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Biomedical subjects

K Christensen

Publications and source records attributed to K Christensen.

At least 19 recordsLinked to original sources
PubMed1999

Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood.

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.

Adolescent↗
PubMed1999

[Why do we age so differently?].

One of the most intriguing aspects of ageing is how different the ageing process is from person to person: some maintain their physical and cognitive abilities throughout a long life while others lose these abilities rather early in adult life. The basis for this variation is largely an enigma. In this review some of the most prominent ageing theories are described and compared with results from Danish genetic-epidemiological aging research.

Adult↗
PubMed1999

Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994.

Studies in the United States have indicated that maternal first trimester smoking and infant transforming growth factor alpha (TGFA) locus mutations are associated with non-syndromic cleft lip and/or palate (CLP) and that a synergistic effect of these two risk factors occurs. Based on a Danish case-control study of CLP, the authors studied the effects of smoking and TGFA alleles in an ethnically homogeneous setting. Interview information was obtained for mothers of 302 CLP cases (96% of eligible) and for 567 mothers of nonmalformed children (94% of eligible). Multivariate logistic regression analyses revealed that smoking was associated with a moderately increased risk of cleft lip +/- cleft palate (CL(P)) (odds ratio = 1.40, 95% confidence interval 0.99-2.00). No association between smoking and isolated cleft palate (CP) was observed. TGFA genotype was not associated with either CL(P) or CP, and no synergistic effect with smoking was observed. The "rare" TGFA allele occurred in 25% of both cases and controls compared with an average of 14% in other white control groups. Furthermore, the frequency of CLP in Scandinavia is among the highest in the world. Hence, it is possible that the previously reported association between TGFA and CLP to some degree can be attributable to confounding by ethnicity.

Adult↗
PubMed1999

Randomized clinical trial of laparoscopic versus open inguinal hernia repair.

BACKGROUND: Several studies have suggested that better results are obtained after laparoscopic repair of inguinal hernia than after conventional operation. This is most obvious for bilateral and recurrent hernias but less accepted for primary unilateral hernias. METHODS: This was a randomized clinical trial comparing transabdominal preperitoneal laparoscopic repair with the Shouldice technique in patients with primary unilateral hernia. Some 138 patients were randomized to laparoscopic hernia repair and 130 to open surgical repair. RESULTS: The complication rates in the two groups were similar. In the laparoscopic group the patients returned to work more rapidly with a median time of 13 versus 18 days (P < 0.005) and had a shorter period of analgesia intake with a median time of 2.1 versus 2.7 days (P < 0.02). The follow-up was 97.8 per cent complete. At a median of 12 months, four recurrences (2.9 per cent) were detected in the laparoscopic group and three (2.3 per cent) in the open group. CONCLUSION: This study shows that in patients with a primary unilateral hernia laparoscopic repair results in less postoperative pain and a quicker recovery than open repair.

Adolescent↗
PubMed1999

Study of environmental, social, and paternal factors in preterm delivery using sibs and half sibs. A population-based study in Denmark.

OBJECTIVE: The aim of this study was to evaluate the influence on preterm delivery of changes in putative genetic and environmental risk factors between two consecutive births. Low social status is a suspected risk indicator of preterm delivery, but the impact of social mobility has not been studied before. PARTICIPANTS: The study uses national cohorts in which women act as their own controls. Subjects were identified by means of registries: 10,455 women who gave birth to a preterm child and had a subsequent live birth between 1980 and 1992 and 9849 women who gave birth to a child after 37 completed weeks of gestation and had a subsequent live born child in the same time period formed the cohorts. METHODS: The risk of having a premature infant in the subsequent pregnancy was analysed in each cohort as a function of changes in male partner, residency, occupation, and social status between the two pregnancies. RESULTS: There was a strong tendency to repeat a preterm delivery (18% v 6% in the general population). Social decline was associated with a moderate increase in the recurrence risk (OR: 1.22; 95% CI: 1.02, 1.47). In the reference cohort the risk of preterm delivery associated with changing from a rural to an urban municipality was 2.03 (95% CI: 1.14, 3.64). CONCLUSIONS: Social decline and moving to an urban municipality may be associated with preterm delivery.

Adolescent↗
PubMed1999

Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential.

