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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 110 (1981), S. 341-344 
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 12 (1996), S. 11-18 
    ISSN: 1437-9813
    Keywords: Key words RET ; RET proto-oncogene ; Hirschsprung’s disease ; Multiple endocrine neoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  RET gene alterations as disease-causative mutations have been demonstrated in five different disease entities: Hirschsprung’s disease (HD); papillary thyroid carcinoma; and three types of inherited cancer syndromes: multiple endocrine neoplasia (MEN) 2A, MEN 2B, and familial medullary thyroid carcinoma. RET is expressed during embryogenesis in a temporally and spatially regulated manner, and plays an important role in the normal development of a variety of cell lineages, particularly in the establishment of the enteric nervous system. RET mutations observed in patients with HD are scattered along the gene without any hot spots, and possess a loss-of-function effect. RET mutations are detected with a higher incidence among familial cases (50%) than sporadic cases (15% – 20%), and are more closely associated with long-segment HD than short-segment disease. In contrast to HD mutations, missense mutations observed in MEN 2 syndromes occur at specific codons, and gene rearrangements are characteristic in papillary thyroid carcinoma. Both missense mutations and gene rearrangements act in a dominant fashion, and cause constitutive phosphorylation on the tyrosine of RET and highly enhance RET kinase activity, leading to transforming or oncogenic activity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1437-9813
    Keywords: Congenital diaphragmatic hernia ; Newborn ; Pulmonary hypertension ; Calcitonin gene-related peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A congenital diaphragmatic hernia (CDH) model was induced in pregnant rats following administration of 100 mg nitrofen. The fetuses were stored and fixed in Bouin's solution for 24 h after caesarean section at term. After fixation, the lungs were dissected out. Immunostaining of the CDH lungs and controls with rabbit anti-rat calcitonin gene-related peptide (CGRP) antibody at “optimal” and “supraoptimal” dilution levels was obtained by examining the intensity of staining with a series of dilutions of the antisera from 1: 1,000 to 1: 20,000. Supraoptimal dilution detects variations in antigen concentration that may be masked if the routine optimal dilution is used. Immunostaining of the lung by antisera to platelet-derived growth factor (PDGF) and alpha-smooth-muscle actin (ASMA) was performed to examine vascular remodelling. The number of CGRP-immunoreactive cells was significantly (P 〈0.001) greater in the lungs of CDH rats (n = 26) (0.74 +-0.19 NEB [neuroepithelial bodies]/mm2; mean +- SEM) compared with controls (n = 21) (0.30+-0.16 NEB/mm2) seen at supraoptimal dilution (1:20,000). Since CGRP is a vasodilator, this could have important implications in the development of pulmonary hypertension. The pattern of ASMA and PDGF immunostaining was similar in CDH lungs and controls, and therefore, vascular remodelling is not a feature of CDH lungs in fetuses delivered by caesarean section and not exposed to hypoxia.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 12 (1996), S. 11-18 
    ISSN: 1437-9813
    Keywords: RET ; RET proto-oncogene ; Hirschsprung's disease ; Multiple endocrine neoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract RET gene alterations as disease-causative mutations have been demonstrated in five different disease entities: Hirschsprung's disease (HD); papillary thyroid carcinoma; and three types of inherited cancer syndromes: multiple endocrine neoplasia (MEN) 2A, MEN 213, and familial medullary thyroid carcinoma. RET is expressed during embryogenesis in a temporally and spatially regulated manner, and plays an important role in the normal development of a variety of cell lineages, particularly in the establishment of the enteric nervous system.RET mutations observed in patients with HD are scattered along the gene without any hot spots, and possess a loss-of-function effect.RET mutations are detected with a higher incidence among familial cases (50%) than sporadic cases (15%–20%), and are more closely associated with long-segment HD than short-segment disease. In contrast to HD mutations, missense mutations observed in MEN 2 syndromes occur at specific codons, and gene rearrangements are characteristic in papillary thyroid carcinoma. Both missense mutations and gene rearrangements act in a dominant fashion, and cause constitutive phosphorylation on the tyrosine of RET and highly enhance RET kinase activity, leading to transforming or oncogenic activity.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 12 (1996), S. 19-23 
