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Biomedical subjects

M De Haan

Publications and source records attributed to M De Haan.

12 recordsLinked to original sources

The cost-effectiveness of the diagnosis of renal artery stenosis.

The objective of this study was to assess the cost effectiveness of eight strategies to diagnose renovascular hypertension (RVHT) followed by treatment with percutaneous transluminal angioplasty (PTRA) with or without stent placement. The eight diagnostic strategies were compared with a reference strategy, i.e. antihypertensive medication. The diagnostic imaging techniques under consideration were captopril renography, spiral computed tomography angiography (CTA), magnetic resonance angiography (MRA) and conventional angiography. Cost-effectiveness analysis was carried out from the perspective of the health care system, based on data from the literature. A model was developed to predict the reduction in 10-year morbidity and 10-year mortality owing to myocardial infarction, stroke and chronic renal failure achieved after PTRA compared with the reference strategy. Life-years gained over a 10-year follow-up period and the incremental cost-effectiveness ratio per life-year saved were the outcome measures. The strategy CTA followed by angiography was more effective, but more costly, than captopril renography followed by angiography, with an incremental cost-effectiveness ratio per life-year gained of Dfl 64700. Combining captopril renography with CTA was even more effective, but the incremental cost-effectiveness ratio per life-year gained was Dfl 236400. Strategies including MRA were not cost-effective. The results suggest that diagnostic strategies that include CTA are more effective than captopril renography in detecting renal artery stenosis (> 50%) and cost saving due to prevented myocardial infarction, stroke or chronic renal failure. MRA is even more effective, but in order to achieve an acceptable cost-effectiveness ratio, the costs would need to be reduced. The cost-effectiveness of the diagnostic strategies is sensitive to the pre-test probability of RVHT. So, careful clinical evaluation, in order to achieve a pre-test probability of at least 20%, is an essential component of the complete workup strategy in patients suspected to have RVHT.

Angioplasty, Balloon↗

Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome X (745 442 bp) reveals a total of 379 open reading frames (ORFs), the coding region covering approximately 75% of the entire sequence. One hundred and eighteen ORFs (31%) correspond to genes previously identified in S. cerevisiae. All other ORFs represent novel putative yeast genes, whose function will have to be determined experimentally. However, 57 of the latter subset (another 15% of the total) encode proteins that show significant analogy to proteins of known function from yeast or other organisms. The remaining ORFs, exhibiting no significant similarity to any known sequence, amount to 54% of the total. General features of chromosome X are also reported, with emphasis on the nucleotide frequency distribution in the environment of the ATG and stop codons, the possible coding capacity of at least some of the small ORFs (<100 codons) and the significance of 46 non-canonical or unpaired nucleotides in the stems of some of the 24 tRNA genes recognized on this chromosome.

Amino Acid Sequence↗

Neural correlates of infants' visual responsiveness to facial expressions of emotion.

An extensive literature documents the infant's ability to recognize and discriminate a variety of facial expressions of emotion. However, little is known about the neural bases of this ability. To examine the neural processes that may underlie infants' responses to facial expressions, we recorded event-related potentials (ERPs) while 7-month-olds watched pictures of a happy face and a fearful face (Experiment 1) or an angry face and a fearful face (Experiment 2). In both experiments an early positive component, a middle-latency negative component and a later positive component were elicited. However, only when the infants saw the happy and fearful faces did the components differ for the two expressions. These results are discussed in the context of the neurobiological processes involved in preceiving facial expressions.

Brain↗

The complete sequence of a 33 kb fragment on the right arm of chromosome II from Saccharomyces cerevisiae reveals 16 open reading frames, including ten new open reading frames, five previously identified genes and a homologue of the SCO1 gene.

We report here the sequence of a 33,117 bp DNA fragment located approximately 30 kb from the centromere on the right arm of Saccharomyces cerevisiae chromosome II. We have detected 16 open reading frames (ORFs) longer than 450 bp, provisionally called YBR0301 to YBR0322, covering 70.4% of the entire sequence. The ORFs YBR0301, YBR0302, YBR0303, YBR0305 and YBR0315 correspond to previously sequenced S. cerevisiae genes GAL10, GAL1, FUR4, CAL1 and L2B, respectively. Translation products of two other ORFs, YBR0308 and YBR0312 exhibit similarity to previously known S. cerevisiae proteins: the mitochondrially associated protein SCO1 and the protein kinase YKR2. The predicted protein product of the ORF YBR0321 shows a 41.6% identity score with the Escherichia coli pyroxamine 5'-phosphate oxidase. The nine other ORFs show no significant homology to known proteins.

