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Biomedical subjects

L B Andersen

Publications and source records attributed to L B Andersen.

68 records · Page 4Linked to original sources
PubMed1991

cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product.

Von Recklinghausen neurofibromatosis, or type 1 neurofibromatosis (NF1), is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the embryonic neural crest. Portions of the gene have been recently identified by positional cloning, and sequence analysis has shown homology to the GTPase activating protein (GAP) family. In this report we present the results of an extensive cDNA walk resulting in the cloning of the complete coding region of the NF1 transcript. Analysis of the sequences reveals an open reading frame of 2818 amino acids, although alternatively spliced products may code for different protein isoforms. The gene extends for approximately 300 kb on chromosome 17, with its promoter in a CpG-rich island.

Adult↗
PubMed1991

cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene.

The gene responsible for neurofibromatosis type 1 (NF1), one of the more common inherited human disorders, was identified recently, and segments of it were cloned. Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segment of DNA that contains the EV12A locus (previously reported as the EV12 locus), the human homolog of a mouse gene, Evi-2A, implicated in retrovirus-induced murine myeloid tumors. EVI2A lies within an intron of the NF1 gene and is transcribed from telomere toward centromere, opposite to the direction of transcription of the NF1 gene. Here we describe a second locus, EVI2B, also located between the two NF1 translocation breakpoints. Full-length cDNAs from the EV12B locus detect a 2.1-kb transcript in bone marrow, peripheral blood mononuclear cells, and fibroblasts. Sequencing studies predict an EV12B protein of 448 amino acids that is proline-rich and contains an N-terminal signal peptide, an extracellular domain with four potential glycosylation sites, a single hydrophobic transmembrane domain, and a cytoplasmic hydrophilic domain. At the level of genomic DNA the EV12B locus lies within the same intron of the NF1 gene as EV12A and contains a 57-bp 5' exon that is noncoding, an 8-kb intron, and a 2078-bp 3' exon that includes the entire open reading frame. EV12B is transcribed in the same direction as EV12A; its 5' exon lies only 4 kb downstream from the 3' exon of the EV12A locus. In the mouse the 5' exon of the homologous gene, Evi-2B, lies approximately 2.8 kb from the 3' end of Evi-2A, in the midst of a cluster of viral integration sites identified in retrovirus-induced myeloid tumors; thus, Evi-2B may function as an oncogene in these tumors.

Amino Acid Sequence↗
PubMed1990

Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct efforts to identify the gene. The chromosome location of the NF1 gene has been previously mapped genetically to 17q11.2, and data from two NF1 patients with balanced translocations in this region have further narrowed the candidate interval. The use of chromosome jumping and yeast artificial chromosome technology has now led to the identification of a large (approximately 13 kilobases) ubiquitously expressed transcript (denoted NF1LT) from this region that is definitely interrupted by one and most likely by both translocations. Previously identified candidate genes, which failed to show abnormalities in NF1 patients, are apparently located within introns of NF1LT, on the antisense strand. A new mutation patient with NF1 has been identified with a de novo 0.5-kilobase insertion in the NF1LT gene. These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.

Adult↗
PubMed1990

A chromosome jump crosses a translocation breakpoint in the von Recklinghausen neurofibromatosis region.

The von Recklinghausen neurofibromatosis (NFI) gene has been previously localized to the region 17q11.2 by genetic analysis. Consistent with this, two NFI patients have been described with autosomal translocations with breakpoints in 17q11.2, and these represent presumed markers for the location of the NFI gene. Recent work has defined the two breakpoints on a physical map, and they lie less than 100 kb apart. To characterize further the distance between these breakpoints and clone additional DNA, a chromosome jump was made from a DNA fragment that maps between the breakpoints. The end of the jump crosses one of the NFI translocation breakpoints and detects that breakpoint on Southern analysis, placing the probe less than 15 kb telomeric to this breakpoint. Pulsed field analysis with the jump clone allows revision of the previous NFI region map and indicates that the two breakpoints lie no more than 60 kb apart. This jump clone will be useful for further mapping, breakpoint cloning, analysis of patient DNA, and the search for transcripts in the NFI region.

Cell Line↗
PubMed1990

Pancreatic function in Crohn's disease.

We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease.

