Science.gov

Sample records for phenylketonuria pku development

  1. Phenylketonuria (PKU): A problem solved?

    PubMed

    Brown, Christine S; Lichter-Konecki, Uta

    2016-03-01

    Phenylketonuria (PKU) is a rare metabolic disorder characterized by impaired conversion of phenylalanine (Phe) to tyrosine. If left untreated, the resultant accumulation of excess blood Phe can cause physiological, neurological, and intellectual disabilities. The National PKU Alliance (NPKUA) conducted a survey of its membership to assess current health status and interest in new treatments for PKU. Of the 625 survey respondents, less than half (46.7%) reported blood Phe within (120-360 μmol/L) - the range recommended by the American College of Medical Genetics and Genomics (ACMG). The survey results also showed that younger (≤ 18 years) individuals were about 3-times as successful in keeping their blood Phe concentrations within the recommended clinical range compared with adults. Blood Phe over 360 μmol/L was reported in one-quarter (25.5%) of ≤ 18 year old individuals and almost two-thirds (61.5%) of adults. A little more than half (51.7%) of respondents reported having difficulty in managing their PKU, including the maintenance of a Phe-restricted diet. Individuals with PKU desire new treatments that would allow them to increase their intake of natural protein, discontinue or reduce their intake of medical foods (medical formula and foods modified to be low in protein), improve their mental health (including a reduction in depression and anxiety), and a reduction of their blood Phe concentrations. Respondents preferred oral administration of any newly developed therapies and, in general, disliked therapeutic injections. Injections at home were preferred over injections at a clinic. Payers, government agencies, clinicians, and industry partners should consider patient input when developing and approving new therapies and treatments for PKU. PMID:27014571

  2. How Do Health Care Providers Diagnose Phenylketonuria (PKU)?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose phenylketonuria (PKU)? Skip sharing on social ... disabilities. 2 How are newborns tested for PKU? Health care providers conduct a PKU screening test using a ...

  3. Muscle-directed gene therapy for phenylketonuria (PKU): Development of transgenic mice with muscle-specific phenylalanine hydroxylase expression

    SciTech Connect

    Harding, C.O.; Messing, A.; Wolff, J.A.

    1994-09-01

    Phenylketonuria (PKU) is an attractive target for gene therapy because of shortcomings in current therapy including lifelong commitment to a difficult and expensive diet, persistent mild cognitive deficits in some children despite adequate dietary therapy, and maternal PKU syndrome. Phenylalanine hydroxylase (PAH) is normally expressed only in liver, but we propose to treat PKU by introducing the gene for PAH into muscle. In order to evaluate both the safety and efficacy of this approach, we have a developed a trangenic mouse which expresses PAH in both cardiac and skeletal muscle. The transgene includes promoter and enhancer sequences from the mouse muscle creatine kinase (MCK) gene fused to the mouse liver PAH cDNA. Mice which have inherited the transgene are healthy, active, and do not exhibit any signs of muscle weakness or wasting. Ectopic PAH expression in muscle is not detrimental to the health, neurologic function, or reproduction of the mice. Pah{sup enu2} hyperphenylalaninemic mice, a model of human PAH deficiency, bred to carry the transgene have substantial PAH expression in cardiac and skeletal muscle but none in liver. Muscle PAH expression alone does not complement the hyperphenylalaninemic phenotype of Pah{sup enu2} mice. However, administration of reduced tetrahydrobiopterin to transgenic Pah{sup enu2} mice is associated with a 25% mean decrease in serum phenylalanine levels. We predict that ectopic expression of PAH in muscle along with adequate muscle supplies of reduced biopterin cofactor will decrease hyperphenylalaninemia in PKU.

  4. Phenylketonuria (PKU). ARC Q&A #101-53.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This fact sheet uses a question-and-answer format to summarize what is known about phenylketonuria (PKU), an inherited metabolic disease that leads to mental retardation and other developmental disabilities if untreated in infancy. Questions and answers address the following topics: what PKU is; how PKU is inherited; the diagnosis of PKU; the…

  5. What Are Common Treatments for Phenylketonuria (PKU)?

    MedlinePlus

    ... better functioning and improved overall health. A PKU Formula People who follow the PKU diet will not ... from food. Therefore, they must drink a special formula. A newborn who is diagnosed with PKU should ...

  6. "I Feel Lucky" - Gratitude Among Young Adults with Phenylketonuria (PKU).

    PubMed

    Diesen, Plata Sofie

    2016-10-01

    If persons with phenylketonuria (PKU) do not start a protein restricted diet in early infancy, they will suffer severe brain damage. Previous qualitative research on adults and adolescents with PKU has identified stigmatization, uncertain risk perceptions, considerable time spent on preparing food, and incongruence between the PKU diet and certain lifestyle demands. The aim of this study was to explore young and early treated Norwegian adults' experiences, by conducting in-depth interviews in 2011 with 11 adults with PKU, aged 20-30. Being the first qualitative study on people with PKU in Norway, the process was inspired by grounded theory. All participants reflected on their own health and existence by expressing positive counterfactual thoughts. They considered themselves lucky to have had parents who had managed the diet, they were grateful for the time and place they were born, and for information and treatment availability, although the results also show some ambiguous attitudes towards the hospital which provided the treatment. The expression of gratitude in association with having PKU suggests a major positive coping strategy. It contributes to a more holistic understanding of the experiences and attitudes of young, Norwegian adults with PKU, as it provides a counterweight to the negative experiences.

  7. A Current Look at Phenylketonuria (PKU).

    ERIC Educational Resources Information Center

    Fischer, Margaret

    Research was reviewed on the current status of phenylketonuria, an hereditary amino acid metabolic disorder that can cause severe mental retardation, physical complications, and emotional difficulties if not detected and treated early in childhood. A majority of the research cited was published in the 1960's. Topics covered were: discovery of…

  8. Mental health and social functioning in early treated Phenylketonuria: the PKU-COBESO study.

    PubMed

    Jahja, Rianne; Huijbregts, Stephan C J; de Sonneville, Leo M J; van der Meere, Jaap J; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, M Estela; Brouwers, Martijn C G J; Hofstede, Floris C; de Vries, Maaike C; Janssen, Mirian C H; van der Ploeg, Ans T; Langendonk, Janneke G; van Spronsen, Francjan J

    2013-01-01

    This article presents a new Dutch multicenter study ("PKU-COBESO") into cognitive and behavioral sequelae of early and continuously treated Phenylketonuria (PKU) patients. Part of the study sample will consist of young adult PKU patients who have participated in a large neuropsychological study approximately 10 years ago, when they were 7-to-15-year-olds (Huijbregts et al., 2002 [1]). Their neurocognitive development will be mapped in association with their earlier and continued metabolic history, taking into account possible changes in, for instance, medication. A second part of the sample will consist of PKU patients between the ages of 7 and approximately 40 years (i.e., born in or after 1974, when neonatal screening was introduced in The Netherlands), who have not participated in the earlier neuropsychological study. Again, their cognitive functioning will be related to their metabolic history. With respect to aspects of cognition, there will be an emphasis on executive functioning. The concept of executive functioning will however be extended with further emphasis on the impact of cognitive deficits on the daily lives of PKU patients, aspects of social cognition, social functioning, and behavior/mental health (i.e., COgnition, BEhavior, SOcial functioning: COBESO). In addition to a description of the PKU-COBESO study, some preliminary results with respect to mental health and social functioning will be presented in this article. Thirty adult PKU patients (mean age 27.8, SD 6.4) and 23 PKU patients under the age of 18 years (mean age 11.0, SD 3.3) were compared to 14 (mean age 26.9 years, SD 5.9) and 7 matched controls (mean age 10.5, SD 2.6) respectively, with respect to their scores on the Adult Self-Report or Child Behavior Checklist (measuring mental health problems) and the Social Skills Checklist or Social Skills Rating System (measuring social skills). Whereas there were very few significant group differences (except for mental health problems in the

  9. Phenylketonuria

    MedlinePlus

    ... without the ability to properly break down an amino acid called phenylalanine. Causes Phenylketonuria (PKU) is inherited, which ... which is needed to break down the essential amino acid phenylalanine. Phenylalanine is found in foods that contain ...

  10. Education of Students with Phenylketonuria (PKU): Information for Teachers, Administrators and Other School Personnel.

    ERIC Educational Resources Information Center

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

    This booklet summarizes current knowledge about phenylketonuria (PKU), an inherited condition that results in severe mental retardation if untreated, and discusses the psychoeducational implications of the condition. The introduction stresses the importance of early diagnosis (during the first days of life) and the effectiveness of a diet that…

  11. Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in European families with phenylketonuria (PKU).

    PubMed

    Daiger, S P; Chakraborty, R; Reed, L; Fekete, G; Schuler, D; Berenssi, G; Nasz, I; Brdicka, R; Kamarýt, J; Pijácková, A

    1989-08-01

    DNA haplotype data from the phenylalanine hydroxylase (PAH) locus are available from a number of European populations as a result of RFLP testing for genetic counseling in families with phenylketonuria (PKU). We have analyzed data from Hungary and Czechoslovakia together with published data from five additional countries--Denmark, Switzerland, Scotland, Germany, and France--representing a broad geographic and ethnographic range. The data include 686 complete chromosomal haplotypes for eight RFLP sites assayed in 202 unrelated Caucasian families with PKU. Forty-six distinct RFLP haplotypes have been observed to date, 10 unique to PKU-bearing chromosomes, 12 unique to non-PKU chromosomes, and the remainder found in association with both types. Despite the large number of haplotypes observed (still much less than the theoretical maximum of 384), five haplotypes alone account for more than 76% of normal European chromosomes and four haplotypes alone account for more than 80% of PKU-bearing chromosomes. We evaluated the distribution of haplotypes and alleles within these populations and calculated pairwise disequilibrium values between RFLP sites and between these sites and a hypothetical PKU "locus." These are statistically significant differences between European populations in the frequencies of non-PKU chromosomal haplotypes (P = .025) and PKU chromosomal haplotypes (P much less than .001). Haplotype frequencies of the PKU and non-PKU chromosomes also differ significantly (P much less than .001. Disequilibrium values are consistent with the PAH physical map and support the molecular evidence for multiple, independent PKU mutations in Caucasians. However, the data do not support a single geographic origin for these mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in Asian families with phenylketonuria (PKU).

    PubMed

    Daiger, S P; Reed, L; Huang, S S; Zeng, Y T; Wang, T; Lo, W H; Okano, Y; Hase, Y; Fukuda, Y; Oura, T

    1989-08-01

    DNA polymorphisms at the phenylalanine hydroxylase (PAH) locus have proved highly effective in linkage diagnosis of phenylketonuria (PKU) in Caucasian families. More than 10 RFLP sites have been reported within the PAH structural locus in Caucasians. With information from affected and unaffected offspring in PKU families it is often possible to reconstruct complete RFLP haplotypes in parents and to use these haplotypes to follow the segregation of PKU within families and to determine the distribution of PKU chromosomes within populations. To establish the utility of these RFLPs in characterizing Asian families with PKU, we typed eight DNA sites in 21 Chinese families and 12 Japanese families with classical PKU. The eight RFLPs were chosen for their informativeness in Caucasians. From these families we reconstructed a total of 91 complete PAH haplotypes, 44 from non-PKU chromosomes and 47 from PKU-bearing chromosomes. Although all eight marker sites are polymorphic in both Chinese and Japanese, there is much less haplotypic variation in Asians than in Caucasians. In particular, one haplotype alone, haplotype 4, accounts for more than 77% of non-PKU chromosomes and for more than 80% of PKU-bearing chromosomes. Haplotype 4 is also relatively common in Caucasians. The next most common Asian haplotype is 10 times less frequent than haplotype 4. By contrast, in many Caucasian populations the sum of the frequencies of the five most common haplotypes is still less than 80%, and several of the most common haplotypes are equally frequent. Even though the extent of haplotypic variation in Asians is severely limited, the few haplotypes that are found often differ at a number of RFLP sites.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Phenylketonuria

    MedlinePlus

    Phenylketonuria (PKU) is a type of amino acid metabolism disorder. It is inherited. If you have it, your body can't process part of a protein called phenylalanine (Phe). Phe is in almost all foods. If your Phe level gets too high, it can damage your brain and cause severe ...

  14. [Evaluation of physical development in children with classical phenylketonuria].

    PubMed

    Bushueva, T V; Borovik, T E; Ladodo, K S; Kuzenkova, L M; Maslova, O I; Gevorkyan, A K

    2015-01-01

    Classical phenylketonuria (PKU) is hereditary disease, which is based on the disturbance of phenylalanine conversion to tyrosine. The basic treatment of PKU is low phenylalanine diet. Prolonged restriction of natural protein may have a negative impact to PKU patient growth and physical development. The objective was to evaluate the physical development of patients with classical PKU at birth and on the diet based on the products with different chemical composition without phenylalanine. 257 PKU patients have been examined with the computer program "WHO Anthroplus 2009". All patient were born at term. Z-score of body weight, height and body mass index (BMI) to age has been retrospectively estimated. Patients were divided into 2 groups: group 1--101 children born in 1980-1993 were fed by unadapted specialty products based on protein hydrolyzate with restricted phenylalanine, and group 2--156 children born in 1995-2012 were fed by contemporary amino acid mixtures without phenylalanine. All newborn PKU patients had the middle for age Z-score of weight and BMI, 21% of neonates had high Z-score growth. Before the diet therapy BMI Z-score was normal in 84.1% patients in group 1 and 87.2% patients of group 2. After 6 mo of treatment with low phenylalanine diet the number of patient with normal BMI Z-score was 71.3% in group 1 against 95.6% in group 2. Thus, using of modern amino acid mixtures without phenylalanine, enriched with essential nutrients can promote the normal physical development of PKU patients.

  15. What Is Phenylketonuria (PKU)?

    MedlinePlus

    ... have it? For more information... Acknowledgments Concept 15 : DNA and proteins are key molecules of the cell nucleus. Learn the basic chemistry of DNA and proteins. Concept 27 : Mutations are changes in ...

  16. Learning about Phenylketonuria (PKU)

    MedlinePlus

    ... Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers Genomic ...

  17. Hepatitis virus protein X-Phenylalanine Hydroxylase fusion proteins identified in PKU mice treated with AAV-WPRE vectors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing the Pahenu2 mouse model for phenylketonuria (PKU), we developed an improved expression vector containing the Woodchuck Hepatitis Virus post-transcriptional regulatory element inserted into a rAAV-mPAH construct (rAAV-mPAH-WPRE) for treatment of PKU. Following portal vein delivery of these ...

  18. Classic Phenylketonuria: Diagnosis Through Heterozygote Detection

    ERIC Educational Resources Information Center

    Griffin, Robert F.; Elsas, Louis J.

    1975-01-01

    In an attempt to improve the identification of the asymptomatic carrier of classic phenylketonuria (PKU) 59 male and female normal control Ss were differentiated from 18 males and females heterozgous for PKU. (DB)

  19. Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

    PubMed

    DeWard, Stephanie J; Wilson, Ashley; Bausell, Heather; Volz, Ashley S; Mooney, Kimberly

    2014-02-01

    Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion. PMID:24014152

  20. Requirements for a minimum standard of care for phenylketonuria: the patients’ perspective

    PubMed Central

    2013-01-01

    Phenylketonuria (PKU, ORPHA716) is an inherited disorder that affects about one in every 10,000 children born in Europe. Early and continuous application of a modified diet is largely successful in preventing the devastating brain damage associated with untreated PKU. The management of PKU is inconsistent: there are few national guidelines, and these tend to be incomplete and implemented sporadically. In this article, the first-ever pan- European patient/carer perspective on optimal PKU care, the European Society for Phenylketonuria and Allied Disorders (E.S.PKU) proposes recommendations for a minimum standard of care for PKU, to underpin the development of new pan-European guideline for the management of PKU. New standards of best practice should guarantee equal access to screening, treatment and monitoring throughout Europe. Screening protocols and interpretation of screening results should be standardised. Experienced Centres of Expertise are required, in line with current European Union policy, to guarantee a defined standard of multidisciplinary treatment and care for all medical and social aspects of PKU. Women of childbearing age require especially intensive management, due to the risk of severe risks to the foetus conferred by uncontrolled PKU. All aspects of treatment should be reimbursed to ensure uniform access across Europe to guideline-driven, evidence-based care. The E.S.PKU urges PKU healthcare professionals caring for people with PKU to take the lead in developing evidence based guidelines on PKU, while continuing to play an active role in serving as the voice of patients and their families, whose lives are affected by the condition. PMID:24341788

  1. Nutritional issues in treating phenylketonuria.

    PubMed

    Feillet, François; Agostoni, Carlo

    2010-12-01

    A phenylalanine (Phe)-restricted diet is the mainstay of phenylketonuria (PKU) treatment, and, in recent years, the nutritional management of PKU has become more complex in order to optimize patients' growth, development and diet compliance. Dietary restriction of Phe creates a diet similar to a vegan diet, and many of the nutritional concerns and questions applicable to vegans who wish to avoid animal products are also relevant to patients with PKU. Owing to their nutritional characteristics, breast milk and breastfeeding should be given greater consideration as a useful food in patients with PKU and in those with other inborn errors of metabolism. Further key issues for consideration include the quality of the available amino acid substitutes, the neurotrophic and neuroprotective effects of added long-chain polyunsaturated fatty acids (e.g. docosahexaenoic acid), micronutrient deficiencies, bone disease and antioxidant status. Long-term dietary guidance and monitoring of the nutritional status of patients with PKU should be part of a follow-up programme that continues for life. PMID:20151202

  2. PKU (Phenylketonuria) in Your Baby

    MedlinePlus

    ... which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in your body. Without treatment, ... which your body can’t break down an amino acid called phenylalanine. Amino acids help build protein in ...

  3. Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.

    PubMed

    Schuck, Patrícia Fernanda; Malgarin, Fernanda; Cararo, José Henrique; Cardoso, Fabiola; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-09-01

    Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition. PMID:26425393

  4. Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

    PubMed Central

    Schuck, Patrícia Fernanda; Malgarin, Fernanda; Cararo, José Henrique; Cardoso, Fabiola; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition. PMID:26425393

  5. Relationship between age and white matter integrity in children with phenylketonuria.

    PubMed

    Wesonga, Erika; Shimony, Joshua S; Rutlin, Jerrel; Grange, Dorothy K; White, Desiree A

    2016-06-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU.

  6. [Phenylketonuria as a model system for DNA diagnosis of hereditary disorders].

    PubMed

    Meijer, H; Hekking, M; van den Enden, A T; Jongbloed, R J; Schrander-Stumpel, C T; Geraedts, J P

    1990-10-01

    Phenylketonuria (PKU), due to a defect in phenylalanine hydroxylase (PAH), is presented as a model system for computer-aided DNA diagnosis of genetic diseases. Eight different restriction fragment length polymorphism (RFLP) markers have been localized within the introns of the 90 kb PAH gene (located on chromosome 12). These RFLPs can be combined in 384 different ways and each combination has been defined as a particular haplotype. A special computer program has been developed to calculate the possible haplotype combinations in a PKU core family (index patient and parents), with the goal to derive unambiguously both the PAH and PKU alleles. Taking into account that participation of other members of the family (grandparents or brothers/sisters) is sometimes necessary, haplotyping by itself is sufficient to establish (or exclude) the PKU status of an individual in approximately eight out of ten PKU families.

  7. Neuropsychology of Early-Treated Phenylketonuria: Specific Executive Function Deficits.

    ERIC Educational Resources Information Center

    Welsh, Marilyn C.; And Others

    1990-01-01

    Early-treated phenylketonuria (PKU) children and unaffected peers were evaluated on four executive function (EF) tasks and one nonexecutive task. The PKU children scored lower than unaffected children on EF tasks, but not on the nonexecutive task. The PKU children's composite EF score was correlated with concurrent and mean lifetime phenylalanine…

  8. Management of Newborn Infants with Phenylketonuria.

    ERIC Educational Resources Information Center

    Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

    The booklet covers the identification, diagnosis, and clinical treatment of newborns with Phenylketonuria (PKU), an inborn error of metabolism, which, if untreated, can lead to mental retardation. An initial section considers biochemical and genetic factors of PKU including a diagram of aromatic amino acid hydroxylation systems. Screening…

  9. The birth prevalence of PKU in populations of European, South Asian and sub-Saharan African ancestry living in South East England.

    PubMed

    Hardelid, P; Cortina-Borja, M; Munro, A; Jones, H; Cleary, M; Champion, M P; Foo, Y; Scriver, C R; Dezateux, C

    2008-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

  10. State-of-the-art 2003 on PKU gene therapy

    PubMed Central

    Ding, Zhaobing; Harding, Cary O.; Thöny, Beat

    2009-01-01

    Phenylketonuria (or PKU) is a well-known and widespread genetic disease for which many countries perform newborn screening, and life-long dietary restriction is still the ultimate and effective therapy. However, the diet is complicated, unpalatable, and expensive. The long-term effects of diet discontinuation in adults, except for the serious adverse effects of maternal hyperphenylalaninemia upon the developing fetus, have not been systematically studied, but congnitive decline and neurologic abnormalities have been anecdotally reported. Thus, alternative approaches for PKU therapy, including gene therapy, must be further explored. Here we summarize past present nonviral and viral gene transfer approaches, both in vitro studies and preclinical animal trials, to delivering the PAH gene into liver or other organs as potential alternatives to life-long phenylalanine-restricted dietary theraphy. PMID:14728985

  11. Breastfeeding Infants with Phenylketonuria in the United States and Canada

    PubMed Central

    Press, Nancy; Knafl, Kathleen A.; Steiner, Robert D.; Houck, Gail M.

    2014-01-01

    Abstract Objective: This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Subjects and Methods: Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Results: Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ2=30.33, p<0.001; n=72 vs. n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one modal duration category (n=20, 22%) at less than 1 month. The timing of the addition of commercial infant formula to supplement breastfeeding or expressed mothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ2 (42, n=73)=88.13, p<0.001. Conclusions: PKU is treated with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is challenging in part because Phe intake is difficult to determine precisely. We studied breastfeeding duration in infants with PKU and factors associated with success. Further research should identify the unique needs of mothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU. PMID:24350704

  12. PHENYLKETONURIA, A COMPREHENSIVE BIBLIOGRAPHY, 1964.

    ERIC Educational Resources Information Center

    Children's Bureau (DHEW), Washington, DC.

    INTENDED AS AN AID TO PROFESSIONAL AND TECHNICAL PERSONS INTERESTED IN PHENYLKETONURIA (PKU), THE BIBLIOGRAPHY LISTS AND ANNOTATES 817 ITEMS. CONTENT DIVISIONS ARE (1) GENERAL--MONOGRAPHS AND ARTICLES, (2) BIOCHEMISTRY--METABOLISM, EXPERIMENTS, TESTS, AND CASES IN WHICH THE EMPHASIS IS ON BIOCHEMISTRY, (3) GENETICS--GENE STUDIES, HEREDITARY…

  13. Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

    NASA Astrophysics Data System (ADS)

    Javanmard, M.; Davis, R. W.

    2014-02-01

    Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

  14. The role of intelligence in phenylketonuria: a review of research and management.

    PubMed

    Brumm, V L; Grant, M L

    2010-01-01

    Phenylketonuria (PKU) results in profound intellectual disability in untreated individuals and more subtle cognitive deficits in individuals treated early and continuously. The assessment of intellectual functioning has been an important outcome variable and the focus of extensive research. Since the implementation of neonatal PKU screening programs in the 1960s, research on intellectual functioning in individuals with PKU has played a significant and positive role in guiding therapy and improving results. This is a literature review examining the relationship between intellectual outcome and treatment parameters including initiation of treatment, duration of treatment, and blood phenylalanine (Phe) levels from infancy through adulthood. While current PKU treatment practices have eliminated severe neurological and cognitive impairment, evidence suggests that intellectual functioning, although typically within the average range when PKU is treated early and continuously, may not be maximized under the current definition of well-controlled PKU, which is based on blood Phe levels. Future research assessing intellectual and neurocognitive outcome in PKU will enhance the development of new treatment strategies.

  15. Caring for children with phenylketonuria

    PubMed Central

    Casey, Linda

    2013-01-01

    Abstract Objective To provide an overview of the diagnosis and management of phenylketonuria (PKU) in childhood with an emphasis on aspects relevant to family physicians providing ongoing care. Sources of information The author’s experience as the clinic physician in a regional pediatric PKU clinic is supplemented with references providing evidence for key points. Main message While metabolic clinics typically provide guidance regarding the specific management of PKU, the family doctor has an essential role in providing ongoing medical care. Conclusion Children and families have much to gain from strong relationships with family doctors, and family doctors can confidently provide care with awareness of the very few potential special needs of patients with PKU. PMID:23946023

  16. Mouse Models of Human Phenylketonuria

    PubMed Central

    Shedlovsky, A.; McDonald, J. D.; Symula, D.; Dove, W. F.

