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M Mikkelsen

Publications and source records attributed to M Mikkelsen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Use of short sequence repeat DNA polymorphisms after PCR amplification to detect the parental origin of the additional chromosome 21 in Down syndrome.

The origin of nondisjunction in trisomy 21 has so far been studied using cytogenetic heteromorphisms and DNA polymorphisms using Southern blot analysis. Short sequence repeats have recently been described as an abundant class of DNA polymorphisms in the human genome, which can be typed using the polymerase chain reaction (PCR) amplification. We describe the usage of such markers on chromosome 21 in the study of parental origin of the additional chromosome 21 in 87 cases of Down syndrome. The polymorphisms studied were (a) two (GT)n repeats and a poly(A) tract of an Alu sequence within the HMG14 gene and (b) a (GT)n repeat of locus D21S156. The parental origin was determined in 68 cases by studying the segregation of polymorphic alleles in the nuclear families (either by scoring three different alleles in the proband or by dosage comparison of two different alleles in the proband). Our results demonstrate the usefulness of highly informative PCR markers for the study of nondisjunction in Down syndrome.

Alleles↗
PubMed1990

Incidence, survival, and mortality in Down syndrome in Denmark.

The incidence of Down syndrome (DS) has been studied intensively for the two periods 1960-1972 and 1980-1985. The age distribution of birth-giving mothers has changed to older age at child birth from the first to the second period. Non-disjunction studies were carried out in 328 families. Most cases were first maternal meiotic division failures (43%). Nearly 12% were paternal meiotic failures, half of them in first meiosis and half in second. Both newborn infants and fetuses were studied. There was an excess of males, especially among newborn DS children, which was related to a failure at paternal first meiosis. A positive sex ratio was found in all newborn infants as well as in free trisomics as in those with de novo translocations. Survival was studied in the cohort of 278 infants born 1980 to 1985. The highest death-rate occurred between 22 days to 1 year (10.4%), 30 times more than the death probability in the Danish population. There was a significant difference between DS cases with congenital heart defect and those without. The probability of infants without heart disease of reaching the first year was 93.1% and the age of 6 years 88.0%. The probability of survival of children with congenital heart defect was 71.7% and 45.2%, respectively, reflecting also the increasing number of infants born prematurely with low birth weight or small-for-date infants. The predominant heart problems were atrio-ventricular canal defects. Infections and malformations added to the high mortality rate. Three cases of leukemia were significantly more than expected.

Child↗
PubMed1990

Clinical, cytogenetic, and molecular genetic characterization of two unrelated patients with different duplications of 21q.

We present 2 patients with dup(21q). Patient MP01 had mild mental retardation, facial findings characteristic of Down syndrome (DS), and a terminal duplication of chromosome 21. His karyotype was 46,XY,dup(21) (q22.1-qter). Patient MP03 had mild mental retardation, minor anomalies not characteristic of DS, and a duplication of the proximal long arm of chromosome 21, karyotype 46,XX,dup(21) (q11.2-q21.2). The patients were studied with single-copy DNA sequences from 20 loci on chromosome 21 to characterize the extent of the duplicated regions at the DNA level. DNA loci from D21S55 to COL6A1 were triplicated in patient MP01 while loci from D21S13 to D21S8 were triplicated in patient MP03. Our results support the hypothesis of a critical region of chromosome 21, which in triplicate is responsible for many of the facial changes associated with DS. Other genes outside this region may also contribute to other abnormalities observed in DS.

Adult↗
PubMed1990

[Prenatal diagnosis in Denmark, development, current status and future trends].

The fields of indication for prenatal diagnostics in Denmark have hardly varied since 1981. The number of amniocenteses has remained almost constant since 1984 while the number of chorion villus biopsies has risen in the past year. This reflects the fact that many women seek prenatal diagnosis while this can be made before attainment of the abortion limit in the 12th week of pregnancy. There is at present no political desire to extent the age limits for prenatal diagnostics, or to introduce serum-AFP-screening or general ultrasonic screening of expectant mothers.

Abortion, Induced↗
PubMed1989

[Accidental explosions in Denmark when working on containers for combustible fluids].

Gases may be formed in containers for inflammable fluids and these may burn explosively if lit. Even apparently empty containers may contain sufficient quantities of gas to result in violent explosions precipitated by procedures which produce heat or sparks in the neighbourhood of the container. Seventeen persons were found to be injured in accidents of this type in a Danish investigation. Two of the accidental injuries proved fatal. The serious risk involved in handling and treating containers which contain or have contained inflammable fluids is, therefore, emphasized.

