colon crypts. Analysis of target mRNAs and global expression profiling at E12.5 indicated that Igf2 translation was downregulated, whereas the postnatal intestine showed reduced expression of transcripts encoding extracellular matrix components, such as galectin- 1, lumican, tenascin-C, procollagen transcripts, and the Hsp47 procollagen chaperone. Taken together, the results demonstrate that IMP1 is essential for normal growth and development. Moreover, IMP1 may facilitate intestinal morphogenesis via regulation of extracellular matrix formation.

Animals↗
PubMed2003

The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless.

Imerslund-Gräsbeck syndrome (I-GS, megaloblastic anemia 1) is an autosomal recessive disorder characterized by intestinal cobalamin (vitamin B(12)) malabsorption and proteinuria. I-GS-causing mutations are found in either of 2 genes encoding the epithelial proteins: cubilin and amnionless (AMN). Cubilin recognizes intrinsic factor (IF)-cobalamin and various other proteins to be endocytosed in the intestine and kidney, respectively, whereas the function of AMN is unknown. Here we show that cubilin and AMN colocalize in the endocytic apparatus of polarized epithelial cells and copurify as a tight complex during IF-cobalamin affinity and nondenaturing gel filtration chromatography. In transfected cells expressing either AMN or a truncated IF-cobalamin-binding cubilin construct, neither protein alone conferred ligand endocytosis. In cubilin transfectants, cubilin accumulated in early biosynthetic compartments. However, in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to the cell surface and endosomes, and the cells exhibited IF-cobalamin endocytosis and lysosomal degradation of IF. These data indicate that cubilin and AMN are subunits of a novel cubilin/AMN (cubam) complex, where AMN binds to the amino-terminal third of cubilin and directs subcellular localization and endocytosis of cubilin with its ligand. Therefore, mutations affecting either of the 2 proteins may abrogate function of the cubam complex and cause IG-S.

Amino Acid Sequence↗
PubMed2003

Characteristics of Hodgkin's lymphoma after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population-based Danish cohorts of patients who were tested for infectious mononucleosis: 17,045 with serologic evidence of having had acute EBV infection, and 24,614 with no such evidence. We combined the cohort of patients who had serologically verified infectious mononucleosis with a cohort of 21,510 Swedish patients with infectious mononucleosis (combined total, 38,555). Biopsy specimens of Hodgkin's lymphomas occurring during follow-up in this combined cohort were tested serologically for the presence of EBV. Using this information, we modeled the relative risk of EBV-negative and EBV-positive Hodgkin's lymphoma in different periods after the diagnosis of infectious mononucleosis and estimated the median incubation time for mononucleosis-related EBV-positive Hodgkin's lymphoma. RESULTS: Only serologically confirmed infectious mononucleosis was associated with a persistently increased risk of Hodgkin's lymphoma. Sixteen of 29 tumors (55 percent), obtained from patients with infectious mononucleosis, had evidence of EBV. There was no evidence of an increased risk of EBV-negative Hodgkin's lymphoma after infectious mononucleosis. In contrast, the risk of EBV-positive Hodgkin's lymphoma was significantly increased (relative risk, 4.0; 95 percent confidence interval, 3.4 to 4.5). The estimated median incubation time from mononucleosis to EBV-positive Hodgkin's lymphoma was 4.1 years (95 percent confidence interval, 1.8 to 8.3). CONCLUSIONS: A causal association between infectious mononucleosis-related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.

Adolescent↗
PubMed2003

[Lymphedema praecox with an unusual localization].

We report the case of a 13-year-old girl with swelling of her left hand. Primary lymphedema was the conclusion of the examination. The case is published because this localisation of lymphedema praecox is extremely rare and it should therefore be considered as a possible differential diagnosis, when finding swelling of hand in adolescent girls.

Adolescent↗
PubMed2003

The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the Danish MONICA registry.