    1993-01-01

    Phenylketonuria (PKU) results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine (PHE) to tyrosine. Although this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known of the mechanism(s) involved in the pathology of PKU. We have combined mouse germline mutagenesis with screens for hyperphenylalaninemia to isolate three mutants deficient in phenylalanine hydroxylase (PAH) activity and cross-reactive protein. Two of these have reduced PAH mRNA and display characteristics of untreated human PKU patients. A low PHE diet partially reverses these abnormalities. Our success in using high frequency random germline point mutagenesis to obtain appropriate disease models illustrates how such mutagenesis can complement the emergent power of targeted mutagenesis in the mouse. The mutants now can be used as models in studying both maternal PKU and somatic gene therapy. PMID:8375656

  17. PKU-related dysgammaglobulinaemia: the effect of diet therapy on IgE and allergic sensitization.

    PubMed

    Riva, E; Fiocchi, A; Agostoni, C; Biasucci, G; Sala, M; Banderali, G; Luotti, D; Giovannini, M

    1994-01-01

    The effect of diet on the development of immunoallergic signs and symptoms in children with phenylketonuria (PKU) was evaluated. Immunological indices of 58 children with PKU treated with diets were compared to the immunological indices of 58 healthy (non-PKU) children. In the PKU group, 39 children had been placed on diet therapy within the first month of life; 19 children had been placed on diet therapy after 6 months of age. Total circulating lymphocytes; CD3+, CD4+, CD8+ circulating lymphocytes; and serum IgA, IgM, IgG and total IgE levels were measured for each child. Skin prick tests were performed for common inhalant and food allergens. Every 3 months over the 2-year period of this study, the signs and symptoms of eczema, allergic rhinitis and asthma were recorded. The PKU group had lower IgG levels (p = 0.004) and higher total IgE levels (p = 0.0001) than the control group. Significantly lower IgE levels were found in children started on diet therapy within the first month of life compared with those started on diet therapy after 6 months of age (p = 0.0001). Allergic sensitization was significantly more frequent in the PKU group (24/58 vs 13/58, z = 2.00, p < 0.05), but no significant difference in the incidence of eczema and allergic rhinitis was found. Asthma was less frequent in the PKU group than in the control group (5/58 vs 14/58, z = 2.09, p < 0.05). Thus, diet appeared to prevent the development of immunoallergic signs and symptoms.

  18. Late-Treated Phenylketonuria and Partial Reversibility of Intellectual Impairment

    ERIC Educational Resources Information Center

    Grosse, Scott D.

    2010-01-01

    Individuals with late-treated phenylketonuria (PKU) not detected by newborn screening but who followed dietary treatment for at least 12 months before 7 years of age have intelligence quotient (IQ) scores that range from severe impairment to the low-normal range. Among adults with late-treated PKU in California, 85% of those who were born from…

  19. Transitory Hyperphenylalaninaemia in Children with Continuously Treated Phenylketonuria.

    ERIC Educational Resources Information Center

    Griffiths, Peter; Smith, Caroline; Harvie, Ann

    1997-01-01

    Cognitive and behavioral effects of temporarily elevating levels of phenylalanine in treated phenylketonuria (PKU) were investigated in a triple-blind crossover study with 16 early and continuously treated children and adolescents with PKU. Results suggest that intellectual ability, memory, and conduct are not affected by medium-term elevated…

  20. Phenylketonuria in adulthood: a collaborative study.

    PubMed

    Koch, R; Burton, B; Hoganson, G; Peterson, R; Rhead, W; Rouse, B; Scott, R; Wolff, J; Stern, A M; Guttler, F; Nelson, M; de la Cruz, F; Coldwell, J; Erbe, R; Geraghty, M T; Shear, C; Thomas, J; Azen, C

    2002-09-01

    During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural

  1. PKU and the Schools: Information for Teachers, Administrators and Other School Personnel.

    ERIC Educational Resources Information Center

    Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

    Designed to acquaint teachers, administrators and other school personnel with phenylketonuria (PKU - an inborn error of metabolism which requires dietary intervention), the booklet reviews school problems related to the condition. Introductory information concerns the nature, treatment, and screening and diagnosis of PKU. Diet management is…

  2. A GC/MS-based metabolomic approach for reliable diagnosis of phenylketonuria.

    PubMed

    Xiong, Xiyue; Sheng, Xiaoqi; Liu, Dan; Zeng, Ting; Peng, Ying; Wang, Yichao

    2015-11-01

    Although the phenylalanine/tyrosine ratio in blood has been the gold standard for diagnosis of phenylketonuria (PKU), the disadvantages of invasive sample collection and false positive error limited the application of this discriminator in the diagnosis of PKU to some extent. The aim of this study was to develop a new standard with high sensitivity and specificity in a less invasive manner for diagnosing PKU. In this study, an improved oximation-silylation method together with GC/MS was utilized to obtain the urinary metabolomic information in 47 PKU patients compared with 47 non-PKU controls. Compared with conventional oximation-silylation methods, the present approach possesses the advantages of shorter reaction time and higher reaction efficiency at a considerably lower temperature, which is beneficial to the derivatization of some thermally unstable compounds, such as phenylpyruvic acid. Ninety-seven peaks in the chromatograms were identified as endogenous metabolites by the National Institute of Standards and Technology (NIST) mass spectra library, including amino acids, organic acids, carbohydrates, amides, and fatty acids. After normalization of data using creatinine as internal standard, 19 differentially expressed compounds with p values of <0.05 were selected by independent-sample t test for the separation of the PKU group and the control group. A principal component analysis (PCA) model constructed by these differentially expressed compounds showed that the PKU group can be discriminated from the control group. Receiver-operating characteristic (ROC) analysis with area under the curve (AUC), specificity, and sensitivity of each PKU marker obtained from these differentially expressed compounds was used to evaluate the possibility of using these markers for diagnosing PKU. The largest value of AUC (0.987) with high specificity (0.936) and sensitivity (1.000) was obtained by the ROC curve of phenylacetic acid at its cutoff value (17.244 mmol/mol creatinine

  3. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  4. Pattern reversal visual evoked potentials in phenylketonuria.

    PubMed

    Giovannini, M; Valsasina, R; Villani, R; Ducati, A; Riva, E; Landi, A; Longhi, R

    1988-01-01

    The pathogenesis of brain dysfunction in phenylketonuria (PKU) is still under investigation. Hyperphenylalaninaemia results in increased turnover of myelin. In order to demonstrate the derangement of myelinization in PKU we studied the visual evoked potentials (VEP) in 14 PKU patients and in 20 normal subjects. VEP findings were correlated with the metabolic control of the disease and with the electroencephalographic findings. VEP were more sensitive than the EEG in detecting a neurological dysfunction. VEP are influenced by dietary control and are normal only in children with good metabolic control.

  5. Diet Management of PKU for Infants and Preschool Children.

    ERIC Educational Resources Information Center

    Acosta, Phyllis B.; Wenz, Elizabeth

    The report focuses on the diet management of infant and preschool children with phenylketonuria (PKU), a congenital deficiency resulting in brain damage. The effective methods for rapidly lowering serum phenylalanine levels following diagnosis are discussed, a method for prescribing and calculating the phenylalanine-restricted diet is described,…

  6. Intelligence and Phenylketonuria: Effects of Diet Termination.

    ERIC Educational Resources Information Center

    Koff, Elissa; And Others

    1979-01-01

    Trends in intellectual functioning before and after diet termination were examined in 30 children (5-11 years old) with PKU (Phenylketonuria, a metabolic disorder) treated before 6 weeks of age and on a liberal diet for a mean of 3 years since the mean age of 59 months. Journal availability: C.V. Mosby Company, 11830 Westline Industrial Drive, St.…

  7. Early-Treated Phenylketonuria: Neuropsychologic Consequences.

    ERIC Educational Resources Information Center

    Brunner, Robert L.; And Others

    1983-01-01

    The neuropsychologic performance of 27 children (about 6 to 13 years old) with early-treated phenylketonuria (PKU) was evaluated and correlated with their serum phenylalanine concentrations at several ages. (Author/SEW) Journal Availability: The Journal of Pediatrics; The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, MO 63141.

  8. Current situation and prospects of newborn screening and treatment for Phenylketonuria in China — compared with the current situation in the United States, UK and Japan

    PubMed Central

    Mei, Lin; Song, Peipei; Kokudo, Norihiro; Xu, Lingzhong; Tang, Wei

    2013-01-01

    Summary Phenylketonuria (PKU) is a treat-able and prevent-able inborn error of metabolism which leads to severe mental retardation and neurobehavioral abnormalities. A screening program, especially for early detection, combined with a Phe-restricted therapeutic diet can help to control the process of PKU of most patients. The China government has put more emphasis on newborn screening and treatment against PKU, yet by comparing the situation of newborn screening and treatment against PKU in China and the relatively developed countries — United States, United Kingdom and Japan, the newborn screening and treatment against PKU in China is relatively weak and many deficiencies are found. More studies concerning multi-stage target blood Phe concentration criteria, a policy that requires newborn screening has to be taken, better financial support for newborn screening, publicity for newborn screening, and national guidelines for treatment of PKU may be prospects in China and may provide some support for better development of newborn screening and treatment against PKU in China. PMID:25343113

  9. National PKU News

    MedlinePlus

    ... and History Staff & Board How Much Phe Guthrie-Koch Scholarship Books Resources Support Us Contact Us Donors ... new Amino Acid Analysis Results This Year’s Guthrie-Koch PKU Scholarship Winners © 2016 National PKU News

  10. Phenylketonuria Scientific Review Conference: state of the science and future research needs.

    PubMed

    Camp, Kathryn M; Parisi, Melissa A; Acosta, Phyllis B; Berry, Gerard T; Bilder, Deborah A; Blau, Nenad; Bodamer, Olaf A; Brosco, Jeffrey P; Brown, Christine S; Burlina, Alberto B; Burton, Barbara K; Chang, Christine S; Coates, Paul M; Cunningham, Amy C; Dobrowolski, Steven F; Ferguson, John H; Franklin, Thomas D; Frazier, Dianne M; Grange, Dorothy K; Greene, Carol L; Groft, Stephen C; Harding, Cary O; Howell, R Rodney; Huntington, Kathleen L; Hyatt-Knorr, Henrietta D; Jevaji, Indira P; Levy, Harvey L; Lichter-Konecki, Uta; Lindegren, Mary Lou; Lloyd-Puryear, Michele A; Matalon, Kimberlee; MacDonald, Anita; McPheeters, Melissa L; Mitchell, John J; Mofidi, Shideh; Moseley, Kathryn D; Mueller, Christine M; Mulberg, Andrew E; Nerurkar, Lata S; Ogata, Beth N; Pariser, Anne R; Prasad, Suyash; Pridjian, Gabriella; Rasmussen, Sonja A; Reddy, Uma M; Rohr, Frances J; Singh, Rani H; Sirrs, Sandra M; Stremer, Stephanie E; Tagle, Danilo A; Thompson, Susan M; Urv, Tiina K; Utz, Jeanine R; van Spronsen, Francjan; Vockley, Jerry; Waisbren, Susan E; Weglicki, Linda S; White, Desirée A; Whitley, Chester B; Wilfond, Benjamin S; Yannicelli, Steven; Young, Justin M

    2014-06-01

    New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use

  11. Phenylketonuria Scientific Review Conference: state of the science and future research needs.

    PubMed

    Camp, Kathryn M; Parisi, Melissa A; Acosta, Phyllis B; Berry, Gerard T; Bilder, Deborah A; Blau, Nenad; Bodamer, Olaf A; Brosco, Jeffrey P; Brown, Christine S; Burlina, Alberto B; Burton, Barbara K; Chang, Christine S; Coates, Paul M; Cunningham, Amy C; Dobrowolski, Steven F; Ferguson, John H; Franklin, Thomas D; Frazier, Dianne M; Grange, Dorothy K; Greene, Carol L; Groft, Stephen C; Harding, Cary O; Howell, R Rodney; Huntington, Kathleen L; Hyatt-Knorr, Henrietta D; Jevaji, Indira P; Levy, Harvey L; Lichter-Konecki, Uta; Lindegren, Mary Lou; Lloyd-Puryear, Michele A; Matalon, Kimberlee; MacDonald, Anita; McPheeters, Melissa L; Mitchell, John J; Mofidi, Shideh; Moseley, Kathryn D; Mueller, Christine M; Mulberg, Andrew E; Nerurkar, Lata S; Ogata, Beth N; Pariser, Anne R; Prasad, Suyash; Pridjian, Gabriella; Rasmussen, Sonja A; Reddy, Uma M; Rohr, Frances J; Singh, Rani H; Sirrs, Sandra M; Stremer, Stephanie E; Tagle, Danilo A; Thompson, Susan M; Urv, Tiina K; Utz, Jeanine R; van Spronsen, Francjan; Vockley, Jerry; Waisbren, Susan E; Weglicki, Linda S; White, Desirée A; Whitley, Chester B; Wilfond, Benjamin S; Yannicelli, Steven; Young, Justin M

    2014-06-01

    New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use

  12. Classroom Demonstration of a Spot Test for Pbenylpyruvic Acid and Its Relationship to Phenylketonuria

    ERIC Educational Resources Information Center

    Halkides, Christopher J.

    2004-01-01

    Classical phenylketonuria (PKU) is caused by a lack activity in the enzyme phenylalanine hydroxylase, leading to elevated concentrations of phenylalanine in the blood. A simple demonstration and three advanced demonstrations of a spot test for phenylpyruvic acid and its relationship to phenylketonuria are given.

  13. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    PubMed

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging. PMID:26962957

  14. CRISPR RNA-guided FokI nucleases repair a PAH variant in a phenylketonuria model

    PubMed Central

    Pan, Yi; Shen, Nan; Jung-Klawitter, Sabine; Betzen, Christian; Hoffmann, Georg F.; Hoheisel, Jörg D.; Blau, Nenad

    2016-01-01

    The CRISPR/Cas9 system is a recently developed genome editing technique. In this study, we used a modified CRISPR system, which employs the fusion of inactive Cas9 (dCas9) and the FokI endonuclease (FokI-dCas9) to correct the most common variant (allele frequency 21.4%) in the phenylalanine hydroxylase (PAH) gene - c.1222C>T (p.Arg408Trp) - as an approach toward curing phenylketonuria (PKU). PKU is the most common inherited diseases in amino acid metabolism. It leads to severe neurological and neuropsychological symptoms if untreated or late diagnosed. Correction of the disease-causing variants could rescue residual PAH activity and restore normal function. Co-expression of a single guide RNA plasmid, a FokI-dCas9-zsGreen1 plasmid, and the presence of a single-stranded oligodeoxynucleotide in PAH_c.1222C>T COS-7 cells – an in vitro model for PKU – corrected the PAH variant and restored PAH activity. Also in this system, the HDR enhancer RS-1 improved correction efficiency. This proof-of-concept indicates the potential of the FokI-dCas9 system for precision medicine, in particular for targeting PKU and other monogenic metabolic diseases. PMID:27786189

  15. The use of gelatin capsules for ingestion of formula in dietary treatment of maternal phenylketonuria.

    PubMed

    Kecskemethy, H H; Lobbregt, D; Levy, H L

    1993-01-01

    Maternal phenylketonuria (PKU) represents a high risk for birth defects, including mental retardation, in offspring. Thus, it could cancel gains represented by the prevention of PKU-induced mental retardation in the current generation. Effective dietary treatment of maternal PKU pregnancies could avoid this potentially tragic occurrence. However, dietary compliance is often difficult because a necessary component of the diet, medical nutritional formulas, often have an unpleasant taste and odour. We treated the second pregnancy of a phenylketonuric women who had required extended hospitalization during her first pregnancy because of poor formula tolerance, and who had similar difficulty in the second pregnancy. To alleviate this problem, we developed a system whereby she could pack the formula into gelatin capsules for ingestion. Packing and ingestion of 20 capsules required less than 30 minutes three times a day. With capsules her blood phenylalanine level was almost always within the recommended range of 120-360 mumol/L (2-6 mg/dl) and hospitalization was not required. The phenylalanine content of the capsules was easily accommodated by a small reduction in allowable food. Other amino acid levels, including tyrosine and other essential nutrient levels, were normal. We believe that using gelatin capsules for formula ingestion can be very beneficial in the management of maternal PKU pregnancies and could be extended to the dietary treatment of other inborn errors of metabolism.

  16. Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria.

    PubMed

    Silva, L C; Pires, R F; Coelho, J C; Jardim, L B; Giugliani, R

    1997-04-01

    Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2/Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2/Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions.

  17. Management of phenylketonuria in Europe: survey results from 19 countries.

    PubMed

    Blau, Nenad; Bélanger-Quintana, Amaya; Demirkol, Mübeccel; Feillet, François; Giovannini, Marcello; MacDonald, Anita; Trefz, Friedrich K; van Spronsen, Francjan

    2010-02-01

    To gain better insight in the most current diagnosis and treatment practices for phenylketonuria (PKU) from a broad group of experts, a European PKU survey was performed. The questionnaire, consisting of 33 questions, was sent to 243 PKU professionals in 165 PKU centers in 23 European countries. The responses were compiled and descriptive analyses were performed. One hundred and one questionnaires were returned by 93/165 centers (56%) from 19/23 European countries (83%). The majority of respondents (77%) managed patients of all age groups and more than 90% of PKU teams included physicians or dieticians/nutritionists. The greatest variability existed especially in the definition of PKU phenotypes, therapeutic blood phenylalanine (Phe) target concentrations, and follow-up practices for PKU patients. The tetrahydrobiopterin (BH4; sapropterin) loading test was performed by 54% of respondents, of which 61% applied a single dose test (20mg/kg over 24h). BH4 was reported as a treatment option by 34%. This survey documents differences in diagnostic and treatment practices for PKU patients in European centers. In particular, recommendations for the treatment decision varied greatly between different European countries. There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline. PMID:19800826

  18. Congenital and Neurological Abnormalities in Infants with Phenylketonuria

    ERIC Educational Resources Information Center

    Johnson, Charles F.; And Others

    1978-01-01

    Examined was the occurrence of congenital and neurological abnormalities in 150 children with phenylketonuria (PKU--a metabolic disorder which may result in mental retardation) age 1 year or older, who have been treated with a restricted phenylalanine diet, according to the protocol used in a nation-wide longitudinal collaborative study.…

  19. The Long-Term Use of a Low-Phenylalanine Diet in Late-Treated Phenylketonuria: A Single Case Report

    ERIC Educational Resources Information Center

    Hewitt, Philippa; Cottle, Mandy; Coleman, Carol

    2006-01-01

    Background: When phenylketonuria (PKU) is not diagnosed and long-term treatment commenced within the first few weeks of life, permanent brain damage will occur. There is some evidence to show that late diagnosed or untreated people with PKU who have severe challenging behaviours may benefit from a low phenylalanine diet [Harper & Reid (1987)…

  20. Executive functioning, memory, and learning in phenylketonuria.

    PubMed

    Channon, Shelley; German, Elaine; Cassina, Cristina; Lee, Philip

    2004-10-01

    The executive deficit hypothesis of treated phenylketonuria (PKU) suggests that dopaminergic depletion in the lateral prefrontal cortex leads to selective executive impairment. This was examined by comparing adults with PKU on a lifelong diet with a matched healthy control group. Those with PKU were impaired on selective and sustained attention, working memory (Self-Ordered Pointing), and letter fluency. However, they failed to show differential sensitivity to increased cognitive load on the attentional and working memory tasks, and they did not differ significantly on the remaining executive tasks (rule finding, inhibition, and multitasking). Nor did they differ significantly on recall or recognition memory. Overall, the findings provided little support for the executive deficit hypothesis. A possible explanation in terms of slowed information processing speed is explored.

  1. Phenylketonuria: nutritional advances and challenges

    PubMed Central

    2012-01-01

    Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed. In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients. PMID:22305125

  2. How Is PKU Monitored?

    MedlinePlus

    ... people with PKU. The visit should include a blood draw, a short exam by a pediatrician, and a chance to discuss ways to manage the low-phe food pattern. The nutrition education activity for children and parent ...

  3. A cross-sectional study of docosahexaenoic acid status and cognitive outcomes in females of reproductive age with phenylketonuria.

    PubMed

    Yi, Sarah H L; Kable, Julie A; Evatt, Marian L; Singh, Rani H

    2011-04-01

    Diet therapy for phenylketonuria (PKU) requires restricted phenylalanine (Phe) intake, with the majority of protein and other nutrients coming from synthetic medical food. The fatty acid docosahexaenoic acid (DHA) is important in brain development and function; however, there are reports of low blood DHA concentrations in people treated for PKU. Although the implications of this low blood DHA are unclear, subtle cognitive deficits have been reported in those treated early and continuously for PKU. For this study, we investigated the relationship between DHA status and cognitive performance in 41 females 12 years and older with PKU. Participants were attending the baseline visit of a research-based camp or a supplementation trial. We assessed the domains of verbal ability, processing speed, and executive function using standardized tests, and the proportions of DHA in plasma and red blood cell (RBC) total lipids using gas chromatography/mass spectrometry. Percent plasma and RBC total lipid DHA were significantly lower in the participants compared with laboratory controls (P < .001), and participants consumed no appreciable DHA according to diet records. Plasma and RBC DHA both negatively correlated with plasma Phe (P < .02), and performance on the verbal ability task positively correlated with RBC DHA controlling for plasma Phe (R = .32, P = .03). The relationship between DHA and domains related to verbal ability, such as learning and memory, should be confirmed in a controlled trial. Domains of processing speed and executive function may require a larger sample size to clarify any association with DHA. PMID:21305356

  4. Nutritional status of patients with phenylketonuria in Japan.

    PubMed

    Okano, Yoshiyuki; Hattori, Toshikazu; Fujimoto, Hiroki; Noi, Kaori; Okamoto, Miki; Watanabe, Toshiaki; Watanabe, Ryoko; Fujii, Rika; Tamaoki, Tomoko

    2016-09-01

    Accumulating evidence suggests that hyperphenylalaninemia in phenylketonuria (PKU) can cause neuropsychological and psychosocial problems in diet-off adult patients, and that such symptoms improve after resumption of phenylalanine-restricted diet, indicating the need for lifetime low-phenylalanine diet. While limiting protein intake, dietary therapy should provide adequate daily intake of energy, carbohydrates, fat, vitamins, and microelements. We evaluated nutrient balance in 14 patients with classical PKU aged 4-38 years. Approximately 80-85% of the recommended dietary allowance (RDA) of protein in Japanese was supplied through phenylalanine-free (Phe-free) milk and Phe-free amino acid substitutes. Nutritional evaluation showed that the calorie and protein intakes were equivalent to the RDA. Phenylalanine intake was 9.8 ± 2.2 mg/kg of body weight/day, which maintained normal blood phenylalanine concentration by the 80% Phe-free protein rule. The protein, fat, and carbohydrate ratio was 9.5:23.9:66.6% with relative carbohydrate excess. Phe-free milk and amino acid substitutes provided 33.7% of carbohydrate, 82.1% of protein, and 66.7% of fat intake in all. Selenium and biotin intakes were 25.0% and 18.1% of the RDA and adequate intake (AI) for Japanese, respectively; both were not included in Phe-free milk. PKU patients showed low serum selenium, low urinary biotin, and high urinary 3-hydroxyisovaleric acid in this study. The intakes of magnesium, zinc, and iodine were low (71.5%, 79.5%, and 71.0% of the RDA, respectively) and that of phosphorus was 79.7% of the AI, although they were supplemented in Phe-free milk. PKU patients depend on Phe-free milk and substitutes for daily requirement of microelements and vitamins as well as protein and fat. Development of low-protein food makes it possible to achieve the aimed phenylalanine blood level, but this lowers the intake of microelements and vitamins from natural foods. The dietary habits vary continuously with

  5. Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

    ERIC Educational Resources Information Center

    Guest, J. F.; Bai, J. J.; Taylor, R. R.; Sladkevicius, E.; Lee, P. J.; Lachmann, R. H.

    2013-01-01

    Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the…

  6. Extremely high phenylalanine levels in a newborn on parenteral nutrition: phenylketonuria in the neonatal intensive care unit.