Adolescent↗
PubMed1990

A 90 kb DNA deletion associated with neurofibromatosis type 1.

A deletion of 90 kb of DNA has been identified in a patient with neurofibromatosis type 1, using pulsed field gel electrophoresis. The deletion lies between probes 17L1A and AC5 in the critical region of chromosome 17 and represents the only molecular alteration found by PFGE in a series of 90 unrelated patients. The subject showing the deletion is an isolated case, shows typical clinical features, and represents one of the first examples of a molecular deletion to be found in this disorder.

Chromosome Deletion↗
PubMed1990

Formation of a minichromosome by excision of the proximal region of 17q in a patient with von Recklinghausen neurofibromatosis.

An interstitial deletion, 17cen----q11.2 (or q12), and a small extra chromosome was found in a sporadic case of von Recklinghausen neurofibromatosis (NF1). In situ hybridization with a chromosome 17-specific alpha-satellite probe showed that the small chromosome was derived from the deleted region, most likely by an excision/ring formation. This chromosome rearrangement is in agreement with the localization of the von Recklinghausen neurofibromatosis (NF1) locus to the proximal region of 17q, but with a more distal breakpoint than observed in two previously described reciprocal translocations associated with NF1. If the NF1 gene has been truncated by the present rearrangement, it may suggest that the NF1 gene is a very large gene at the genomic level. Alternatively, NF1 in this patient may be caused by the gradual loss in somatic cells of the small chromosome carrying an intact NF1 gene, thereby suggesting a recessive mechanism at the gene level. Finally, an intact NF1 gene may have been placed in close proximity with alpha-satellite sequences, which might cause inactivation of the gene. The small supernumerary chromosome may not only facilitate the cloning of the NF1 gene itself, but also offers explanations of the mechanism underlying development of the disease.

Chromosome Aberrations↗
PubMed1989

Risk factors for cardiovascular disease in 16-19-year-old teenagers.

In a representative sample of Danish school children (124 boys and 169 girls), 16-19 years of age, blood pressure, blood lipids, body fat content, maximal aerobic power, alcohol consumption and smoking habits were studied. No systematic variation was noticed within this age in the risk factor profile. The mean values for blood pressure (BP) (systolic/diastolic) were 125/73 mmHg for the boys and 117/71 mmHg for the girls. As much as 14% of the boys and 5% of the girls had either a systolic BP above 140 mmHg or a diastolic BP above 90 mmHg. Total serum cholesterol averaged 4.13 mmol l-1 for the boys and 4.53 mmol l-1 for the girls, which is also high compared with adolescents from other countries. The ratios for high density lipoprotein cholesterol to total serum cholesterol were normal and in the range of 0.25-0.28 for both sexes. Other factors associated with coronary heart disease in adults, such as body fat content, serum triglycerides, physical activity, as well as smoking and alcohol habits were similar to that reported for teenagers in other countries. No correlation was found between aerobic power (ml min-1.kg-1) and the risk factors measured.

Adipose Tissue↗
PubMed1987

Maximal oxygen uptake in Danish adolescents 16-19 years of age.

A random sample of schoolchildren, 119 boys and 153 girls, was tested in the fall of 1983. The data presented here are anthropometric data (height, weight, fat % and vital capacity) and oxygen uptake directly measured on a bicycle ergometer. The mean height and weight for boys were 179.1 cm and 67.7 kg, and those for girls were 168.0 cm and 59.6 kg. The mean fat content was 9.1% for boys and 19.1% for girls, and their mean vital capacities were 4.91 and 3.61 respectively. The boys had a high maximal oxygen uptake (51.7 ml X kg-1 X min-1) showing no reduction over the age span studied. The girls' maximal oxygen uptake was lower (overall mean 40.0 ml X kg-1 X min-1) with a small reduction from 16 to 19 years of age. When comparing maximal oxygen uptake per kg lean body mass in the two sexes, the boys had 18.4% higher values than the girls, indicating that girls of this age have the lower fitness level. The results of maximal aerobic power measurement in the boys compare well with findings from other investigations using direct measurements, indicating that the fitness of teenage boys is kept at a high level. Comparable data from various countries for girls show different pictures, but it appears that in general they have a low fitness level.