Amino Acid Sequence↗

Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease whose notorious pathologic feature is insulitis accompanied by destruction of beta-cells. In this morphological study, we examined the pancreatic events during the onset of diabetes in spontaneously diabetic BB/Organon rats. Dendritic cells were the first cells to accumulate around the islets, followed by lymphocytes. Scavenger macrophages and MHC class II-positive beta-cells were only seen late in the disease. These observations suggest a role for antigen-presenting dendritic cells in the onset of the beta-cell-specific autoimmune reaction and emphasize the necessity to distinguish between the several monocyte-macrophage subtypes in studies on the pathogenesis of IDDM.

Animals↗

Inactivation of the gene encoding the 11-kDa subunit VIII of the ubiquinol-cytochrome-c oxidoreductase in Saccharomyces cerevisiae.

The single nuclear gene encoding the 11-kDa subunit VIII of the ubiquinol-cytochrome-c oxidoreductase (complex III) in Saccharomyces cerevisiae has been inactivated by a one-step gene disruption procedure. Inactivation results in a loss of ubiquinol-cytochrome-c oxidoreductase activity (less than 1% wild type) and respiratory deficiency. Cells lacking the 11-kDa protein also display lowered steady-state levels of other complex-III subunits encoded by nuclear genes including the 14-kDa subunit VII and the Rieske Fe-S protein and of the mitochondrially encoded cytochrome b. The steady-state levels of the transcripts from the genes encoding these proteins are however not reduced. The results strongly imply that the 11-kDa protein plays an important role in regulating the synthesis of complex III at the post-transcriptional level, most likely assembly. Separation of chromosomes by pulsed-field gel electrophoresis of DNA of wild-type and of the mutant lacking the 11-kDa-protein gene followed by Southern blot analysis reveals that the latter gene is located on chromosome X rather than on XII as reported by Van Loon et al. [Mol. Gen. Genet. 197 (1984) 219-224].

Chromosome Mapping↗

Intrathyroidal dendritic cells.

The presence, marker pattern, and ultrastructure of antigen-presenting dendritic cells were studied in normal thyroid glands from 9 subjects (6 obtained at surgery; 3 at autopsy) and in the thyroid glands form 13 patients with Graves' hyperthyroidism, 10 patients with simple nontoxic goiter, and 1 patient with Hashimoto's disease (all obtained at surgery). The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OKIa (class II MHC determinants), RFD1 and L25. These latter monoclonal antibodies react strongly with active dendritic cells in T-cell areas of secondary lymphoid organs (the interdigitating cells in lymph nodes and spleen). Antigen-presenting dendritic cells were defined as cells with an eccentric reniform nucleus, long cytoplasmic protrusions, and strong membrane-bound class II MHC positivity combined with little or no cytoplasmic acid phosphatase activity. According to these criteria normal human thyroid tissue contained a few dendritic cells; they were localized outside the thyroid follicles. These dendritic cells in normal thyroid tissue lacked the marker molecules identified by the monoclonal antibodies RFD1 and L25. In fact, the majority of the dendritic cells were strongly positive for the C3bi receptor (identified by the monoclonal antibody FK 24), which indicates a more monocyte/macrophage character of the cell. In Hashimoto's goiter, Graves' disease, and sporadic nontoxic goiter (which we consider an autoimmune thyroid disease) the numbers of dendritic cells were higher compared to those in the normal gland, and these dendritic cells were clearly positive for RFD1 and L25. The cells were often seen in contact with a few intrathyroidal lymphocytes, forming small lymphoid cell clusters. They were also found in the T-cell zones of larger well organized intrathyroidal lymphoid structures (focal thyroiditis). On ultrastructural examination the dendritic cells in Graves' glands, Hashimoto's goiter, and sporadic nontoxic goiter were similar to the interdigitating cells present in secondary lymphoid organs. The data suggest active involvement of dendritic cells in the immune process in the thyroids of patients with autoimmune thyroid disease.

Adult↗

The biosynthesis of the ubiquinol-cytochrome c reductase complex in yeast. DNA sequence analysis of the nuclear gene coding for the 14-kDa subunit.

The nuclear gene coding for the imported 14-kDa subunit of the ubiquinol-cytochrome c reductase of yeast mitochondria has been sequenced in an attempt to define regulatory and protein topogenic elements. The gene has a length of 381 base pairs and is potentially capable of encoding a polypeptide of 14561 Da. It is transcribed into a single low-abundance RNA of 680 nucleotides whose 5' and 3' termini map, respectively, 30-35 nucleotides upstream and 180-190 nucleotides downstream of the initiator and termination codons. Consistent with the estimated low level of the mRNA, codon usage in the gene is not strongly biased and other features, characteristic of highly expressed genes in yeast, are absent. The 14-kDa protein is predicted to be a predominantly hydrophilic protein, with only a single, short hydrophobic stretch located between positions 19-38. Comparison with other imported mitochondrial proteins so far sequenced has failed to reveal unifying features that might serve as targeting elements. Steady-state levels of the 14-kDa and 11-kDa subunits are reduced in mit- mutants which synthesize truncated forms of apocytochrome b and in these, newly synthesized subunits exhibit a specifically increased turnover rate. We suggest that association of these two subunits with the complex may be mediated or enhanced by interaction with other subunits, in particular cytochrome b.

