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Biomedical subjects

E De Boer

Publications and source records attributed to E De Boer.

13 recordsLinked to original sources
PubMed1999

Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats.

This study aims to dissociate the respective roles of systemic nephrosis and of the intrarenal effects of proteinuria in the pathogenesis of focal segmental glomerulosclerosis (FGS) in adriamycin nephrosis. To this purpose, this study examined proteinuria and FGS in bilateral (BAP) and unilateral proteinuria (UAP) in two different rat strains. UAP was obtained by protecting one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was present in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. FGS correlated significantly with proteinuria per kidney in BAP and UAP. Remarkably, for a given proteinuria per kidney, the sclerosis score was higher in BAP than in UAP, reflected by a higher ratio of FGS score per mg proteinuria per kidney (Wistar: 0.09 +/- 0.01 in BAP versus 0.05 +/- 0.01%/mg protein per d in UAP, P < 0.05; Lewis: 0.12 +/- 0.01 in BAP versus 0.07 +/- 0.01%/mg protein per d in UAP, P < 0.05), indicating that the local damaging effects of proteinuria are modified by other factors. Cholesterol correlated with total proteinuria in BAP and UAP. FGS score was positively correlated with cholesterol. The latter correlation was similar in BAP and UAP, indicating that cholesterol was a more uniform predictor for FGS than proteinuria per kidney. This was independent of strain-specific factors. On multilinear regression analysis, cholesterol turned out to be the most consistent predictor of FGS in proteinuric kidneys, with a stronger predictive value than proteinuria per kidney. It is concluded that although systemic sequelae of nephrosis do not induce renal damage in nonproteinuric kidneys, they modify the severity of proteinuria-induced FGS in proteinuric kidneys.

Animals↗
PubMed1998

The dynamics of globin gene expression and gene therapy vectors.

The most important level of regulation of the beta-globin genes is by activation of all of the genes by the Locus Control Region (LCR) and repression of the early genes by an as yet unknown factor acting on sequences flanking the genes. Superimposed on this is a mechanism in which the early genes (epsilon and gamma) suppress the late genes (delta and beta) by competition for the interaction with the LCR. Although this extra level of gene regulation is quantitatively of less importance than the direct repression mechanism, it has important implications and has provided an excellent assay system to probe the regulation of transcription at the single cell level. These studies indicate that the LCR interacts with individual globin genes and that LCR/gene interactions are dynamic with complexes forming and dissociating continually. The levels of expression of each of the genes appear to depend on: 1) the frequency of interaction which is itself dependent on the distance of the gene to the LCR, 2) the affinity of the LCR for the gene and 3) the stability of the LCR/gene complex. The latter two are dependent on the balance of transcription factors. We conclude that transcription only appears to take place while the LCR and gene interact and that the level of transcription is determined by the frequency and duration of such interaction rather than by changes in the rate of transcription of promoters.

Animals↗
PubMed1993

The regulation of human globin gene switching.

This paper describes the mechanism of regulation of the human beta-globin on the basis of a number of natural mutations and experiments in transgenic mice. From these data we conclude that this multigene locus is regulated at a number of different levels involving specific interactions between the Locus Control Region (LCR) and the individual genes. Most important is the action of stage specific transcription factors acting on sequences immediately flanking the genes. In addition, specificity is obtained through specific interaction of the genes with the LCR and through competition of the genes for interaction with the LCR.

Animals↗
PubMed1988

Structure and function of vanadium-containing bromoperoxidases.

The properties of the vanadium-containing bromoperoxidases from the seaweeds Ascophyllum nodosum, Laminaria saccharina and the lichen Xanthoria parietina were studied. Upon reduction with sodium dithionite, these bromoperoxidases show EPR spectra which are typical of a vanadyl cation (VO2+). From the spectral parameters and a comparison with inorganic vanadyl complexes, we conclude that the ligand environment largely consists of oxygen donors. The data also show that the structure of the active sites in these enzymes is very similar. Since EPR spectra of vanadium(IV) bromoperoxidase are only obtained after reduction, the metal ion is present in the native enzymes in the 5+ oxidation state. All these enzymes loose their enzymic activity upon dialysis against citrate-phosphate (PO4(3-)) buffer at pH 3.8, containing EDTA. The brominating activity could be reconstituted by the addition of vanadate (VO4(3-)). The experiments suggest that vanadate is incorporated into these enzymes. In line with the EPR data, we propose a structure of the active site in which at least 4 oxygen atoms are present as donors for the central vanadium(V) ion. Since several inorganic peroxovanadium(V) complexes have been described, we suggest that the vanadium ion in bromoperoxidases serves as a binding site for H2O2. Upon subsequent binding of bromide this ion is oxidized by the peroxo-intermediate to form hypobromite. This model does not require valence state changes of the metal ion itself and indeed no changes in the EPR spectrum of reduced bromoperoxidase are observed upon addition of H2O2 or Br-. Further, bromoperoxidase reduced with a small excess of sodium dithionite is not active in the bromination reaction. The bromoperoxidases from the various sources show similarity in the amino-acid composition with a predominance of acidic amino acids. Distinct pH optima are observed in the bromination reaction catalysed by the bromoperoxidases. Despite the presence of the same prosthetic group in these enzymes with comparable vanadium ligand-field environment, the enzymic properties are very different. The specific activity as well as the Km for bromide differ greatly. Unlike the enzymes from the seaweeds A. nodosum and L. saccharina the bromoperoxidase from the lichen X. parietina is inhibited by low concentrations (1-5 mM) of nitrate. These bromoperoxidases have a remarkable resistance towards organic solvents such as methanol, ethanol and propanol.

