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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. The present report examines the affects of these analogues on the metabolism of neuroblastoma cells. p-Chlorophenylalanine inhibited growth and was toxic to neuroblastoma cells. Although in vivo this analogue increased cell monoribosomes by 42%, it did not significantly affect poly(U)-directed protein synthesis in vitro. P-Chlorophenylalanine did not compete with phenylalanine or tyrosine for aminoacylation of tRNA and was therefore not substituted for those amino acids in nascent polypeptides. The initial cellular uptake of various large neutral amino acids was inhibited by this analogue but did not affect the flux of amino acids already in the cell; this suggested that an alteration of the cell's amino acid pools was not responsible for the cytotoxicity of the analogues. In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture. The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed.
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PMID:Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells. 15 35

The liver in an infant or child is as liable to the same pathologies afflicting the adult liver but with certain differences in prevalence and causes. Genetic disorders are more likely to present in the paediatric age group where many involve metabolic processes such as galactosemia, phenylketonuria, glycogen storage disease and others. Many of these present in the newborn period. However, neoplasms and hamartomas also present in the newborn period, such as congenital neuroblastoma with an enormously enlarged liver, hepatoblastoma and haemangioma. The latter may present with intractable cardiac failure as a result of considerable shunting of blood. Acquired liver lesions often present in the newborn period or early infancy and this includes hepatitis and biliary atresia. The difficulties in the differentiation of the two lesions will be discussed together with the management of biliary atresia. As the child grows older, Reyes encephalopathy with microvesicular fat in the liver is not uncommon. The pathophysiology of Reyes encephalopathy as seen locally will be described. The choledochal cyst with direct (Caroli's disease) or indirect effect on the liver will be described. Problems of childhood portal hypertension as well as congenital hepatic fibrosis will be described. Hemosiderosis of the liver is chiefly seen in homozygous beta-thalassaemia patients who have been kept alive with repeated blood transfusions. Amoebic and pyogenic hepatitis, fatty liver due to protein malnutrition, biliary ascariasis, etc, which are common in tropical and subtropical countries are rarely seen now in Singapore children.
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PMID:Paediatric liver disorders in Singapore. 346 38

Gas chromatographic retention indices (methylene units) are reported for 101 urinary organic acids as their trimethylsilyl and oximated trimethylsilyl derivatives on a 5% phenylmethyl silicone fused silica capillary column. Using anion exchange chromatography, organic acids were extracted from urines of five healthy individuals, seven patients with neuroblastoma, and nine patients with inherited organic acidurias. Separation of the various acids was achieved by capillary gas chromatography and identification was done by mass spectrometry using a computerized library search program. All identifications were confirmed by visual comparison with reference mass spectra. Standard deviations of the retention indices for all acids were less than 0.035 methylene units and for 46 acids less than 0.01 methylene units. Three chromatograms of urine from individuals with neuroblastoma, phenylketonuria, and propionic acidemia and one from a healthy individual are shown.
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PMID:Capillary gas chromatographic separation of urinary organic acids. Retention indices of 101 urinary acids on a 5% phenylmethyl silicone capillary column. 672 93

We have developed a routine capillary gas-chromatographic profiling method for simultaneous quantitative determination of the tert-butyldimethylsilyl derivatives of homovanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 3,4-dihydroxyphenylacetic acid and the estimation of 5-hydroxyindole-3-acetic acid in urine. The method is useful for diagnosis and followup of patients with functional tumors characterized by increased urinary excretion of metabolites originating from the metabolism of tyrosine and tryptophan--e.g., neuroblastoma, pheochromocytoma, carcinoid, and melanoma. It may also be applicable in pharmacokinetic studies of administered aromatic amino acids (parkinsonism, mental diseases, loading tests) and for diagnosis and followup of patients with inborn errors of metabolism that are characterized by organic aciduria (for instance, tyrosyluria and phenylketonuria).
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PMID:Simultaneous determination of the four major catecholamine metabolites and estimation of a serotonin metabolite in urine by capillary gas chromatography of their tert-butyldimethylsilyl derivatives. 746 Feb 71

Informed consent is essential for bioethical considerations when physicians treat severely neurologically disturbed children. Because these patients are immature for their decision-making, proxy consent must be given to their physicians by their guardian to accept within agreeable limits of treatments and care for them. Prior to obtaining the consent, given by their guardians, physicians are obliged to provide their guardians with necessary informations regarding patients' physical conditions and details of procedures for proposed treatments, as well as possible risks involved in these treatments and care to be provided. Clinical applications of bioethical considerations are given to the patients with following diseases: spina bifida cystica and other neural tube defects, congenital metabolic disorders such as cretinism and phenylketonuria, malignant tumors such as neuroblastoma and retinoblastoma, and intractable epilepsy. Bioethical considerations are also given to prenatal diagnosis for early discovery, diagnosis and possible treatments of severely neurologically disturbed fetuses.
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PMID:[Bioethics in severely neurologically disturbed children]. 954 72