Adolescent↗
PubMed1987

Maximal voluntary isometric strength in Danish adolescents 16-19 years of age.

The force in maximal voluntary isometric contraction of elbow flexors, knee extensors, trunk flexors, and trunk extensors was measured in a representative sample of Danish school children 16-19 years of age (128 boys and 165 girls). The 16 year old boys were 177.8 cm in height, with a mean increase of 1.4 cm per year up to 19 years, and they weighed 66.0 kg, with a mean increase of 1.8 kg per year up to age 19. The girls were 168.0 cm in height with no increase up to age 19, and their mean weight was 59.6 kg, which increased by 1.8 kg per year up to age 19 (p greater than 0.05). The strength in the four muscle groups for boys a girls respectively was 281 N and 182 N for elbow flexors, 574 N and 419 N for knee extensors, 601 N and 404 N for trunk flexors and 664 N and 499 N for trunk extensors. An increase in strength in the elbow and trunk flexors and a decrease in strength in the trunk extensors in relation to values obtained in 1956 was seen, and a difference in strength per kg lean body mass between the boys and the girls was also observed. The estimated strength per unit cross-sectional area of muscle was 38 N X cm-2 in both boys and girls.

Adolescent↗
PubMed1987

Sweat pore density on the fingertips of atopic patients.

Investigation of 18 patients with atopic eczema and 22 normal controls showed that women in both groups had significantly more sweat pore openings on their fingertips than men and that there were more glands per unit area on fingers 3 and 4 compared with the thumb and the first and second fingers. There was no significant difference in the number of sweat pores between normal and atopic individuals, although fingertip topography in the latter was disturbed.

Adolescent↗
PubMed1984

Hepatic drug metabolism and physical fitness.

Physical fitness, as expressed by maximal oxygen uptake (Vo2max), was measured in 14 subjects before and during physical education consisting of 4 to 8 hr of daily physical training. Mean pulse rate during training was 115 bpm. After 3 mo of physical training, Vo2max increased a mean 6% (range -5% to +23%). Corresponding mean increases in hepatic drug metabolism, as expressed by the metabolism of the model drugs antipyrine and aminopyrine, were 12% (range -12% to +59%) and 13% (range -21% to +47%). Changes in the two groups were still present 6 mo after physical education. There was only a moderately close but nonetheless significant correlation (r = 0.7) between the extent of change in Vo2max and the corresponding relative change in antipyrine metabolism during the 3-mo period of this investigation. The correlation between oxygen uptake and aminopyrine metabolism (r = 0.6) was slightly less and was not significant. Improved physical fitness associated with enhanced drug metabolism may lead to changes in drug efficacy and drug toxicity that may be clinically important in the case of drugs with low therapeutic indices.

Adult↗
PubMed1981

Adaptive changes in work capacity, skeletal muscle capillarization and enzyme levels during training and detraining.

Six male subjects exercised on a bicycle ergometer 30 min with left leg and 30 min with right leg 3 times a week for 8 weeks. This training resulted in a 14.6% increase in VO2 max with two-leg exercise and a 23.1% increase with one-leg exercise. A significant decrease towards pretraining VO2 max was seen during the following 8 weeks of detraining. Muscle biopsy samples were obtained at rest from m. vastus lateralis before and after training and 4 and 8 weeks after training. During training the number of capillaries per mm2 and the number of capillaries per fiber increased about 20%. The number of capillaries around each fiber type (CA) increased 20--30%. The average area of each fibre type increased only about 5%. The fibre area per CA decreased by about 10%. During 8 weeks of detraining decreases were seen in the number of capillaries per fibre, CA and in fibre area, while fibre area per CA and number of capillaries per mm2 were almost unchanged at the end of the detraining period. Pronounced increases in activities of oxidative enzymes were observed after training, while only minor increases were seen in glycolytic enzyme activities. All enzyme activities decreased towards pre-training levels during detraining. The results indicate that the training-induced improvement in oxidative capacity and in muscle capillarization expressed as capillaries per fibre and CA disappears within 8 weeks after cessation of training. However, the fibre area per CA and number of capillaries per mm2 point at a favourable long term effect on the average diffusion distance between capillaries and muscle fibres.

Adaptation, Physiological↗