We analyzed the validity of the diagnosis of acute myocardial infarction (MI) in national registries by individual record linkage with the Danish MONICA registry. MI events were identified by record linkage between The National Hospital Registry and The National Death Registry. The sensitivity and specificity were estimated based on three different definitions of an MI event. For events with MI as the primary diagnosis or underlying cause of death the predictive value was 93.6% and sensitivity 77.6% when compared to DANMONICA definite or possible MI. Compared to DANMONICA, definite MI the predictive value was 75.0% and the sensitivity 92.8%. When secondary diagnosis and contributory cause of death were included, the sensitivity increased and the predictive value decreased only slightly. The combination of the national registries was found to be a valid and powerful tool for monitoring the population incidence of MI.

Adult↗
PubMed2003

Generation of a haptoglobin-hemoglobin complex-specific Fab antibody blocking the binding of the complex to CD163.

During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage-display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic epitopes specific for the complex. By Hp-Hb-affinity screening of a phage-Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp-Hb, whereas no binding was measured for non-complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I-labeled Hp-Hb complexes to CD163 and blocked their uptake in CD163-transfected cells. In conclusion, we have raised a receptor-blocking antibody specifically recognizing the Hp-Hb complex. In addition to provide new insight into the changes occurring when Hp and Hb bind, the present study provides a new potential tool for measuring and removal of Hp-Hb complexes from plasma/serum.

Antigens, CD↗
PubMed2003

Smoking patterns among adolescents with asthma attending upper secondary schools: a community-based study.

OBJECTIVE: Smoking among people who have asthma may be a serious health problem. We studied the prevalence of smoking and the relations between smoking and asthma, symptoms, medicine, and gender differences among adolescents with asthma. METHODS: A national cross-sectional study on health and lifestyles was performed in 1996-1997 using a computerized questionnaire in upper secondary schools in Denmark. We included 1887 pupils with asthma (defined as self-reported asthma diagnosed by a physician) and 20 688 controls. Smoking was categorized as daily, occasional, ex-smokers, and never smoked. We adjusted for age, gender, parents' job and smoking, family type, body mass index, and exercise habits. RESULTS: In total, 37.7% smoked currently and 16.5% smoked daily; more girls than boys smoked. More pupils with asthma than without smoked daily (adjusted odds ratio [OR]: 1.15; 95% confidence interval [CI]: 1.04-1.33), they smoked significantly more cigarettes daily (10.3 vs 9.6), and more were heavy smokers (> or =15 cigarettes daily; adjusted OR: 1.47; 95% CI:1.14-1.91). Furthermore, nearly twice as many pupils who had asthma with symptoms but were not using medicine smoked as pupils who had asthma without symptoms and were using medicine (adjusted OR: 1.84; 95% CI: 0.99-3.41). More boys with asthma than without started smoking before 14 years of age (adjusted OR: 1.75; 95% CI: 1.09-2.81). However, more pupils with asthma had tried to quit (adjusted OR: 1.26; 95% CI: 0.99-1.60). Pupils with and without asthma were occasional smokers and ex-smokers at a similar prevalence. CONCLUSIONS: More pupils with asthma than without smoked daily, and they also smoked more cigarettes per day. This is a major health concern, as adolescents have a high smoking prevalence in Denmark.

Adolescent↗
PubMed2003

The Danish National Cohort Study (DANCOS).