Amino Acids↗
PubMed1985

Fat distribution of overweight persons in relation to morbidity and subjective health.

The association between fat distribution, morbidity and subjective health was studied in 95 overweight adult men and 210 overweight adult women. Retrospective morbidity data were taken from a continuous morbidity registration made by general practitioners over a period of maximally 17 years. In addition information about subjective health and weight history was obtained from a self-administered questionnaire. Anthropometric measurements were taken and, on the basis of waist-hip and waist-thigh circumference ratios, subjects were classified into upper body segment obesity, intermediate obesity, and lower body segment obesity. It was found that, adjusted for age and body mass index, a high waist-thigh circumference ratio was a risk factor for hypertension and for gout or diabetes in women and arthrosis in men. A low waist-thigh ratio was associated with a high prevalence of varicose veins in women. The associations of waist-hips circumference ratio with morbidity were less pronounced, with the exception of hypertension in men. Information from the questionnaire revealed that persons with upper body segment obesity (especially men) felt less healthy and had more health complaints. These findings were more pronounced for subjects less than 50 years of age than for those of 50 years and older. The weight histories suggest that women with lower body segment obesity had a longer history of obesity than women with upper body segment obesity. This was not found in men. It is concluded that classification of obesity on the basis of circumference ratios is useful for the evaluation of health hazards of overweight subjects.

Adipose Tissue↗
PubMed1978

Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance.

Total human DNA was cleaved with a variety of restriction enzymes, and the fragments were fractionated by gel electrophoresis and transferred to nitrocellulose filter strips. The restricted DNA was then hybridized to nick-translated radioactive recombinant plasmid DNA containing sequences derived from human beta-globin messenger RNA. Under suitable conditions, this probe hybridizes with both the beta--and delta-globin genes. Using this probe, a restriction map of the human beta--and delta-globin genes and the surrounding genomic DNA regions has been constructed. The beta-globin gene contains a nonglobin DNA insert approximately 899-1000 base pairs in length, present within the sequence coding for amino acids 101-120 of the 146 amino acid long globin polypeptide. A similar sequence may be present within the same sequence of the delta-globin gene. The distance between the beta--and delta-globin genes is approximately 7000 nucleotide pairs, and the delta-globin gene is to the 5' side of the beta-globin gene, as predicted by genetic evidence. Both genes are transcribed from the same DNA strand. The structure of the Hb Lepore gene is shown to be a fused delta--and beta-globin gene, and to be completely consistent with the derived map of normal beta--and delta-globin genes. [Restriction enzyme nomenclature follows that of Smith and Nathans (1973) and Roberts (1976). A genomic DNA restriction fragment containing part or all of one globin gene will be designated by that globin chain--for instance, the Pst I fragment containing the beta-globin gene sequence will be designated Pst I beta. A similar convention will be used for double digests. Throughout this paper, when reference is made to the 5' or 3' side or fragment of a gene, this refers to the 5' or 3' side of the mRNA coded by that sequence. Thus the 5' side (N terminal) of the beta-globulin gene is the sequence to the 5' side of the anti-sense strand.].

Chromosome Mapping↗
PubMedDate not supplied

The photoreactivity of the copper-NO complexes in cytochrome c oxidase and in other copper-containing proteins.

The complexes of NO with CuB of cytochrome c oxidase in which cytochrome a3 may or may not be ligated to cyanide or fluoride are photodissociable. NO does not appear to react with CuB in complexes of cytochrome c oxidase in which sulphide or mercaptans are ligated to the haem iron of cytochrome a3. A comparison is made between the photoreactivity of the complexes of NO with cytochrome c oxidase and those with ceruloplasmin, ascorbate oxidase, and haemocyanin. It is shown that the photoreactivity of CuB 2+.NO in cytochrome c oxidase is not unique for this enzyme, but may also be observed in the complexes of NO with type-1 copper-containing enzymes. This would suggest that the ligation of CuB in cytochrome c oxidase shows some similarity to type-1 copper in blue oxidases.

Animals↗
PubMedDate not supplied

Low-level frequency-following response.

In man, the scalp-recorded 'Frequency-following response' (FFR) can be well observed only at fairly high levels of stimulation. As a consequence, it is difficult to ascertain whether the low or the high-frequency channels of the peripheral auditory system mediate this response. It is shown that the sensitivity of the recording method is considerably increased when the averaged recorded waveform is subjected to frequency analysis. Results from experiments with high-pass masking noise become unequivocal and they suggest that the low-level FFR is caused by nervous activity arising in the apical part of the cochlea and mediated by the low-frequency in the brain stem.

Acoustic Stimulation↗