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Biomedical subjects

J L van den Brande

Publications and source records attributed to J L van den Brande.

At least 19 recordsLinked to original sources

Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on CCl4-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-beta in cocultures with sinusoidal endothelial cells.

Transforming growth factor beta (TGF-beta), a potent fibrogenic cytokine, is secreted in latent form. We examined which cell type in both normal and carbon tetrachloride (CCl4)-induced fibrotic rat liver bears surface type II IGF/mannose 6-phosphate (IGF-II/M6P) receptor, known to facilitate activation of TGF-beta. In addition, the role of the IGF-II/M6P receptor in activation of latent TGF-beta was investigated in a coculture system with sinusoidal endothelial cells. Northern hybridization analysis for IGF-II/M6P receptor messenger RNA (mRNA) was performed on total RNA of different isolated and purified liver cell types. In normal liver, cells expressed little IGF-II/M6P receptor mRNA. In fibrotic liver, we found significant expression only in fat-storing cells. The presence of IGF-II/M6P receptors was established by [125I]IGF-II binding assays on freshly isolated fat-storing cells from normal and CCl4-exposed rat livers. We found specific binding of [125I]IGF-II only on CCl4 exposed fat-storing cells. As determined by polyacrylamide gel electrophoresis after affinity labeling, the specific binding involved 220 kD type II IGF receptors. Scatchard analysis revealed the presence of 3,043 +/- 1,378 IGF-II/M6P high-affinity receptors/fat-storing cell, with a Kd of 387 = 165 pmol/L. With a mink lung epithelial cell (Mv1Lu) proliferation inhibition assay, inhibition of proliferation (a measure of active TGF-beta function) was determined using conditioned media of activated fat-storing cells, cocultures of fat-storing cells, and endothelial cells and pure endothelial cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Translational control of gene expression.

Translational regulation of mRNA is an important step in the control of gene expression. In a general way, the efficiency of the translational apparatus can be influenced either positively or negatively by changing the level or the activity of rate-limiting protein factors taking part in the process of translation. But translational control can also be very specific, affecting only a single mRNA or class of mRNA molecules. In most of these cases regulation takes place at the level of initiation of translation, which is often attributable to structural peculiarities of the mRNA in question, especially of the 5'-untranslated region or leader. This review summarizes the mechanisms which lie at the root of translational control. A better understanding of these mechanisms will eventually provide us with new drugs and antisense oligonucleotide technology, aimed at influencing the level of expression of single proteins. These developments are of interest to basic researchers and clinicians alike, because they may profoundly change the ways in which we treat, e.g. viral infections and malignancies in the future.

Animals↗

Insulin-like growth factors (IGFs) and IGF binding protein-3 display disulfide isomerase activity.

Insulin-like growth factors (IGF-I and -II) bind with high affinity to IGF-binding proteins (IGFBPs). IGFBP-3 contains vicinal cysteines in sequence which is similar to the active sites in thioredoxin and protein disulfide isomerase. We tested if, in analogy with these redox enzymes, IGFBP-3 could catalyze the isomerization of intramolecular disulfide bridges in protein substrates. IGFBP-3 (30 microM) was able to reactivate reduced ribonuclease at a rate of 38% of that of thioredoxin. Also recombinant IGF-I induced the regeneration of ribonuclease activity. Thiol redox reactions are known to play a role in regulating conformational changes in the insulin receptor and possibly also in the IGF-I receptor. Therefore, the intrinsic isomerase activities of IGF-I may be important in the activation of its receptor. The observed effects of IGFBP-3 may help to elucidate the mechanism by which this binding protein can modulate the actions of IGF-I.

Amino Acid Sequence↗

Transient hypothyroxinaemia associated with developmental delay in very preterm infants.