Accidents, Occupational↗
PubMed1989

[Crush accidents in mechanical revolving doors].

During recent years, mechanical revolving doors have become commoner. A hitherto unnoticed traumatic mechanism resulted in a case of crushing endangering life in a revolving door of this type is presented. Prophylactic measures are suggested.

Accident Prevention↗
PubMed1989

The European collaborative study on mosaicism in chorionic villus sampling: data from 1986 to 1987.

Data on a total of 11,855 diagnostic chorionic villus samples obtained in the years 1986 and 1987 were compiled from a questionnaire filled in by 36 European cytogenetic centres. Mosaicism was reported in 141 cases. The cytogenetic findings were followed by induced abortion in 24 cases. Spontaneous abortion was observed in nine mosaic pregnancies, a rate not significantly different from that observed for CVS in total. Mosaicism was found in 1.2 per cent of analyses by direct analysis/short-term culture, in contrast to the 0.6 per cent found after long-term culture. Evidence for fetal non-mosaicism was found in 99 of the 141 cases. The finding of mosaicism in first-trimester CVS should always elicit further analyses, preferably after amniocentesis, to substantiate the suspected fetal chromosome aberration.

Chorionic Villi Sampling↗
PubMed1989

Molecular genetic approach to the characterization of the "Down syndrome region" of chromosome 21.

The cytogenetically defined "Down syndrome region" of chromosome 21 has been characterized by DNA analysis in patients with partial trisomy 21 with or without Down syndrome features. Single-copy DNA sequences mapped on chromosome 21 were used to determine copy number by polymorphism and/or dosage analysis in the patients. Given our results, which in some patients were in disagreement with their cytogenetic descriptions, trisomy for locus D21S13 through locus D21S58 is excluded from significant contribution to many Down syndrome features. The minimal chromosome region necessary in triplicate to result in the Down syndrome phenotypes in the patients characterized includes the area from locus D21S55 to locus COL6A1. We could not analyze the region between loci D21S58 and D21S55 and between COL6A1 and 21qter at the molecular level due to a lack of DNA probes and, consequently, the contribution of these areas to a Down syndrome phenotype when present in three copies is unknown. The molecular cloning and mapping of chromosome 21 and the expansion of the patient population studied will likely result in a more precise molecular definition of the Down syndrome region.

Blotting, Southern↗
PubMed1989

[Medical treatment of epilepsy].

The most important single factor in achieving control of epileptic seizures is a correct diagnosis of seizures and syndromes. It is essential to realise that treatment should be directed against the rate of seizures, not the plasma levels. Monotherapy with the new retarded formulations of carbamazepine or valproate should be the first drugs chosen. The most promising new antiepileptic drugs are oxcabazepine and vigabatrin, which should be made available to all neurologists.

Aminocaproates↗
PubMed1989

Renal side effects of high and low cyclosporin A doses in patients with rheumatoid arthritis.

Thirty-nine patients with classical or definite rheumatoid arthritis (RA) entered a randomized double-blind placebo controlled study with low dose cyclosporin A (CyA) (mean whole blood CyA level after 26 weeks 282 +/- 33 micrograms/l) or placebo treatment for 48 weeks. The placebo treatment had to be withdrawn before 48 weeks in 9 out of 19 patients because of a deterioration of their arthritis symptoms. All 20 patients in the CyA group completed 26 weeks of treatment. Fourteen of them were followed up for 48 weeks of treatment on CyA and then 12 weeks after CyA treatment was withdrawn. The side effects in the CyA group were compared with the results from another study with high CyA doses (mean whole blood CyA level 419 +/- 71 micrograms/l) for 26 weeks in 11 other patients with RA. Serum creatinine increased 19.7% (p less than 0.01) in the low CyA dose group after 26 weeks as compared with 59.5% in the high CyA dose group. Creatinine clearance was reduced by 17.9% (low dose) (p less than 0.01) and 26.2% (high dose), respectively. Twelve weeks after withdrawal of the low dose CyA treatment, serum creatinine values were still higher than before treatment (p less than 0.05), but creatinine clearance had normalized. Eight of the 20 patients treated with low CyA doses also started with nonsteroidal anti-inflammatory drugs (NSAIDs) after 20-36 weeks of CyA treatment. Serum creatinine was 16.6% above baseline 4 weeks before NSAIDs compared with an increase of 40.4% (p less than 0.05) 4 weeks after start of NSAID treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The incidence of Down's syndrome and progress towards its reduction.

