The IGF system during growth and differentiation of the mouse

The insulin-like growth factors (IGFs) were first discovered in 1957 by Salmon and Daughaday (1957). They found that in vivo administration of growth hormone (GH) induced a serum factor capable of stimulating sulfate uptake in cartilage. In 1972 this 'sulfation factor' was renamed somatomedin (mediator of the effects of somatotropin, GH) and classified as a growth factor (Daughaday et aI., 1972). At the same time, a compound named NSILA (nonsuppressible insulin-like activity) was found (Froesch et aI., 1966). NSILA and somatomedin each stimulated glucose incorporation into fat and sulfate incorporation into cartilage (Froesch et aI., 1976). The amino acid sequence of NSILA showed 48% homology with human pro-insulin. Therefore it was called insulin-like growth factor-I (IGF-I) (Rinderknecht and Humbel, 1978a). A second bioactive insulin-like molecule appeared to be similar, but not identical, and was named IGF-II (Rinderknecht and Humbel, 1978b). Somatomedin appeared to be identical to IGF-I (Svoboda et aI., 1980). Now, over forty years later, in vivo studies, gene expression experiments, and determination of signalling pathways have provided more insight into IGF actions. IGF receptors and IGF binding proteins (IGFBPs) have been characterized (Chernausek et aI., 1981; Kasuga et aI., 1981; Brinkman et aI., 1988; Binkert et aI., 1989; Margot et aI., 1989; Shimasaki, 1989; Murphy et aI., 1990; Shimasaki, 1990; 1991a/b; Schuller et aI., 1994). This, and the recent discovery of IGFBP related proteins, have shown the complexity of the IGF system (Oh et aI., 1996). It is clear that the IGFs, together with the other IGF system compounds, playa pivotal role in body and organ development and growth. Therefore, this chapter will review in more detait characteristics of the separate components of the IGF system. Then, focus is put on the IGF system during mouse development. A summary of the data generated to elucidate the functions of the IGF system during mouse development is described

Decision making in clinical oncology : an ethical exploration of cancer treatment refusal

Leeuwen, E. van [Promotor]Baarsen, B. van [Copromotor

The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are found elevated in various conditions characterized by renal growth (e.g. diabetes mellitus, hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was administered alone or in combination with IGF-I to Snell dwarf mice, an in vivo model without compensatory feedback effects on growth hormone (GH) secretion. In three control groups of Snell dwarf mice, placebo, GH or IGF-I was administered. Compared with placebo, kidney weight increased in all treated groups, however, with different effects on kidney morphology. Administration of IGF-I, alone or in combination with IGFBP-1, tended to increase glomerular volume, while no changes were seen in the other groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation of the thin limbs of Henle's loop, while GH or IGF-I administration had no visible effect. Furthermore, IGF-I administration resulted in an increased mean number of nuclei per cortical area and renal weight, whereas GH, IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ hybridization and immunohistochemistry showed specific changes of the renal IGF system expression patterns in the different groups. Particularly, IGFBP-1 administration resulted in extensive changes in the mRNA expression of the renal IGF system, whereas the other administration regimen resulted in less prominent modifications. In contrast, administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes in the protein expression of the renal IGF system. Our results indicate that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on the renal tubular system that differ from the effects of IGF-I

Determination of the accuracy of implant reconstruction and dose delivery in brachytherapy in The Netherlands and Belgium

Purpose: To gain insight into the accuracy of brachytherapy treatments, the accuracy of implant reconstruction and dose delivery was investigated in 33 radiotherapy institutions in The Netherlands and Belgium. Materials and methods: The accuracy of the implant reconstruction method was determined using a cubic phantom containing 25 spheres at well-known positions. Reconstruction measurements were obtained on 41 brachytherapy localizers, 33 of which were simulators. The reconstructed distances between the spheres were compared with the true distances. The accuracy of the dose delivery was determined for high dose rate (HDR), pulsed dose rate (PDR) and low dose rate (LDR) afterloading systems using a polymethyl methacrylate cylindrical phantom containing a NE 2571 ionization chamber in its centre. The institutions were asked to deliver a prescribed dose at the centre of the phantom. The measured dose was compared with the prescribed dose. Results: The average reconstruction accuracy was -0.07 mm (±0.4 mm, 1 SD) for 41 localizers. The average deviation of the measured dose from the prescribed dose was +0.9% (±1.3%, 1 SD) for 21 HDR afterloading systems, +1.0% (±2.3%, 1 SD) for 12 PDR afterloaders, and +1.8% (±2.5%, 1 SD) for 15 LDR afterloaders. Conclusions: This comparison showed a good accuracy of brachytherapy implant reconstruction and dose delivery in The Netherlands and Belgium

Health behaviors and risk factors in those who use complementary and alternative medicine

<p>Abstract</p> <p>Background</p> <p>Surveys have generally found that individuals more likely to use complementary and alternative medicine are female, live in the western United States, are likely to have a health complaint, and have a higher socioeconomic status than do nonusers. What is not known is the extent to which those who use complementary and alternative medicine also engage in positive health behaviors, such as smoking cessation or increased physical activity and/or exhibit fewer health risk factors such as obesity. This has been identified as a key research question in a recent Institute of Medicine report. In the present study we sought to determine whether the use of complementary and alternative medicine is associated with health behaviors or risk factors known to impact on health status.</p> <p>Methods</p> <p>The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in-person from 31,044 adults throughout the 50 states and the District of Columbia.</p> <p>Results</p> <p>After controlling for a range of other factors, we found that engaging in leisure-time physical activity, having consumed alcohol in one's life but not being a current heavy drinker, and being a former smoker are independently associated with the use of CAM. Obese individuals are slightly less likely to use CAM than individuals with a healthy body-mass index. No significant associations were observed between receipt of an influenza vaccine and CAM use.</p> <p>Conclusion</p> <p>Those engaging in positive health behaviors and exhibiting fewer health risk factors are more likely to use CAM than those who forgo positive health behaviors or exhibit more health risk factors. The fact that users of CAM tend to pursue generally healthy lifestyles suggests that they may be open to additional recommendations toward optimizing their health.</p

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Speech of Mr van Kleffens

Speech on Dutch delegation going to a conference in San FranciscoOut of the newspaper "Trouw" special edition for West-Friesland, 13 April 1945, no 103, the speech was made on Radio Oranje. Original size 285mmX225mm on pink paper. Scanned on HP5300C scanner at 150dpi. 1 page