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Biomedical subjects

H Reimann

Publications and source records attributed to H Reimann.

At least 19 recordsLinked to original sources
PubMed2001

Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions.

Homologous recombination between poorly characterized regions flanking the NF1 locus causes the constitutional loss of approximately 1.5 Mb from 17q11.2 covering > or =11 genes in 5%-20% of patients with neurofibromatosis type 1 (NF1). To elucidate the extent of microheterogeneity at the deletion boundaries, we used single-copy DNA fragments from the extreme ends of the deleted segment to perform FISH on metaphase chromosomes from eight patients with NF1 who had large deletions. In six patients, these probes were deleted, suggesting that breakage and fusions occurred within the adjacent highly homologous sequences. Reexamination of the deleted region revealed two novel functional genes FLJ12735 (AK022797) and KIAA0653-related (WI-12393 and AJ314647), the latter of which is located closest to the distal boundary and is partially duplicated. We defined the complete reading frames for these genes and two expressed-sequence tag (EST) clusters that were reported elsewhere and are associated with the markers SHGC-2390 and WI-9521. Hybrid cell lines carrying only the deleted chromosome 17 were generated from two patients and used to identify the fusion sequences by junction-specific PCRs. The proximal breakpoints were found between positions 125279 and 125479 in one patient and within 4 kb of position 143000 on BAC R-271K11 (AC005562) in three patients, and the distal breakpoints were found at the precise homologous position on R-640N20 (AC023278). The interstitial 17q11.2 microdeletion arises from unequal crossover between two highly homologous WI-12393-derived 60-kb duplicons separated by approximately 1.5 Mb. Since patients with the NF1 large-deletion syndrome have a significantly increased risk of neurofibroma development and mental retardation, hemizygosity for genes from the deleted region around the neurofibromin locus (CYTOR4, FLJ12735, FLJ22729, HSA272195 (centaurin-alpha2), NF1, OMGP, EVI2A, EVI2B, WI-9521, HSA272196, HCA66, KIAA0160, and WI-12393) may contribute to the severe phenotype of these patients.

Base Sequence↗
PubMed2000

A common set of at least 11 functional genes is lost in the majority of NF1 patients with gross deletions.

Large deletions of the NF1 locus occur in 5 to 10% of patients with neurofibromatosis and are commonly associated with specific additional abnormalities characterized by mental retardation, dysmorphic features, and intellectual impairment. To characterize the extent of codeleted genes we constructed a long-range physical BAC/PAC map around the NF1 locus between D17S117 and D17S57 and determined the deletion boundaries in seven unrelated patients. Surprisingly, the proximal and distal breakpoints in five of seven patients fall at almost identical positions, resulting in the loss of at least 11 functional genes. Five of six patients investigated showed a de novo deletion on the maternally derived chromosome. Since D17S117 and D17S57 were previously reported as the outer limits for the great majority of NF1 deletions, we suggest that most NF1 patients with deletion of the entire NF1 gene are hemizygous for the same set of at least 10 additional genes, including SHGC-37343, SHGC-2390, SHGC-34232, OMG, EVI2B, EVI2A, WI-9521, WI-6742, SHGC-34334, and KIAA0160, and thus present with a relatively uniform clinical phenotype.

Cell Culture Techniques↗
PubMed1998

The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz-Jeghers syndrome.

The Drosophila gene dead ringer (dri) was isolated as a novel gene encoding a sequence-specific DNA-binding protein. DRI is a founding member of a growing protein family whose members share a conserved DNA binding domain termed the A/T-rich interaction domain. dri is developmentally regulated, being expressed in a restricted set of cells including some neural cells and differentiating cells of the gut and salivary gland ducts. The mouse homolog of dri, bright, has been shown to be expressed in mature B-cells in the immune system, its product trans-activating expression through an IgH enhancer in transient transfection assays. We have cloned a human dri/bright homolog, termed DRIL1. Here we report the exon-intron structure of the gene and show physical linkage within 80 kb to the D19S886 marker on 19p13.3. As this marker is intimately linked to the Peutz-Jeghers syndrome in several large pedigrees, human dri (DRIL1) is a candidate gene for this disorder.