    PubMed

    Lin, H J; Kwong, A M; Carter, J M; Ferreira, B F; Austin, M F; Devarajan, K; Coleman, R J; Feuchtbaum, L B; Lorey, F; Jonas, A J

    2011-07-01

    A 1890-g newborn on total parenteral nutrition (TPN) had phenylalanine levels reaching 4164 μM indicating phenylketonuria (PKU). Review of 64 PKU cases from the California Newborn Screening Program disclosed another newborn diagnosed while on TPN. Phenylalanine levels rose five times faster with TPN, as estimated from rates in these infants. Thus, TPN use is associated with very high phenylalanine levels in newborns with PKU. When starting TPN soon after birth (for example, on day 1), early detection of PKU-by newborn screening 12 to 24 h after infusions are begun-should be helpful in limiting exposures to toxic levels of phenylalanine.

  7. Advances in the nutritional and pharmacological management of phenylketonuria

    PubMed Central

    Ney, Denise M.; Blank, Robert D.; Hansen, Karen E.

    2014-01-01

    Structural Abstract Purpose of review The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). Recent findings Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phe intact protein that represents a new dietary alternative to synthetic amino acids (AAs) for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an AA diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin (BH4), acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral AAs (LNAA) inhibit phe transport across the intestinal mucosa and blood brain barrier; LNAA are most effective for individuals unable to comply with the low-phe diet. Summary Although a low-phe synthetic AA diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to AA formula that may improve bone health, and BH4 permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management. PMID:24136088

  8. The oxidative molecular regulation mechanism of NOX in children with phenylketonuria.

    PubMed

    He, Ying-Zhong; Gu, Xue-Fan; Lu, Li-Hua; Liang, Li-Li

    2014-11-01

    Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism. In our previous work, we investigated the role of NADPH oxidase (NOX) in a Pahenu2-BTBR PKU mouse model, and an in vitro cell culture model of PKU. In the current study, we evaluated various oxidative stress parameters, namely total antioxidant capacity (T-AOC), glutathione (GSH) and maleic dialdehyde (MDA) in the plasma of 40 PKU children, for further investigating the oxidative molecular regulation mechanism of NOX in PKU. It was observed that T-AOC and GSH markedly decreased in PKU as compared with the control group (P<0.01), and seemed to correlate negatively with Phe level. However, there was no statistical difference in MDA level among the three groups. And 8-isoprostane in the blood samples of PKU2 groups was slightly higher than control group (P<0.05). Additionally, mRNA levels of subunits of NOX included p47(phox) and p67(phox) significantly increased in PKU group (P<0.01). These results reflected that NOX is the important source of reactive oxygen species and is involved in the oxidative molecular regulation mechanism in PKU, which shows a new perspective toward understanding the biological underpinnings of PKU.

  9. Multiple origins for phenylketonuria in Europe

    PubMed Central

    Eisensmith, R. C.; Okano, Y.; Dasovich, M.; Wang, T.; Güttler, F.; Lou, H.; Guldberg, P.; Lichter-Konecki, U.; Konecki, D. S.; Svensson, E.; Hagenfeldt, L.; Rey, F.; Munnich, A.; Lyonnet, S.; Cockburn, F.; Connor, J. M.; Pembrey, M. E.; Smith, I.; Gitzelmann, R.; Steinmann, B.; Apold, J.; Eiken, H. G.; Giovannini, M.; Riva, E.; Longhi, R.; Romano, C.; Cerone, R.; Naughten, E. R.; Mullins, C.; Cahalane, S.; Özalp, I.; Fekete, G.; Schuler, D.; Berencsi, G. Y.; Nász, I.; Brdicka, R.; Kamaryt, J.; Pijackova, A.; Cabalska, B.; Boszkowa, K.; Schwartz, E.; Kalinin, V. N.; Jin, L.; Chakraborty, R.; Woo, S. L. C.

    1992-01-01

    Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12nt1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population. PMID:1361100

  10. Tyrosine monitoring in children with early and continuously treated phenylketonuria: results of an international practice survey.

    PubMed

    Sharman, Rachael; Sullivan, Karen A; Young, Ross McD; McGill, James J

    2010-12-01

    Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly associated with EF deficit than phe alone. A high phe:tyr ratio is hypothesized to lead to a reduction in dopamine synthesis within the brain, which in turn results in the development of EF impairment. This paper provides a snapshot of current practice in the monitoring and/or treatment of tyrosine levels in children with PKU, across 12 countries from Australasia, North America and Europe. Tyrosine monitoring in this population has increased over the last 5 years, with over 80% of clinics surveyed reporting routine monitoring of tyrosine levels in infancy alongside phe levels. Twenty-five percent of clinics surveyed reported actively treating/managing tyrosine levels (with supplemental tyrosine above that contained in PKU formulas) to ensure tyrosine levels remain within normal ranges. Anecdotally, supplemental tyrosine has been reported to ameliorate symptoms of both attention deficit hyperactivity disorder and depression in this population. EF assessment of children with ECT-PKU was likewise highly variable, with 50% of clinics surveyed reporting routine assessments of intellectual function. However when function was assessed, test instruments chosen tended towards global measures of IQ prior to school entry, rather than specific assessment of EF development. Further investigation of the role of tyrosine and its relationship with phe and EF development is needed to establish whether routine tyrosine monitoring and increased supplementation is recommended. PMID:20882350

  11. Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria.

    PubMed

    Christ, Shawn E; Price, Mason H; Bodner, Kimberly E; Saville, Christopher; Moffitt, Amanda J; Peck, Dawn

    2016-05-01

    The most widely-reported neurologic finding in individuals with early-treated phenylketonuria (PKU) is abnormality in the white matter of the brain. In contrast, much less is known regarding the impact of PKU on cortical gray matter (GM) structures. Presently, we applied advanced morphometric methods to the analysis of high-resolution structural MRI images from a sample of 19 individuals with early-treated PKU and an age- and gender-matched comparison group of 22 healthy individuals without PKU. Data analysis revealed decreased GM volume in parietal cortex for the PKU group compared with the non-PKU group. A similar trend was observed for occipital GM volume. There was no evidence of group-related differences in frontal or temporal GM volume. Within the PKU group, we also found a significant relationship between blood phenylalanine levels and GM volume for select posterior cortical sub-regions. Taken together with previous research on white matter and gray matter abnormalities in PKU, the present findings point to the posterior cortices as the primary site of neurostructural changes related to early-treated PKU.

  12. Intellectual Assessment of 111 Four-Year-Old Children with Phenylketonuria

    ERIC Educational Resources Information Center

    Dobson, James C.; And Others

    1977-01-01

    Available from: Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A sample of 4-year-old children (n=111) with PKU (phenylketonuria) who were placed on dietary therapy between 3 and 92 days of age were assigned to two treatment groups based on "moderate" and "low" serum phenylalanine levels.…

  13. PHENYLKETONURIA, DETECTION IN THE NEWBORN INFANT AS A ROUTINE HOSPITAL PROCEDURE.

    ERIC Educational Resources Information Center

    GUTHRIE, ROBERT; WHITNEY, STEWART

    A FIELD TRIAL OF AN INHIBITION ASSAY METHOD FOR SCREENING FOR PHENYLKETONURIA (PKU) TESTED MORE THAN 400,000 NEWBORN INFANTS PRIOR TO DISCHARGE FROM THE HOSPTIAL. IN ALL, 39 CASES WERE FOUND, A HIGHER INCIDENCE THAN HAD PREVIOUSLY BEEN EXPECTED. THE PRACTICALITY OF THE INHIBITION ASSAY METHOD WAS ALSO DEMONSTRATED. THE REPORT DETAILS THE TRIAL'S…

  14. Loss of Intellectual Function in Children with Phenylketonuria after Relaxation of Dietary Phenylalanine Restriction.

    ERIC Educational Resources Information Center

    Seashore, Margretta R.; And Others

    1985-01-01

    Discontinuation at ages five to six of dietary restriction in 14 children with classic phenylketonuria (PKU--a metabolic disorder which, if untreated, is associated with mental retardation) resulted in deterioration in intellectual function for some of the Ss. Deficits included visual motor integration and cognitive problem solving. (CL)

  15. Phenylketonuria and the peoples of Northern Ireland.

    PubMed

    Zschocke, J; Mallory, J P; Eiken, H G; Nevin, N C

    1997-08-01

    The comparison of regional patterns of recessive disease mutations is a new source of information for studies of population genetics. The analysis of phenylketonuria (PKU) mutations in Northern Ireland shows that most major episodes of immigration have left a record in the modern genepool. The mutation 165T can be traced to the Palaeolithic people of western Europe who, in the Mesolithic period, first colonised Ireland. R408W (on haplotype 1) in contrast, the most common Irish PKU mutation, may have been prevalent in the Neolithic farmers who settled in Ireland after 4500 BC. No mutation was identified that could represent European Celtic populations, supporting the view that the adoption of Celtic culture and language in Ireland did not involve major migration from the continent. Several less common mutations can be traced to the Norwegian Atlantic coast and were probably introduced into Ireland by Vikings. This indicates that PKU has not been brought to Norway from the British Isles, as was previously argued. The rarity in Northern Ireland of IVS12nt1, the most common mutation in Denmark and England, indicates that the English colonialization of Ireland did not alter the local genepool in a direction that could be described as Anglo-Saxon. Our results show that the culture and language of a population can be independent of its genetic heritage, and give some insight into the history of the peoples of Northern Ireland.

  16. PKU Self-Management Timeline

    MedlinePlus

    ... language skills and becomes more interested in his environment, it will be time for him to have a role in his own PKU management. Thankfully, this process can be quite natural. One of the parents in our clinic has ...

  17. Parents of Children With PKU

    ERIC Educational Resources Information Center

    Schild, Sylvia

    1972-01-01

    Excerpted from What Do You Know About PKU," a pamphlet published by the U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, (HSM)71-5703. (Author)

  18. Optimal serum phenylalanine for adult patients with phenylketonuria.

    PubMed

    Okano, Yoshiyuki; Nagasaka, Hironori

    2013-12-01

    High serum phenylalanine in adult patients with phenylketonuria (PKU) causes neuropsychological and psychosocial problems that can be resolved by phenylalanine-restricted diet. Therefore, PKU patients must continue to adhere to phenylalanine-restricted diet for life, although the optimal serum phenylalanine level in later life has yet to be established. The purpose of this review was to establish the optimal serum phenylalanine level in later life of PKU patients. We evaluated oxidative stress status, nitric oxide metabolism, cholesterol-derived oxysterols, vitamin D and bone status, and magnetic resonance imaging (MRI) in adult PKU patients according to serum phenylalanine level. Oxidative stress increased markedly at serum phenylalanine of 700-800 μmol/L. Serum phenylalanine higher than 700-850 μmol/L correlated with the disturbance of nitric oxide regulatory system. Adult PKU patients had poor vitamin D status and exhibited predominance of bone resorption over bone formation. In the brain, the levels of 24S-hydroxycholesterol, a marker of brain cholesterol elimination, were low at serum phenylalanine levels exceeding 650 μmol/L. MRI studies showed high signal intensity in deep white matter on T2-weighted and FLAIR images of PKU patients with serum phenylalanine greater than 500 μmol/L, with decreased apparent diffusion coefficients. Changes in most parameters covering the entire body organs in adult PKU were almost acceptable below 700-800 μmol/L of phenylalanine level. However, the optimal serum phenylalanine level should be 500 μmol/L or less in later life for the brain to be safe.

  19. An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

    ERIC Educational Resources Information Center

    Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

    2011-01-01

    Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

  20. [Phenylketonuria: illness experience and coping mechanisms].

    PubMed

    Weglage, J; Fünders, B; von Teeffelen-Heithoff, A; Ullrich, K

    1993-09-01

    If patients with PKU follow a strict diet low in phenylalanine from soon after birth their intellectual and psychomotor development will be within the normal range. Recent studies have shown that it is necessary to continue the burdensome diet throughout one's life. This is in contrast to past practice and puts additional emphasis on psychosocial aspects of PKU. In the present retrospective study we investigated how adolescent patients and their relatives' experience and cope with this chronic disease. PMID:8237123

  1. Adult phenylketonuria outcome and management.

    PubMed

    Trefz, F; Maillot, F; Motzfeldt, K; Schwarz, M

    2011-01-01

    The problem to evaluate treatment outcome in adult PKU (phenylketonuric) patients lies in the heterogeneity of the adult PKU population. This heterogeneity is not only based on the different treatment history of every individual patient but also on the different severity of the underlying defect of the enzyme phenylalanine hydroxylase. Recent, partly double blind studies in adult PKU patients further support recommendation for lifelong treatment. However, it has become evident that dietary treatment is suboptimal and continuation to adulthood often not accepted. Late detected PKU patients (up to 4-6 years of age) benefit from strict dietary treatment and are able to catch up in intellectual performance. Untreated, severely retarded patients with behavioral changes may benefit from introduction of dietary treatment. However, individual decision is necessary and based on the personal situation of the patient. In early and well treated patients a number of studies have demonstrated that cognitive and neurosychologic tests are different from controls. In addition there is evidence that patients with higher blood phenylalanine (phe) levels demonstrate more often psychiatric symptoms like depression and anxiety. Medical problems are more often observed: there are certain risks as impaired growth, decreased bone mineral density and nutrional deficits probably caused by dietary treatment with an artificial protein substitute and/or missing compliance with an unpleasant diet. The long term risk of a strict dietary treatment must be balanced with the risk of higher blood phe (mean blood phenylalanine >600-900 μmol/L) on cognitive and neuropsychological functions and psychiatric symptoms. Further studies should consider the role of blood phe exposure for brain development in childhood and for brain function in all ages. Besides mean blood phe, fluctuation of blood phe over time is important. Fluctuation of blood phe is decreased by sapropterin treatment in responsive

  2. Analysis of body composition and nutritional status in Brazilian phenylketonuria patients

    PubMed Central

    Mazzola, Priscila Nicolao; Nalin, Tatiele; Castro, Kamila; van Rijn, Margreet; Derks, Terry G.J.; Perry, Ingrid D.S.; Mainieri, Alberto Scofano; Schwartz, Ida Vanessa D.

    2016-01-01

    Background Phenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to the low activity of phenylalanine-hydroxylase. PKU patients must follow a Phe-restricted diet, which may put them in risk of nutritional disturbances. Therefore, we aimed to characterize body composition parameters and nutritional status in Brazilian PKU patients also considering their metabolic control. Methods Twenty-seven treated PKU patients older than 5 years, and 27 age- and gender-matched controls, were analyzed for anthropometric features and body composition by bioelectrical impedance (BIA). Patients' metabolic control was assessed by historical Phe levels. Results There was no effect of PKU type, time of diagnosis, or metabolic control for any analyzed parameter. About 75% of patients and controls were eutrophic, according to their BMI values. There were no difference between groups regarding body composition and other BIA-derived parameters. Conclusions Brazilian PKU patients do not show differences in body composition and nutritional status in comparison with controls, regardless metabolic control. Although similar to controls, PKU patients may be in risk of disturbed nutritional and metabolic markers as seen for the general population. PMID:27014574

  3. Psychosocial issues and outcomes in maternal PKU.

    PubMed

    Koch, Richard; Trefz, Friedrich; Waisbren, Susan

    2010-01-01

    Elevated phenylalanine (Phe) levels in pregnant women with PKU are teratogenic. Fetal damage due to elevated maternal Phe levels during pregnancy is known as maternal phenylketonuria (MPKU). The risk of birth defects in MPKU, including global developmental delays, microcephaly, congenital heart disease, and low birth weight, can be dramatically reduced by controlling Phe levels during pregnancy (metabolic control). Phe levels should be maintained in the range of 120-360 micromol/L, ideally starting before pregnancy begins (i.e., when planning a pregnancy). If control is not achieved before pregnancy (e.g., if the pregnancy was unplanned), good outcomes are still possible if metabolic control is established by 8 weeks of pregnancy. Unfortunately, metabolic control before and during pregnancy can be poor. As well, many mothers stop treatment after pregnancy, which can decrease the mother's ability to focus on her child and increase her risk of behavioral and psychological problems. This can have a negative effect on the home environment. Many factors affect adherence to the strict diet used to control Phe levels, including poor access to medical care, lack of reimbursement for medical foods (in some regions, such as parts of the United States), practical difficulties with implementing the diet, financial constraints, demographics, and psychosocial issues. A comprehensive treatment approach that begins prior to pregnancy and continues after the infant is born may help to improve the management of MPKU. This approach should include education of girls about MPKU at an early age, interventions to prevent unplanned pregnancies, psychosocial support, improved treatment access and reimbursement for medical foods, and treatment guidelines. Treatments such as sapropterin may also have a role in improving metabolic control during pregnancy.

  4. PKU and Maternal PKU: The Cure and the Problem.

    ERIC Educational Resources Information Center

    Henderson, Robert A.

    1989-01-01

    A longitudinal study is evaluating the efficacy of a phenylalanine-restricted diet in reducing disabling conditions associated with maternal hyperphenylalaninemia. Titled the Maternal PKU Collaborative Study, it is studying 162 American and Canadian women and involves diet therapy, prenatal examinations, laboratory tests, nutritional evaluation,…

  5. Age-Related Psychophysiological Vulnerability to Phenylalanine in Phenylketonuria

    PubMed Central

    Leuzzi, Vincenzo; Mannarelli, Daniela; Manti, Filippo; Pauletti, Caterina; Locuratolo, Nicoletta; Carducci, Carla; Carducci, Claudia; Vanacore, Nicola; Fattapposta, Francesco

    2014-01-01

    Background: Phenylketonuria (PKU) is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). Neonatal screening programs and early treatment have radically changed the natural history of PKU. Nevertheless, an increased risk of neurocognitive and psychiatric problems in adulthood remains a challenging aspect of the disease. In order to assess the vulnerability of complex skills to Phe, we explored: (a) the effect of a rapid increase in blood Phe levels on event-related potentials (ERP) in PKU subjects during their second decade of life; (b) the association (if existing) between psychophysiological and neurocognitive features. Methods: Seventeen early-treated PKU subjects, aged 10–20, underwent ERP [mismatch negativity, auditory P300, contingent negative variation (CNV), and Intensity Dependence of Auditory Evoked Potentials] recording before and 2 h after an oral loading of Phe. Neurocognitive functioning, historical and concurrent biochemical values of blood Phe, Tyr, and Phe/Tyr ratio, were all included in the statistical analysis. Results: Event-related potential components were normally detected in all the subjects. In subjects younger than 13 CNV amplitude, W2-CNV area, P3b latency, and reaction times in motor responses were negatively influenced by Phe-loading. Independently from the psychophysiological vulnerability, some neurocognitive skills were more impaired in younger patients. No correlation was found between biochemical alterations and neurocognitive and psychophysiological findings. Conclusion: The vulnerability of the emerging neurocognitive functions to Phe suggests a strict metabolic control in adolescents affected by PKU and a neurodevelopmental approach in the study of neurocognitive outcome in PKU. PMID:25003100

  6. Recommended Guidelines for PKU Programs.

    ERIC Educational Resources Information Center

    Children's Bureau (DHEW), Washington, DC.

    A discussion of screening tests for phenylketonuria recommends and provides some data on two tests, lists five disadvantages of urine tests, and discusses three new tests. Also considered are the role of the central laboratory facility and seven suggestions for screening different types of infants at different times. Treatment or followup programs…

  7. Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino Acid-based medical foods for nutrition management of phenylketonuria.

    PubMed

    van Calcar, Sandra C; Ney, Denise M

    2012-08-01

    Phenylketonuria (PKU), an inborn error in phenylalanine metabolism, requires lifelong nutrition management with a low-phenylalanine diet, which includes a phenylalanine-free amino acid-based medical formula to provide the majority of an individual's protein needs. Compliance with this diet is often difficult for older children, adolescents, and adults with PKU. The whey protein glycomacropeptide (GMP) is ideally suited for the PKU diet because it is naturally low in phenylalanine. Nutritionally complete, acceptable medical foods and beverages can be made with GMP to increase the variety of protein sources for the PKU diet. As an intact protein, GMP improves protein use and increases satiety compared with amino acids. Thus, GMP provides a new, more physiologic source of low-phenylalanine dietary protein for people with PKU.

  8. A Systematic Review of Bone Mineral Density and Fractures in Phenylketonuria

    PubMed Central

    Hansen, Karen E.; Ney, Denise

    2014-01-01

    Introduction Our objective was to systematically review and analyze published data on bone mineral density (BMD) and fracture rates in patients with phenylketonuria (PKU), and relationships between BMD and phenylalanine levels. Methodology We searched PubMed, CINAHL and Cochrane databases from January 1966 to November 2013 for studies of spine BMD or fracture in PKU and control subjects. We excluded studies assessing skeletal health by ultrasound or peripheral quantitative computer tomography. Both authors reviewed abstracts for inclusion, and read full text papers to extract data. Results Sixteen studies met eligibility criteria. Meta-analysis of 3 studies found that spine BMD was 0.100 g/cm2 lower (95% CI, −0.110, −0.090 g/cm2) in 67 subjects with PKU, compared to 161 controls. Among 6 studies, 20% (53 of 263) of PKU subjects experienced clinical fractures. In the single study with controls, the fracture rate was 2.6 fold higher (95% CI, 1.1–6.1) after age 8 in PKU subjects, compared to healthy sibling controls. When considering a total of 12 studies in 412 subjects, 9 or 75% of studies representing 71% of studied subjects reported no association between phenylalanine levels and BMD. Summary Spine BMD is lower in PKU than control subjects, but only one study controlled for smaller body size. Existing studies suggest a clinical fracture rate of 20% among PKU subjects, but fracture rates in controls are lacking. Finally, existing data shows no consistent relationship between phenylalanine levels and BMD. Future studies are needed to clarify the etiology and health consequences of low BMD in PKU. PMID:25005329

  9. Acid-base status in dietary treatment of phenylketonuria.

    PubMed

    Manz, F; Schmidt, H; Schärer, K; Bickel, H

    1977-10-01

    Blood acid-base status, serum electrolytes, and urine pH were examined in 64 infants and children with phenylketonuria (PKU) treated with three different low phenylalanine protein hydrolyzates (Aponti, Cymogran, AlbumaidXP) and two synthetic amino acid mixtures (Aminogran, PAM). The formulas caused significant differences in acid-base status, serum potassium, and chloride, and in urine pH. In acid-base balance studies in two patients with PKU, Aponti, PAM, and two modifications of PAM (P2 + P3) were given. We observed a change from mild alkalosis to increasing metabolic acidosis from Aponti (serum bicarbonate 25,8 mval/liter) to P3 (24,0Y, P2 (19, 3) and PAM (17,0). Urine pH decreased and renal net acid excretion increased. In the formulas PAM, P2 and P3 differences in renal net acid excretion correlated with differences in chloride and sulfur contents of the diets and of the urines. New modifications of AlbumaidXP and of PAM, prepared according to our recommendations, showed normal renal net acid excretion (1 mEq/kg/24 hr) in a balance study performed in one patient with PKU and normal acid base status in 20 further patients.

  10. Phenylketonuria: a review of current and future treatments

    PubMed Central

    Al Hafid, Naz

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  11. The Use of Glycomacropeptide in Dietary Management of Phenylketonuria

    PubMed Central

    Zaki, Osama K.; El-Wakeel, Lamia; Ebeid, Yasmin; Ez Elarab, Hanan S.; Moustafa, Aisha; Abdulazim, Nayera; Karara, Hala; Elghawaby, Ahmed

    2016-01-01

    Dietary therapy is the most common therapy applied in treatment of Phenylketonuria (PKU) with restriction of intake of most natural proteins that are rich in Phenylalanine (Phe). Recently, it has been claimed that caseinoglycomacropeptide (GMP), derived of whey, may be used to replace the amino acid formulae (AAF). The Aim of Work. To study the feasibility of use of GMP for partial replacement of artificial formula in treatment of children with PKU. Methods. Ten patients with PKU were included in the study. They received the recommended daily allowances of protein in the form of AAF or a combination of AAF and GMP. The percent of intake of GMP in phases 1 and 2 was 50% and zero%, respectively. Results. The median and interquartiles of phenyl alanine Phe levels phase were not significantly different in phases I and II, 376 (167–551) μmol/L versus 490 (289–597) μmol/L, respectively. Phenylalanine/tyrosine ratio, amino acids, and other laboratory data showed no significant difference between the two phases. Conclusion. GMP may be used to replace 50% of the protein intake to improve the nutritive value and palatability of diet and to provide a more satisfactory diet. No toxicity or side effects were reported in patients on that regimen. PMID:27313877

  12. What Is the Diet for PKU?

    MedlinePlus

    ... range helps to prevent problems with thinking and problem solving. In the past, people with PKU were advised to stop their low phe diet when they were children. Most young people with PKU ... with paying attention, concentrating, and remembering. Recently, many ...

