Pulmonary embolism--a rare complication of Schimke immunoosseous dysplasia.
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Child, Preschool↗
Biomedical subjects
J Dötsch
Publications and source records attributed to J Dötsch.
Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat.
Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation of acute mesangioproliferative GN in former IUGR rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. Litter size was reduced to six male neonates in low protein animals (LP) and normal protein animals (NP). At 8 weeks GN was induced by injection of an anti-Thy-1.1 antibody. Rats were killed on days 4 and 14 after induction of GN and kidneys were investigated for inflammation and sclerosis using real-time polymerase chain reaction and histological methods. On day 4 after induction of GN, LP animals showed more glomerulosclerosis and tubulointerstitial lesions. On day 14, inflammatory markers (expression of monocyte chemoattractant protein 1, osteopontin, tumor necrosis factor and interleukin-6), extracellular matrix accumulation and markers of sclerosis (plasminogen activator inhibitor-1 expression, transforming growth factor-beta1 expression, score for glomerulosclerosis, glomerular deposition of collagen I and collagen IV) were more severe in LP animals. Some degree of induction of inflammatory and profibrotic markers was also present in non-nephritic LP animals. However, these rats did not display marked glomerulosclerosis or interstitial fibrosis. We conclude that after IUGR inflammatory damage is aggravated and the reparation of the kidney is impaired during the course of acute mesangioproliferative GN, leading to more sclerotic lesions.
Animals↗
No evidence for angiotensin type 2 receptor gene polymorphism in intron 1 in patients with coarctation of the aorta and Ullrich-Turner syndrome.
In male patients with congenital anomalies of the kidney and urinary tract, an increased incidence of a polymorphism in the angiotensin type 2 receptor gene (AT2R) has been identified. The AT2R has been shown to be involved in apoptosis, particularly during embryogenesis. The aim of this study was to examine the A-->1675G transition polymorphism in intron 1 of the AT2R gene that is located on the X chromosome in patients with coarctation of the aorta (CoA) with and without Ullrich-Turner syndrome (UTS). Screening of DNA samples was performed with restriction fragment length polymorphism analysis. Ninety-seven patients with CoA, 28 girls with UTS, 10 girls with UTS and CoA, and 96 control individuals were studied. There was no significant difference in the distribution of A and G-genotypes in any of the patient groups compared to controls. An A-->1675G transition in the AT2R gene seems not to be involved in the pathogenesis of aortic coarctation.
Aortic Coarctation↗
Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation.
The microfibrillar protein fibrillin-1 is present in many organs, including the vasculature, eye, and dermis, and is thought to convey structural anchorage and elastic strength. Fibrillin-1 is also a component of the mesangial matrix. To assess the functional relevance of fibrillin-1 for cell-matrix interactions in the glomerulus, we studied the attachment, spreading, migration and proliferation of mesangial cells on fibrillin-1 and the regulation of fibrillin-1 in experimental anti-Thy1.1 nephritis displaying mesangial cell migration and proliferation in vivo. During the acute phase of experimental Thy1.1 nephritis, glomerular fibrillin-1 messenger ribonucleic acid expression and protein immunoreactivity were significantly induced as compared to controls. In a hexosaminidase-based adhesion assay, mesangial cells showed concentration-dependent attachment to fibrillin-1, similar to what was observed for fibronectin. The cell attachment was Arg-Gly-Asp dependent. Further, fibrillin-1 significantly promoted spreading and focal contact formation detected by immunostaining for vinculin. Mesangial cell migration, assessed by a transmigration assay, and proliferation, measured by a 5-bromo-2'-deoxy-uridine incorporation assay, were augmented by fibrillin-1. In diabetic mice underexpressing fibrillin-1, glomerular cell proliferation, determined by counting proliferating cell nuclear antigen-positive cells in renal sections, was significantly lower than in diabetic control mice. We conclude that fibrillin-1 promotes mesangial cell attachment, spreading, migration, and proliferation. We speculate that fibrillin-1 may thus contribute to mesangial hypercellularity during glomerular disease.