    ISSN: 1437-9813
    Keywords: Key words Hirschsprung’s disease ; Endothelin-B receptor gene ; Endothelin-3 gene ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have recently been recognized as susceptibility genes for Hirschsprung’s disease (HD). Novel EDNRB mutations have been detected in non-syndromic HD patients with heterozygous forms, and homozygous mutations of the EDNRB or the EDN3 genes have been reported in HD patients associated with type 2 Waardenburg syndrome. These observations confirm that impaired function of the endothelin-B receptor or endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations appear to be associated with short-segment HD, in contrast to RET mutations, which are found mainly in long-segment aganglionosis.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 13 (1998), S. 253-255 
    ISSN: 1437-9813
    Keywords: Key words Infantile hypertrophic pyloric stenosis ; Insulin-like growth factor-I ; mRNA ; In-situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The etiology of infantile hypertrophic pyloric stenosis (IHPS) is unknown. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that elicits various biological activities (cellular growth, replication, and differentiation) by binding to its receptors. IGF-I has been suggested to play an important role in both gastrointestinal (GI) maturation and smooth-muscle-cell (SMC) hypertrophy. Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients (age range 14–64 days, mean 28.1 days) at pyloromyotomy and from 8 age-matched controls (15–60 days, mean 33.8 days) without GI disease at autopsy. In-situ hybridization was performed using an IGF-I-specific and digoxigenin (DIG)-labeled oligonucleotide probe and visualized by nitroblue tetrazolium staining. In normal controls, IGF-I mRNA expression was absent or weak in both circular and longitudinal smooth-muscle layers of pyloric muscle. In contrast, the pyloric muscle in IHPS patients demonstrated strong IGF-I mRNA expression in the circular smooth-muscle layer and moderate expression in the longitudinal smooth-muscle layer. The increase in IGF-I mRNA in pyloric muscle in IHPS suggests that SMCs are actively synthesizing IGF-I, contributing to the development of pyloric muscle hypertrophy.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1437-9813
    Keywords: Key words Hirschsprung's disease ; Neuromuscular junction ; Synapse-associated proteins ; Neurotransmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined immunohistochemically the expression and localisation of synapse-associated proteins, syntaxin (SNT) and synaptotagmin (STG) in the entire resected specimens of colon obtained at the time of pull-through operation from 15 patients with Hirschsprung's disease (HD) and 6 age-matched controls. Both antibodies showed a similar pattern of staining. In the normal colon and ganglionic colon from HD, there was strong reactivity in the submucous and myenteric plexuses in addition to staining of nerve fibres in the smooth-muscle layers. In the aganglionic colon, there was an absence or marked decrease in SNT and STG-positive nerve fibres in the smooth-muscle layers and in hypertrophic nerve trunks. Our data indicate that important proteins necessary for the docking of synaptic vesicles at the presynaptic plasma membrane are lost in fibres innervating the smooth muscle of HD and suggest that abnormal neurotransmission may have a role in the maintenance of muscle spasticity.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 15 (1999), S. 198-200 
    ISSN: 1437-9813
    Keywords: Key words Infantile hypertrophic pyloric stenosis ; Smooth-muscle cells ; Transforming growth factor-α (TGF-α)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth-muscle cells (SMCs) is regulated by several growth factors. Transforming growth factor-α (TGF-α) is a growth-regulatory peptide found in a wide range of embryonic and adult tissues. It has been recognized that TGF-α has growth-promoting effects in vascular and visceral SMCs. The aim of this study was to investigate whether TGF-α plays a role in the pyloric-muscle hypertrophy in IHPS. Full-thickness pyloric-muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 IHPS patients (age range 24–76 days). Age-matched control material included 10 pyloric-muscle specimens taken at autopsy in patients without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the ABC method with anti-TGF-α polyclonal antibody. In-situ hybridization was performed using a digoxigenin-labelled, TGF-α-specific oligonucleotide probe. There was a marked increase in TGF-α immunoreactivity and messenger RNA (mRNA) expression in SMCs in pyloric circular and longitudinal muscle in IHPS specimens compared to controls. The increased expression of TGF-α mRNA together with increased TGF-α immunoreactivity in IHPS suggests increased local synthesis of TGF-α by pyloric SMCs, causing pyloric-muscle hypertrophy.