  13. Possible chemical initiators of cognitive dysfunction in phenylketonuria, Parkinson's disease and Alzheimer's disease.

    PubMed

    Soloway, Albert H; Soloway, Paul D; Warner, Victor D

    2013-10-01

    Though a great deal is known of the pathophysiology of phenylketonuria (PKU), Parkinson's disease (PD) and Alzheimer's disease (AD) very little is known regarding possible chemical species responsible for initiating the cascade of events that ultimately cause cognitive dysfunction. Can these be viewed as inborn errors in metabolism, occurring at various stages in the life cycle, analogous to adult onset diabetes? One major deficiency in understanding such conditions is the paucity of information regarding the total metabolic pathway for various amino acids that may be implicated in their causation. For example in PKU, its etiology was reported in 1934 and dietary restriction of phenylalanine proved effective for individuals with unsatisfactory metabolism of phenylalanine. Yet, current phenylalanine metabolism does not take into account fully the multiple biochemical pathways operating whose role is preventing burdensome accumulations of intermediates that can contribute to morbidity and toxicity. The same may apply for metabolism of tyrosine in PD and methionine in AD. Especially important, are the presence of labile and reactive chemical species which may be causative agents in protein alteration, misfolding and the creation of prions in neurodegenerative diseases, thereby preventing normal protein catabolism and excretion. Though genetic or epigenetic factors must be responsible, the question remains how are these translated into the chemical structures responsible for disease initiation? The purpose of this presentation is to explore potential labile metabolites in those biochemical pathways, which may be contributing factors. Finally it is worth noting, that drug development has been increasingly designed based upon targeting genetic deficiencies. The effectiveness of this approach for the treatment of these neurodegenerative illnesses will be determined in the future.

  14. Learning and behavioural difficulties but not microcephaly in three brothers resulting from undiagnosed maternal phenylketonuria.

    PubMed

    Shaw-Smith, C; Hogg, S L; Reading, R; Calvin, J; Trump, D

    2004-09-01

    Universal screening introduced in the 1960s has reduced the incidence of learning disability resulting from phenylketonuria (PKU), which is a treatable condition. Nonetheless, PKU may still be having an impact on the paediatric-age population. We report a woman with previously undiagnosed PKU who was born before the onset of universal screening. She is of normal intelligence, and so the diagnosis was not suspected until after the birth of her three children. Her serum phenylalanine concentration was found to be in excess of 1 mmol/L, well into the toxic range. She has had three sons, all of whom have a significant degree of learning disability resulting from intrauterine exposure to toxic levels of phenylalanine. None of the sons had microcephaly, a physical sign that, if present, might have helped to point towards the correct diagnosis. We suggest that maternal PKU should be suspected where there is sibling recurrence of cognitive impairment, particularly where the mother was born before the initiation of the neonatal screening programme for PKU.

  15. Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing

    PubMed Central

    Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Schwartz, Ida Vanessa Doederlein

    2016-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

  16. Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.

    PubMed

    Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Roesch, Luiz Fernando Würdig; Schwartz, Ida Vanessa Doederlein

    2016-01-01

    Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

  17. Access to treatment for phenylketonuria by judicial means in Rio Grande do Sul, Brazil.

    PubMed

    Trevisan, Luciano Mangueira; Nalin, Tatiele; Tonon, Tassia; Veiga, Lauren Monteiro; Vargas, Paula; Krug, Bárbara Corrêa; Leivas, Paulo Gilberto Cogo; Schwartz, Ida Vanessa Doederlein

    2015-05-01

    Treatment of phenylketonuria (PKU) includes the use of a metabolic formula which should be provided free of charge by the Unified Health System (SUS). This retrospective, observational study sought to characterize judicial channels to obtain PKU treatment in Rio Grande do Sul (RS), Brazil. Lawsuits filed between 2001- 2010 and having as beneficiaries PKU patients requesting treatment for the disease were included. Of 20 lawsuits filed, corresponding to 16.8% of RS patients with PKU, 19 were retrieved for analysis. Of these, only two sought to obtain therapies other than metabolic formula. In all the other 17 cases, prior treatment requests had been granted by the State Department of Health. Defendants included the State (n = 19), the Union (n = 1), and municipalities (n = 4). In 18/19 cases, the courts ruled in favor of the plaintiffs. Violation of the right to health and discontinuation of State-provided treatment were the main reasons for judicial recourse. Unlike other genetic diseases, patients with PKU seek legal remedy to obtain a product already covered by the national pharmaceutical assistance policy, suggesting that management failures are a driving factor for judicialization in Brazil.

  18. Unrestricted fruits and vegetables in the PKU diet: a 1-year follow-up.

    PubMed

    Rohde, C; Mütze, U; Schulz, S; Thiele, A G; Ceglarek, U; Thiery, J; Mueller, A S; Kiess, W; Beblo, S

    2014-03-01

    Phenylketonuria (PKU) therapy demands phenylalanine (Phe) calculation. In most countries, almost all food is taken into account, even fruits and vegetables. We investigated whether unrestricted consumption of fruits and vegetables negatively influences metabolic control. Nineteen PKU children (2-10 years) started with 2 weeks of free or restricted fruit and vegetable intake. After 2 weeks, the regime changed from free to restricted or restricted to free (cross-over design). Over the first 4 weeks, dried blood Phe concentration was measured, fruit and vegetable consumption recorded and nutrient intake calculated from diet records. Thereafter the diet was changed to free use of fruits and vegetables for all patients. Six and 12 months later, diet and Phe concentrations were monitored. Median Phe intake increased significantly by 65 mg/day (week 4, P<0.001), 68 mg/day (month 6, P<0.001) and 70 mg/day (month 12, P<0.001). Dried blood Phe concentrations remained stable (P=0.894), as did the frequency of Phe concentrations above the recommended range (P=0.592). In conclusion, PKU diet liberalization for fruits and vegetables seems unproblematic. PMID:24398645

  19. The discovery of phenylketonuria: the story of a young couple, two retarded children, and a scientist.

    PubMed

    Centerwall, S A; Centerwall, W R

    2000-01-01

    In the 1920s, a little girl 3 years of age was brought from China to the United States by her American mother. Although the child was beautiful, her mind was not developing. The grief-stricken mother had consulted doctors in China, but they could neither diagnose the problem nor provide treatment. Morning and night the same questions occupied her mind: "What is the matter with my little girl? What is causing it? Is there any doctor, anywhere, who can cure her?" In the United States, she also went from doctors to psychologists to clinics looking for someone who could help. Finally, she went to the Mayo Clinic in Rochester, Minnesota. When she had answered all of the doctor's questions, and all the tests were finished, they still could not tell her what was wrong. There was nothing they could do. The disease from which the little girl suffered was unknown at that time. The mother was Pearl Buck. In her book, The Child Who Never Grew,(1) she described her first infant: "I remember when she was only 3 months old she lay in her basket on the sun deck of a ship. I had taken her there for the morning air. The people who promenaded on deck often stopped to look at her, and my pride grew as they spoke of her unusual beauty and of the intelligent look of her deep, blue eyes. I do not know at what moment the growth of her intelligence stopped, nor to this day why it did." This is a classical description of the disease, phenylketonuria (PKU). A perfect infant seems to develop normally for several months, then the development slows and at some point seems to stop. "Look at Mommy-look at Daddy!" the parents say as they try to coax the treasured smiles. Instead, the child drifts into a dream world and into irreversible mental retardation. All Pearl Buck's devotion and determination was of no avail in finding the cause of her child's retardation. It was to be another mother with the same commitment to her beautiful but retarded children, who approximately 10 years later followed

  20. Phone-based motivational interviewing to increase self-efficacy in individuals with phenylketonuria

    PubMed Central

    Viau, Krista S.; Jones, Jessica L.; Murtaugh, Maureen A.; Gren, Lisa H.; Stanford, Joseph B.; Bilder, Deborah A.

    2016-01-01

    Objective To measure change in patient activation and self-efficacy in individuals with phenylketonuria (PKU) before and after a 6-month phone-based motivational interviewing (MI) intervention and determine the feasibility of implementing dietary counseling for PKU using an MI approach. Methods Participants (n = 31) included preadolescents (7–12 years), adolescents (13–17 years), and adults (18–35 years) with early-treated PKU. Participants completed online questionnaires assessing self-reported stage of change (SOC), patient activation, and self-efficacy for PKU self-management behaviors. The intervention included monthly phone-based dietary counseling using MI during which participants set monthly goals. Results Patient activation and self-efficacy were significantly different by age group (both p < 0.01) with higher scores in older participants. Self-efficacy significantly increased from baseline to month 6 among adolescents and adults (7.4 ± 1.9 and 8.6 ± 1.3, respectively, p = 0.002). Preadolescents did not have a significant change in self-efficacy (p = 0.79). There was no increase in patient activation for preadolescents or adolescents/adults (p = 0.19 and p = 0.24, respectively). Indicators of learning problems were not significantly associated with self-efficacy (p = 0.33) or patient activation (p = 0.83). Conclusion These results demonstrate the feasibility of implementing phone-based dietary counseling for PKU using MI. This study also supports further investigation of MI as an intervention approach to improving self-efficacy and self-management behaviors in adolescents and adults with PKU. PMID:27014576

  1. Parental problem-solving skills, stress, and dietary compliance in phenylketonuria.

    PubMed

    Fehrenbach, A M; Peterson, L

    1989-04-01

    Parents of 30 children with phenylketonuria (PKU) who were classified as being in good dietary control (compliant, measured as within the medically acceptable range of blood phenylalanine levels of 2-10 mg) or poor dietary control (noncompliant, measured as either below or above medically acceptable 2-10 mg blood phenylalanine levels) engaged in verbal and written problem-solving situations under conditions of both high and low time-pressure induced stress. Overall, compliant parents gave higher quality verbal and written problem-solving solutions than noncompliant parents. Stress reduced the quality of problem solving in both compliant and noncompliant parents, but even under high stress, compliant parents demonstrated better problem-solving abilities than noncompliant parents. The potential importance of these findings for preventive intervention in PKU families is discussed.

  2. BH4 treatment in BH4-responsive PKU patients: preliminary data on blood prolactin concentrations suggest increased cerebral dopamine concentrations.

    PubMed

    van Vliet, Danique; Anjema, Karen; Jahja, Rianne; de Groot, Martijn J; Liemburg, Geertje B; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; Derks, Terry G J; Kema, Ido P; van Spronsen, Francjan J

    2015-01-01

    In phenylketonuria (PKU), cerebral neurotransmitter deficiencies have been suggested to contribute to brain dysfunction. Present treatment aims to reduce blood phenylalanine concentrations by a phenylalanine-restricted diet, while in some patients blood phenylalanine concentrations also respond to cofactor treatment with tetrahydrobiopterin (BH4). Recently, a repurposing approach of BH4 was suggested to increase cerebral neurotransmitter synthesis. To investigate whether BH4 may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, we investigated blood prolactin concentrations-as a parameter of brain dopamine availability. We retrospectively compared blood prolactin in relation to blood phenylalanine concentrations of nine (male) BH4-responsive PKU patients, when being treated without and with BH4. Blood prolactin concentrations positively correlated to blood phenylalanine concentrations (p=0.002), being significantly lower with than without BH4 treatment (p=0.047). In addition, even in this small number of male patients, blood prolactin concentrations tended to be lower at increasing BH4 dose (p=0.054), while taking blood phenylalanine concentrations into account (p=0.002). In individual BH4-responsive patients, median blood prolactin concentrations were significantly lower while using BH4 than before using BH4 treatment (p=0.024), whereas median blood phenylalanine concentrations tended to be lower, but this did not reach statistical significance (p=0.107). Therefore, these data show that high blood phenylalanine in BH4-responsive PKU male patients seems to be associated with increased blood prolactin concentrations, suggesting reduced cerebral dopamine availability. Moreover, these data suggest that BH4 treatment in itself could decrease blood prolactin concentrations in a dose-responsive way, independent of blood phenylalanine concentrations. We conclude that these preliminary data

  3. Phenylketonuria mutation analysis in Northern Ireland: A rapid stepwise approach

    SciTech Connect

    Zschocke, J.; Graham, C.A.; Nevin, N.C.

    1995-12-01

    We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, 165T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting. 19 refs., 5 tabs.

  4. Depression and anxiety among parents of phenylketonuria children

    PubMed Central

    Gunduz, Mehmet; Arslan, Nur; Unal, Ozlem; Cakar, Sevim; Kuyum, Pınar; Bulbul, Selda F.

    2015-01-01

    Objective: To investigate the existence of depression and/or anxiety with underlying risk factors among parents of children with classical phenylketonuria (PKU). Methods: This cross-sectional study was conducted in the Division of Pediatric Metabolism, Ankara Children’s Hospital, Dokuz Eylul University, Kırıkkale University, and Erzurum Local Research Hospital, Turkey, between January and July 2014. Parents of 61 patients and 36 healthy controls completed the self-report questionnaires. We used Beck Depression Inventory (BDI) to assess the parental depression and State-Trait Anxiety Inventory S-T (STAI S-T) to assess parental anxiety. Results: Depression and anxiety scores were significantly higher in the case group (BDI 12.3±9.1; STAI-S: 38.2±9.6; STAI-T: 43.2±6.9) than controls (BDI: 5.4±4.1 p=0.000; STAI-S: 31.8±7.6 p=0.001; STAI-T: 37.0±7.2 p=0.000). Mothers of the patients had higher scores than the other parental groups (BDI: p=0.000, STAI-S: p=0.001 and STAI-T: p=0.000). Logistic regression analysis showed that low educational level of the parent was the only independent factor for depression (OR 9.96, 95% CI: 1.89-52.35, p=0.007) and state anxiety (OR: 6.99, 95% CI: 1.22-40.48, p=0.030) in the case group. Conclusion: A subset of parents with PKU patients have an anxiety or depressive disorder. Supportive services dealing with the parents of chronically ill children such as PKU are needed in order to reduce the level of anxiety. PMID:26492114

  5. Effect of high-protein meal plus aspartame ingestion on plasma phenylalanine concentrations in obligate heterozygotes for phenylketonuria.

    PubMed

    Curtius, H C; Endres, W; Blau, N

    1994-04-01

    The effect of a protein-rich meal alone or in combination with 85 mumol/kg body weight aspartame (APM) on plasma phenylalanine and large neutral amino acids (LNAA) was evaluated in obligate heterozygotes for phenylketonuria (PKU) and normal subjects (controls). Thirteen PKU heterozygotes (seven women, six men) and 13 controls (five women, eight men) ingested a 12-noon meal providing approximately 303 mumol/kg Phe. In addition, 10 PKU heterozygotes (five women, five men) and 10 controls (five women, five men) ingested the same meal with 85 mumol/kg APM (providing 75 mumol/kg Phe). Plasma amino acids were analyzed at baseline (-4 and 0 hours) and at 1, 3, and 20 hours after the meal or meal plus APM. Compared with the meal alone, ingestion of the meal plus APM significantly increased plasma Phe concentrations in both controls and PKU heterozygotes. Mean plasma Phe values were higher for controls at 1 hour (95 +/- 7 mumol/L) and for PKU heterozygotes at 3 hours (153 +/- 21 mumol/L). After the addition of APM to the meal, the highest mean plasma Phe concentration was only slightly greater than the usual postprandial range for both controls and PKU heterozygotes. Ingestion of the meal did not increase the plasma Phe/LNAA ratio in either controls or PKU heterozygotes. Compared with baseline, the plasma Phe/LNAA ratio increased significantly 1 hour after combined ingestion of the meal plus APM in both groups (P = .020 and P = .008, respectively); however, the ratios were well below the range of Phe/LNAA values in individuals with mild hyperphenylalaninemia, who are clinically normal and do not require a Phe-restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria

    PubMed Central

    Bruinenberg, Vibeke M.; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C.; Kuhn, Mirjam; van Spronsen, Francjan J.; van der Zee, Eddy A.

    2016-01-01

    The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice. PMID:27102170

  7. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria.

    PubMed

    Bruinenberg, Vibeke M; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C; Kuhn, Mirjam; van Spronsen, Francjan J; van der Zee, Eddy A

    2016-01-01

    The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice. PMID:27102170

  8. Phenylalanine hydroxylase gene mutations in the United States: Report from the maternal PKU collaborative study

    SciTech Connect

    Guldberg, P.; Henriksen, K.F.; Guettler, F.

    1996-07-01

    The major cause of hyperphenylalaninemia is mutations in the gene encoding phenylalanine hydroxylase (PAH). The known mutations have been identified primarily in European patients. The purpose of this study was to determine the spectrum of mutations responsible for PAH deficiency in the United States. One hundred forty-nine patients enrolled in the Maternal PKU Collaborative Study were subjects for clinical and molecular investigations. PAH gene mutations associated with phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) were identified on 279 of 294 independent mutant chromosomes, a diagnostic efficiency of 95%. The spectrum is composed of 71 different mutations, including 47 missense mutations, 11 splice mutations, 5 nonsense mutations, and 8 microdeletions. Sixteen previously unreported mutations were identified. Among the novel mutations, five were found in patients with MHP, and the remainder were found in patients with PKU. The most common mutations were R408W, IVS12nt1g{r_arrow}a, and Y414C, accounting for 18.7%, 7.8% and 5.4% of the mutant chromosomes, respectively. Thirteen mutations had relative frequencies of 1%-5%, and 55 mutations each had frequencies {le}1%. The mutational spectrum corresponded to that observed for the European ancestry of the U.S. population. To evaluate the extent of allelic variation at the PAH locus within the United States in comparison with other populations, we used allele frequencies to calculate the homozygosity for 11 populations where >90% ascertainment has been obtained. The United States was shown to contain one of the most heterogeneous populations, with homozygosity values similar to Sicily and ethnically mixed sample populations in Europe. The extent of allelic heterogeneity must be a major determining factor in the choice of mutation-detection methodology for molecular diagnosis in PAH deficiency. 47 refs., 1 fig., 5 tabs.

  9. Utility of phenylalanine hydroxylase genotype for tetrahydrobiopterin responsiveness classification in patients with phenylketonuria

    PubMed Central

    Quirk, Meghan E.; Dobrowolski, Steven F.; Nelson, Benjamin E.; Coffee, Bradford; Singh, Rani H.

    2014-01-01

    Background A need exists to expand the characterization of tetrahydrobiopterin (BH4) responsiveness in patients with phenylketonuria (PKU), beyond simply evaluating change in blood phenylalanine concentrations. The clinical interpretation of BH4 responsiveness should be evaluated within the context of phenylalanine hydroxylase (PAH) genotype. Aim This investigation seeks to use a modified version of a previously developed PAH genotype severity tool, the assigned value (AV) sum, to assess the molecular basis of responsiveness in a clinical cohort and to explore the tool’s ability to differentiate BH4 responsive groups. Methods BH4 response was previously clinically classified in 58 patients with PKU, with three response groups emerging: definitive responders, provisional responders, and non-responders. Provisional responders represented a clinically ambiguous group, with an initial decrease in plasma phenylalanine concentrations, but limited ability to improve dietary phenylalanine tolerance. In this retrospective analysis, mutations in the PAH gene were identified in each patient. PAH genotype was characterized through the AV sum approach, in which each mutation is given an AV of 1, 2, 4, or 8; the sum of both mutations’ AV corresponds to genotype severity, with a lower number representing a more severe phenotype. An AV sum cutoff of 2 (indicative of the most severe genotypes) was used to dichotomize patients and predict BH4 responsiveness. Provisional responders were classified with the definitive responders then the non-responders to see with which group they best aligned. Results In 17/19 definitive responders, at least one mutation was mild or moderate in severity (AV sum>2). In contrast, 7/9 provisional responders carried two severe or null mutations (AV sum=2), suggesting little molecular basis for responsiveness. Non-responders represent a heterogeneous group with 15/25 patients carrying two severe mutations (AV sum=2), 5/25 patients carrying one

  10. Variability in phenylalanine control predicts IQ and executive abilities in children with phenylketonuria.

    PubMed

    Hood, Anna; Grange, Dorothy K; Christ, Shawn E; Steiner, Robert; White, Desirée A

    2014-04-01

    A number of studies have revealed significant relationships between cognitive performance and average phenylalanine (Phe) levels in children with phenylketonuria (PKU), but only a few studies have been conducted to examine the relationships between cognitive performance and variability (fluctuations) in Phe levels. In the current study, we examined a variety of indices of Phe control to determine which index best predicted IQ and executive abilities in 47 school-age children with early- and continuously-treated PKU. Indices of Phe control were mean Phe, the index of dietary control, change in Phe with age, and several indices of variability in Phe (standard deviation, standard error of estimate, and percentage of spikes). These indices were computed over the lifetime and during 3 developmental epochs (<5, 5.0-9.9, and ≥10 years of age). Results indicated that variability in Phe was generally a stronger predictor of cognitive performance than other indices of Phe control. In addition, executive performance was better predicted by variability in Phe during older than younger developmental epochs. These results indicate that variability in Phe should be carefully controlled to maximize cognitive outcomes and that Phe control should not be liberalized as children with PKU age. PMID:24568837

  11. Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes.

    PubMed

    Cleary, Maureen; Trefz, Friedrich; Muntau, Ania C; Feillet, François; van Spronsen, Francjan J; Burlina, Alberto; Bélanger-Quintana, Amaya; Giżewska, Maria; Gasteyger, Christoph; Bettiol, Esther; Blau, Nenad; MacDonald, Anita

    2013-12-01

    Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.

  12. Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria.

    PubMed

    Stegink, L D; Filer, L J; Bell, E F; Ziegler, E E; Tephly, T R; Krause, W L

    1990-10-01

    Six adults heterozygous for phenylketonuria (PKU) ingested eight successive servings of unsweetened and aspartame (APM)-sweetened beverage at 1-hour intervals in a randomized, balanced, crossover design. In one part, the eight beverage servings were not sweetened. In the other, each of the eight beverage servings provided 600 mg of APM, a dose equivalent to the amount provided by 36 oz of an APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine concentrations 2.35 to 4.03 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady-state after administration of five servings of APM-sweetened beverage and were slightly, but significantly higher than usual postprandial values for adults heterozygous for PKU. Similarly, the ratio of the plasma phenylalanine concentration to the sum of the concentration of the large neutral amino acids was significantly higher than usual postprandial values. Blood methanol and formate concentrations remained within normal limits. These data indicate that a fasting adult heterozygous for PKU could consume the equivalent of 24 12-oz servings of APM-sweetened beverage over an 8-hour period and only increase plasma phenylalanine concentration to a modest degree.

  13. Child and Parent Attributions in Chronic Pediatric Conditions: Phenylketonuria (PKU) as an Exemplar

    ERIC Educational Resources Information Center

    Antshel, Kevin M.; Brewster, Scott; Waisbren, Susan E.

    2004-01-01

    Background: Attribution theory, self-regulation, self-handicapping and sick role theories all suggest that children with chronic disease may be held to different standards. This study assesses child and parent attributions in pediatric chronic health conditions and addresses how attributional style may be related to treatment adherence. Methods:…

  14. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    PubMed

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  15. Shape analysis of corpus callosum in phenylketonuria using a new 3D correspondence algorithm

    NASA Astrophysics Data System (ADS)

    He, Qing; Christ, Shawn E.; Karsch, Kevin; Peck, Dawn; Duan, Ye

    2010-03-01

    Statistical shape analysis of brain structures has gained increasing interest from neuroimaging community because it can precisely locate shape differences between healthy and pathological structures. The most difficult and crucial problem is establishing shape correspondence among individual 3D shapes. This paper proposes a new algorithm for 3D shape correspondence. A set of landmarks are sampled on a template shape, and initial correspondence is established between the template and the target shape based on the similarity of locations and normal directions. The landmarks on the target are then refined by iterative thin plate spline. The algorithm is simple and fast, and no spherical mapping is needed. We apply our method to the statistical shape analysis of the corpus callosum (CC) in phenylketonuria (PKU), and significant local shape differences between the patients and the controls are found in the most anterior and posterior aspects of the corpus callosum.

