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Biomedical subjects

J S Starreveld

Publications and source records attributed to J S Starreveld.

15 recordsLinked to original sources

Cerebral white matter abnormalities in 6p25 deletion syndrome.

Submicroscopic deletion of the terminal part of the short arm of chromosome 6, including 6p25, leads to developmental retardation, hearing impairment, ocular dysgenesis, and dysmorphic features. We diagnosed 3 patients referred because of white matter abnormalities of unknown origin. MR imaging showed multifocal areas of abnormal signal and enlarged perivascular spaces in the cerebral white matter that were stable during follow-up. Multifocal white matter abnormalities are most commonly seen in static, nonmetabolic encephalopathies, including chromosomal abnormalities.

Abnormalities, Multiple↗

[Summary of the practice guideline 'Lower urinary-tract symptoms in middle-aged and elderly men' (second revision) from the Dutch College of General Practitioners].

The 1997 practice guideline from the Dutch College of General Practitioners concerning lower urinary-tract symptoms (LUTS) in middle-aged and elderly men has been revised and some points have been adapted. The underlying cause of LUTS in middle-aged and elderly men is an improperly functioning voiding mechanism of the bladder associated with ageing. Symptoms are not simply due to prostate enlargement. In uncomplicated LUTS the patient's perception of the level of inconvenience is very important in considering and choosing therapeutic options. Percussion of the bladder after micturition is no longer universally advised. In general, invasive treatment is more effective in relieving symptoms than medical treatment, although invasive treatment causes more adverse effects. LUTS and prostate cancer are different entities, and LUTS is not a risk factor for prostate cancer. The issue of prostate cancer is discussed in this practice guideline in order to clear up popular misconceptions and to enhance the practical implementation of this guideline.

Aged↗

Rapid formation of collateral arteries in a neonate with interruption of the aortic arch.

In a neonate born prior to term with a weight of 1825 grams, and diagnosed prenatally as having atrioventricular septal defect and Down's syndrome, we found the aortic arch to be interrupted between the left carotid artery and the left subclavian artery, with the arterial duct being the only route of distal perfusion. Three days later, however, echocardiographic interrogation revealed marked collateral connections between the aortic arch and the descending aorta, the picture then mimicking coarctation rather than interruption of the aortic arch. The rapid development of the collateral arteries was confirmed by magnetic resonance imaging and during cardiac surgery.

Aorta, Thoracic↗

Morphological differentiation of cytotrophoblasts cultured in Medium 199 and in keratinocyte growth medium.

In culture, cytotrophoblast cells differentiate biochemically as well as morphologically into syncytiotrophoblast-like structures. Morphological and biochemical differentiation can be affected by the composition of the culture medium. The aim of this study was to analyze the morphological differentiation (syncytium formation) of cytotrophoblasts cultured in Medium 199 (M199) and keratinocyte growth medium (KGM). Term human cytotrophoblast cells were cultured in either M199 or KGM with daily refreshment of the media. Both media induced biochemical differentiation, as monitored by measuring hCG secretion. Syncytium formation was visualized by immunocytochemical staining of desmosomes (cell membranes). Cytotrophoblasts rapidly formed aggregates; however, single cells were seen throughout culture. Though the aggregates developed into syncytia, approximately 15% of the nuclei were still found in cell aggregates at the end of the culture period (4 days). The final percentage of nuclei in syncytia (60-70%) did not differ between the culture media used. Syncytium formation occurred more rapidly in KGM medium. Approximately 50% of the nuclei were found in syncytia after 40 and 50 h in KGM and M199, respectively. The number of nuclei per syncytium was slightly higher in M199, but the average surface area of the syncytia was larger in KGM cultured cells (162-132 mm2). These differences did not reach significance. We conclude that there is no major difference in morphological differentiation between cytotrophoblast cells in KGM or M199. Moreover, both media sustain equal rates of hCG secretion.

