830 research outputs found
Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth hormone-releasing hormone neurons of the rat during development
Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a role of interleukin-1beta and interleukin-6
An accumulation of antigen-presenting dendritic cells (DC) in the thyroid
gland, followed by thyroid autoimmune reactivity, occurs in normal Wistar
rats during iodine deficiency, and spontaneously in diabetic-prone
Biobreeding rats. This intrathyroidal DC accumulation coincides with an
enhanced growth rate and metabolism of the thyrocytes, suggesting that
both phenomena are related. Because DC are known to regulate the hormone
synthesis and growth in other endocrine systems (i.e. the pituitary, the
ovary, and the testis), we tested the hypothesis that DC, known for their
superb accessory cell function in T cell stimulation, act as regulators of
thyrocyte proliferation (and hormone secretion). We investigated the
effect of (Nycodenz density gradient) purified splenic DC from Wistar rats
on the growth rate of and thyroid hormone secretion by Wistar thyroid
follicles (collagenase dispersion) in culture. Various numbers of DC and
follicles were cocultured during 24 h. The proliferative capacity of
thyrocytes was measured by adding tritiated thymidine (3H-TdR) and
bromodeoxyuridine, the hormone secretion into the culture fluid was
measured by using a conventional T3 RIA. Furthermore, antibodies directed
against interleukin-1beta (IL-1beta), IL-6, and tumor necrosis
factor-alpha (TNF-alpha) were added to these cocultures to determine the
role of these cytokines in a possible DC regulation of thyrocyte growth.
Cocultures were also carried out in the presence of antimajor
histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular
adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated
antigen-1alpha (LFA-1alpha) antibodies to possibly interfere with
DC-thyrocyte interactions. The addition of DC to thyroid follicles clearly
inhibited their 3H-TdR uptake, particularly at a 10:1 ratio, in comparison
to follicle cultures alone, both under basal conditions and after TSH
stimulation (75 +/- 7% and 49 +/- 11% reduction, respectively, n = 4). The
follicle T3 secretion (after TSH stimulation) was also suppressed by DC in
this system, but to a lesser extent (at best at an 1:1 ratio, 25 +/- 7%
reduction, n = 4). The DC-induced inhibition of thyroid follicle growth
was totally abrogated after addition of anti-IL-1beta antibodies;
anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated
thyrocytes, whereas anti-TNF-alpha demonstrated no effect at all. The
antibodies to MHC and to adhesion molecules had also no effect on this
DC-induced growth inhibition. The effect of the different anti-cytokine
and anti-adhesion antibodies on the T3 secretion from thyroid follicles
was not investigated. The cl
Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response
Thyroid autoimmune reactions start with an accumulation of mainly
dendritic cells in the thyroid. There is increasing evidence that, apart
from being antigen-presenting cells, they are also able to control the
growth and hormone synthesis of neighbouring endocrine cells. The
questions thus arise: are dendritic cells accumulating in the
pre-autoimmune thyroid in response to an altered proliferative or
metabolic activity of thyrocytes, and do cytokines, monocyte
chemoattractants, or both, have a role in their accumulation? We have
investigated these questions in thyrocytes of the biobreeding
diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid
accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP
rats and Wistar rats (controls) were studied from 3 to 20 weeks of age.
Hyperplastic goitre development was studied by assessing the thyroid
weight and by measuring the number of thyrocyte nuclei per 0.01 mm2
thyroid section. In addition, the in situ expression of interleukin-6
(IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic
protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were
studied by immunohistochemistry. The in vitro proliferative capacity of
BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR)
and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and
non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies
consisted of measurement of the production of thyroxine (T4),
triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the
thyroid follicles. BB-DP rats developed a small hyperplastic goitre
between the ages of 9 and 12 weeks. The in vitro proliferative rate of
thyrocytes isolated from hyperplastic BB-DP thyroids was significantly
lower than that of Wistar thyrocytes. This phenomenon also occurred in
follicles isolated from BB-DP rats before hyperplastic goitre development,
which produced significantly less T4, but more T3, than did Wistar
follicles of the same age. At the time of and after hyperplastic goitre
development, BB-DP follicles exhibited altered metabolic behaviour and
produced significantly more T4, but equal amounts of T3 compared with both
Wistar follicles of the same age and follicles of younger BB-DP rats (both
under basal conditions and TSH-st
Consequences of intrauterine growth restriction for the kidney
Low birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. The purpose of this review is to describe the effects of intrauterine growth restriction on the kidney. Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction, leading to a low nephron endowment. The compensatory hyperfiltration in the remaining nephrons results in glomerular and systemic hypertension. Hyperfiltration is attributed to several factors, including the renin-angiotensin system (RAS), insulin-like growth factor (IGF-I) and nitric oxide. Data from human and animal studies are presented, and suggest a faltering IGF-I and an inhibited RAS in intrauterine growth restriction. Hyperfiltration makes the kidney more vulnerable during additional kidney disease, and is associated with glomerular damage and kidney failure in the long run. Animal studies have provided a possible therapy with blockage of the RAS at an early stage in order to prevent the compensatory glomerular hyperfiltration, but this is far from being applicable to humans. Research is needed to further unravel the effect of intrauterine growth restriction on the kidney
Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells
From the biobreeding-diabetic prone (BB-DP) rat, an animal model for
endocrine autoimmunity, phenotype and function of splenic dendritic cells
(DC) were studied. Furthermore, the suppressive effect of peritoneal
macrophages (pMphi) from the BB-DP rat in the MLR was investigated. Lower
numbers of splenic DC were isolated from BB-DP rats than from control
Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower
surface MHC class II expression (and in preliminary data, a lower CD80
expression), ingested more bacteria, and had a lower stimulatory potency
in the syngeneic (syn)MLR as compared with control DC. During disease
development, the MHC class II expression further decreased, and a low
stimulatory activity became evident in the allogeneic (allo)MLR. With
regard to the expansion of suppressor/regulatory T cells, a lower
percentage of RT6+ T cells but higher percentages of CD45RClow T cells
were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the
CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a
relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident
pMphi isolated from BB-DP or Wistar rats were equally effective in
suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP
rat have a lower accessory cell function already at young age, before the
development of disease, and expanded different subsets of
effector/suppressor T cells in vitro as compared with those from Wistar
rats. The dysfunction of DC from BB-DP rats is likely to be caused by
their relative immaturity as indicated by their low class II and
costimulatory molecule expression and relatively high phagocytic activity
School functioning in 8- to 18-year-old children born after in vitro fertilization
The aim of this study was to examine the school
functioning of 8- to 18-year-old children born after in vitro
fertilization (IVF). We compared 233 children born after
IVF to 233 matched control children born spontaneously
from parents with fertility problems on measures of
education level, general cognitive ability, school performance
(need for extra help, repeating a grade, special
education), and rates of learning and developmental
disorders. No differences were found between IVF and
control children on these measures of school functioning.
More than 60% of adolescents at secondary school attended
high academic levels (with access to high school or
university). We conclude that children and adolescents
born after IVF show good academic achievement and
general cognitive ability. They do not experience any more
educational limitations than the naturally conceived children
and adolescents of the control group. The tendency of
reassuring school functioning already found in younger IVF
children has been shown to continue at secondary school
age
Body size in five-year-old twins: Heritability and comparison to singleton standards
The aim of this study is to examine causes of individual differences in height, weight and body mass index (BMI) in 5-year-old children registered with the Netherlands Twin Register. In addition, we examine whether the results of twin studies can be expanded to the singleton population by comparing the data from twins to Dutch reference growth data and by looking at the twins' target height, which was derived from parental height. For 2996 5-year-old twin pairs, information on height and weight and on parental height was available. Univariate and bivariate genetic analyses of height and weight and univariate analyses of BMI were conducted. In order to compare the twins to the singleton population, standard deviation scores (SDS) for height, BMI and target height were calculated based on Dutch reference growth charts for the general population from 1997. Genetic influences were an important source of variation in height, weight and BMI and the main source of covariation between height and weight. Additive genetic factors accounted for 69% and 66% of the individual differences in height in boys and girls, respectively. For weight, heritability estimates were 59% in boys and 78% in girls and for BMI 34% and 74%. The influence of common environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and 12% in boys and girls. The bivariate model showed a large overlap between the genes influencing height and weight. Genes explain 78% (in boys) and 76% (in girls) of the covariance between weight and height. At the age of 5 years, female twins were as tall as singleton children, while male twins were shorter than singletons. For both boys and girls, however, mean height SDS was 0.6 standard deviation scores below the mean target height. All twins had lower BMI than singletons. Twins grow fairly well compared to singletons, but they grow below their target height. This may be due to the above average height of twin parents
The association between low birth weight and high levels of cholesterol is not due to increased cholesterol synthesis or absorption: analysis in twins
Low birth weight may be associated with high levels of cholesterol in later life through genetic factors that affect both birth weight and cholesterol metabolism. Alterations in cholesterol synthesis and absorption may play an important role in this association. We examined birth weight and plasma ratios of a precursor of cholesterol, lathosterol (an estimate of cholesterol synthesis), and plant sterols, campesterol and �-sitosterol (estimates of cholesterol absorption), to cholesterol in 53 dizygotic and 58 monozygotic adolescent twin pairs. After adjustment for current weight, birth weight was not associated with the ratios of lathosterol, campesterol, and �-sitosterol either in the overall sample [�0.07 �mol/mmol/kg (95 % confidence interval: �0.11 to 0.25), p � 0.5; �0.02 �mol/mmol/kg (�0.33 to 0.37), p � 0.9; and �0.04 �mol/mmol/kg (�0.23 to 0.15), p � 0.8, respec-Low birth weight is associated with an increased risk o
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