  16. A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement.

    PubMed

    Guldberg, P; Zschocke, J; Dagbjartsson, A; Henriksen, K F; Güttler, F

    1997-01-01

    Iceland was settled during the late 9th and early 10th centuries AD by Vikings who arrived from Norway and the British Isles. Although it is generally acknowledged that the Vikings brought with them Celtic slaves, the relative contribution of these peoples to the modern Icelandic gene pool has been a matter of considerable discussion. Most population genetic studies using classical markers have indicated a large Irish genetic contribution. We have investigated the molecular basis of phenylketonuria (PKU) in 17 Icelandic patients and found 9 different mutations in the phenylalanine hydroxylase gene. One novel mutation, Y377fsdelT, accounts for more than 40% of the mutant chromosomes. Haplotype data support a common ancestral origin of the mutation, and genealogical examination extending back more than 5 generations shows that this mutation has probably arisen in an isolated part of southern Iceland and was enriched by a founder effect. At least 7 PKU mutations have originated outside iceland. The almost exclusively Scandinavian background of these mutations and the complete absence of common Irish PKU mutations strongly support historical and linguistic evidence of a predominant Scandinavian heritage of the Icelandic people.

  17. Time and space clusters of the French-Canadian MIV phenylketonuria mutation in France

    PubMed Central

    Lyonnet, Stanislas; Melle, Dominique; de Braekeleer, Marc; Laframboise, Rachel; Rey, Françoise; John, Simon W. M.; Berthelon, Monique; Berthelot, Jacques; Journel, Hubert; Le Marec, Bernard; Parent, Philippe; de Parscau, Loïc; Saudubray, Jean-Marie; Rozen, Rima; Rey, Jean; Munnich, Arnold; Scriver, Charles R.

    1992-01-01

    We performed mutation analysis and RFLP haplotype analysis of chromosomes associated with classical phenylketonuria (PKU) in contemporary French families. We also did genealogical reconstructions for seven obligate carriers in five contemporary French-Canadian families living in eastern Quebec, who carry the M1V mutation causing PKU. The M1V mutation, heretofore considered to be associated exclusively with French-Canadians, was found on 4 of 152 independent French chromosomes. The French and Quebec M1V mutations all occurred on RFLP haplotype 2. The contemporary mutant French chromosomes clustered in southern Brittany (Finistère Sud). Genealogical reconstructions of the Quebec families identified 53 shared ancestors and a center of diffusion in the Perche region in 17th century France. The two clusters in France, one historical and the other contemporary, are not incompatible, if one assumes the possibilities that settlers returned from Nouvelle France or moved from Perche to southern Brittany. The M1V mutation is serving as a useful marker for historical demography. ImagesFigure 1Figure 3 PMID:1609797

  18. Mutations of the phenylalanine hydroxylase gene in Iranian patients with phenylketonuria.

    PubMed

    Biglari, Alireza; Saffari, Fatemeh; Rashvand, Zahra; Alizadeh, Safarali; Najafipour, Reza; Sahmani, Mehdi

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene. The aim of this study was the identification of sixteen different mutations in Iranian patients with hyperphenylalaninemia. The mutations were detected during the characterization of PAH genotypes of 39 PKU patients from Qazvin and Zanjan provinces of Iran. PAH mutations have been analyzed by PCR and direct sequencing of PCR products of the promoter region and all 13 exons of PAH gene, including the splicing sites. A mutation detection rate of 74.3 % was realized. Two mutations were found at high frequencies: R176X (10.25 %) and p.P281L (10.25 %). The frequencies of the other mutations were: IVS2+5G>A (2.56 %), IVS2+5G>C (2.56 %), p.L48S (2.56 %), p.R243Q (2.56 %), p.R252Q (5.12 %), p.R261Q (7.69 %), p.R261X (5.12 %), p.E280K (2.56 %), p.I283N (2.56 %), IVS9+5G>A (2.56 %), IVS9+1G>A (1.28 %), IVS11+1G>C (1.28 %), p.C357R (1.28 %), c.632delC (2.56 %). The present results confirm the high heterogeneity of the PAH locus and contribute to information about the distribution and frequency of PKU mutations in the Iranian population. PMID:26413448

  19. The Electro-Encephalogram in Phenylketonuria

    ERIC Educational Resources Information Center

    Todd, Peter G.; Pitt, D. B.

    1973-01-01

    Evaluated were electroencephalographic findings in 24 untreated (ages from 4 to 38 years) patients suffereing from phenylketonuria (a metabolic disorder producing severe mental retardation if not treated with proper diet during the early years). (DB)

  20. An Objective Approach to Measurement of Interpersonal Behavior in Phenylketonuria

    ERIC Educational Resources Information Center

    Friedman, C. J.; And Others

    1971-01-01

    Among the findings were that PKU Children judged to be emotionally disturbed and inadequate in communication performed more poorly than those PKU children judged nondisturbed and more adequate in communication under two of the three social stimulus interaction condictions. (Author)

  1. Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters

    PubMed Central

    Yano, Shoji; Moseley, Kathryn; Fu, Xiaowei; Azen, Colleen

    2016-01-01

    Background Phenylketonuria (PKU) is due to a defective hepatic enzyme, phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU. Objective (1) To evaluate the effects of sapropterin (BH4) and concurrent use of large neutral amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2) To evaluate synergistic effects with BH4 and LNAA. (3) To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations. Methods Nine adults with PKU completed our study consisting of four 4-week phases: (1) LNAA supplementation, (2) Washout, (3) BH4 therapy, and (4) LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase. Results (1) Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2) Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3) The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005) with a trend toward differing slopes among individual subjects (p = 0.066). There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047). Conclusion Blood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring

  2. [Management of patients with phenylketonuria in Mexico].

    PubMed

    Carnevale, A; Velázquez, A; Ruíz, F; Del Castillo, V

    1979-01-01

    This paper shows the results of the dietary management of 9 children with phenylketonuria diagnosed at the Clinic for Inborn Errores of Metabolism of the Hospital del Niño-Instituto de Investigaciones Biomédicas UNAM. The age at which the diet was instituted was variable: in one case before the age of 8 weeks; in another one at 5 months and in the remainder after 10 months. The management is multidisciplinary and involves a geneticist, a pediatrician, a neurologist a psychologist, a nutritionist, and a social worker. In spite of the difficult control of the diet in some patients, in most cases satisfactory phenylalanine levels were maintained most of the time. The body growth and development have been normal. With regard to the mental development, the results support the importance of an early diagnosis since the case treated from the age of one month has shown normal development; the patient diagnosed at 5 months has had a low normal IQ and the rest, all diagnosed after 10 months of age, show some improvement, but do not reach normal levels. The need of neonatal screening for early diagnosis is emphazised.

  3. Complexities of Parental Understanding of Phenylketonuria

    ERIC Educational Resources Information Center

    Sibinga, Maarten S.; Friedman, C. Jack

    1971-01-01

    Parental understanding of PKU, investigated through a questionnaire, was evaluated as to completeness and with respect to distortion. Education of parents was found to be unrelated to their understanding or tendency to distort. Effectiveness of the pediatrician's communication with parents is discussed. (Author/KW)

  4. Intense beams from gases generated by a permanent magnet ECR ion source at PKU.

    PubMed

    Ren, H T; Peng, S X; Lu, P N; Yan, S; Zhou, Q F; Zhao, J; Yuan, Z X; Guo, Z Y; Chen, J E

    2012-02-01

    An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about 120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and 65 mA of He(+) extracted at 50 kV through a φ 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 π mm mrad. Tungsten samples were irradiated by H(+) or He(+) beam extracted from this ion source and H∕He holes and bubbles have been observed on the samples. A method to produce a high intensity H∕He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He(+) beam injector for coupled radio frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He(+) beam. PMID:22380337

  5. Intense beams from gases generated by a permanent magnet ECR ion source at PKU

    SciTech Connect

    Ren, H. T.; Chen, J. E.; Peng, S. X.; Lu, P. N.; Yan, S.; Zhou, Q. F.; Zhao, J.; Yuan, Z. X.; Guo, Z. Y.

    2012-02-15

    An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O{sup +}, H{sup +}, and D{sup +} to N{sup +}, Ar{sup +}, and He{sup +}. Up to now, about 120 mA of H{sup +}, 83 mA of D{sup +}, 50 mA of O{sup +}, 63 mA of N{sup +}, 70 mA of Ar{sup +}, and 65 mA of He{sup +} extracted at 50 kV through a {phi} 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 {pi} mm mrad. Tungsten samples were irradiated by H{sup +} or He{sup +} beam extracted from this ion source and H/He holes and bubbles have been observed on the samples. A method to produce a high intensity H/He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He{sup +} beam injector for coupled radio frequency quadruple and SFRFQ cavity, He{sup +} beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He{sup +} beam.

  6. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial

    PubMed Central

    ten Hoedt, Amber E.; de Sonneville, Leo M. J.; Francois, Baudouin; ter Horst, Nienke M.; Janssen, Mirian C. H.; Rubio-Gozalbo, M. Estela; Wijburg, Frits A.; Hollak, Carla E. M.

    2010-01-01

    The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients’ mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted “diet for life” might be an advisable option for many. PMID:21153445

  7. Phenylketonuria and Complex Spatial Visualization: An Analysis of Information Processing.

    ERIC Educational Resources Information Center

    Brunner, Robert L.; And Others

    1987-01-01

    The study of the ability of 16 early treated phenylketonuric (PKU) patients (ages 6-23 years) to solve complex spatial problems suggested that choice of problem-solving strategy, attention span, and accuracy of mental representation may be affected in PKU patients, despite efforts to maintain well-controlled phenylalanine concentrations in the…

  8. Heat-transfer-based detection of SNPs in the PAH gene of PKU patients.

    PubMed

    Vanden Bon, Natalie; van Grinsven, Bart; Murib, Mohammed Sharif; Yeap, Weng Siang; Haenen, Ken; De Ceuninck, Ward; Wagner, Patrick; Ameloot, Marcel; Vermeeren, Veronique; Michiels, Luc

    2014-01-01

    Conventional neonatal diagnosis of phenylketonuria is based on the presence of abnormal levels of phenylalanine in the blood. However, for carrier detection and prenatal diagnosis, direct detection of disease-correlated mutations is needed. To speed up and simplify mutation screening in genes, new technologies are developed. In this study, a heat-transfer method is evaluated as a mutation-detection technology in entire exons of the phenylalanine hydroxylase (PAH) gene. This method is based on the change in heat-transfer resistance (R(th)) upon thermal denaturation of dsDNA (double-stranded DNA) on nanocrystalline diamond. First, ssDNA (single-stranded DNA) fragments that span the size range of the PAH exons were successfully immobilized on nanocrystalline diamond. Next, it was studied whether an R(th) change could be observed during the thermal denaturation of these DNA fragments after hybridization to their complementary counterpart. A clear R(th) shift during the denaturation of exon 5, exon 9, and exon 12 dsDNA was observed, corresponding to lengths of up to 123 bp. Finally, R(th) was shown to detect prevalent single-nucleotide polymorphisms, c.473G>A (R158Q), c.932T>C (p.L311P), and c.1222C>T (R408W), correlated with phenylketonuria, displaying an effect related to the different melting temperatures of homoduplexes and heteroduplexes.

  9. Newborn screening 50 years later: access issues faced by adults with PKU.

    PubMed

    Berry, Susan A; Brown, Christine; Grant, Mitzie; Greene, Carol L; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C; Wiles, Judy; Cederbaum, Stephen

    2013-08-01

    Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.

  10. PKU-RBRC Workshop on Transverse Spin

    SciTech Connect

    Avakian,H.; Bunce, G.; Yuan, F.

    2008-06-30

    Understanding the structure of the nucleon is a fundamental question in subatomic physics, and it has been under intensive investigation for the last several years. Modern research focuses in particular on the spin structure of the nucleon. Experimental and theoretical investigations worldwide over the last few decades have established that, contrary to nave quark model expectations, quarks carry only about 30% of the totd spin of the proton. The origin of the remaining spin is the key question in current hadronic physics and also the major driving forces for the current and future experiments, such as RHIC and CEBAF in US, JPARC in Japan, COMPASS at CERN in Europe, FAIR at GSI in Germany. Among these studies, the transverse-spin physics develops actively and rapidly in the last few years. Recent studies reveal that transverse-spin physics is closely related to many fundamental properties of the QCD dynamics such as the factorization, the non-trivial universality of the parton distribution and fragmentation functions. It was very timely to bring together the theorists and experimentalists in this field at this workshop to review and discuss the latest developments and future perspective in hadronic spin physics. This workshop was very success iu many aspects. First of all, it attracted almost every expert working in this field. We had more than eighty participants in total, among them 27 came from the US institutes, 13 from Europe, 3 from Korea, and 2 from Japan. The rest participants came from local institutes in China. Second, we arranged plenty physics presentations, and the program covers all recent progresses made in the last few years. In total, we had 47 physics presentations, and two round table discussions. The discussion sessions were especially very useful and very much appreciated by all participants. In addition, we also scheduled plenty time for discussion in each presentation, and the living discussions impressed and benefited all participants.

  11. Application of natural and amplification created restriction sites for the diagnosis of PKU mutations.

    PubMed Central

    Eiken, H G; Odland, E; Boman, H; Skjelkvåle, L; Engebretsen, L F; Apold, J

    1991-01-01

    PCR amplification, either conventional, or as site directed mutagenesis using primers with mismatched 3'-ends, followed by restriction endonuclease digestion, provides rapid, non-isotope assays of known mutations in the human phenylalanine hydroxylase gene. Such assays were shown to have the potential to detect all of the 18 presently reported phenylketonuria mutations. The practical applicability of this approach was demonstrated for eight mutations in Norwegian phenylketonuria patients, among them the most common ones. Images PMID:1851292

  12. Psychosocial factors in maternal phenylketonuria: women's adherence to medical recommendations.

    PubMed Central

    Waisbren, S E; Hamilton, B D; St James, P J; Shiloh, S; Levy, H L

    1995-01-01

    OBJECTIVES. This study identified factors predicting adherence to medical recommendations in maternal phenylketonuria, which can result in severe fetal damage. METHODS. Sixty-nine women with phenylketonuria, 68 of their acquaintances, and 69 women with diabetes mellitus were interviewed annually for 5 years. A model in which each stage in the maternal phenylketonuria life cycle represented a treatment-related goal provided a means to assess adherence. RESULTS. At the stages of prevention of unplanned pregnancy, treatment initiation, and diet continuation throughout pregnancy, attitudes and social support were associated with adherence to medical recommendations. No specific variables were associated with outcome at reproductive decision making, but women with phenylketonuria were more likely to delay making a decision, resulting in unplanned and, hence, untreated or late-treated pregnancy. CONCLUSIONS. Women with phenylketonuria differed from their acquaintances and diabetic women in many respects, suggesting that special programs are needed. Greater emphasis on reproductive decision making is especially needed. Interventions that focus on improving social support networks and attitudes about treatment may increase adherence to recommendations. PMID:7503337

  13. Phenylketonuria presenting in adulthood as progressive spastic paraparesis with dementia

    PubMed Central

    Kasim, S; Moo, L; Zschocke, J; Jinnah, H

    2001-01-01

    A 57 year old woman living independently in the community presented with four years of progressive spastic paraparesis and dementia. An extensive evaluation for the usual causes of these difficulties was unrevealing, but her serum phenylalanine concentration was markedly elevated and genetic analysis demonstrated mutations in the phenylalanine hydroxylase gene consistent with classic phenylketonuria. A protein restricted diet was associated with improvement in her condition. Although untreated phenylketonuria is typically associated with severe neurological dysfunction beginning in early childhood, this case shows that disability may be delayed until adulthood.

 PMID:11723206

  14. Collaborative Study of Children Treated for Phenylketonuria: Study Design

    ERIC Educational Resources Information Center

    Williamson, Malcolm; And Others

    1977-01-01

    Available from: Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. Described is a study in which a large sample of children (n=444) with phenylketonuria (an inborn metabolic error usually related to impaired cognitive ability) were treated under controlled conditions from near birth to 6 years of age.…

  15. PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

    ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

  16. Phase 1 Trial of Subcutaneous rAvPAL-PEG in Subjects with Phenylketonuria

    PubMed Central

    Longo, Nicola; Harding, Cary O.; Burton, Barbara K.; Grange, Dorothy K.; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M.; Musson, Donald G.; Gu, Zhonghua; Sile, Saba

    2014-01-01

    Objective Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. A phenylalanine-restricted diet initiated early in life can ameliorate the toxic effects of phenylalanine. However, the diet is onerous and compliance is extremely difficult. Phenylalanine ammonia lyase (PAL) is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. This Phase 1, multicenter clinical trial evaluated the safety, tolerability, pharmacokinetics and efficacy of rAvPAL-PEG (recombinant Anabaena variabilis PAL produced in E. coli conjugated with polyethylene glycol [PEG] to reduce immunogenicity) in reducing phenylalanine levels in subjects with phenylketonuria. Methods Single subcutaneous injections of rAvPAL-PEG in escalating doses (0·001, 0·003, 0·01, 0·03, and 0·1 mg/kg) were administered to 25 adults with phenylketonuria recruited from those attending metabolic clinics in North America whose blood phenylalanine concentrations were ≥600 μmol/L. Results The most frequently reported adverse events were injection-site reactions and dizziness. Reactions were self-limited without sequelae. During the trial, two subjects had adverse reactions to intramuscular (IM) medroxyprogesterone acetate, a drug containing polyethylene glycol as an excipient. Three subjects developed a generalized skin rash at the highest rAvPAL-PEG dose (0·1 mg/kg). Drug levels peaked ∼5 days after the injection. Treatment was effective in reducing blood phenylalanine in all five subjects receiving the highest dose (0·1 mg/kg, mean percent change of -58 from baseline), with a nadir ∼6 days after injection and inverse correlation between drug and phenylalanine concentrations in plasma. Phenylalanine concentrations returned to near-baseline levels ∼20 days after the single injection. Conclusions

  17. Results of loading doses of aspartame by two phenylketonuric (PKU) children compared with two normal children.

    PubMed

    Koch, R; Schaeffler, G; Shaw, N F

    1976-11-01

    Separate tolerance tests with aspartame at 34 mg/kg-day and phenylalanine at 19 mg/kg-day were compared. The results reveal that slight serum elevation of phenylalanine and tyrosine occurred in the two PKU and the normal healthy adolescents. It would appear that the phenylalanine in the sweetener aspartame is small enough to be of little clinical significance.

  18. The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply

    PubMed Central

    Thiele, Alena G.; Rohde, Carmen; Mütze, Ulrike; Arelin, Maria; Ceglarek, Uta; Thiery, Joachim; Baerwald, Christoph; Kiess, Wieland; Beblo, Skadi

    2015-01-01

    Background and aims BH4-sensitive phenylketonuria (PKU) patients relax their phenylalanine (Phe) restricted diet due to increased Phe tolerance, while keeping dried blood Phe concentrations with in the therapeutic range. We aimed to investigate metabolic control, eating habits and nutrient supply under long-term BH4-therapy. Patients and methods Retrospective analysis of mean dried blood Phe concentrations and their variability, food and nutrient intake in BH4-sensitive patients (n = 8, 3f, age 6.0–16.6 y) under classical dietary treatment for one year and during the three years after initiation of BH4. Results Phe concentrations of BH4-sensitve PKU patients remained within therapeutic range throughout the observation period, independent of therapeutic regime. Under BH4, Phe tolerance increased significantly (493.2 ± 161.8 mg/d under classical diet vs 2021.93 ± 897.4 mg/d two years under BH4; P = 0.004). Variability of Phe concentrations remained unchanged (mean SD; P = 1.000). Patients adjust their food choice and significantly increased their intake of cereals, potatoes, dairy products and meat (P = 0.019, P = 0.016, P = 0.016 and P = 0.016, respectively). Under diet changes after implementation of BH4 a drop in micronutrient intake (vitamin D, folic acid, iron, calcium, iodine) could be revealed (P = 0.005, P < 0.001, P = 0.004, P = 0.001, P = 0.003, respectively). Conclusions BH4-sensitive PKU patients can achieve good metabolic control under an adjuvant BH4- or a BH4 monotherapy. The liberalized diet under BH4 seems to jeopardize the quality of patients' nutrition, and these patients require close follow-up and special nutrition education to minimize the risk for imbalanced diet and nutrient deficiencies. PMID:26937412

  19. Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

    ERIC Educational Resources Information Center

    Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

    1997-01-01

    Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

  20. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  1. Preservation of high phenylalanine ammonia lyase activities in roots of Japanese Striped corn: a potential oral therapeutic to treat phenylketonuria.

    PubMed

    López-Villalobos, Arturo; Lücker, Joost; López-Quiróz, Ana Angela; Yeung, Edward C; Palma, Kristoffer; Kermode, Allison R

    2014-06-01

    Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, the enzyme responsible for the disposal of excess amounts of the essential amino acid phenylalanine (Phe). Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) has potential to serve as an enzyme substitution therapy for this human genetic disease. Using 7-day-old Japanese Striped corn seedlings (Japonica Striped maize, Zea mays L. cv. japonica) that contain high activities of PAL, we investigated a number of methods to preserve the roots as an intact food and for long-term storage. The cryoprotectant effects of maple syrup and other edible sugars (mono- and oligosaccharides) were evaluated. Following thawing, the preserved roots were then examined to determine whether the rigid plant cell walls could protect the PAL enzyme from proteolysis during simulated (in vitro) digestion comprised of gastric and intestinal phases. While several treatments led to retention of PAL activity during freezing, upon thawing and in vitro digestion, root tissues that had been previously frozen in the presence of maple syrup exhibited the highest residual PAL activities (∼50% of the initial enzyme activity), in marked contrast to all of the treatments using other edible sugars. The structural integrity of the root cells, and the stability of the functional PAL tetramer were also preserved with the maple syrup protocol. These results have significance for the formulation of oral enzyme/protein therapeutics. When plant tissues are adequately preserved, the rigid cell walls constitute a protective barrier even under harsh (e.g. gastrointestinal-like) conditions.

  2. Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria

    PubMed Central

    De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

    2015-01-01

    A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies. PMID:26510963

  3. Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria.

    PubMed

    De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

    2015-10-29

    A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies.

  4. Neuropsychological Studies on Adolescents with Phenylketonuria Returned to Phenylalanine-Restricted Diets.

    ERIC Educational Resources Information Center

    Clarke, J. T. R.; And Others

    1987-01-01

    The study evaluated neuropsychological effects of high or low phenylalanine diets on nine phenylketonuric (PKU) adolescents who had been on unrestricted diets for 2 to 11 years. Results found that PKU adolescents on unrestricted diets have a neuropsychological deficit which can be partly reversed by returning to dietary phenylalanine restricted…

  5. Distribution of the PKU mutation 165T in Spain and Latin America

    SciTech Connect

    Perez, B.; deLucca, M.; Desviat, L.R.

    1994-09-01

    The 165T mutation is the second most common mutation in the Spanish PKU patients. In order to provide some additional data about the origin of this mutation, we have analyzed 452 PKU alleles from all regions of Spain. The mutation was found in 9% of alleles. We have found a South-North gradient with a highest frequency in the South and the lowest in the North. In the North-West regions (which has the greatest Celtic influence in Spain) the frequency was 7%. The chromosomes bearing this mutation contained the 8 repeat VNTR allele, as has been described in other populations. In view of these results, we suggest an origin other than Celtic for this mutation. On the other hand, we have analyzed 406 PKU alleles from five Latin American countries, 158 from Brazil, 170 from Chile, 56 from Argentina, 14 from Mexico and 8 from Venezuela. Unlike the results of the IVS10 mutation, 165T is present in Latin America with a low frequency. The results show that this mutation is rare in Chile (1%) and is absent in the chromosomes analyzed from Argentina, Mexico and Venezuela. Only in Brazil has this mutation been found in 5% of the alleles. Up to now, Spain is the only Mediterranean country where this mutation is present with a relatively high frequency. This mutation has been detected in the Portuguese patients and would also have migrated to Brazil.

  6. Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Zhang, A. L.; Ren, H. T.; Zhang, T.; Zhang, J. F.; Xu, Y.; Guo, Z. Y.; Chen, J. E.

    2016-02-01

    In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observed during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment.

  7. Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state, and IQ.