Animals↗
PubMed1998

Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.

Peutz-Jeghers (PJ) syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. The PJ gene was recently mapped to chromosome 19p13.3 by linkage analysis, with the highest lod score at marker D19S886. In a distance of 190 kb proximal to D19S886, we identified and characterized a novel human gene encoding the serine threonine kinase STK11. In a three-generation PJ family, we found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 segregating with the disease. Sequence analysis of STK11 exons in four unrelated PJ patients has identified three nonsense and one acceptor splice site mutations. All five germline mutations are predicted to disrupt the function of the kinase domain. We conclude that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome.

AMP-Activated Protein Kinase Kinases↗
PubMed1990

[15N tracer technical studies of protein metabolism in arteriosclerosis patients].

The incorporation of the stable isotope 15N in plasma proteins and blood cells after oral application of 3 g 15NH4Cl (95 At% 15N) per 70 kg body weight was followed up in 11 patients with ischemic heart disease or peripheral arteriosclerosis and in 7 healthy control subjects. Preliminary results indicate that the turnover of plasma protein, especially fibrin, is elevated in patients with arteriosclerosis. Investigations of platelets intimate a decreased turnover of platelet protein in patients with arteriosclerosis as compared to control subjects. Possible reasons for these alterations are discussed.

Arteriosclerosis↗
PubMed1990

[Recording protein metabolism and cell proliferation with the stable isotope 15N].

Investigations of nitrogen and protein metabolism with the stable isotope 15N were carried out on 11 patients with atherosclerosis and 7 healthy control subjects. After oral application of 3 g 15NH4Cl (95 At% 15N) per 70 kg body weight the incorporation of the isotope 15N in plasma proteins and blood cells and the 15N elimination in urine were followed up. Retardations of 15N elimination, an accelerated incorporation of 15N in fibrin and a retarded 15N incorporation in platelet protein were observed in patients with atherosclerosis. The described method enables complex assertions about protein metabolism of the whole body and so represents a possibility to evaluate objectively the influence of an intervention on metabolism.

Adult↗
PubMed1989

[Influencing the fibrinolytic activity by antithrombotics in patients with atherosclerosis].

In 106 atherosclerotic patients receiving an anticoagulant therapy and 91 patients receiving acetylsalicylic acid, fibrinogen and fibrin degradation products were determined as well as euglobulin lysis before and after venous occlusion. Platelet function data and thromboxane (TXB2) were also determined. Since "moderate" anticoagulant therapy with thromboplastin time values 26-40% results in deteriorated fibrinolysis data, anticoagulant therapy is strictly to remain within the therapeutic range of 15-20% up to 25% thromboplastin time at maximum. Treatment with acetylsalicylic acid proved useful on condition that the required dose was determined individually. This type of treatment will then be able to reduce the thromboxane level and positively influence the fibrinolytic potential.

Anticoagulants↗
PubMed1988

Determination of serum level of myoglobin and plasma level of autoantibodies to myoglobin in patients with angina pectoris.

The serum level of myoglobin (Mb) was determined in 11 male patients with chronic ischemic heart disease (angiographically studied) by the mean of an enzyme immunoassay (EIA). By a second EIA we could detect in all our patients autoantibodies (autoAB) to Mb. While the level of Mb in all cases was normal (less than 100 ng/ml) we found differences in the level of autoAB to Mb (normal value 90-100%). 7 patients with unstable Angina pectoris exhibited decreased levels of autoAB to Mb (65%). In 4 patients with stable Angina pectoris autoAB to Mb were 93%. The physiological role of the autoAB to Mb remains still unclear. The simultaneous determination of Mb and the autoAB to Mb may be helpful in differential diagnosis of stable and unstable Angina pectoris.

Adult↗