Animals↗

Regulation of transferrin receptor synthesis by human cytotrophoblast cells in culture.

The aim of this study was to examine the capacity of the syncytiotrophoblast to regulate transferrin receptor (TfR) synthesis in response to modulations in maternal iron supply. The model used was the primary trophoblast cell culture. Trophoblast cells isolated from term human placentas were cultured in iron-poor (Medium 199), iron-depleted (desferrioxamine (DFO)) and iron-supplemented (diferric transferrin (hTf-2Fe), ferric ammonium citrate (FAC) medium. TfR synthesis was reduced in response to hTf-2Fe supplementation. FAC did not modulate TfR synthesis. Iron deprivation by DFO resulted in clear stimulation of TfR synthesis. These results show that the differentiating trophoblast cells respond to pertubations in the (transferrin-mediated) iron supply by adjustments in the rate of TfR synthesis. Taking syncytiotrophoblast in culture as model for the maternal/fetal interface in vivo, our results would suggest that the placenta is able to make short term adjustments of the capacity for iron uptake.

Cells, Cultured↗

Effects of iron supplementation on iron uptake by differentiating cytotrophoblasts.

Cultured in Medium-199, cytotrophoblasts isolated from human placentae differentiate morphologically (e.g. syncytium formation) as well as biochemically (e.g. expression of transferrin receptors, TfRs) into syncytiotrophoblast-like structures. The highest TfR numbers are observed in cells cultured in iron-poor culture medium. Investigated were the implications of the variation in surface TfR numbers on the uptake of iron by cytotrophoblasts cultured in iron-poor Medium-199. Despite differences in TfR densities induced by culture time and iron availability, the initial rate of iron uptake did not change (80-100 pmol/mg protein/h). Homeostasis of iron uptake could be explained by adaptive changes in the rate constant for TfR endocytosis (kend), exocytosis (kexo) and TfR cycle times. In undifferentiated cells (cultured for 18 h) kend was 0.299 min-1. In differentiated cells (culture time 65 h, higher surface TfR densities), kend changed to 0.138 min-1. Culture for 65 h in diferric transferrin-enriched medium resulted in intermediate TfR densities together with an intermediate kend (0.210 min-1). Adaptive changes in the corresponding rate constant of exocytosis were less pronounced (0.192, 0.192 and 0.260 min-1 respectively). It is concluded that differentiating cytotrophoblasts regulate iron uptake by variation of both TfR numbers and the rate of receptor-mediated endocytosis and exocytosis.

Adaptation, Physiological↗

Expression of haemopexin receptors by cultured human cytotrophoblast.

The expression of cell-surface haemopexin (Hx) receptors on human cytotrophoblasts was assessed by using four different Hx species purified from plasma: human Hx isolated by wheatgerm-affinity chromatography, human Hx isolated by haem-agarose-affinity chromatography and rabbit and rat Hx, also isolated by haem-agarose-affinity chromatography. About 3500-7000 high-affinity (Kd 0.34-0.85 nM) receptors per cell were measured by Scatchard-type analysis at 4 degrees C using human (species obtained by both methods) or rabbit 125I-labelled haem-Hx. Measured simultaneously, transferrin receptor number and affinity were 40,000/cell and 0.83 nM respectively. In contrast with transferrin receptors, the number of Hx receptors did not increase during 24 h in cytotrophoblast culture. Rat Hx showed no specific binding to human Hx receptors in cytotrophoblast cultures.

Animals↗

Ferritin in cultured human cytotrophoblasts: synthesis and subunit distribution.