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the possibility of foetal damage. The results of our own investigations of maternal PKU are discussed. The significance of mass-screening for galactosemia is still under discussion. In our opinion, mass-screening for galactosemia is not useful and we have discontinued it. Selective screening has been started combined with molecular genetic studies in high risk families. In the future, we plan to prepare guidelines on the principles of diagnosis and treatment of galactosemia in children and women in the reproductive age. Mass-screening for cystic fibrosis is also still under discussion. The results of the early screening programmes were not satisfactory and the tests were discontinued. In 1998, after reorganisation of the whole system, CF screening, using tripsin-radioimmune assays, was started again. The new screening programme is combined with molecular genetic investigation of different mutations. It is still too early to assess the importance and success of this CF mass-screening programme. We decided to discontinue the screening for homocystinuria, histidinemia, tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not comply with criteria of mass-screening. In 1997, major reorganisation of screening programmes for inborn errors of metabolism, at NRIMC, was undertaken. The Guthrie test for PKU was changed to a quantitative colorimetric method. The immuno-luminometric method is used for TSH estimation. The whole system is based on complete computer control of all the steps of screening, from blood sampling on filter paper until the final diagnosis. The advantages of this modern system of organisation of the screening programme are discussed.
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PMID:[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience]. 1091 Jun 78

Phenylketonuria is a genetic defect that, without strict dietary control, results in the accumulation of phenylalanine (Phe) in body fluids. If a low-Phe diet is not maintained during pregnancy, the offspring of phenylketonuric women are born with mental retardation and microcephaly. Primary cultures of rat cerebellar granule cells, rat cortical astrocytes, human fetal astrocytes, and human neuroblastoma (SY5Y) cells and human astrocytoma (1321N1) cells were used to test the hypothesis that the microencephaly may be a result of neuronal cell death and reduced astrocyte proliferation. Exposure to Phe or to six Phe metabolites [phenylacetic acid (PAA), phenyllactic acid, hydroxyphenylacetic acid, phenylpyruvic acid, phenylethylamine (PEA), and mandelic acid] did not result in astroglial or neuronal cell cytotoxicity. Treatment of 1321N1 cells, human fetal astrocytes, or rat astrocytes with 5 mM Phe for 24 h decreased DNA synthesis 19 +/- 4, 30 +/- 4, and 60 +/- 6%, respectively. This effect was concentration dependent, and flow cytometry revealed that Phe treatment resulted in the accumulation of cells in the G(0)/G(1) phase of the cell cycle. In addition, in 1321N1 cells, exposure to 5 mM PAA, and in rat astrocytes, exposure to 0.5 mM PEA inhibited cell proliferation 42 +/- 4 and 55 +/- 4%, respectively. These metabolites also resulted in the accumulation of cells in the G(0)/G(1) phase of the cell cycle. In human fetal astrocytes, 0.5 mM PEA and 0.5 mM PAA resulted in a 41 +/- 12 and 52 +/- 11% reduction proliferation, respectively.
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PMID:Effect of phenylalanine and its metabolites on the proliferation and viability of neuronal and astroglial cells: possible relevance in maternal phenylketonuria. 1099 93

We report the outline and results of our experience with a group training course of neonatal screening for health care professionals in developing countries. Sapporo City Institute of Public Health (SCIPH) has been offered a training course on neonatal screening once a year since 1991 under the Technical Training Program of the Japan International Cooperation Agency (JICA). The aims of this training course are to enhance the participants' technical knowledge and skills, and also to deepen their understanding of the principle of neonatal screening as well as the relevant diseases. Lectures and laboratory practice on phenylketonuria (PKU), congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and neuroblastoma are included in the 3-month program. After the completion of the training, participants are expected to play a major role in establishing and expanding neonatal screening system in each of their countries. We have received a total of 67 participants from 25 countries until March 1998: 58 pediatricians; 2 gynecologists; 6 biochemists; 1 administrative officer. After they returned to their countries, 11 engaged in neonatal screening and started PKU and CH screening in their institute, city or province in Argentina, Brazil, Mexico, Peru and Thailand. We believe that these results fulfilled our objectives. Also, for follow-up, SCIPH has been giving information and consultation to the participants on requests. This international cooperation network could also benefit our present network of the International Society Screening in the future.
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PMID:International cooperation in neonatal screening: technical training course for newborn and infant screening. 1140 Jul 77

The Quebec Network of Genetic Medicine (QNGM), implemented in 1971, has been an integrated program of community genetics serving the population (approximately 7.5 million) of Quebec province in Canada. QNGM reported to the Minister of Social Affairs and operated under an umbrella of universal health insurance in the province. The Network's programs have been run by members of the four university medical schools of the province under the direction of a central committee. A global annual budget was awarded to QNGM from its inception. Among its many programs, QNGM supported: (1) two newborn screening programs (using blood and urine samples) for early diagnosis, treatment and research in phenylketonuria, hereditary tyrosinemia, congenital hypothyroidism, and in a large number of other hereditary metabolic diseases; (2) follow-up of confirmatory diagnostic tests at regional centers, followed by supervision of ambulatory treatment modalities; (3) carrier screening and reproductive counseling for Tay-Sachs and beta-thalassemia diseases; (4) a spectrum of feasibility (research) studies (e.g., screening for biotinidase deficiency, neuroblastoma, hemoglobinopathies, and cystic fibrosis) to inform policy decisions. QNGM performed economic analyses of its major programs and followed prevailing ethical guidelines. Its global budget and integrated structure terminated in 1994, although some of its programs continue independently.
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PMID:Community genetics and dignity in diversity in the Quebec Network of Genetic Medicine. 1674 43

Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results.
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PMID:Universal newborn screening and adverse medical outcomes: a historical note. 1718 76


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