A series of subclonal cell lines with high or low differentiation/mineralization potential after growth in the presence of ascorbic acid (AA) were derived from murine MC3T3-E1 cells. Subclones were characterized in terms of their ability to mineralize a collagenous extracellular matrix both in vitro and in vivo and express osteoblast-related genes. When compared with nonmineralizing cells, mineralizing subclones selectively expressed mRNAs for the osteoblast markers, bone sialoprotein (BSP), osteocalcin (OCN), and the parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor. In contrast, alkaline phosphatase mRNA was present in certain nonmineralizing as well as mineralizing subclones, suggesting that its expression may be subject to different controls from other osteoblast markers. Only highly differentiating subclones exhibited strong AA-dependent induction of a transiently transfected OCN promoter-luciferase reporter gene, indicating that there was a good correlation between mRNA levels and transcriptional activity. Consistent with its postulated role in biomineralization, BSP as measured by Western blotting was only present in mineralizing subclones. After implantation into immunodeficient mice, highly differentiating subclones formed bone-like ossicles resembling woven bone, while poorly differentiating cells only produced fibrous tissue. Interestingly, subclones with both high and low differentiation potential produced similar amounts of collagen in culture and expressed comparable basal levels of mRNA encoding Osf2/Cbfa1, an osteoblast-related transcription factor. Although some strongly differentiating cells exhibited a modest AA-dependent up-regulation of Osf2/Cbfa1 mRNA, there was no clear relationship between levels of this message and induction of mRNAs for other differentiation markers. Thus, the mere presence of Osf2/Cbfa1 in a subclone was not sufficient for osteoblast differentiation. These subclones will be very useful for studying critical events in osteoblast differentiation and mineralization.

Animals↗
PubMed1999

The 20th century Danish facial cleft population--epidemiological and genetic-epidemiological studies.

Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.

Child, Preschool↗
PubMed1999

A case of trisomy 22 in a live hereford calf.

A case of the rare genetic trisomy 22 in a live calf is described. The calf had low blood thyroxine level and low growth rate. It had several defects including brachygnathia superior, strabismus convergence, aortal cusp insufficiency and hypertrophy of clitoris. Chromosome analysis was performed on cultured blood lymphocytes and fibroblast cells. In all counted metaphases 61 chromosomes were present. The extra chromosome was identified as a chromosome 22 by R-banding. The defects of the calf have similarities with cases of partial trisomy 3p25-pter in human. This section of the human chromosome 3 corresponds to sections of cattle chromosome 22.

Animals↗
PubMed1998

Biodemographic trajectories of longevity.

Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.

Aging↗
PubMed1998

Low birth weight and preterm birth after short interpregnancy intervals.

OBJECTIVE: Our purpose was to study low birth weight and preterm birth after short interpregnancy intervals. STUDY DESIGN: Follow-up of a cohort of a register-based random sample of women who had at least two live births in Denmark between 1980 and 1992. Frequency of preterm birth (gestational age <37 weeks) and low birth weight (<2500 gm) were studied as a function of the interpregnancy interval in 10,187 women. RESULTS: Short interpregnancy intervals (< or =8 months) were associated with preterm birth but not with low birth weight. The adjusted odds ratios for preterm birth were 3.60 (95% confidence interval 2.04 to 6.35) for intervals up to 4.00 months and 2.28 (1.49 to 3.48) for intervals between 4.01 and 8.00 months compared with deliveries after 24 to 36 months, in which the risk of preterm birth was 3.5%. Risks were higher in women with a previous pregnancy at term. Social status, age, and parity were adjusted for. CONCLUSIONS: Short interpregnancy intervals were associated with an increased risk of premature delivery. This risk should be taken into account when planning a new pregnancy.

Cohort Studies↗
PubMed1998

The genetic component of discrete disability traits: an analysis using liability models with age-dependent thresholds.

The presence of familial and genetic effects in the Activities-of-Daily-Life (ADL) data collected in the first wave of the 1995 Longitudinal Study of Aging of Danish Twins (LSADT) older than 75 is tested using multithreshold liability models of disability with age-dependent thresholds. These models are developed for discrete scores represented by five disability scales of male and female Danish twins. The presence of familial effects is revealed in all five scales of disability data for females and in three scales of data for males. Genetic effects are found to be significant in all four levels of aggregation of the Upper Limb-T (T = tiredness) disability scale for females and in the PADL-H (H = need for help) scale for males. Genetic effects are also pronounced in the Mobility-T scale for females and in the Lower Limb-T scale for males and females. For females, the genetic effects in the T-scale seem to be more pronounced than in the H-scale. For males, genetic effects are more pronounced in the H-scale. The estimates for MZ correlations in liability tend to be higher than the estimates for DZ correlations in almost all cases, which suggests that additional genetic effects may be revealed should the sample size of the ADL data be increased.