Animals↗
Absence of exercise-induced leptin suppression associated with insufficient epinephrine reserve in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency suffer from glucocorticoid and mineralocorticoid deficiency. They have insufficient epinephrine reserves and increased basal leptin levels and are often insulin resistant. In healthy subjects, an inhibitory effect of acute catecholamine elevation on the leptin plasma concentrations has been reported. However, it is not yet known how leptin levels respond to exercise in CAH patients. METHODS: We performed a cycle ergometer test in six CAH patients to measure the response of plasma leptin, glucose and the catecholamines, epinephrine (E) and norepinephrine (N), as well as their respective metabolites, metanephrine (M) and normetanephrine (NM), to intense exercise. RESULTS: Baseline leptin concentrations in CAH patients were not different from those of controls. Leptin levels decreased significantly with exercise in healthy controls, whereas they remained unchanged in CAH patients. In contrast to controls, CAH patients showed no rise of plasma glucose. Basal and stimulated E and M levels were significantly lower in CAH patients compared to controls. Baseline and stimulated N and NM levels were comparable, showing a significant rise after exercise. Peak systolic blood pressure and peak heart rate in both groups were comparable. CONCLUSION: CAH patients do not manifest exercise-induced leptin suppression. The most probable reason for this is their severely impaired epinephrine stress response. In addition, epinephrine deficiency is leading to secondary changes in various catecholamine dependent metabolic pathways, e. g., energy balance. Although obvious clinical sequelae are so far unknown, the catecholamine-deficient state and the resulting hyperleptinemia might contribute to the severity of the disease in CAH.
Adolescent↗
Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor.
OBJECTIVE: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. MATERIALS AND METHODS: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/- 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. RESULTS: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance. CONCLUSIONS: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.
Adolescent↗
Serum cortisol and cortisone levels in newborns with congenital adrenal hyperplasia before the start of therapy.
Sodium loss in infants with salt wasting (SW) congenital adrenal hyperplasia (CAH) does usually not occur within the first week of life. We hypothesized that sufficient mineralocorticoid activity might by temporarily maintained by still appropriate concentrations of cortisol. Plasma samples were obtained from 15 infants with SW-CAH before the onset of sodium loss, 17 patients with simple virilizing (SV)-CAH and 28 healthy infants under 14 days of age. Plasma aldosterone concentrations were significantly lower in SW-CAH infants than in SV-CAH patients and in healthy neonates. Plasma cortisol levels and cortisol/cortisone (F/E) ratios in SW-CAH patients were almost the same as in the SV-CAH and control group. While declining plasma aldosterone levels precede the onset of SW in CAH patients, plasma cortisol concentrations are kept normal in SW-CAH infants, temporarily maintaining sufficient mineralocorticoid activity.
Adrenal Hyperplasia, Congenital↗
[Denys-Drash syndrome. Experience gathered in Erlangen illustrated by two case reports].
Denys-Drash syndrome is a rare symptom complex associated with obligatory childhood nephrotic syndrome, male pseudohermaphroditism, and Wilms' tumor. The etiology of Denys-Drash syndrome is attributed to a mutation of the WT1 gene. We report on two cases of Deny-Drash syndrome confirmed by genetic testing. Rapidly evolving terminal renal insufficiency was detected in both patients necessitating bilateral nephrectomies with prophylactic intent. In one of the patients, a Wilms' tumor had already been verified in one kidney so that chemotherapy had to be initiated.The risk of Wilms' tumor is very high in patients with a WT1 mutation, which leads to the need for removal of both kidneys during or before transplantation. It would be important to perform a diagnostic work-up for WT1 gene mutation in children who develop renal failure in the 1st year of life.
Denys-Drash Syndrome↗
Maturation of the expression of adrenomedullin, endothelin-1 and nitric oxide synthases in adipose tissues from childhood to adulthood.