Amino Acid Sequence↗

The DNA sequence of the nuclear gene coding for the 17-kd subunit VI of the yeast ubiquinol-cytochrome c reductase: a protein with an extremely high content of acidic amino acids.

We have determined the DNA sequence of the nuclear gene coding for the 17-kd subunit VI of the ubiquinol-cytochrome c reductase. The reading frame found encodes a putative polypeptide of 17 394 daltons. This protein is highly unusual: 38% of its residues are acidic and 14% are basic amino acids. The most notable feature in the protein sequence is a stretch of 25 consecutive acidic amino acids. The polypeptide has homology with the 9-kd so-called 'hinge' protein of beef-heart complex III, which also has a cluster of acidic residues. Acidic amino acids are likely to be essential for the function of these proteins, since their degree of conservation is higher than that of other residues.

Amino Acid Sequence↗

A nonanucleotide sequence involved in promotion of ribosomal RNA synthesis and RNA priming of DNA replication in yeast mitochondria.

We have examined the initiation of transcription of the mitochondrial genes for ribosomal RNA (rRNA) in the yeast Kluyveromyces lactis and show that these are transcribed independently from individual promoters. The mature large rRNA contains a 5' di- or triphosphate end which can be labelled in vitro with [alpha-32P]GTP using guanylyltransferase and this enabled us to determine the nucleotide sequence of its 5' terminus. For the small rRNA, a minor in vitro capped RNA species hybridizes in the region where--as judged from S1 nuclease protection experiments--the precursor of this RNA starts. We have determined the DNA sequence around the beginning of both rRNA genes and this reveals the existence of an identical nonanucleotide sequence (5' -ATATAAGTA- 3') just preceding the positions where the rRNAs start. This sequence is identical to the one preceding the rRNA genes in the mtDNA of the distantly related yeast Saccharomyces cerevisiae (Osinga, K.A. and Tabak, H.F. (1982) Nucl.Acids Res. 10, 3617-3626) and supports our proposal that this sequence motif is part of a yeast mitochondrial promoter. We have noticed that the same sequence is located in the putative origin of replication present in hypersuppressive petite mutants of S. cerevisiae and consider the possibility that this sequence is involved in RNA priming of DNA replication.

Ascomycota↗

Mutations affecting RNA splicing and the interaction of gene expression of the yeast mitochondrial loci cob and oxi-3.

In Saccharomyces cerevisiae strains KL14-4A and 777-3A, four intervening sequences of 1900 (l alpha beta), 1400 (l beta gamma), 1300 (l gamma delta) and 650 bp (l delta epsilon) separate the five coding sequences (alpha-epsilon) of the structural gene (cob) for cytochrome b. Its major transcript is an 18S RNA (2200 nucleotides) which is likely to be the functional mRNA. The lengths of a series of larger transcripts and their hybridization with probes specific for different intervening sequences are consistent with their being intermediates in a splicing process which generates 18S RNA from a giant primary transcript (greater than or equal to 7.5 kb) covering the whole cob region. There is no absolute order of splicing. The intervening sequence l alpha beta is excised in two stages. The first generates a stable 10S RNA, coded for by sequences immediately downstream of the 18S RNA coding segment alpha. The function of this RNA is unknown. Its excision is an early step in processing, whereas excision of the remainder of l alpha beta is a late event. We have studied four cytochrome b-deficient mutants. These map in intervening sequences and are splicing-defective. They accumulate 22S-28S RNAs which contain one or more intervening sequences. The l alpha beta mutants synthesize long, novel polypeptides, antigenically related to cytochrome b, possibly as a result of read-through into the intervening sequences. Several cob mutants also display alterations in their transcripts of oxi-3, the locus which codes for cytochrome c oxidase subunit I. This indicates that interactions between cob and oxi-3 exist at the level of RNA processing.

Cytochromes↗

Microscopic theory of irreversible processes.

The microscopic theory of irreversible processes that we developed is summarized and illustrated, using as a simple example the Friedrichs model. Our approach combines the Poincaré's point of view (dynamical interpretation of irreversibility) with the Gibbs-Einstein ensemble point of view. It essentially consists in a nonunitary transformation theory based on the symmetry properties of the Liouville equation and dealing with continuous spectrum. The second law acquires a microscopic content in terms of a Liapounov function which is a quadratic functional of the density operator. In our new representation of dynamics, which is defined for a restricted set of observables and states, this functional takes a universal form. We obtain, in this way, a semi-group description, the generator of which contains a part directly related to the microscopic entropy production. The Friedrichs model gives us a simple field theoretical example for which the entropy production can be evaluated. The thermodynamical meaning of life-times is explicitly displayed. The transition from pure states to mixtures, as well as the occurrence of long tails in thermodynamic systems, are also briefly discussed.

Journal Article↗