In 563 surviving very preterm (less than 32 weeks gestational age) and/or very low birthweight (less than 1500 g) infants the relationship between neonatal thyroxine concentration and psychomotor development at 2 years of age (corrected for preterm birth) was studied. A significant association was found between low neonatal thyroxine concentration and a negative score on the three milestones of development. These findings do not support the view that transient hypothyroxinaemia in preterm infants is harmless.

Child, Preschool↗

Primary sequences of insulin-like growth factors 1 and 2 isolated from porcine plasma.

Insulin-like growth factors 1 and 2 were purified from porcine plasma. In addition to the determination of their isoelectric points, the primary structures of both proteins were determined, using low microgram quantities of protein, by the versatile combination of time-of-flight plasma desorption mass spectrometry and automated Edman degradation. Porcine insulin-like growth factor 1 was shown to be homologous to both human and bovine proteins; the type 2 growth factor showed one mutation to both human and bovine type 2 proteins.

Amino Acid Sequence↗

Immunologic studies in Turner syndrome before and during treatment with growth hormone. The Dutch Growth Hormone Working Group.

Immunologic studies of 14 girls with Turner syndrome were done before and during treatment with biosynthetic growth hormone (GH). Compared with control subjects, the patients before treatment had a decreased CD4/CD8 ratio and an increased number of cells bearing the natural killer cell marker CD16; serum immunoglobulin levels were within the normal range. During GH treatment some of the girls had a slight reduction in the percentage of CD20+ B cells, but we observed no impairment of B lymphocyte function as demonstrated by the normal in vivo antibody response to the primary antigen Helix Pomatia hemocyanin, administered 6 months after the start of GH treatment. The number of CD16+ natural killer cells returned to normal. Although the number of children with thyroid antibodies increased from two before treatment to five after 1 year, no conclusion about an adverse effect of GH is warranted, because the phenomenon might be part of the natural course of the disease. We conclude that girls with Turner syndrome have minor changes in some immunologic measurements and that GH treatment resulted in some alterations that have no effect on immune function.

Adolescent↗

Heterozygotes for 17 alpha-hydroxylase deficiency can be detected with a short ACTH test.

A short ACTH test was performed in the six parents, and four siblings, of three cases with 17 alpha-hydroxylase deficiency. Baseline steroid levels were all normal in female heterozygotes but in males 17 alpha-hydroxyprogesterone levels were elevated. After ACTH-stimulation, plasma levels of corticosterone were elevated in five obligate heterozygotes and 18-hydroxydeoxycorticosterone levels were increased in four of them. Two of the four siblings had biochemical signs of heterozygosity. The short ACTH test appears to be an efficient method for detecting heterozygosity, but the abnormalities found are more heterogeneous than previously suggested.

Adolescent↗

[Growth regulation].

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Epidermal Growth Factor↗

Sex hormone profiles of premenarcheal athletes.

Female gymnasts have a delayed onset and probably retarded progression of puberty. The aim of this study was to test the hypothesis that the delay in onset of puberty in gymnasts as compared to girl swimmers is modulated by a lower estrone level due to a smaller amount of body fat. The sex-hormone and gonadotropin levels of 46 gymnasts and 37 girl swimmers of the same biological maturation (breast development: M = 1 or M = 2) were studied. In each subject the following hormones were measured in plasma: estrone, 17-beta-estradiol, DHEAS, testosterone, androstenedione, LH, and FSH. In prepubertal children (M = 1) the levels of estrone, testosterone, and androstenedione were lower in the gymnastic group as compared to the swimming group. In the early pubertal (M = 2) gymnastic and swimming groups these hormone levels were no longer different. The other hormone levels were not significantly different in either the prepubertal groups or the early pubertal ones. Within the total prepubertal group there is a clear relationship between the estrone levels and the levels of testosterone and androstenedione, but not between estrone and 17-beta-estradiol, nor between the calculated fat mass and any of the hormone levels. It appears that the androstenedione and testosterone levels are responsible for the difference in estrone level, rather than the amount of body fat.

Adolescent↗