OBJECTIVE: To investigate if the vasoactive systems adrenomedullin (ADM) and endothelin-1 (ET-1) are expressed in human adipose tissues in children and in adults and to determine the distribution pattern of nitric oxide synthases (NOS). DESIGN AND SUBJECTS: Subcutaneous, mesenterial and omental adipose tissue specimens taken from 15 children (age 0.5-16 y, median 6 y) and 13 adults (age 43-79 y, median 60 y) were analyzed. The body mass indices (BMI) were within the normal range. All patients were normotensive, and were free of infectious disease, and metabolic or endocrine disorders. The specimens were taken during elective laparotomies after informed consent was obtained. MEASUREMENTS: ADM, ET-1, the endothelial (eNOS) and inducible (iNOS) NOS as well as two housekeeping genes were measured using quantitative real-time PCR. RESULTS: ADM gene expression was found at all locations, and was significantly higher in adults than in children (P<0.01 for subcutaneous and omental adipose tissue). ET-1 mRNA was distributed in a similar way, showing significantly higher levels in the subcutaneous and mesenterial adipose tissue sections of adults than of children. For eNOS, the adult patients exhibited a higher expression in subcutaneous and mesenterial specimens than the children (P<0.01 and P<0.05). The iNOS mRNA was increased in subcutaneous, mesenterial and omental adipose tissues in the adult cohort compared to the children's levels (P<0.05 to P<0.01). CONCLUSION: Human adipose tissue expresses many vasoactive substances including ADM and ET-1. In adults, the amounts of ET-1 and ADM as well as eNOS and iNOS mRNA are higher, possibly due to a physiological upregulation with increasing age. Although there are differences depending on the locations of the tissues, the expression patterns of the antagonists ADM and ET-1 are quite similar, indicative of a well-balanced pattern of local gene expression in normotensive individuals with normal body weight.
Adipose Tissue↗
[Early factors influencing body weight and prevalence of overweight in 4610 children prior to school entry in the Erlangen District (Northern Bavaria)].
OBJECTIVE: Childhood obesity is a growing health problem among German children. Birth weight is considered to have a major influence on the course of postnatal weight. The present study investigates the relation between birth weight and body weight at health examination prior to school entry. We tested other parameters influencing childhood obesity, and hypothesized that within a 5-year interval the prevalence of obesity in children has increased significantly. METHODS: Our study is based on the retrospective analysis of the school enrolment health examinations of 4610 children in North Bavaria, e. g. the town Erlangen and administrative district Erlangen-Hoechstadt in 1995/96 and 2000/01. RESULTS: A higher birth weight was associated with a higher weight and BMI at school entry examination (p < 0.0001). An increased birth weight is therefore a considerable risk factor for later overweight in childhood. Hypotrophic newborn, however, gain less weight and exhibit a lower BMI in our study group. In general, boys were significantly heavier than girls (p < 0.001). Children of foreign origin were heavier and had a higher BMI corrected for age than German pupils but they were also 0.07 years older. Our regional survey revealed local differences in the prevalence of obesity. Comparing the cohorts 1995/96 and 2000/01 at school entry, a significant increase of BMI in the latter was found (p < 0.0001). CONCLUSIONS: A highly significant increase in the prevalence of infantile overweight has to be faced. Early prevention of childhood obesity is therefore mandatory to avoid the complications and higher morbidity.
Age Factors↗
Salivary leptin induces increased expression of growth factors in oral keratinocytes.
We investigated the influence of salivary leptin, purified by affinity chromatography, on the proliferation of human oral keratinocytes. Furthermore we determined the time- and dose-dependency of the incubation with salivary leptin on the production of epidermal growth factor (EGF) and keratinocyte growth factor (KGF), which are growth factors relevant to keratinocyte proliferation. The analysis was performed both intra- and extracellularly. The relationship between the three cytokines in cell proliferation was studied by successive blocking with specific antibodies. The incubation of oral keratinocytes with recombinant and native leptin led to a significantly increased, dose-dependent cell proliferation (P<0.001). A further significant increase in proliferation was observed after incubating the cells with sterile filtered saliva (P<0.001). The increase in proliferation could not be observed by simultaneous incubation with salivary leptin and specific antibodies against either leptin or KGF (P<0.001). We found a significant dose-dependency between leptin incubation and production of KGF and EGF at the RNA and protein level. Both cytokines were expressed intracellularly and released into the culture medium, where they could be quantified by ELISA. Furthermore, there was a dose- and time-dependent increase in the phosphorylation of STAT-1 and STAT-3, indicating that Ob-R(b) (the long form of the leptin receptor) expressed by the keratinocytes is functional. It is conceivable that the leptin-induced proliferation in keratinocytes is mediated by this signalling pathway. This is the first study to show a physiological role of salivary leptin as a growth factor for keratinocyte proliferation in the oral cavity. We could demonstrate its influence on the production of other growth factors essential for this proliferative effect. Based on the findings of our study we assume an important role for salivary leptin in wound healing within the vulnerable oral cavity.