    PubMed Central

    Jones, S J; Turano, G; Kriss, A; Shawkat, F; Kendall, B; Thompson, A J

    1995-01-01

    At separate institutions, pattern reversal visual evoked potentials (VEPs) were recorded in children and older patients with phenylketonuria and compared with MRI of the brain. In nine patients aged less than 14 years, who were still on a diet low in phenylalanine, VEPs were clearly abnormal in only one and the abnormalities seen on MRI were mild. In 27 patients aged 14-31 years VEPs were abnormal in more than 80%, with significant reduction of amplitude and prolongation of latency despite the general absence of visual symptoms and abnormalities on routine neuro-ophthalmological examination. Among the older patients there was no significant correlation between VEP measures and plasma phenylalanine or tyrosine concentrations; neither was the incidence of VEP abnormalities dependent on whether or not the patients were still on a low phenylalanine diet. Some VEP amplitude measures were inversely correlated with the MRI lesion score, perhaps reflecting the severity of white matter abnormalities in the parieto-occipital region. In the older patients the amplitude of VEPs to stimulation of the central 8 degrees of the visual field was significantly correlated with IQ. The study confirms the high incidence of subclinical visual pathway involvement in older children and adults with phenylketonuria, and suggests the possibility of a link between the abnormal appearance of subcortical white matter on MRI and a physiological index of function of the CNS. As there was no evidence of general intellectual decline, it is suggested that the correlation between central field VEP amplitude and IQ may reflect abnormal development during infancy. Abnormalities on MRI, on the other hand, seem to be more closely related to current dietary state and phenylalanine concentration. PMID:7673953

  8. Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU Who Were Screened in a National Program

    PubMed Central

    Aghasi, Parisa; Setoodeh, Arya; Sayarifard, Azadeh; Rashidiyan, Maryam; Sayarifard, Fatemeh; Rabbani, Ali; Mahmoudi-Gharaei, Javad

    2015-01-01

    Background: Hyperphenylalaninemia (HPA) and Phenylkeonuria (PKU) are metabolic errors caused by deficiency of phenylalanine hydroxylase enzyme, which results in increased level of phenylalanine. This increase is toxic to the growing brain. Objectives: The purpose of this study was to compare the intellectual and developmental status in HPA and PKU children with normal population in national screening program. Patients and Methods: In a historical cohort study, 41 PKU patients who had the inclusion criteria and 41 healthy children were evaluated. Wechsler preschool and primary scale of intelligence-3rd edition (WPPI-3) was used in order to assess the intellectual status of children 4 years and older and Ages and stages questionnaire (ASQ) was used to assess the developmental status of children 5 years and younger. Results: In intellectual test comparison, the two groups showed significant difference in Wechsler’s performance intelligence score and some performance subscales (P-value < 0.01). In comparison of developmental status, no significant difference was observed between the two groups (P-value > 0.05). Conclusions: Even with early diagnosis and treatment of PKU patients, these children show some deficiencies intellectually compared to normal children. This study emphasizes on necessity for screening intellectual and developmental status of PKU patients so that effective medical or educational measures can taken in case of deficiencies. PMID:26635939

  9. Use of an Amino Acid Mixture in Treatment of Phenylketonuria

    PubMed Central

    Bentovim, A.; Clayton, Barbara E.; Francis, Dorothy E. M.; Shepherd, Jean; Wolff, O. H.

    1970-01-01

    Twelve children with phenylketonuria diagnosed and treated from the first few weeks of life were grouped into pairs. Before the trial all of them were receiving a commercial preparation containing a protein hydrolysate low in phenylalanine (Cymogran, Allen and Hanburys Ltd.) as a substitute for natural protein. One of each pair was given an amino acid mixture instead of Cymogran for about 6 months. Use of the mixture involved considerable modification of the diet, and in particular the inclusion of greater amounts of phenylalanine-free foods. All six accepted the new mixture without difficulty, food problems were greatly reduced, parents welcomed the new preparation, and the quality of family life improved. Normal growth was maintained and with a mixture of l amino acids the plasma and urinary amino acid levels were normal. Further studies are needed before the mixture can be recommended for children under 20 months of age. PMID:5477678

  10. Hepatocyte transplantation using the domino concept in a child with tetrabiopterin nonresponsive phenylketonuria.

    PubMed

    Stéphenne, X; Debray, F G; Smets, F; Jazouli, N; Sana, G; Tondreau, T; Menten, R; Goffette, P; Boemer, F; Schoos, R; Gersting, S W; Najimi, M; Muntau, A C; Goyens, P; Sokal, E M

    2012-01-01

    Phenylketonuria is a metabolic disease caused by phenylalanine hydroxylase deficiency. Treatment is based on a strict natural protein-restricted diet that is associated with the risk of malnutrition and severe psychosocial burden. Oral administration of tetrahydrobiopterin can increase residual enzyme activity, but most patients with severe clinical phenotypes are nonresponders. We performed liver cell transplantation in a 6-year-old boy with severe tetrahydrobiopterin nonresponsive phenylketonuria who failed to comply with diet prescriptions. The transplanted hepatocytes were obtained in part from an explanted glycogen storage type 1b liver. Following two infusions, blood phenylalanine levels returned within the therapeutic target while the phenylalanine half-life assessed by loading tests decreased from 43 to 19 h. However, 3 months later, blood phenylalanine concentrations increased and the phenylalanine intake had to be reduced. Cell-based therapy is a promising therapeutic option in phenylketonuria, and the domino concept may solve the issue of cell sources for hepatocyte transplantation. PMID:22889463

  11. [Blood serum proteins studied by a method of polyacrylamide gel disc electrophoresis in children with phenylketonuria].

    PubMed

    Lupinovich, V L; Kopylova, N V

    1980-01-01

    Protein spectra of blood serum were studied in 25 children suffering from phenlyketonuria (PKU) by disc electrophoresis in polyacrylamide gel. 14 children were examined in the course of being given a specialized diet on the basis of berlafen and 11 children were examined after they were switched over to common diet. PKU patients had an increased protein content in the zone of transferrins. After switching over to common diet the patients demonstrated the reduced protein content, increased amount of postalbumins of medium and low electrophoretic mobility, and transferrins as well.

  12. Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis.

    PubMed

    de Groot, Martijn J; Sijens, Paul E; Reijngoud, Dirk-Jan; Paans, Anne M; van Spronsen, Francjan J

    2015-02-01

    In phenylketonuria, elevated plasma phenylalanine concentrations may disturb blood-to-brain large neutral amino acid (LNAA) transport and cerebral protein synthesis (CPS). We investigated the associations between these processes, using data obtained by positron emission tomography with l-[1-(11)C]-tyrosine ((11)C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for (11)C-Tyr transport from arterial plasma to brain tissue (K1), while CPS was modeled by the rate constant for (11)C-Tyr incorporation into cerebral protein (k3). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOIs): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k3 and each predictor variable were analyzed by multiple linear regression. The rate constant k3 was inversely associated with brain phenylalanine concentrations in VOIs 2 and 3 (adjusted R(2)=0.826, F=19.936, P=0.021). Since brain phenylalanine concentrations in these VOIs highly correlated with each other, the specific associations of each predictor with k3 could not be determined. The associations between k3 and plasma phenylalanine concentration, K1, and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k3 and increased brain phenylalanine concentrations.

  13. Polymorphic haplotypes on R408BW PKU and normal PAH chromosomes in Quebec and European populations

    SciTech Connect

    Byck, S.; Morgan, K.; Scriver, C.R.

    1994-09-01

    The R408W mutation in the phenylalanine hydroxylase gene (PAH) is associated with haplotype 2.3 (RFLP haplotype 2, VNTR 3 of the HindIII system) in most European populations. Another chromosome, first observed in Quebec and then in northwest Europe, carries R408W on haplotype 1.8. The occurrence of the R408W mutation on two different PKU chromosomes could be the result of intragenic recombination, recurrent mutation or gene conversion. In this study, we analyzed both normal and R408W chromosomes carrying 1.8 and 2.3 haplotypes in Quebec and European populations; we used the TCTA{sub (n)} short tandem repeat sequence (STR) at the 5{prime} end of the PAH gene and the HindIII VNTR system at the 3{prime} end of the PAH gene to characterize chromosomes. Fourteen of sixteen R408W chromosomes from {open_quotes}Celtic{close_quotes} families in Quebec and the United Kingdom (UK) harbor a 244 bp STR allele; the remaining two chromosomes, carry a 240 bp or 248bp STR allele. Normal chromosomes (n=18) carry the 240 bp STR allele. R408W chromosomes are different from mutant H1.8 chromosomes; mutant H2.3 carries the 240 bp STR allele (14 of 16 chromosomes) or the 236 allele (2 of 16 chromosomes). The HindIII VNTR comprises variable numbers of 30 bp repeats (cassettes); the repeats also vary in nucleotide sequence. Variation clusters toward the 3{prime} end of cassettes and VNTRs. VNTR 3 alleles on normal H2 (n=9) and mutant R408W H2 (n=19) chromosomes were identical. VNTR 8 alleles on normal H1 chromosomes (n=9) and on R408W H1 chromosomes (n=15) differ by 1 bp substitution near the 3{prime} end of the 6th cassette. In summary, the mutant H1.8 chromosome harboring the R408W mutation has unique features at both the 5{prime} and 3{prime} end of the gene that distinguish it from the mutant H2.3 and normal H1.8 and H2.3 counterparts. The explanation for the occurrence of R408W on two different PAH haplotypes is recurrent mutation affecting the CpG dinucleotide in PAH codon 408.

  14. Linking genotypes database with locus-specific database and genotype–phenotype correlation in phenylketonuria

    PubMed Central

    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

    2015-01-01

    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (rs=0.479), between protein stability and allelic phenotype (rs=−0.458), as well as between enzyme activity and allelic phenotype (rs=0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database. PMID:24939588

  15. Neonatal Screening Tests.

    ERIC Educational Resources Information Center

    Vigue, Charles L.

    1986-01-01

    Describes several laboratory experiments that are adaptations of clinical tests for certain genetic diseases in babies. Information and procedures are provided for tests for phenylketonuria (PKU), galactosemia, tyrosinemia, cystinuria, and mucopolysaccharidosis. Discusses the effects of each disease on the infants' development. (TW)

  16. Newborn screening tests

    MedlinePlus

    ... disorders Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Human immunodeficiency disease (HIV) Organic acid metabolism disorders Phenylketonuria (PKU) Sickle cell disease and other ...

  17. Seizures

    MedlinePlus

    ... brain defects) Brain tumor (rare) Drug abuse Electric shock Epilepsy Fever (particularly in young children ) Head injury Heart disease Heat illness ( heat intolerance ) High fever Phenylketonuria ( PKU ), which ...

  18. Does a single plasma phenylalanine predict quality of control in phenylketonuria?

    PubMed Central

    MacDonald, A; Rylance, G; Asplin, D; Hall, S; Booth, I

    1998-01-01

    A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 µmol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 µmol/l occurred in 46% of children below 11 years, three having concentrations < 30 µmol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = −0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.

 PMID:9579152

  19. Effect of dietary phenylalanine restriction on visual attention span in mentally retarded subjects with phenylketonuria.

    PubMed

    Giffin, F D; Clarke, J T; d'Entremont, D M

    1980-05-01

    An ABA within-subject study design was used to assess the effect of dietary phenylalanine restriction on the visual attention span of three mentally retarded males (9, 15, and 21 years old) with phenylketonuria. Visual attention span was measured by recording the amount of time the subjects visually fixated pictures projected on a screen according to a standardized test protocol. After 4-6 weeks of baseline testing (A-phase), each subject was placed on a phenylalanine-restricted diet, designed to maintain plasma phenylalanine levels at 0.3-0.9 mM, for 8-14 weeks (B-phase). A return to baseline phenylalanine intake (A-phase) was achieved by surreptitiously adding sufficient L-phenylalanine to the therapeutic diets to increase plasma concentrations of the amino acid to pretreatment levels. Diet treatment (B-phase) was associated with highly significant improvements in visual attention span in two subjects (multivariate analysis of variance, P less than 0.001); the third subject, the most retarded, showed no effect. No objectively demonstrable change in behavior was documented in any subject. However, the results support the view that phenylalanine toxicity extends beyond early childhood and that some component of the toxicity is reversible, even in severely retarded patients with phenylketonuria.

  20. Transcultural pediatrics: compliance and outcome of phenylketonuria patients from families with an immigration background.

    PubMed

    Ipsiroglu, Osman S; Herle, Marion; Spoula, Elisabeth; Möslinger, Dorothea; Wimmer, Banu; Burgard, Peter; Bode, Harald; Stöckler-Ipsiroglu, Sylvia

    2005-08-01

    Living in a foreign country with a different lifestyle and a different orientation is a many-faceted challenge for immigrants. A considerable percentage (30-50%) of patients with metabolic disease come from immigrant families from Turkey and the Middle East. Phenylketonuria is one example of metabolic disease in which severe mental retardation can be entirely prevented by early detection via newborn screening and consistent dietary treatment. We report 7 phenylketonuria patients from 3 Turkish families who had considerable difficulty in coping with the diagnosis and adherence to the diet. Blood phenylalanine levels beyond recommended limits and IQ values below average, clearly demonstrate the risks arising from language as well as psychological and cultural communication barriers, despite standardized follow-up care structures and the observance of continuity by medical caregivers. To propose a basis for systematic improvement in the care of patients from immigrant families we suggest that a) the services of professional interpreters be used in case of language barriers; b) social workers with appropriate sociocultural and language competence should accompany the family in a professional manner; c) it would be meaningful to introduce treatment contracts that clearly establish the limits of the client's rights and duties as well as those of the care-givers. From the viewpoint of legislation, providing medical information is duty of the hospital and the use of translator is mandatory with patients from foreign countries and with foreign languages. PMID:16158204

  1. CW/Pulsed H- ion beam generation with PKU Cs-free 2.45 GHz microwave driven ion source

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Ren, H. T.; Xu, Y.; Zhang, T.; Zhang, A. L.; Zhang, J. F.; Zhao, J.; Guo, Z. Y.; Chen, J. E.

    2015-04-01

    Circular accelerators used for positron emission tomography (PET, i.e. accelerator used for make radio isotopes) need several mA of CW H- ion beam for their routine operation. Other facilities, like Space Radio-Environment Simulate Assembly (SPRESA), require less than 10 mA pulsed mode H- beam. Caesium free negative hydrogen ion source is a good choice for those facilities because of its compact structure, easy operation and low cost. Up to now, there is no H- source able to produce very intense H- beams with important variation of the duty factor[1]. Recently, a new version of 2.45 GHz microwave H- ion source was designed at PKU, based on lessons learnt from the previous one. This non cesiated source is very compact thanks to its permanent magnet configuration. Special attention was paid on the design of the discharge chamber structure, electron dumping and extraction system. Source test to produce H- ion beams in pulsed and CW mode was carried out on PKU ion source test bench. In CW mode, a 10.8 mA/30keV H- beam with rms emittance about 0.16 π.mm.mrad has been obtained with only 500 W rf power. The power efficiency reaches 21 mA/kW. In pulsed mode with duty factor of 10% (100Hz/1ms), this compact source can easily deliver 20 mA H- ion beam at 35 keV with rms emittance about 0.2 π.mm.mrad when RF power is set at 2.2 kW (peak power). Several hour successive running operation in both modes and totaling more than 200 hours proves its high quality. The outside dimension of this new H- source body is ϕ116 mm × 124 mm, and the entire H- source infrastructure, including rf matching section, plasma chamber and extraction system, is ϕ310 × 180 mm. The high voltage region is limited with in a ϕ310 mm × 230 mm diagram. Details are given in this paper.

  2. Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria.

    PubMed

    Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

    2014-01-27

    Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria.

  3. Neuropsychological Deficits in Early Treated Phenylketonuric Children.

    ERIC Educational Resources Information Center

    Pennington, Bruce F.; And Others

    1985-01-01

    Six early treated children with phenylketonuria (PKU) were compared at 9 to 14 years of age on a neuropsychological measure with three groups of children with documented neurological disorders. PKU Ss had overall level of neuropsychological impairment similar to that of brain-damaged groups. PKU Ss did not show consistent pattern of…

  4. Determination of unconjugated aromatic acids in urine by capillary electrophoresis with dual electrochemical detection--potential application in fast diagnosis of phenylketonuria.

    PubMed

    Zhang, Dong-li; Li, Wen-li; Zhang, Jun-bo; Tang, Wan-rong; Chen, Xiao-fei; Cao, Kai-wen; Chu, Qing-cui; Ye, Jian-nong

    2010-09-01

    A novel method of CE coupled with dual electrochemical detection has been developed for the determination of pathological metabolites of phenylalanine in urine samples. Factors influencing the separation and detection were examined and optimized. Five aromatic acid metabolites and a major coexisting interfering compound uric acid could be well separated within 23 min at a separation voltage of 16 kV using a 35 mmol/L SDS/60 mmol/L H(3)BO(3)-Na(2)B(4)O(7) running buffer (pH 8.2). Highly linear response was obtained for these five biomarker compounds over three orders of magnitude with detection limits ranging from 6.6 to 0.064 μg/mL (S/N=3). The average recovery and RSD were within the range of 92.6-121.0 and 1.0-12.0%, respectively. The proposed method has been used to detect the unconjugated aromatic acids simultaneously in urine samples with the advantages of obtaining more information about target analytes and avoiding redundant measurements and high assay cost, thus could find potential applications involving assays of biomarker compounds for the purpose of fast diagnose of some metabolic diseases including phenylketonuria.

  5. Phenylketonuria: protein content and amino acids profile of dishes for phenylketonuric patients. The relevance of phenylalanine.

    PubMed

    Pimentel, Filipa B; Alves, Rita C; Costa, Anabela S G; Torres, Duarte; Almeida, Manuela F; Oliveira, M Beatriz P P

    2014-04-15

    Phenylketonuria is an inborn error of metabolism, involving, in most cases, a deficient activity of phenylalanine hydroxylase. Neonatal diagnosis and a prompt special diet (low phenylalanine and natural-protein restricted diets) are essential to the treatment. The lack of data concerning phenylalanine contents of processed foodstuffs is an additional limitation for an already very restrictive diet. Our goals were to quantify protein (Kjeldahl method) and amino acid (18) content (HPLC/fluorescence) in 16 dishes specifically conceived for phenylketonuric patients, and compare the most relevant results with those of several international food composition databases. As might be expected, all the meals contained low protein levels (0.67-3.15 g/100 g) with the highest ones occurring in boiled rice and potatoes. These foods also contained the highest amounts of phenylalanine (158.51 and 62.65 mg/100 g, respectively). In contrast to the other amino acids, it was possible to predict phenylalanine content based on protein alone. Slight deviations were observed when comparing results with the different food composition databases.

  6. Aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults and adults heterozygous for phenylketonuria.

    PubMed

    Stegink, L D; Wolf-Novak, L C; Filer, L J; Bell, E F; Ziegler, E E; Krause, W L; Brummel, M C

    1987-11-01

    Twelve normal subjects ingested either unsweetened beverage (n = 6) or beverage providing 4 mg/kg body weight as aspartame (APM) (n = 6). Neither beverage had any significant effect on plasma aspartate or phenylalanine concentrations. After this study, eight normal and six obligate phenylketonuric (PKU) heterozygous adults each ingested a 354-mL (12-oz) beverage serving on two occasions in a randomized cross-over design. On one occasion the beverage was not sweetened; on the other occasion, the beverage provided 10 mg APM/kg body weight. Plasma amino acid concentrations were measured throughout the 2-h study period. The addition of 10 mg APM/kg body weight to the beverage had no significant effect on plasma aspartate concentration. APM ingestion increased plasma phenylalanine levels of normal subjects from a mean +/- SD baseline value of 5.09 +/- 0.82 mumol/dL to a high mean value of 6.73 +/- 0.75 mumol/dL. In PKU heterozygous subjects the plasma phenylalanine level increased from a mean +/- SD of 9.04 +/- 1.71 to a high mean value of 12.1 +/- 2.08 mumol/dL. The data indicate ready metabolism of the aspartate and phenylalanine portion of APM when administered at levels likely to be ingested by individuals who drink diet beverages.

  7. CW/Pulsed H{sup −} ion beam generation with PKU Cs-free 2.45 GHz microwave driven ion source

    SciTech Connect

    Peng, S. X. Ren, H. T.; Xu, Y.; Zhang, T.; Zhang, J. F.; Zhao, J.; Guo, Z. Y.; Zhang, A. L.; Chen, J. E.

    2015-04-08

    Circular accelerators used for positron emission tomography (PET, i.e. accelerator used for make radio isotopes) need several mA of CW H- ion beam for their routine operation. Other facilities, like Space Radio-Environment Simulate Assembly (SPRESA), require less than 10 mA pulsed mode H{sup −} beam. Caesium free negative hydrogen ion source is a good choice for those facilities because of its compact structure, easy operation and low cost. Up to now, there is no H{sup −} source able to produce very intense H{sup −} beams with important variation of the duty factor{sup [1]}. Recently, a new version of 2.45 GHz microwave H{sup −} ion source was designed at PKU, based on lessons learnt from the previous one. This non cesiated source is very compact thanks to its permanent magnet configuration. Special attention was paid on the design of the discharge chamber structure, electron dumping and extraction system. Source test to produce H{sup −} ion beams in pulsed and CW mode was carried out on PKU ion source test bench. In CW mode, a 10.8 mA/30keV H{sup −} beam with rms emittance about 0.16 π·mm·mrad has been obtained with only 500 W rf power. The power efficiency reaches 21 mA/kW. In pulsed mode with duty factor of 10% (100Hz/1ms), this compact source can easily deliver 20 mA H{sup −} ion beam at 35 keV with rms emittance about 0.2 π·mm·mrad when RF power is set at 2.2 kW (peak power). Several hour successive running operation in both modes and totaling more than 200 hours proves its high quality. The outside dimension of this new H{sup −} source body is ϕ116 mm × 124 mm, and the entire H{sup −} source infrastructure, including rf matching section, plasma chamber and extraction system, is ϕ310 × 180 mm. The high voltage region is limited with in a ϕ310 mm × 230 mm diagram. Details are given in this paper.

  8. Health-related quality of life in children and adolescents with phenylketonuria: unimpaired HRQoL in patients but feared school failure in parents.

    PubMed

    Thimm, Eva; Schmidt, Lisa Elena; Heldt, Katrin; Spiekerkoetter, Ute

    2013-09-01

    Aim of the study was the evaluation of health-related quality of life (HRQoL) and the detection of deviant behavior in early-treated children and adolescents with PKU in comparison with healthy peers. Special focus was laid on the impact of compliance with treatment as defined by the national recommendations on HRQoL. Our investigation in 50 children and adolescents and their parents for the first time demonstrates that despite an overall normal HRQoL in our PKU patient collective, parents are concerned about performance in school especially when phenylalanine concentrations in their children are mainly above the therapeutic range. Adherence to target phenylalanine concentrations ameliorated markedly in patients above 10 years in comparison to younger patients due to relaxed treatment recommendations. Interestingly, this alleged improvement in metabolic control has an impact on the parent assessed but not on the patient assessed appraisal of HRQoL. However, a positive correlation between poor metabolic control and conduct problems was identified by patients' self-assessment. In conclusion, lacking adherence to the strict treatment recommendations in infancy results in significant concern about school success and success in life in parents of PKU patients. With relaxation of dietary phenylalanine restriction at 10 years of age, these concerns diminish. PMID:23296365

  9. Amino Acid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  10. Contact with Phenylketonurics and Their Families Beyond Pediatric Age: Conclusion from a Survey and Conference

    ERIC Educational Resources Information Center

    Fisch, Robert O.; And Others

    1977-01-01

    Twenty parents of children 12 years and older with PKU (phenylketonuria, a metabolic disorder which if untreated can result in mental retardation) were surveyed to determine their level of knowledge and their needs. (CL)

  11. Genetics of the mammalian phenylalanine hydroxylase system. Studies of human liver phenylalanine hydroxylase subunit structure and of mutations in phenylketonuria.

    PubMed Central

    Choo, K H; Cotton, R G; Danks, D M; Jennings, I G

    1979-01-01

    Phenylalanine hydroxylase was purified from crude extracts of human livers which show enzyme activity by usine two different methods: (a) affinity chromatography and (b) immunoprecipitation with an antiserum against highly purified monkey liver phenylalanine hydroxylase. Purified human liver phenylalanine hydroxylase has an estimated mol. wt. of 275 000, and subunit mol. wts. of approx. 50 000 and 49 000. These two molecular-weight forms are designated H and L subunits. On two-dimensional polyacrylamide gel under dissociating conditions, enzyme purified by the two methods revealed at least six subunit species, which were resolved into two size classes. Two of these species have a molecular weight corresponding to that of the H subunit, whereas the other four have a molecular weight corresponding to that of the L subunit. This evidence indicates that active phenylalanine hydroxylase purified from human liver is composed of a mixture of sununits which are different in charge and size. None of the subunit species could be detected in crude extracts of livers from two patients with classical phenylketonuria by either the affinity or the immunoprecipitation method. However, they were present in liver from a patient with malignant hyperphenylalaninaemia with normal activity of dihydropteridine reductase. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:496890

  12. Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity

    SciTech Connect

    Desviat, L.R.; Perez, B.; De Lucca, M.