The present study aims at the role of ferritin in the regulation of syncytiotrophoblast free iron levels. The differentiated cytotrophoblast cell in culture is used as a model for this maternal-fetal interface. Cytotrophoblast cells isolated from term placentae are cultured in iron-poor (Medium 199), iron-depleted [desferrioxamine(DFO)] and iron-supplemented [diferric transferrin (hTF-2Fe), ferric ammonium citrate (FAC)] medium. Distribution and de novo synthesis of isoferritins is studied, together with the cellular iron concentration and the ferritin iron saturation. Compared to ferritin isolated from total placenta, ferritin obtained from villous tissue is enriched with acidic isoforms. This observation is in agreement with measured light (L) to heavy (H) subunit ratios < 1 of de novo synthesized ferritin in cultured cytotrophoblast cells. Neither iron-poor culture medium, nor hTf-2Fe supplemented medium affects the cellular iron or ferritin concentration. FAC increased the cellular ferritin iron saturation and (by synthesis) the acidic isoferritin concentrations. The results strongly suggest, that the term syncytiotrophoblast is able to balance transferrin-mediated iron uptake and iron release. In case of FAC supplementation, the syncytiotrophoblast is unable to keep intracellular iron low, and ferritin synthesis is stimulated. The predominance of acidic ferritins and the preferential synthesis of H subunits can be functionally explained by the established fact that iron incorporation in acidic ferritins is faster due to the presence of ferroxidase centres. Damage by free iron catalysed hydroxyl radical formation is therefore minimized.

Cells, Cultured↗

Regulation of transferrin receptor expression and distribution in in vitro cultured human cytotrophoblasts.

During gestation the transplacental iron transport is very important to the fetus. Iron uptake by the placenta can be studied in cultured cytotrophoblasts. The influence of culture time and human differic transferrin on the number and distribution of transferrin receptors (TfRs) was investigated in human cytotrophoblasts. Cytotrophoblasts cultured for 2.5 h had few TfRs (0.28 pmol/mg protein). With time, total TfR amounts increase (4.14 pmol/mg protein at 70 h). They increase to a higher level in cells cultured in iron-poor medium, indicating that iron has an effect on the TfR synthesis/breakdown ratio. TfRs were distributed between two 'active' (located at the cell surface and intracellularly) and one 'inactive' (located intracellularly) receptor pools. TfR distribution among these pools was modulated by culture time and iron. Trophoblasts regulated iron uptake by variation of number of surface TfRs via changes in total TfRs and redistribution of TfRs among the receptor pools.

Cell Differentiation↗

Number and affinity of transferrin-receptors at the placental microvillous plasma membrane of the guinea pig: influence of gestational age and degree of transferrin glycan chain complexity.

Transferrin receptors (TfR's) on the syncytiotrophoblast mediate transferrin (Tf) dependent Fe uptake and transfer to the fetus. We studied TfR number and density at the microvillous membrane isolated from guinea pig placentas at day 40, 50 and 64 (near term), together with the K(a) values for the main serum isotransferrins being biantennary Tf(slow) and triantennary Tf(fast). The effect of desialylation of either the microvillous membranes or of Tf(slow) and Tf(fast) on the binding characteristics was also studied. The number of TfR's per mg placenta- or membrane protein increased significantly from day 40 to term (P < 0.01 resp. P < 0.025). The K(a) values for Tf(slow) and Tf(fast) did not change during pregnancy. K(a)Tf(slow) = 0.3 nM-1, K(a)Tf(fast) = 0.19 nM-1 (P < 0.01). It is suggested that the increase in F(e) transfer during pregnancy is directly related to number and density of the TfR's at the syncytial border, and that adaptive adjustment of K(a) values does not play a role in the maturation of the transfer process. The pregnancy dependent shift to iso-transferrins with a higher degree of glycosylation offers no explanation for the increase of F(e) transfer during pregnancy. Desialylation of the microvillous membranes did not effect the binding parameters of Tf(slow) and Tf(fast), unless desialylation surpassed the 50% level. Then Ka values decreased and TfR number increased (P < 0.05). Desialylation of Tf(slow) and Tf(fast) had no effect on K(a) nor on the number of TfR. The maternal fetal interface therefore lacks an asialo-glycoprotein receptor.