Cell Proliferation↗
Endogenous retroviral syncytin: compilation of experimental research on syncytin and its possible role in normal and disturbed human placentogenesis.
Placental syncytin was first described in the year 2000 as a fusogenic glycoprotein originally derived from a human endogenous retroviral envelope gene. Although the presence of stable integrated retroviral elements within the human genome has been known for many years, their biological significance is still obscure and has usually been designated as irrelevant or even harmful. Syncytin, however, demonstrates tissue-specific expression and distinctive receptor interaction during trophoblast cell differentiation and syncytium formation. These findings indicate an involvement of syncytin in the development of the human placenta. Disturbances in placental architecture leading to severe placental dysfunction, such as pre-eclampsia, may therefore be discussed as a consequence of an altered syncytin system. We evaluate the hypothesis that syncytin is essential for human placenta formation and may also have played an important role in human placental evolution.
Amino Acid Transport System ASC↗
Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery pressure.
The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet model. Animals received either aerosolised ADM (50 ng.kg(-1).min(-1), ADM, n=6), or aerosolised normal saline solution (control, n=6). Aerosol therapy was performed for a 2 h treatment period followed by a 22 h observation period. Ventilator settings were adapted to keep arterial oxygen tension and carbon dioxide arterial tension between 13.3-14.6 kPa and 4.9-5.7 kPa, respectively. Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the control group (end-point median 24 h after therapy start: DeltaMPAP -14.0 versus -8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic arterial pressure (MAP) was not significantly different between the groups (end-point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and endothelin-1 protein expression in pulmonary arteries was reduced compared with controls (median semi-quantitative immunhistochemical score: ADM 0.21, control 0.76). Aerosolised adrenomedullin significantly reduced mean pulmonary artery pressure independently of arterial oxygen tension.
Administration, Inhalation↗
Comparison of leptin gene expression in different adipose tissues in children and adults.
OBJECTIVE: Adipose tissue displays depot-specific metabolic properties and a predominant gene expression of leptin in subcutaneous tissue. The aim of the study was to evaluate leptin mRNA expression in various adipose tissues and to relate it to plasma leptin concentrations. Furthermore, developmental changes in leptin gene expression from childhood to adulthood were examined. DESIGN AND METHODS: Thoracic subcutaneous and intrathoracic adipose tissue specimens were obtained in 22 adults (51-81 years) and 23 children (0.1-17 years) undergoing cardiac surgery, and abdominal subcutaneous, omental and mesenterial fat specimens were collected from 21 adults (38-79 years) and 22 children (0.2-17 years) before abdominal surgery. Preoperative plasma leptin concentrations were measured by RIA. Leptin mRNA expression was quantified by TaqMan real-time PCR. RESULTS: In adults, there was no difference between leptin gene expression in subcutaneous and intrathoracic fat, whereas in children leptin mRNA expression was significantly higher in subcutaneous adipose tissue. In omental fat, leptin mRNA levels were significantly lower compared with subcutaneous and mesenterial sites in both children and adults. Adults revealed a significantly higher leptin gene expression in subcutaneous, omental and mesenterial adipose tissues than children. Subcutaneous and omental leptin gene expression are independent factors for plasma leptin concentrations in children and adults. CONCLUSION: Leptin is differentially expressed at different adipose tissue sites, a situation which is even more pronounced in children. There is a developmental increase in leptin mRNA expression in adipose tissue during childhood, reaching maximal capacity in adulthood.
Abdomen↗
Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo: up-regulation of vascular endothelial growth factor in clinically relevant hypoxic ischemia in birth asphyxia.