    1995-08-01

    Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. In vitro, the V388M mutant enzyme has similar immunoreactive protein and phenylalanine hydroxylase mRNA and had 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous patients. In Spain it has been detected in 5.7% of the mutant alleles and is always associated with haplotype 1.7. This mutation is also present in high frequency in some Latin American countries (Brazil, 9% Chile, 13%). It is interesting that in Chile most of the alleles bearing this mutation carry haplotype 4.3, although in Brazil it is found only on the background of haplotype 1.7. The origin of V388M in Spain on haplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recurrence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutation from haplotype 1 to 4 is unlikely. 29 refs., 2 figs., 3 tabs.

  13. Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine).

    PubMed

    Trefz, F; de Sonneville, L; Matthis, P; Benninger, C; Lanz-Englert, B; Bickel, H

    1994-04-01

    Aspartame, a high intensity sweetener, is used extensively worldwide in over 5,000 products. Upon ingestion, aspartame is completely metabolized to two amino acids and methanol (approximately 50% phenylalanine, 40% aspartic acid, and 10% methanol). The effects of aspartame on cognitive function, electroencephalograms (EEGs) and biochemical parameters were evaluated in 48 adult (21 men, 27 women) heterozygotes for phenylketonuria (PKUH), PKUH subjects whose carrier status had been proven by DNA analysis ingested aspartame (either 15 or 45 mg/kg/day) and placebo for 12 weeks on each treatment using a randomized, double-blind, placebo-controlled, crossover study. A computerized battery of neuropsychological tests was administered at baseline weeks -2 and -1, and during treatment at weeks 6, 12, 18, and 24. Samples for plasma amino acids and urinary organic acids were also collected during these visits. EEGs were evaluated by conventional and spectral analysis at baseline week -1 and treatment weeks 12 and 24. The results of the neuropsychological tests demonstrated that aspartame had no effect on cognitive function. Plasma phenylalanine significantly increased, within the normal range for PKUH, at 1 and 3 h following the morning dose of aspartame in the group receiving the 45 mg/kg per day dose only. There were no significant differences in the conventional or spectral EEG analyses, urinary organic acid concentrations, and adverse experiences when aspartame was compared with placebo. This study reaffirms the safety of aspartame in PKUH and refutes the speculation that aspartame affects cognitive performance, EEGs, and urinary organic acids.

  14. Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria.

    PubMed

    Stegink, L D; Filer, L J; Baker, G L; Bell, E F; Ziegler, E E; Brummel, M C; Krause, W L

    1989-01-01

    It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.

  15. Outcome of pregnancy in the rat with mild hyperphenylalaninaemia and hypertyrosinaemia: implications for the management of "human maternal PKU".

    PubMed

    Lewis, S A; Lyon, I C; Elliott, R B

    1985-01-01

    In attempting to determine the effects of mildly elevated maternal phenylalanine (Phe) blood levels on the developing fetal rat brain, a dietary supplement of Phe was given, under taste cover of Aspartame. Phe and tyrosine (Tyr) levels were mildly elevated throughout pregnancy without evidence of malnutrition. Mild hyperphenylalaninaemia with concurrent hypertyrosinaemia induced in rats prior to conception resulted in microcephaly and lasting behavioural problems in the offspring, specifically hyperactivity and learning difficulties. Dams fed Tyr to produce Tyr levels equivalent to the Phe-fed animals showed only the learning difficulties among the offspring. alpha-Methyl Phe, a Phe hydroxylase inhibitor, fed in conjunction with Phe, at the level relevant to these experiments, resulted in raised Tyr levels and does not provide a better method of determining whether mildly elevated maternal Phe levels alone, or Phe and Tyr in combination, cause the abnormality found in the offspring of Phe-supplemented dams. Therapeutic addition of Tyr to diets of mothers with even mild hyperphenylalaninaemia should be approached with caution as mild co-elevation of Phe and Tyr in the fetus may be harmful. In the face of such a possible therapeutic dilemma alternatives, such as dietary additions of other essential amino acids to limit fetal brain damage, need to be explored.

  16. Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.

    PubMed

    Pascucci, Tiziana; Giacovazzo, Giacomo; Andolina, Diego; Accoto, Alessandra; Fiori, Elena; Ventura, Rossella; Orsini, Cristina; Conversi, David; Carducci, Claudia; Leuzzi, Vincenzo; Puglisi-Allegra, Stefano

    2013-01-01

    Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE.

  17. Genetics Home Reference: phenylketonuria

    MedlinePlus

    ... Phenylalanine is a building block of proteins ( an amino acid ) that is obtained through the diet. It is ... enzyme called phenylalanine hydroxylase . This enzyme converts the amino acid phenylalanine to other important compounds in the body. ...

  18. Phenylketonuria Genetic Screening Simulation

    ERIC Educational Resources Information Center

    Erickson, Patti

    2012-01-01

    After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

  19. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example.

    PubMed

    Camp, Kathryn M; Lloyd-Puryear, Michele A; Huntington, Kathleen L

    2012-09-01

    Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment.

  20. Showing Value in Newborn Screening: Challenges in Quantifying the Effectiveness and Cost-Effectiveness of Early Detection of Phenylketonuria and Cystic Fibrosis

    PubMed Central

    Grosse, Scott D.

    2015-01-01

    Decision makers sometimes request information on the cost savings, cost-effectiveness, or cost-benefit of public health programs. In practice, quantifying the health and economic benefits of population-level screening programs such as newborn screening (NBS) is challenging. It requires that one specify the frequencies of health outcomes and events, such as hospitalizations, for a cohort of children with a given condition under two different scenarios—with or without NBS. Such analyses also assume that everything else, including treatments, is the same between groups. Lack of comparable data for representative screened and unscreened cohorts that are exposed to the same treatments following diagnosis can result in either under- or over-statement of differences. Accordingly, the benefits of early detection may be understated or overstated. This paper illustrates these common problems through a review of past economic evaluations of screening for two historically significant conditions, phenylketonuria and cystic fibrosis. In both examples qualitative judgments about the value of prompt identification and early treatment to an affected child were more influential than specific numerical estimates of lives or costs saved. PMID:26702401

  1. Nutritional Treatment for Inborn Errors of Metabolism: Indications, Regulations, and Availability of Medical Foods and Dietary Supplements Using Phenylketonuria as an Example

    PubMed Central

    Camp, Kathryn M.; Lloyd-Puryear, Michele A.; Huntington, Kathleen L.

    2012-01-01

    Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment. PMID:22854513

  2. ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt.

    PubMed

    Saad, Khaled; Elserogy, Yasser; Abdel Rahman, Ahmed A; Al-Atram, Abdulrahman Abdullah; Mohamad, Ismail L; ElMelegy, Tarek T H; Bjørklund, Geir; El-Houfy, Amira A

    2015-12-01

    The aim of this study is to evaluate the neuropsychological status in a cohort of children with early and continuously treated phenylketonuria in Assiut, Upper Egypt. The study was implemented in seventy-eight phenylketonuria (PKU) children. Only 34 patients met the inclusion criteria. Investigated patients were evaluated according to detailed history, neurological examination, Childhood Autism Rating Scale, full scale Intelligence Quotient, attention deficit hyperactivity disorder, electroencephalography and magnetic resonance imaging (MRI). This study concluded that the prognosis for early diagnosed children with PKU treated from the first weeks of life is generally good. However, they are at increased risk for neurological complications and behavioral problems. So, neonatal screening for PKU is highly recommended in Egypt, for early detection and management. In addition, neuropsychological and MRI assessments in PKU children should be done. PMID:25576444

  3. ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt.

    PubMed

    Saad, Khaled; Elserogy, Yasser; Abdel Rahman, Ahmed A; Al-Atram, Abdulrahman Abdullah; Mohamad, Ismail L; ElMelegy, Tarek T H; Bjørklund, Geir; El-Houfy, Amira A

    2015-12-01

    The aim of this study is to evaluate the neuropsychological status in a cohort of children with early and continuously treated phenylketonuria in Assiut, Upper Egypt. The study was implemented in seventy-eight phenylketonuria (PKU) children. Only 34 patients met the inclusion criteria. Investigated patients were evaluated according to detailed history, neurological examination, Childhood Autism Rating Scale, full scale Intelligence Quotient, attention deficit hyperactivity disorder, electroencephalography and magnetic resonance imaging (MRI). This study concluded that the prognosis for early diagnosed children with PKU treated from the first weeks of life is generally good. However, they are at increased risk for neurological complications and behavioral problems. So, neonatal screening for PKU is highly recommended in Egypt, for early detection and management. In addition, neuropsychological and MRI assessments in PKU children should be done.

  4. Using simple molecular orbital calculations to predict disease: fast DFT methods applied to enzymes implicated in PKU, Parkinson's disease and Obsessive Compulsive Disorder

    NASA Astrophysics Data System (ADS)

    Hofto, Laura; Hofto, Meghan; Cross, Jessica; Cafiero, Mauricio

    2007-09-01

    Many diseases can be traced to point mutations in the DNA coding for specific enzymes. These point mutations result in the change of one amino acid residue in the enzyme. We have developed a model using simple molecular orbital calculations which can be used to quantitatively determine the change in interaction between the enzyme's active site and necessary ligands upon mutation. We have applied this model to three hydroxylase proteins: phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase, and we have obtained excellent correlation between our results and observed disease symptoms. Furthermore, we are able to use this agreement as a baseline to screen other mutations which may also cause onset of disease symptoms. Our focus is on systems where the binding is due largely to dispersion, which is much more difficult to model inexpensively than pure electrostatic interactions. Our calculations are run in parallel on a sixteen processor cluster of 64-bit Athlon processors.

  5. Current Status of Newborn Screening: Decision-Making about the Conditions to Include in Screening Programs

    ERIC Educational Resources Information Center

    Watson, Michael S.

    2006-01-01

    Newborn screening is considered a highly successful public health program that has resulted in the reduction of mortality, mental retardation, and other serious disabilities in thousands of children since the introduction of screening for phenylketonuria (PKU) in the 1960s. Programs are based in state public health departments such that each state…

  6. SOME FACTS AND FIGURES ABOUT CHILDREN AND YOUTH.

    ERIC Educational Resources Information Center

    Children's Bureau (DHEW), Washington, DC.

    IN QUESTION AND ANSWER FORM, THE PAMPHLET PRESENTS STATISTICAL DATA ON CHILDREN AND YOUTH PRIMARILY IN THE UNITED STATES. INFORMATION CONCERNS POPULATION, RESIDENCE, MOBILITY, POVERTY, WORKING MOTHERS, MARRIAGES, DIVORCES, BIRTHS, LIFE EXPECTANCY, MORTALITY, ILLNESS, HANDICAPS, HOSPITALIZATION, ADOPTIONS, PHENYLKETONURIA (PKU) LAWS, CHILD ABUSE…

  7. Monkey Retardate Learning Analysis

    ERIC Educational Resources Information Center

    Chamove, A. S.; Molinaro, T. J.

    1978-01-01

    Seven rhesus monkeys reared on diets high in phenylalanine to induce phenylketonuria (PKU--a metabolic disorder associated with mental retardation if untreated) were compared with normal, pair-fed, and younger controls; frontal brain-lesioned monkeys; and those raised on high-tryptophan diets in three object discrimination tasks. (Author)

  8. Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations.

    PubMed Central

    Kayaalp, E; Treacy, E; Waters, P J; Byck, S; Nowacki, P; Scriver, C R

    1997-01-01

    We analyzed correlations between mutant genotypes at the human phenylalanine hydroxylase locus (gene symbol PAH) and the corresponding hyperphenylalaninemia (HPA) phenotypes (notably, phenylketonuria [OMIM 261600]). We used reports, both published and in the PAH Mutation Analysis Consortium Database, on 365 patients harboring 73 different PAH mutations in 161 different genotypes. HPA phenotypes were classified as phenylketonuria (PKU), variant PKU, and non-PKU HPA. By analysis both of homoallelic mutant genotypes and of "functionally hemizygous" heteroallelic genotypes, we characterized the phenotypic effect of 48 of the 73 different, largely missense mutations. Among those with consistent in vivo expression, 24 caused PKU, 3 caused variant PKU, and 10 caused non-PKU HPA. However, 11 mutations were inconsistent in their effect: 9 appeared in two different phenotype classes, and 2 (I65T and Y414C) appeared in all three classes. Seven mutations were inconsistent in phenotypic effect when in vitro (unit-protein) expression was compared with the corresponding in vivo phenotype (an emergent property). We conclude that the majority of PAH mutations confer a consistent phenotype and that this is concordant with their effects, when known, predicted from in vitro expression analysis. However, significant inconsistencies, both between in vitro and in vivo phenotypes and between different individuals with similar PAH genotypes, reveal that the HPA-phenotype is more complex than that predicted by Mendelian inheritance of alleles at the PAH locus. PMID:9399896

  9. Essentials of PKU for Young Adults with PKU and Their Significant Others

    MedlinePlus

    ... low-phenylalanine food pattern. Food records Often the nutritionist will request a diet record. A diet record ... for each individual's taste, body size, nutritional needs, personal preferences and cooking skills. Just as a person ...

  10. Determination of Phenylalanine and Tyrosine by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Peat, Judy; Garg, Uttam

    2016-01-01

    Hyperphenylalaninemia/phenylketonuria (PKU) is one of the most common inborn errors of amino acid metabolism affecting about 1:15,000 infants in the United States. PKU is an autosomal recessive disorder that if untreated results in mental retardation. The most common cause of PKU is deficiency of the enzyme phenylalanine hydroxylase that converts phenylalanine to tyrosine. Tyrosine deficiency results in impaired synthesis of catecholamines and thyroxine. Less commonly, it can result from defects in the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor for the enzyme phenylalanine hydroxylase. Increased phenylalanine and decreased tyrosine in blood are used in the diagnosis and follow-up of patients with PKU. LC/MS/MS method is described for the quantification of phenylalanine and tyrosine.

  11. [Risk-sharing scheme in Israel--Kuvan as an allegory].

    PubMed

    Abadi-Korek, Ifat; Shemer, Joshua

    2012-06-01

    Healthcare systems worldwide are dealing with the uncertainty characterizing new and expensive health technoLogies, particularly aspects involving drug effectiveness and the extent and doses required for utilization. Reducing this uncertainty can be achieved mainly by using either coverage with evidence development methods or risk-sharing schemes (RSS). In 2011, the first phenylketonuria (PKU) risk-sharing scheme was set up in Israel, through the public funding health services updating process. This was done in order to ensure that people with PKU could access PKU sole treatment--sapropterin dihydrochloride, Kuvan. The apparent effectiveness of the treatment, on one hand, and the uncertainty regarding the number of patients and average treatment dosage, on the other hand, dictated the RRS. This scheme determined a ceiling number of tablets to be funded by the insurer, above this ceiling the manufacturer would finance Kuvan. Furthermore, it was agreed that after 3 years Kuvan would be brought to the public committee for updating reimbursement decisions. It is inevitable that risk sharing and conditional coverage agreements will become a common practice in the reimbursement process in the future. This will allow competent authorities and pharmaceutical companies to build clinical experience and other required data with medicines which might normally not be eLigible for reimbursement. Before it becomes the common practice in Israel, the RSS for Kuvan, process and outcomes, should be monitored and analyzed by the Ministry of Health, to ensure patients access to treatment, the effective collection of the research data and the effective interaction between Israel's four health funds and the manufacturer.

  12. Prevention of fetal damage through dietary control of maternal hyperphenylalaninemia.

    PubMed

    Ghavami, M; Levy, H L; Erbe, R W

    1986-09-01

    Maternal phenylketonuria is a new entity in obstetrics. If unrecognized and for this or other reasons untreated, it produces a substantial risk for fetal damage. Our knowledge of the pathophysiology of the fetal complications in maternal PKU is very limited, but the degree of maternal hyperphenylalaninemia seems to be important. The management differs from the other high-risk pregnancies in the need for a special diet beginning before conception. An effective program of dietary therapy designed in collaboration with a PKU clinic will reduce the likelihood of fetal damage and improve pregnancy outcome.

  13. Options in Education, Transcript for April 12, 1976: Review of "Simple Justice," Writing Seminars for Judges and Lawyers, The Teaching of Writing, Visual Literacy, Teacher Internships, System of Interactive Guidance, Changing Jobs, and PKU Children.

    ERIC Educational Resources Information Center

    George Washington Univ., Washington, DC. Inst. for Educational Leadership.

    "Options in Education" is a radio news program which focuses on issues and developments in education. This transcript contains discussions of the book "Simple Justice" by Richard Kluger; writing seminars for judges and lawyers, held by the American Academy of Judicial Education; the teaching of writing; visual literacy--picture words; teacher…

  14. Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients.

    PubMed

    Deon, Marion; Sitta, Angela; Faverzani, Jessica L; Guerreiro, Gillian B; Donida, Bruna; Marchetti, Desirèe P; Mescka, Caroline P; Ribas, Graziela S; Coitinho, Adriana S; Wajner, Moacir; Vargas, Carmen R

    2015-12-01

    Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro-inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid--PLA and phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di-tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin-6 and interleukin-10, an anti-inflammatory cytokine. Di-tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro-oxidant and pro-inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.

  15. Phenylalaninaemia

    PubMed Central

    Blaskovics, M. E.; Schaeffler, Graciela E.; Hack, Shirley

    1974-01-01

    A method is described for differentiating the phenylalaninaemias based upon blood phenylalanine (phe) responses to ingestion of natural protein diets with standard phe content. A classification scheme derived primarily from these studies is suggested which includes two forms of phenylketonuria (PKU) and four forms of phenylalaninaemia (variants) unrelated to abnormalities in tyrosine metabolism. Dietary therapy is mandatory for types I and II and possibly for type III, but does not appear to be necessary for types IV or V. Evidence provided by family studies supports the concept that the phenylalaninaemias are genetically distinct. The increased incidence of PKU consequent to newborn blood screening programmes may well be related to misdiagnosis as well as to increased recognition of PKU. PMID:4441120

  16. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    PubMed

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine. PMID:2697834

  17. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    PubMed

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

  18. [Lipids composition diet in phenylketonuric children with early diagnosis].

    PubMed

    Cornejo, Verónica; Concha, Miluska; Cabello, Juan Francisco; Raimann, Erna

    2005-12-01

    Phenylketonuria (PKU) is a genetic disorder caused by a partial or complete mutation of the enzyme phenylalanine hydroxylase (PHA), fact that produces high levels of phenylalanine in blood resulting in mental retardation if not diagnosed during the neonatal period. Treatment consists of a phenylalanine (Phe) restricted diet. Several studies have shown that due to restriction of animal protein, this diet is deficient in fatty acids such as alfalinolenic acid (ALA) and provides high levels of linoleic acid (LA). The objective of this study was to determine the lipid composition of the diet consumed by children with early-diagnosed PKU. Lipid composition of the Phenylalanine restricted diet consumed by 29 children with PKU and in follow-up at INTA, University of Chile, were analyzed. Children were paired by sex and age with a control group. A twenty-four hour dietary recall was performed for 3 consecutive days and total fatty acid intake, including saturated, monounsaturated, polyunsaturated, LA and ALA, were calculated. In the restricted diet of children with PKU, 31.8% of total calories are from fat, 13% of which are LA and 0.2% ALA, showing significant differences as compared to the control group. The ratio of saturated:monounsaturated:polyunsaturated fatty acids was 1:1.7:3.9 and the ratio of LA:ALA was ten-fold higher than the recommended ratio of 115:1. It is concluded that the Phenyalanine restricted diet of Chilean children with PKU is high in LA and low in ALA.

  19. Co-administration of creatine plus pyruvate prevents the effects of phenylalanine administration to female rats during pregnancy and lactation on enzymes activity of energy metabolism in cerebral cortex and hippocampus of the offspring.

    PubMed

    Bortoluzzi, Vanessa Trindade; de Franceschi, Itiane Diehl; Rieger, Elenara; Wannmacher, Clóvis Milton Duval

    2014-08-01

    Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth weight and neonatal sequelae, especially microcephaly and intellectual disability. The mechanisms underlying the neuropathology of brain injury in maternal PKU syndrome are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by phenylalanine administration to female Wistar rats during pregnancy and lactation on some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Phenylalanine administration provoked diminution of body, brain cortex an hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic creatine kinase activities. Co-administration of creatine plus pyruvate was effective in the prevention of those alterations provoked by phenylalanine, suggesting that altered energy metabolism may be important in the pathophysiology of maternal PKU. If these alterations also occur in maternal PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric mothers.

  20. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

    PubMed

    Wolf-Novak, L C; Stegink, L D; Brummel, M C; Persoon, T J; Filer, L J; Bell, E F; Ziegler, E E; Krause, W L

    1990-04-01

    Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals.

  1. Development.

    ERIC Educational Resources Information Center

    Boydell, Tom

    1982-01-01

    Explores the theories and models of self-actualization and human development. Twelve tables illustrate developmental stages, ways of knowing, moral and ethical development, management style, goals of learning, organizational development, and other dimensions. Availability: M.E.A.D. Subscriptions, C.S.M.L., University of Lancaster, Lancaster LA1…

  2. Development

    ERIC Educational Resources Information Center

    Childress, Dana C.; Raver, Sharon A.; Michalek, Anne M. P.; Wilson, Corinne L.

    2013-01-01

    All eligible infants and toddlers who receive early intervention services under Part C of Individuals with Disabilities Education Act are entitled to service coordination. To examine the effectiveness of one state's service coordination training and its impact on knowledge and skill development, a pretest--posttest design with follow-up…

  3. Simultaneous determination of urinary creatinine and UV-absorbing amino acids using a novel low-capacity cation-exchange chromatography for the screening of inborn errors of metabolism.

    PubMed

    Yokoyama, Yukio; Yamasaki, Keiko; Sato, Hisakuni

    2005-02-25

    A simple and versatile low-capacity cation-exchange chromatography system for the simultaneous determination of creatinine and UV-absorbing amino acids was developed. The separation column was packed with a newly developed low-capacity sulfoacylated macro-porous polystyrene-divinylbenzene resin selective for amino-acid cations. Urinary creatinine, creatine, tyrosine, histidine, phenylalanine, and tryptophan were simultaneously separated and determined by an isocratic elution with phosphate/acetonitrile eluent in 25 min. Relative standard deviations (R.S.D.) of the retention times for the analytes were between 0.28 and 1.06%. R.S.D. of peak area responses for the analytes were between 0.75 and 3.51%. The r(2) values for the calibration lines were between 0.9994 and 0.9999. The method could provide the creatinine ratios for the analytes, and was applicable to the screening and/or chemical diagnosis of several inherited disorders of amino-acid metabolism such as phenylketonuria (PKU). PMID:15664367

  4. Inborn errors of metabolism: a cause of abnormal brain development.

    PubMed

    Nissenkorn, A; Michelson, M; Ben-Zeev, B; Lerman-Sagie, T

    2001-05-22

    Brain malformations are caused by a disruption in the sequence of normal development by various environmental or genetic factors. By modifying the intrauterine milieu, inborn errors of metabolism may cause brain dysgenesis. However, this association is typically described in single case reports. The authors review the relationship between brain dysgenesis and specific inborn errors of metabolism. Peroxisomal disorders and fatty acid oxidation defects can produce migration defects. Pyruvate dehydrogenase deficiency, nonketotic hyperglycinemia, and maternal phenylketonuria preferentially cause a dysgenetic corpus callosum. Abnormal metabolism of folic acid causes neural tube defects, whereas defects in cholesterol metabolism may produce holoprosencephaly. Various mechanisms have been proposed to explain abnormal brain development in inborn errors of metabolism: production of a toxic or energy-deficient intrauterine milieu, modification of the content and function of membranes, or disturbance of the normal expression of intrauterine genes responsible for morphogenesis. The recognition of a metabolic disorder as the cause of the brain malformation has implications for both the care of the patient and for genetic counseling to prevent recurrence in subsequent pregnancies. PMID:11383558

  5. Spectrofluorimetric determination of phenylalanine based on fluorescence enhancement of europium ion immobilized with sol-gel method

    NASA Astrophysics Data System (ADS)

    Zhang, Kun; Yan, Hong-Tao; Zhou, Tie

    2011-12-01

    The analysis of phenylalanine (Phe) in serum is widely performed for the screening of newborn phenylketonuria (PKU). In this work, a novel spectrofluorimetric method for the determination of Phe was developed based on the fluorescence enhancement of Ruhemann's purple, the reaction product between Phe and ninhydrin, upon coordination with Eu 3+. A filter paper disc containing immobilized reactants (ninhydrin and Eu 3+) was fabricated by sol-gel method. The experimental parameters affecting the determination of Phe, such as the concentrations of immobilized reagents, the pH value, the reaction time and temperature were optimized. Under optimum conditions, the fluorescence intensity of Phe-ninhydrin-Eu 3+ system was linearly proportional to the concentration of Phe in the range from 5 × 10 -5 to 2 × 10 -3 mol L -1, and the limit of detection was found to be 5.2 × 10 -6 mol L -1. The relative standard deviation was 2.6% for ten replicate measurements of 1.5 × 10 -4 mol L -1 of Phe. The method has merits of sensitivity, simplicity and low cost, and has been applied to the determination of Phe in artificial serum.