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 15 (1999), S. 243-247 
    ISSN: 1437-9813
    Keywords: Key words Wilms' tumo ; Apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wilms' tumor (WT) usually has a good outcome, although a poor prognosis is often related to more advanced stages and anaplastic features. Apoptosis occurs with variable frequency in malignant tumors, and may have a role in reducing their growth rate. The bcl-2 proto-oncogene inhibits apoptosis, and the consequent increase in the number of cells may play a role in the development of tumors. The aim of this study was to analyze the role of apoptosis and bcl-2 expression in WT. Twenty-six resected WT specimens were studied; 12 patients had stage I tumor, 4 stage II, 5 stage III, 3 stage IV, and 2 stage V. Twenty-three tumors were classified as favorable histology (FH) and 3 as unfavorable (UH). The mean follow-up was 34 months; 22 patients were alive and 4 were dead (2 with FH: 1 stage III and 1 stage IV, and 2 with UH stages 4). Apoptosis was detected by the in-situ end-labelling technique; bcl-2 expression was detected by immunohistochemistry. An apoptotic index (AI) was calculated as the ratio of apoptotic to normal cells in each specimen. The AI was lower in higher tumor stages, with a significant difference between stages I and IV (P 〈 0.05). In cases with UH, Al was lower than in tumors with FH (P 〈 0.01). The AI was also lower in patients who died than in those who survived (P 〈 0.01). In all specimens no correlation between AI and bcl-2 expression was observed. Progression to advanced stages of WT and a poor prognosis f anaplastic tumors may be linked with disruption of the mechanisms that control apoptosis. Bcl-2 does not play a role as a regulator of apoptosis in WT, other oncogenes and tumor-suppression genes may be more involved in inhibiting apoptosis in WT.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 16 (2000), S. 306-309 
    ISSN: 1437-9813
    Keywords: Key words Renal dysplasia ; Basic fibroblast growth factor (bFGF ; FGF-2) ; Keratinocyte growth factor (KGF ; FGF-7)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Renal dysplasia (RD) is a disorganized development of renal parenchyma that results in a deficit of functional renal tissue. Dysplastic renal tissue is characterized by primitive tubular epithelium associated with increased mesenchyme. Several polypeptide growth factors (GF), which interact with target cells through a cell-surface membrane receptor, have been reported to be involved in the regulation of urothelial cell growth in normal and neoplastic states. Recent reports have demonstrated that basic fibroblast GF (bFGF, FGF-2) is a mitogen for renal proximal-tubule epithelial cells. Keratinocyte GF (KGF, FGF-7), which belongs to the FGF family, is believed to be a paracrine mediator of epithelial-cell proliferation. The aim of this study was to investigate the immunoactivity of bFGF and KGF and their receptors in the dysplastic kidney in order to further understand the pathogenesis of RD. Specimens of dysplastic upper poles of duplex kidneys were surgically resected from ten patients. Age-matched control material included six kidney specimens taken at autopsy from patients without evidence of urologic disease. Indirect immunohistochemistry was performed using the Strept-ABC method with four antibodies: bFGF, KGF, FGF receptor (flg), and KGF receptor (bek). There was absent or weak bFGF, KGF, flg, and bek immunoreactivity in normal kidneys. In the dysplastic kidneys, there was strong immunoreactivity of bFGF and KGF and their receptors in the epithelium of primitive tubules. Increased local expression of bFGF and KGF and their receptors in primitive tubules suggests that bFGF and KGF may play an important role in the development of RD.
    Type of Medium: Electronic Resource
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