OBJECTIVE: We investigated the influence of acute hypoxia on the placental vascular endothelial growth factor system in vitro and in vivo in acute birth asphyxia compared with pregnancies that were complicated by preeclampsia and with healthy control subjects. STUDY DESIGN: Messenger RNA levels for vascular endothelial growth factor, flt-1, and KDR were measured by TaqMan real-time polymerase chain reaction in human placental choriocarcinoma cells (BeWo) that were exposed to hypoxia (1% oxygen, 5% carbon dioxide, 94% nitrogen) and in placental tissue of neonates with birth asphyxia (n = 20), newborn infants of mothers with preeclampsia (n = 20), and gestational age-matched control subjects. Immunhistologically, placental vascular endothelial growth factor protein expression was compared among the groups. RESULTS: In BeWo cells, vascular endothelial growth factor, flt-1 and KDR messenger RNA increased in a time-dependent manner in response to hypoxia. In vivo, vascular endothelial growth factor/beta-actin and KDR/beta-actin messenger RNA were significantly higher in placental tissue of newborn infants with severe hypoxic-ischemic encephalopathy than with newborn infants with mild or no hypoxic-ischemic encephalopathy and control subjects. In chronic placental hypoxia (preeclampsia), vascular endothelial growth factor and both receptors were found to be up-regulated. Increased placental vascular endothelial growth factor expression was confirmed by immunohistologic examination. CONCLUSION: The vascular endothelial growth factor system is up-regulated in response to placental hypoxia and is assumed to be a potential early indicator of severe birth asphyxia.
Actins↗
A new missense mutation of the vasopressin-neurophysin II gene in a family with neurohypophyseal diabetes insipidus.
OBJECTIVE: Autosomal dominant familial neurohypophyseal diabetes insipidus is a rare disorder characterized by polydipsia and polyuria. We present the results of the molecular analysis of the AVP-NPII gene of a German kindred. METHODS: All three exons of the gene were amplified by polymerase chain reaction and sequenced. RESULTS: In 7 affected individuals a new missense mutation (1770G > T) in exon 2 was found predicting a cysteine to phenylalanine substitution at codon 58 in the neurophysin II domain (NPII). CONCLUSION: As a result of this mutation a cysteine residue is exchanged, which is involved in a disulfide bond with cysteine 44 of the NPII moiety, hypothesizing that the resulting misfolded protein may lead to chronic neurotoxicity by accumulation of these products in the endoplasmatic reticulum.
Adolescent↗
Nitric oxide stimulates adrenomedullin secretion and gene expression in endothelial cells.
Adrenomedullin, a peptide with vasorelaxant activity, stimulates nitric oxide (NO) synthesis. We tested whether or not NO regulates the function of the adrenomedullin system. Human umbilical vein endothelial cells (HUVEC) were incubated with the NO donors sodium nitroprusside (SNP), morpholinosydnonimine (SIN-1) and the phospodiesterase V inhibitor zaprinast. In HUVEC, adrenomedullin concentration in the supernatant was measured by radioimmunoassay and mRNA expression was studied by Northern blot and competitive quantitative PCR. SNP, SIN-1, and zaprinast (100 micromol/l each) significantly increased adrenomedullin concentration in the supernatant of HUVEC twofold. The same concentrations increased adrenomedullin mRNA expression four- to tenfold. Similar results were obtained by both quantitative PCR and Northern blot. Thus, NO donor exposure in vitro increases both adrenomedullin secretion and mRNA expression in a dose-dependent manner.
Adrenomedullin↗
Spontaneous nocturnal leptin secretion in children with myelomeningocele and growth hormone deficiency.
OBJECTIVE: To examine the spontaneous leptin secretion in patients with myelomeningocele (MMC) and growth hormone deficiency (GHD). METHODS: Serum leptin levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 +/- 0.5 years), 10 patients with idiopathic GHD (IGHD; CA 7.6 +/- 0.7 years) and 12 children with normal variant short stature (NVSS; CA 7.6 +/- 0.5 years). Mean BMI (kg/m(2)) values of the groups did not differ significantly. Nocturnal leptin levels were analyzed over 10 h (blood samples every 20 min) and measured by specific radioimmunoassay. RESULTS: Mean leptin concentrations did not correlate with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was significantly different to those of children with IGHD and NVSS. Morning leptin levels did not decline as observed in both other groups. CONCLUSION: Since all groups were matched for BMI values, we suggest a hypothalamic dysregulation of leptin secretion in MMC patients.
Body Composition↗