Down's syndrome is the most common autosomal aberration and single cause of mental retardation in man. There is a close relation between advanced maternal age and Down's syndrome. The limitation of family size has made a considerable impact on the incidence of Down's syndrome. In Denmark in the 1950s, 50% of Down's syndrome cases were born to mothers over the age of 35. The percentage went down to 25% in the 1970s and was reduced by prenatal diagnosis to 8% in the 1980s. For the period 1980-85 we followed the birth prevalence closely for different maternal age groups. The birth prevalence was lowered for the age group over 35, but there was a steady rise for the age groups below 35. Early diagnosis, high rate of survival of light-for-date babies and babies with congenital heart defect, and, possibly, exogenous factors working on gametogenesis might be an explanation. To achieve a reduction in incidence, maternal alpha-fetoprotein (AFP)-serum screening for low values may be a possibility. So far, avoidance, but not primary prevention, of Down's syndrome is available.

Adult↗
PubMed1988

Interstitial deletion 13q: further delineation of the syndrome by clinical and high-resolution chromosome analysis of five patients.

Five patients with interstitial deletion 13q are reported. High-resolution chromosome banding established the diagnosis in two cases and stated the exact breakpoints in three remaining cases. All parents had normal chromosomes. An unequal and so far unexplained sex ratio of previously published and present cases was found: M:F = 1:2.75. Moderate to severe growth retardation was prominent in all patients. The patients were followed with psychological tests and growth data for 3-10 years. Mild to moderate mental retardation was present. Considerable phenotypic similarities were found in two patients with del(13)(q21.33 q31.3) and one with del(13)(q14.3q22.3). Repeat ophthalmological examinations showed no evidence of retinoblastoma in a male with del(13)(q13.1q21.1). In conclusion, the long-term study of five patients with interstitial deletion 13q, all evaluated with high-resolution banding, contributed to a more reliable mental and growth prognosis in such patients.

Abnormalities, Multiple↗
PubMed1988

Multiple recurrence of trisomy 21 Down syndrome.

A young family with four chromosomally documented cases of trisomy 21, at least two, further cases of Down syndrome diagnosed only clinically, and no healthy children among their offspring is reported. No sign of mosaicism was found in studies of lymphocytes and skin fibroblasts from the parents. In a biopsy from the mother's ovary a trisomic cell line was found, thus giving some, but not a complete explanation for this extraordinary family. Additional explanations are suggested.

Adult↗
PubMed1988

Gene probes to detect cross-culture contamination in hormone producing cell lines.

Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease-digested cell DNA effectively detects cross-culture contamination to monitor inter-species as well as intra-species cross contamination. An insulin-producing cell-line, Clone-16, originally cloned from a human fetal endocrine pancreatic cell line did not produce human c-peptide as anticipated. DNA from these cells showed no hybridization to the human ALU sequence probe, BLUR, and lacked restriction fragment length polymorphism typical for the human HLA-DQ beta-chain gene. Although a human insulin gene probe showed a weak, nonhuman hybridization pattern, a cDNA probe for the Syrian hamster insulin gene hybridized strongly consistent with a single copy hamster insulin gene. Karyotyping confirmed the absence of human chromosomes in the Clone-16 cells while sizes, centromere indices, and banding patterns were identical to Syrian hamster fibroblasts. We conclude that the insulin-producing Clone-16 cells are of Syrian hamster origin and demonstrate the effective use of gene probes to control the origin of cell cultures.

Adenoma, Islet Cell↗
PubMed1988

Mogens Hauge.

Explore the source record for details and available documents.

Denmark↗
PubMed1988

Molecular analysis of male-viable deletions and duplications allows ordering of 52 DNA probes on proximal Xq.

While performing a systematic search for chromosomal microdeletions in patients with clinically complex X-linked syndromes, we have observed that large male-viable deletions and duplications are clustered in heterochromatic regions of the X chromosome. Apart from the Xp21 band, where numerous deletions have been found that encompass the Duchenne muscular dystrophy gene, an increasing number of deletions and duplications have been observed that span (part of) the Xq21 segment. To refine the molecular and genetic map of this region, we have employed 52 cloned single-copy DNA sequences from the Xcen-q22 segment to characterize two partly overlapping tandem duplications and two interstitial deletions on the proximal long arm of the human X chromosome. Together with a panel of somatic cell hybrids that had been described earlier, these four rearrangements enabled us to order the 52 probes into nine different groups and to narrow the regional assignment of several genes, including those for tapetochoroidal dystrophy and anhidrotic ectodermal dysplasia.

Chromosome Banding↗