Animals↗

The effect of different iron compounds on transferrin receptor expression in term human cytotrophoblast cells.

During pregnancy, the mother is faced with an increased food demand. A good example of this increased demand is iron (Fe). Fe is needed in all growing cells. During pregnancy, the Fe transport to the fetus increases enormously. This amount can easily induce an Fe deficiency in the mother. Fe supplementation is very important for her, but not for the Fe status of the fetus, which is protected against Fe toxicity as well as deficiency. The placenta seems to be autonomous in Fe uptake. Likely there is a regulation mechanism. The human placenta is hemomonochorial. The cell layer of the fetus in contact with the maternal blood is formed by syncytiotrophoblasts. Fe is transported to the placenta by transferrin. Transferrin binds to a transferrin receptor on the trophoblast membrane and is internalized via an endocytic pathway. During this cycle, Fe is released from transferrin and the transferrin-transferrin receptor complex is recycled to the membrane. Isolated trophoblast cells from term placentas form a syncytium in vitro, and transferrin receptors are expressed. Expression depends on the number of cells in culture, culture time, the amount of Fe available, and the Fe compound. By regulation of the number of transferrin receptors, trophoblasts are able to control their Fe uptake.

Binding Sites↗

Isotransferrins and pregnancy: a study in the guinea pig.

During pregnancy the serum isotransferrin pattern changes towards transferrins with more complex carbohydrate chains. The main pregnancy-related isotransferrin (TfFast) and the most common isotransferrin in the non-pregnant guinea pig (TfSlow) were isolated and characterized. TfSlow had one biantennary- and TfFast one triantennary glycan chain. Is there a functional explanation for this pregnancy-related shift towards more complex glycan chain structure? We studied this question in the context of maternal and fetal erythropoiesis. In vitro incubations of maternal bone marrow cells (MBMC) and fetal erythroid liver cells (FELC) with doubly labelled TfSlow and TfFast revealed only slight differences in affinities for the transferrin receptor. Ka(TfSlow) = 0.17 mumol/l; Ka(TfFast) = 0.15 mumol/l. MBMC and FELC had equal Vmax values both for TfSlow and TfFast. Vmax = 100 Fe atoms/transferrin receptor.hour. Irrespective the cell population TfSlow and TfFast showed equal rates for endo- and exocytosis. kendo. = 0.3750 min-1, kexo. = 0.1450 min-1. It is concluded that the described shift in isotransferrin pattern is not functionally related to maternal or fetal erythropoiesis.

Animals↗

The plain abdominal radiograph in the assessment of constipation.

To investigate the value of the plain abdominal radiograph in the assessment of constipation we prospectively studied 30 patients (20 females, 10 males, mean age 48.6 years, range 21-76 years). These patients underwent the following tests: plain abdominal radiograph in supine position, measurement of stool weight (mean of 5 days) and whole gut transit time (20 radioopaque pellets, fluoroscopy of stools). All patients completed a questionnaire regarding their defaecation characteristics (a.o. average defaecation frequency and faecal consistency). The abdominal films were coded and independently scored for the degree of faecal stasis in ascending, transverse, descending colon and rectosigmoid by four gastroenterologists. To each of these parts of the colon a score of 1 (no faeces) to 4 (loaded with faeces) was assigned. The film scores given by the four observers were significantly correlated (p less than 0.001). Significant correlations were found between the radiograph scores and frequency of defaecation, faecal consistency and stool weight. The strength of these correlations were of the same order of magnitude as those between the other subjective and objective defaecation variables. The scores for the left colon (descending colon and rectosigmoid) showed a better correlation with the other defaecation parameters than the scores for the right colon. It is concluded that in the assessment of constipation a simple plain abdominal radiograph is as reliable as measurement of faecal weight or marker transit and can thus be advocated as the first procedure. When an abdominal radiograph is used for this purpose the stasis in the descending and sigmoid colon provides most information.

Adult↗