Activities of Daily Living↗
PubMed1998

A population-based study of Graves' disease in Danish twins.

OBJECTIVE: The aetiology of Graves' disease (GD) is generally thought to fit a multi-factorial pattern of inheritance in which clinical disease develops on the basis of genetic susceptibility interacting with environmental and endogenous factors. In previous twin studies the probandwise concordance rates for hyperthyroidism were as high as 0.86 in monozygotic twins and 0.20 in dizygotic twins, indicating a very strong genetic influence. In these studies, however, no effort was made to distinguish between GD and non-autoimmune hyperthyroidism, and one study also included patients with simple non-toxic goitre, hampering if not invalidating any conclusions. The aim of the present study was to determine whether there is a genetic contribution in the aetiology of GD. DESIGN: Historical cohort study of pairs of same-sex twins, with information on GD being gathered by questionnaire surveys in the 1950s and 1960s. All available hospital material was sought to verify the diagnosis, which was assigned on the basis of clinical and histopathological evidence. The healthy co-twins were followed through middle age by questionnaire surveys in the 1970s and 1980s. PATIENTS: Same-sex twin individuals born between 1870-1920, included in a population-based nationwide register. A total of 118 subjects indicated hospitalization due to GD. A hospital record was available in 76 subjects. Of these, 55 (46 females and 9 males) could be classified as having GD. MEASUREMENTS: Pairwise and probandwise concordance rates for GD in monozygotic and dizygotic twin pairs. RESULTS: The probandwise concordance rates were 0.36 for monozygotic pairs and 0 for dizygotic pairs. The pairwise concordance rates were 0.22 and 0 for monozygotic and dizygotic pairs, respectively. The concordance rates were significantly (P = 0.012) higher in monozygotic than in dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors play an important role in the aetiology of Graves' disease. However, they may not be as powerful as previously thought.

Adolescent↗
PubMed1998

Risk of preterm delivery, low birthweight and growth retardation following spontaneous abortion: a registry-based study in Denmark.

BACKGROUND: Some studies have found an association between spontaneous abortion and adverse birth outcome in the subsequent pregnancy, but results are conflicting, maybe due to lack of confounder control. METHODS: Using population-based registries we identified a cohort of 45 449 women having a livebirth preceded by a spontaneous abortion ('abortion cohort'), and a random sample of 9752 women with two consecutive livebirths ('reference cohort'). We examined the risk of preterm (<37 weeks gestation) and very preterm delivery (<34 weeks), low birthweight and growth retardation in both births in the reference cohort compared with births following an abortion, controlling for social factors and interpregnancy interval. RESULTS: Compared to second births in the reference cohort, the abortion cohort had higher risks for preterm (odds ratio [OR] = 1.74, 95% CI: 1.5-2.0) and very preterm delivery (OR = 2.17, 95% CI : 1.7-2.7), low birthweight (OR = 1.76, 95% CI: 1.5-2.1), and growth retardation (OR = 1.50, 95% CI: 1.4-1.6). In the reference cohort 3.9% of the pregnancies ended as preterm deliveries, 1 % as very preterm, 3.3% as low birthweight, and 8.1% as growth retarded. Women with two or more previous abortions had a higher risk for preterm and very preterm delivery. When first liveborns of women in the reference cohort were compared with first liveborns in the abortion cohort, only deliveries before 34 and 37 weeks' gestation were associated with previous abortion. CONCLUSIONS: Spontaneous abortion is associated with preterm delivery (both <34 and <37 weeks) in the subsequent pregnancy. Women who become pregnant following an abortion should receive special attention in the antenatal clinics.

Abortion, Spontaneous↗
PubMed1998

Mink 5S rRNA genes map to 2q in three loci suggesting conservation of synteny with human 1q.

By in situ hybridization we show that the SS rRNA genes in the mink map to chromosome 2q in three loci. The 2q1.1 locus containing 34% of the 5S rDNA, maps close to the centromere, and the remaining two loci of the 5S rDNA map to 2q1.3 (52%) and to 2q2.3. (14%). These data were obtained with a tritiated transcript of the 5S rRNA gene containing 121 bp. In a comparative FISH study performed with a biotinylated transcript of the 5S rRNA gene the procedure failed to detect the 2q2.3 site. A closely corresponding difference between the two procedures experienced previously in man and in the crab-eating macaque is discussed. The present results suggest a homology between 2q in the mink and part of 1q in man harbouring the 5S rRNA genes in 1q42.13 and 1q31, respectively.

Animals↗