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W Rascher

Publications and source records attributed to W Rascher.

At least 19 recordsLinked to original sources
PubMed2007

[Urinary tract infections in infants and children -- a consensus on diagnostic, therapy and prophylaxis].

Urinary tract infections (UTI) are among the most common bacterial infections in infants and children. The early diagnosis of a pyelonephritis and its rapid, calculated antibacterial therapy are decisive for the prognosis. Urogenital anomalies, renal damage and bladder dysfunction may influence the risk of recurrences of UTI and pyelonephritic scarring. Diagnostic strategies therefore should focus on their early recognition. Pediatricians, urologists and infectiologists are cooperating in diagnostic, therapy and prophylaxis of UTI. The aim of the interdisciplinary consensus presented was to work out a concept which may help to manage childhood UTI in daily practice.

Administration, Oral↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

Leptin and ghrelin expression in adipose tissues and serum levels in gastric banding patients.

BACKGROUND: To determine how leptin and ghrelin are expressed in the adipose tissues of obese adults undergoing gastric banding (LAGB), and to correlate tissue expression with serum concentrations and parameters of the metabolic syndrome. MATERIALS AND METHODS: A cross-sectional analysis of 92 patients: 61 obese patients with a body mass index (BMI) 49.2 +/- 1 kg m(-2) received LAGB, 20 patients underwent band exchange (BMI, 36.6 +/- 1.4 kg m(-2)) and 11 adult patients (BMI, 24.3 +/- 0.6 kg m(-2)) with fundoplication served as controls. Clinical data such as BMI and blood pressure were evaluated along with subcutaneous and visceral adipose tissue gene expression and fasting levels of leptin and ghrelin. Tissue transcripts were measured using real-time PCR, serum protein concentrations radio-immunologically. RESULTS: Leptin gene expression was highest in the primary LAGB group and more pronounced in subcutaneous fat in both sexes (P < 0.0001). Serum leptin concentrations were highest in the LAGB group (P < 0.001), whereby women exhibited higher serum levels than men. Leptin concentrations correlated positively to expression in subcutaneous fat (P < 0.0001), and leptin expression was also correlated to BMI and systolic blood pressure. We detected ghrelin gene expression in both types of fat. The ghrelin mRNA amounts in adipose tissues were similar in both sexes and comparable within groups; serum concentrations were lower in patients with primary LAGB than in controls (P < 0.05). CONCLUSIONS: Human adipose tissue expression of leptin is weight-course dependent and ghrelin is constitutional. Serum levels of leptin, but not of ghrelin, are indicative of an adaptive pattern of local gene expression in obese subjects undergoing weight reduction.

Adipose Tissue↗
PubMed2005

The 'accelerator hypothesis': relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether either increased weight or BMI are associated with the earlier manifestation of type 1 diabetes mellitus in children. METHODS: We evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990-2003 in 116 pediatric clinics throughout Germany and Austria. RESULTS: Patients were divided into four groups according to age (0-4.9 years, 5-9.9 years, 10-14.9 years and 15-20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0-4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5-9.9-years and the 10-14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients' BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of -0.0248 (95% CI -0.0294 to -0.0202, p<0.0001). CONCLUSIONS/INTERPRETATION: A higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes.

Adolescent↗
PubMed2005

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↗
PubMed2005

[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↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

Asymmetric multiplex-polymerase chain reaction - a high throughput method for detection and sequencing genomic fusion sites in t(4;11).

Chromosomal translocations are a characteristic feature of leukaemia and other malignant diseases. As clonal markers, they can be applied to identify and quantify the number of malignant cells by polymerase chain reaction (PCR) methods. The translocation t(4;11) is present in >60% of infant leukaemia. In order to facilitate the sequencing of chromosomal breakpoints, we developed an optimized set of 30 PCR primers and a new approach, designated as asymmetric multiplex PCR (am-PCR). Due to the high number of primers, small breakpoint-spanning DNA fragments are obtained in one nested multiplex PCR reaction. All PCR products contain an identical binding site for the initiation of direct sequencing. By using am-PCR, the translocation t(4;11) was examined in bone marrow and blood samples from children with acute leukaemia. Compared with previously described methods for the determination of genomic breakpoints, am-PCR may be advantageous with regard to its simplicity and rapidity. Breakpoint-spanning sequences were also evaluated with regard to their applicability as unique clonal markers to design primers and probes for minimal residual disease quantification by real-time PCR. This approach can easily be adapted to other chromosomal translocations in malignant diseases for the detection and analysis of clone-specific DNA markers.

Chromosome Breakage↗
PubMed2004

Efficient gene delivery with serum into human cancer cells using targeted anionic liposomes.

Success of human gene therapy depends upon the development of delivery vehicles or vectors, which can selectively deliver therapeutic genes to target cells with efficiency and safety. Previous studies have shown an efficient, systemic trans-gene expression in many cell lines (in vitro) by using an anionic liposomal vector, based on the composition of retroviral envelopes (artificial viral envelopes, AVEs). The AVE-liposomes and their complexes with plasmid (DNA) were characterized according to zeta potential measurements and transmission electron microscopy (TEM). We successfully demonstrated that AVE liposomes, dispersed in 10% serum-containing growth medium, efficiently delivered plasmid DNA to HuH-7 (human hepatoma cell line) cells. We assessed the utility of liver-targeted vesicles as a drug/gene delivery system for the treatment of liver diseases. We found that small unilamellar AVE vesicles containing 15 mol% digalactosyl diglyceride (DGDG) are efficiently targeted to the liver via the hepatic asialoglycoprotein receptor.

Carbohydrates↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

Endocrine effects of food intake: insulin, ghrelin, and leptin responses to a single bolus of essential amino acids in humans.

BACKGROUND: This study deals with the physiological effects of an oral bolus of essential amino acids (AA) on the secretion of insulin, ghrelin and leptin in fasting humans. METHODS: 12 healthy adults (age 18-40 years, 10 males, 2 females, body mass index 18.0-23.5 kg/m(2)) were included in our study. Seven fasted volunteers consumed an AA mixture (0.35 g/kg BW), 5 served as controls. Serum AA, glucose, albumin, urea and hormones were measured at 0, 15, 30 min and thereafter at 30-min intervals up to 5 h. RESULTS: Glucose, albumin and urea remained constant, peak AA concentrations were achieved at 30 min for methionine (Met), at 60 min for all other AA. The insulin peak (533% compared to basal level, p < 0.01) at 30 min was earlier than the peaks of all AA except for Met. Ghrelin showed a continuous rise towards the end of the experiment leading to a 3-fold increase in initial concentrations in the study group (p < 0.001), significantly higher than in the control group (p < 0.05). In contrast, both groups exhibited almost constant leptin concentrations. CONCLUSION: Our data indicate that an oral low-dose AA bolus not only causes considerable hyperaminoacidemia and hyperinsulinemia but is also accompanied by an increased ghrelin secretion in fasted humans. This may be a specific effect or may be due to the fact that a single bolus of AA is not a sufficient stimulus to induce satiety. Leptin, however, is not a key mediator in this setting.

Administration, Oral↗
PubMed2003

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↗