This article gives an overview of a nationally representive public health research database in Denmark, the Danish National Cohort Study (DANCOS). DANCOS combines baseline data from health interview surveys with both pre- and post-baseline data from national health registries with date from a re-interview survey. As part of the national health interview survey programme, three nation-wide surveys were conducted in 1986/1987, 1991 and 1994. The samples in the three cohorts consisted of 23,096 adult Danes ages 16 years and older, and 18,296 (79.2%) were personally interviewed on socio-economic status; living conditions; health behaviour; self-rated health; morbidity; utilization of health services; and the consequences of illness and disability. Each Dane is equipped with a unique identification number that allows highly accurate linkage of data in the health surveys and in the national health and administrative registries. All respondents and non-respondents were followed through 2002, a total of 3,796 had died and 249 had emigrated. The specific cause of death for 2,485 people was recorded in the Danish Register of Causes of Death, updated through 1998. For 1978-1977, the Danish National Hospital Register contained information about 16,503 persons who had been hospitalized for any illness or related health problems, accounting for 70,925 hospital admissions. For 1970-1997, the Danish Psychiatric Central Register comprised information on 1691 persons. For 1990-1997, the Danish National Health Service Register recorded 980,043 contacts with general practitioners and specialist physicians. For 1943-1996, the Danish cancer Registry contained information about one or more cancer diseases among 1,432 people. A total of 4,334 people in the 1994 cohort were re-interview in 2000. DANCOS allows for a wide range of analysis in a historical prospective design of determinants of morbidity and mortality, of health care utilization and of the social effects of ill health. DANCOS also allows studies of methodological issues, including analyzing the characteristics of non-respondents.

Cause of Death↗
PubMed2002

[BMI of Danish school children measured during the periods 1986/1987--1996/1997 compared to Danish measurement in 1971/1972].

INTRODUCTION: A global epidemic in overweight and obesity in children has been postulated. There is a lack of consensus over definitions however, and national standards of BMI centiles have been published in various countries. This has made results on the prevalence of overweight difficult to interpret. Internationally based cut-off points have now been published, and a British study reports trends in overweight and obesity in children, as defined by these. The aim of this study was to compare the BMI of a sample of Danish children attending school in 1986/1987-1996/1997 to that of Danish schoolchildren in 1971/1972. MATERIAL AND METHODS: The school health officers in 23 municipalities representing a "mini-Denmark" collected from the school health records 3-4 routine measurements of height and weight in children attending school in 1986/1987-1996/1997. From these measurements, the children's BMIs were calculated and BMI centiles were constructed. The data covered a total of 11,167 measurements of 3371 children. RESULTS: The children in our study had higher BMI values than had children in 1971/1972, both on average and for the highest centiles. The average BMI values were significantly higher from the age of 8 years in boys and 7 years in girls. The prevalence in overweight and obesity has increased. For 14-16-year-old boys, the average BMI was related to the educational level of the mother (negatively). DISCUSSION: The highest BMI centiles had especially increased. The proportion of overweight and obese 14-16-year-olds according to internationally based cut-off points had increased from 5.1% to 1.5% for boys and from 6.2% to 15.6% for girls since 1971/72. This trend calls for preventive efforts.

Adolescent↗
PubMed2002

[Body height of 6-15-year-old school children measured in the period 1986/1987 to 1996/1997. Compared with Danish measurements in 1971/1972].

INTRODUCTION: Danish schoolchildren are said to have grown taller during the last 25 years. Studies on this topic have not been nationwide, however. The aim of this study was to compare the heights of a nationwide sample of Danish schoolchildren in 1986/1987-1996/1997 to a sample in 1971/1972. MATERIAL AND METHODS: The school health officers in 23 municipalities representing a "mini-Denmark" collected from the school health records 3-4 routinely measured heights in children attending school in 1986/1987-1996/1997. The data covered at total of 11,351 height measurements of 3378 children. From these data, standards of height from the age of 6-16 years were calculated. RESULTS: The schoolchildren's average heights had increased about 1 cm at the start of school, 2-3 cm in girls and 5-6 cm in boys aged 10-15 years and 0.6 cm in girls and 1.6 cm in boys aged 16 years, as compared to growth charts for 1971/1972. CONCLUSION: The children in our study were taller than schoolchildren in 1971/1972, and they seemed to have an earlier pubertal height spurt. A growth study of Danish children is needed.

Adolescent↗
PubMed2002

Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis.

BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer in the infectious mononucleosis family members was expressed as standardized incidence ratios (SIRs; i.e., the ratio between the number of cancers observed and the number of cancers expected, obtained from age-specific, sex-specific, and period-specific incidence rates). RESULTS: We identified 8052 parents, 5264 siblings, and 28,605 offspring of patients with EBV-related infectious mononucleosis who were followed for a total of 892,213 person-years at risk. The risk for Hodgkin's lymphoma was unaltered in the combined group of first-degree relatives of these patients (SIR = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] = 17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). CONCLUSION: The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma.

Adult↗
PubMed2002

Fermentation and microflora of plaa-som, a thai fermented fish product prepared with different salt concentrations.

Plaa-som is a Thai fermented fish product prepared from snakehead fish, salt, palm syrup and sometimes roasted rice. We studied the effects of different salt concentrations on decrease in pH and on microflora composition during fermentation. Two low-salt batches were prepared, containing 6% and 7% salt (w/w) as well as two high-salt batches, containing 9% and 11% salt. pH decreased rapidly from 6 to 4.5 in low-salt batches, whereas in high-salt batches, a slow or no decrease in pH was found. Lactic acid bacteria (LAB) and yeasts were isolated as the dominant microorganisms during fermentation. LAB counts increased to 10(8)-10(9) cfu g(-1) and yeast counts to 10(7)-5 x 10(7) cfu g(-1) in all batches, except in the 11% salt batch, where counts were 1-2 log lower. Phenotypic tests, ITS-PCR, carbohydrate fermentations and 16S rRNA gene sequencing identified LAB isolates as Pediococcus pentosaceus, Lactobacillus alimentarius/farciminis, Weisella confusa, L. plantarum and Lactococcus garviae. The latter species was only isolated from high-salt batches. Phenotypic characteristics, ITS-PCR and carbohydrate assimilation identified 95% of the yeasts as Zygosaccharomyces rouxii. It is concluded that the fermentation of plaa-som is delayed by a salt-level of 9% due to an inhibition of LAB growth. The growth of Z. rouxii has no influence on the fermentation rate, but may contribute positively to the flavour development of the product.

Animals↗
PubMed2002

CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.

CD163 is a highly expressed macrophage membrane protein belonging to the scavenger receptor cysteine rich (SRCR) domain family. The CD163 expression is induced by interleukin-6, interleukin-10 and glucocorticoids. Its function has remained unknown until recently when CD163 was identified as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular hemolysis. Besides having a detoxificating effect by removing Hb from plasma, the CD163-mediated endocytosis of the Hp-Hb complex may represent a major pathway for uptake of iron in the tissue macrophages. The novel functional linkage of CD163 and Hp, which both are induced during inflammation, also reveal some interesting perspectives relating to the suggested anti-inflammatory properties of the receptor and the Hp phenotypes.

Amino Acid Sequence↗
PubMed2002

Significant decline in case fatality after acute myocardial infarction in Denmark--a population-based study from 1994 to 2001.

OBJECTIVE: We evaluated trends in in-hospital case fatality after acute myocardial infarction (AMI) in Denmark and analysed changes in the hospitalization rate for AMI. DESIGN: National population-based registries were used to identify patients (> or =30 years) who were admitted for their first AMI from 1994 to 2001. RESULTS: The annual relative decline in case-fatality rate was constant at 10.5% (95% confidence interval (CI) 9.5-11.5%). The decline was similar for both genders at all ages. The hospitalization rate decreased from 1994 to 1999 at an annual average of 4.3% (95% CI 3.4-5.1%). In 2000 and 2001 the average annual increase was 7-8%. CONCLUSION: The case-fatality rate after AMI declined significantly in Denmark, similar to other Western countries, but the level is still higher than that of the USA. The increasing hospitalization rate coincided with changes in risk factors in the general population. However, the influence of introducing troponins in the diagnosis of AMI and diagnosis-related grouping may in particular account for the increased hospitalization rate.

Adult↗