  6. DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia.

    PubMed

    Simon, Kellen R; Dos Santos, Rosane M; Scaini, Giselli; Leffa, Daniela D; Damiani, Adriani P; Furlanetto, Camila B; Machado, Jéssica L; Cararo, José H; Macan, Tamires P; Streck, Emilio L; Ferreira, Gustavo C; Andrade, Vanessa M; Schuck, Patrícia F

    2013-10-01

    Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients.

  7. Normal vitamin D levels and bone mineral density among children with inborn errors of metabolism consuming medical food-based diets.

    PubMed

    Geiger, Katie E; Koeller, David M; Harding, Cary O; Huntington, Kathleen L; Gillingham, Melanie B

    2016-01-01

    A higher incidence of osteopenia is observed among children with inherited metabolic disorders (inborn errors of metabolism, or IEMs) who consume medical food-based diets that restrict natural vitamin D-containing food sources. We evaluated the vitamin D status of children with IEMs who live in the Pacific Northwest with limited sun exposure and determined whether bone mineral density (BMD) in children with phenylketonuria (PKU), the most common IEM, correlated with diet or biochemical markers of bone metabolism. We hypothesized that children with IEMs would have lower serum vitamin D concentrations than controls and that some children with PKU would have reduced bone mineralization. A retrospective record review of 88 patients with IEMs, and 445 children on unrestricted diets (controls) found the 25-hydroxyvitamin D concentrations were normal and not significantly different between groups (IEM patients, 27.1 ± 10.9; controls, 27.6 ± 11.2). Normal BMD at the hip or spine (-2 PKU. There was a correlation between lumbar spine BMD and dietary calcium intake. We saw no evidence of low serum vitamin D in our population of children with IEMs compared with control children. We also found no evidence for reduced BMD in children with PKU on specialized diets, but BMD was associated with calcium intake. Dietary intake of essential nutrients in medical food-based diets supports normal 25-hydroxyvitamin D levels and BMD in children with IEMs, including PKU. The risk of vitamin D deficiency among patients consuming a medical food-based diet is similar to the general population.

  8. Aspartame: review of recent experimental and observational data.

    PubMed

    Janssen, P J; van der Heijden, C A

    1988-06-01

    In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studies in humans and animals. The issue of common intake levels associated with proposed uses of aspartame is addressed. In brief, the following conclusions can be drawn: When aspartame is consumed at levels within the ADI-limit of 40 mg/kg body wt, there is no significant risk for an aspartate-induced neurotoxic effect in the brain. When aspartame is consumed at levels within the ADI-limit by normal subjects or persons heterozygous for phenylketonuria (PKU) the resultant plasma phenylalanine concentrations are practically always within the normal postprandial range; elevation to plasma concentrations commonly associated with adverse effects has not been observed. Persons suffering from phenylketonuria (PKU-homozygotes) on a phenylalanine-restricted diet should avoid consumption of aspartame. PKU-homozygotes on the (less strict) phenylalanine-liberalized diet should be made aware of the phenylalanine content of aspartame. In the available behavioural studies in humans with acute dosing, no adverse effects were observed. Long-term studies on behaviour and cognitive function in (sensitive) humans are lacking. Analyses of adverse reaction reports made by consumers in the U.S.A. have not yielded a specific constellation of symptoms clearly related to aspartame that would suggest a widespread public health hazard associated with aspartame use. Focussed clinical studies are now being carried out in the U.S.A.; the results should provide additional evidence concerning the interpretation of the reports on adverse reactions ascribed to aspartame. In the regulation of admitted uses for aspartame the possibility of intake levels exceeding the ADI-limit in some groups

  9. Women's Attitudes Regarding Prenatal Testing for a Range of Congenital Disorders of Varying Severity.

    PubMed

    Norton, Mary E; Nakagawa, Sanae; Kuppermann, Miriam

    2014-01-21

    Little is known about women's comparative attitudes towards prenatal testing for different categories of genetic disorders. We interviewed women who delivered healthy infants within the past year and assessed attitudes towards prenatal screening and diagnostic testing, as well as pregnancy termination, for Down syndrome (DS), fragile X (FraX), cystic fibrosis (CF), spinal muscular atrophy (SMA), phenylketonuria (PKU) and congenital heart defects (CHD). Ninety-five women aged 21 to 48 years participated, of whom 60% were Caucasian, 23% Asian, 10% Latina and 7% African American; 82% were college graduates. Ninety-five to ninety-eight percent indicated that they would have screening for each condition, and the majority would have amniocentesis (64% for PKU to 72% for SMA). Inclinations regarding pregnancy termination varied by condition: Whereas only 10% reported they would probably or definitely terminate a pregnancy for CHD, 41% indicated they would do so for DS and 62% for SMA. Most women in this cohort reported that they would undergo screening for all six conditions presented, the majority without the intent to terminate an affected pregnancy. These women were least inclined to terminate treatable disorders (PKU, CHD) versus those associated with intellectual disability (DS, FraX) and were most likely to terminate for SMA, typically lethal in childhood.

  10. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  11. Phenylalanine hydroxylase: function, structure, and regulation.

    PubMed

    Flydal, Marte I; Martinez, Aurora

    2013-04-01

    Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. In humans, mutations in the PAH gene lead to phenylketonuria (PKU), and most mutations are mainly associated with PAH misfolding and instability. The established treatment for PKU is a phenylalanine-restricted diet and, recently, supplementation with preparations of the natural tetrahydrobiopterin cofactor also shows effectiveness for some patients. Since 1997 there has been a significant increase in the understanding of the structure, catalytic mechanism, and regulation of PAH by its substrate and cofactor, in addition to improved correlations between genotype and phenotype in PKU. Importantly, there has also been an increased number of studies on the structure and function of PAH from bacteria and lower eukaryote organisms, revealing an additional anabolic role of the enzyme in the synthesis of melanin-like pigments. In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms.

  12. Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome.

    PubMed

    Kaiser, Lucia Lynn; Allen, Lindsay

    2002-10-01

    It is the position of the American Dietetic Association that women of childbearing potential should maintain good nutritional status through a lifestyle that optimizes maternal health and reduces the risk of birth defects, suboptimal fetal growth and development, and chronic health problems in their children. The key components of a health-promoting lifestyle during pregnancy include appropriate weight gain; consumption of a variety of foods in accordance with the Food Guide Pyramid; appropriate and timely vitamin and mineral supplementation; avoidance of alcohol, tobacco, and other harmful substances; and safe food-handling. Prenatal weight gain within the Institute of Medicine (IOM) recommended ranges is associated with better pregnancy outcomes. The total energy needs during pregnancy range between 2,500 to 2,700 kcal a day for most women, but prepregnancy body mass index, rate of weight gain, maternal age, and physiological appetite must be considered in tailoring this recommendation to the individual. The consumption of more food to meet energy needs and the increased absorption and efficiency of nutrient utilization that occurs in pregnancy are generally adequate to meet the needs for most nutrients. However, vitamin and mineral supplementation is appropriate for some nutrients and situations. This statement also includes recommendations pertaining to use of alcohol, tobacco, caffeine, street drugs, and other substances during pregnancy; food safety; and management of common complaints during pregnancy and specific health problems. In particular for medical nutrition therapy, pregnant women with inappropriate weight gain, hyperemesis, poor dietary patterns, phenylketonuria (PKU), certain chronic health problems, or a history of substance abuse should be referred to a qualified dietetics professional. PMID:12396171

  13. Comparison of alpha-methylphenylalanine and p-chlorophenylalanine as inducers of chronic hyperphenylalaninaemia in developing rats.

    PubMed Central

    Delvalle, J A; Dienel, G; Greengard, O

    1978-01-01

    alpha-Methylphenylalanine is a very weak competitive inhibitor of rat liver phenylalanine hydroxylase in vitro but a potent suppressor in vivo. The loss of the hepatic activity (the renal one is unaffected) becomes maximal (70-75% decrease; cf. control) 18h after the administration (per 10g body wt.) of 24 mumol of alpha-methylphenylalanine with or without 52 mumol of phenylalanine. Chronic suppression of hepatic phenylalanine hydroxylase was obtained by injections of alpha-methylphenylalanine plus phenylalanine to suckling rats, and by their addition to the diet after weaning. A series of comparisons of the effects of this treatment, and one with p-chlorophenylalanine, was then carried out. In both cases there was a rise (1.3-2-fold) in phenylalanine-pyruvate amino-transferase activity (but no change in four other enzyme activities) in the liver; in brain there was a rise in phosphoserine phosphatase activity, but the total activity and subcellular distribution of nine enzymes revealed no other abnormalities in cerebral development. Striking increases in the concentration of plasma phenylalanine during 26 of the 31 experimental days (with a transient fall at 18-22 days) were maintained by treatment with both analogues plus phenylalanine. However, p-chlorophenylalanine-treated animals had a 30-60% mortality rate and 27-52% decrease in body weight. Developing rats treated with alpha-methylphenylalanine, showing no growth deficit or signs of toxicity (e.g. cataracts), appear to be a more suitable model for the human disease of phenylketonuria. Their phenylalanine concentrations exhibited at least 20-40-fold increase during 50% of each of the first 18 days of life, and 30-fold after weaning. PMID:148273

  14. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:27512458

  15. The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population.

    PubMed

    Liang, Ying; Huang, Miao-Zeng; Cheng, Cheng-Yi; Chao, Hung-Kun; Fwu, Victor Tramjay; Chiang, Szu-Hui; Hsiao, Kwang-Jen; Niu, Dau-Ming; Su, Tsung-Sheng

    2014-03-01

    Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study. The most common mutations, R241C, R408Q and Ex6-96A>G, account for 23.2%, 12.0% and 9.2%, of the mutant alleles, respectively. Haplotype analysis shows that R241C and Ex6-96A>G are exclusively associated with haplotype 4.3 to suggest founder effects. On the other hand, R408Q is found on two distinct haplotypes suggesting recurrent mutations. The spectrum of PAH mutations in Taiwan shows various links to those of other Asian regions, yet remarkable differences exist. Notably, R408Q, E286K and -4173_-407del, accounting for 21% of all mutant alleles in Taiwan, are very rare or are undetected among PKU cohorts of other Asian regions to suggest local founder effects. Moreover, the low homozygosity value of 0.092 hints at a high degree of ethnic heterogeneity within the Taiwanese population. Our study of PAH mutation spectrum and the associated haplotypes is useful for subsequent study on the origin and migration pattern via Taiwan, an island at the historical crossroad of migration of ancient populations.

  16. Estimation of carrier frequencies of six autosomal-recessive Mendelian disorders in the Korean population.

    PubMed

    Song, Min-Jung; Lee, Seung-Tae; Lee, Mi-Kyung; Ji, Yongick; Kim, Jong-Won; Ki, Chang-Seok

    2012-02-01

    Although many studies have been performed to identify mutations in Korean patients with various autosomal-recessive Mendelian disorders (AR-MDs), little is known about the carrier frequencies of AR-MDs in the Korean population. Twenty common mutations from six AR-MDs, including Wilson disease (WD), non-syndromic hearing loss (NSHL), glycogen storage disease type Ia (GSD Ia), phenylketonuria (PKU), congenital hypothyroidism (CH), and congenital lipoid adrenal hyperplasia (CLAH) were selected to screen for based on previous studies. A total of 3057 Koreans were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry followed by confirmation using the Sanger sequencing. We found 201 and 8 carriers with either one or two mutations in different genes, respectively, yielding a total carrier frequency of 1 in 15 (6.7%). Of the six AR-MDs, NSHL has the highest carrier frequency followed by WD, CH, CLAH, GSD Ia, and PKU. As carrier screening tests are becoming prevalent and the number of mutations known and tested is rising, a priori data on the carrier frequencies in different ethnic groups is mandatory to plan a population screening program and to estimate its efficiency. In light of this, the present results can be used as a basis to establish a screening policy for common AR-MRs in the Korean population. PMID:22170460

  17. Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid

    PubMed Central

    Sanayama, Yoshitami; Matsumoto, Akio; Shimojo, Naoki; Kohno, Yoichi; Nakaya, Haruaki

    2014-01-01

    Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model. Here, we present a novel in vitro cellular model using K562-D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range, but not phenylpyruvate. The increased expression of the L-type amino acid transporter (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine over phenylalanine effectively restored cell proliferation, although other amino acids did not improve K562-D cell proliferation over phenylalanine. Biochemical analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal target of phenylalanine in K562-D cell proliferation, and supplementation of valine restored mTORC1 activity. Our results show that K562-D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease. PMID:25373594

  18. Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid.

    PubMed

    Sanayama, Yoshitami; Matsumoto, Akio; Shimojo, Naoki; Kohno, Yoichi; Nakaya, Haruaki

    2014-11-06

    Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model. Here, we present a novel in vitro cellular model using K562-D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range, but not phenylpyruvate. The increased expression of the L-type amino acid transporter (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine over phenylalanine effectively restored cell proliferation, although other amino acids did not improve K562-D cell proliferation over phenylalanine. Biochemical analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal target of phenylalanine in K562-D cell proliferation, and supplementation of valine restored mTORC1 activity. Our results show that K562-D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease.

  19. Adolescent development

    MedlinePlus

    Development - adolescent; Growth and development - adolescent ... During adolescence, children develop the ability to: Understand abstract ideas. These include grasping higher math concepts, and developing moral ...

  20. An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand

    PubMed Central

    Thiboonboon, Kittiphong; Leelahavarong, Pattara; Wattanasirichaigoon, Duangrurdee; Vatanavicharn, Nithiwat; Wasant, Pornswan; Shotelersuk, Vorasuk; Pangkanon, Suthipong; Kuptanon, Chulaluck; Chaisomchit, Sumonta; Teerawattananon, Yot

    2015-01-01

    Background Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. Method A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality-adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. Results The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. Conclusion At the current ceiling threshold, neonatal screening using MS

  1. Web-Based Newborn Screening System for Metabolic Diseases: Machine Learning Versus Clinicians

    PubMed Central

    Chen, Wei-Hsin; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

    2013-01-01

    Background A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. Objective The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. Methods The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets

  2. Screening Children with Autism for Fragile-X Syndrome and Phenylketonuria. Brief Report.

    ERIC Educational Resources Information Center

    Pueschel, Siegfried M.; And Others

    1985-01-01

    Family histories, comprehensive physical examinations, and chromosome analyses of 35 males with autism were performed. Results indicated that the fragile X syndrome may be present in less than 16 percent of persons whose family history or physical features suggest the condition's possible presence. Screening 42 autistic children for…

  3. A resolution designating December 3, 2012, as "National Phenylketonuria Awareness Day".

    THOMAS, 112th Congress

    Sen. Isakson, Johnny [R-GA

    2012-09-19

    09/19/2012 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (consideration: CR S6469-6472; text as passed Senate: CR S6470; text of measure as introduced: CR S6465) (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  4. A resolution designating December 3, 2013, as "National Phenylketonuria Awareness Day".

    THOMAS, 113th Congress

    Sen. Isakson, Johnny [R-GA

    2013-11-21

    11/21/2013 Referred to the Committee on the Judiciary. (text of measure as introduced: CR S8465) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  5. A resolution designating December 3, 2014, as "National Phenylketonuria Awareness Day".

    THOMAS, 113th Congress

    Sen. Isakson, Johnny [R-GA

    2014-11-20

    12/03/2014 Resolution agreed to in Senate without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  6. [Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

    PubMed

    Bozkowa, K; Cabalska, B; Radomyska, B; Ołtarzewski, M; Lenartowska, I

    1999-01-01

    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

  7. Child Development

    MedlinePlus

    ... content Start of Search Controls Search Form Controls Child Development Cancel Submit Search The CDC CDC A-Z ... Z # Start of Search Controls Search Form Controls Child Development Cancel Submit Search The CDC Child Development Note: ...

  8. Child Development

    MedlinePlus

    As children grow older, they develop in several different ways. Child development includes physical, intellectual, social, and emotional changes. Children grow and mature at very different rates. It's ...

  9. Consumerism & Development.

    ERIC Educational Resources Information Center

    Ockenden, Sandy

    1991-01-01

    This material asks social studies students in Canada to recognize the implications of the lifestyles of citizens in developed countries, and the power that consumers have to create change for a better world, to be agents of positive development. Development is seen as a four faceted process. This model implies that development is an approach to…

  10. PAHdb 2003: what a locus-specific knowledgebase can do.

    PubMed

    Scriver, Charles R; Hurtubise, Mélanie; Konecki, David; Phommarinh, Manyphong; Prevost, Lynne; Erlandsen, Heidi; Stevens, Ray; Waters, Paula J; Ryan, Shannon; McDonald, David; Sarkissian, Christineh

    2003-04-01

    PAHdb, a legacy of and resource in genetics, is a relational locus-specific database (http://www.pahdb.mcgill.ca). It records and annotates both pathogenic alleles (n = 439, putative disease-causing) and benign alleles (n = 41, putative untranslated polymorphisms) at the human phenylalanine hydroxylase locus (symbol PAH). Human alleles named by nucleotide number (systematic names) and their trivial names receive unique identifier numbers. The annotated gDNA sequence for PAH is typical for mammalian genes. An annotated gDNA sequence is numbered so that cDNA and gDNA sites are interconvertable. A site map for PAHdb leads to a large array of secondary data (attributes): source of the allele (submitter, publication, or population); polymorphic haplotype background; and effect of the allele as predicted by molecular modeling on the phenylalanine hydroxylase enzyme (EC 1.14.16.1) or by in vitro expression analysis. The majority (63%) of the putative pathogenic PAH alleles are point mutations causing missense in translation of which few have a primary effect on PAH enzyme kinetics. Most apparently have a secondary effect on its function through misfolding, aggregation, and intracellular degradation of the protein. Some point mutations create new splice sites. A subset of primary PAH mutations that are tetrahydrobiopterin-responsive is highlighted on a Curators' Page. A clinical module describes the corresponding human clinical disorders (hyperphenylalaninemia [HPA] and phenylketonuria [PKU]), their inheritance, and their treatment. PAHdb contains data on the mouse gene (Pah) and on four orthologous mutant mouse models and their use (for example, in research on oral treatment of PKU with the enzyme phenylalanine ammonia lyase [EC 4.3.1.5]).

  11. Individualized long-term outcomes in blood phenylalanine concentrations and dietary phenylalanine tolerance in 11 patients with primary phenylalanine hydroxylase (PAH) deficiency treated with Sapropterin-dihydrochloride.

    PubMed

    Stockler-Ipsiroglu, Sylvia; Yuskiv, Nataliya; Salvarinova, Ramona; Apatean, Delia; Ho, Gloria; Cheng, Barbara; Giezen, Alette; Lillquist, Yolanda; Ueda, Keiko

    2015-03-01

    We analyzed long-term sustainability of improved blood Phenylalanine (Phe) control and changes to dietary Phe tolerance in 11 patients (1 month to 16 years), with various forms of primary PAH deficiency (classic, moderate, severe phenylketonuria [PKU], mild hyperphenylalaninemia [HPA]), who were treated with 15-20mg/kg/d Sapropterin-dihydrochloride during a period of 13-44 months. 7/11 patients had a sustainable, significant reduction of baseline blood Phe concentrations and 6 of them also had an increase in mg/kg/day Phe tolerance. In 2 patients with mild HPA, blood Phe concentrations remained in the physiologic range even after a 22 and 36% increase in mg/kg/day Phe tolerance and an achieved Phe intake at 105% and 268% of the dietary reference intake (DRI) for protein. 2 of these responders had classic PKU. 1 patient with mild HPA who started treatment at 2 months of life, had a significant and sustainable reduction in pretreatment blood Phe concentrations, but no increase in the mg/kg/day Phe tolerance. An increase in Phe tolerance could only be demonstrated when expressing the patient's daily Phe tolerance with the DRI for protein showing an increase from 58% at baseline to 78% of normal DRI at the end of the observation. Long-term follow-up of patients with an initial response to treatment with Sapropterin is essential to determine clinically meaningful outcomes. Phenylalanine tolerance should be expressed in mg/kg/day and/or % of normal DRI to differentiate medical therapy related from physiologic growth related increase in daily Phe intake.

  12. Community Development in Developed Countries.

    ERIC Educational Resources Information Center

    Franklin, Richard; And Others

    Part of a report of seminar proceedings, six papers on community development in developed nations review the conceptual dimensions, issues, and directions of community development in the United States; pilot programs of social research, training, and consultation in rural Saskatchewan; the community development efforts of the University of New…

  13. Sustainable Development.

    ERIC Educational Resources Information Center

    Auerbach, Raymond

    1994-01-01

    Discusses South African national development priorities, sustainable development, and the future of agriculture and presents three scenarios of possible national action: production for sale and export, household food security, and conservation of natural resources. (MKR)

  14. Toddler development

    MedlinePlus

    Toddlers are children ages 1 to 3. CHILD DEVELOPMENT THEORIES Cognitive (thought) development skills typical for toddlers include: Early use of instruments or tools Following visual (then later, invisible) displacement (moving from ...

  15. Technology Development.

    ERIC Educational Resources Information Center

    Gomory, Ralph E.

    1983-01-01

    The evolutionary character and complexity of technological development is discussed, focusing on the steam engine and computer as examples. Additional topics include characteristics of science/technology, cultural factors in technological development, technology transfer, and problems in technological organization. (JN)

  16. Developer Network

    SciTech Connect

    2012-08-21

    NREL's Developer Network, developer.nrel.gov, provides data that users can access to provide data to their own analyses, mobile and web applications. Developers can retrieve the data through a Web services API (application programming interface). The Developer Network handles overhead of serving up web services such as key management, authentication, analytics, reporting, documentation standards, and throttling in a common architecture, while allowing web services and APIs to be maintained and managed independently.

  17. Teacher Development.

    ERIC Educational Resources Information Center

    1997

    Eight conference papers on language teacher development are presented, including: "Mosaics of Teacher Development and Socialization" (Andrew Barfield, Paul A. Beaufait, Sean Conley, Tim Murphey, Katsura Haruko), a panel presentation on aspects of and experiments in teacher development; "Questions About Teaching? Answers from Teachers!" (David…

  18. Faculty Development.

    ERIC Educational Resources Information Center

    Gillan, Bob, Ed.; McFerrin, Karen, Ed.

    This document contains the following papers on faculty development and technology: "Involving Faculty in Faculty Development" (Kristine Blair and Dan Madigan); "Technology Use in Higher Education: A Faculty Development Model" (Jessica Kahn); "A Faculty of Education as a Community of Learners: Growing to Meet the Demands of Instruction and…

  19. Program Development

    SciTech Connect

    Atencio, Julian J.

    2014-05-01

    This presentation covers how to go about developing a human reliability program. In particular, it touches on conceptual thinking, raising awareness in an organization, the actions that go into developing a plan. It emphasizes evaluating all positions, eliminating positions from the pool due to mitigating factors, and keeping the process transparent. It lists components of the process and objectives in process development. It also touches on the role of leadership and the necessity for audit.

  20. Developable resources

    SciTech Connect

    Hunt, R.T.; Hunt, J.M.

    1995-01-01

    In the United States, it has become the conventional wisdom that all developable conventional hydropower resources have been exhausted. Studies by the US Department of Energy (DOE) and other agencies find differently. The root of disagreement may lie in the definition of what is developable. Environmental special interest groups now define developable hydropower sites as those having zero effect on the environment. As a result they conclude there are no additional developable hydropower sites. By contrast, the definition used by DOE and others is broader as it balances economic, technical, and environmental factors in accordance with the Federal Power Act.

  1. KENO developments

    SciTech Connect

    Hollenbach, D.F.; Landers, N.F.; Petrie, L.M.

    1997-06-01

    Modifications and developments to the series of KENO multigroup, criticality safety transport codes are very briefly summarized. Three areas are addressed: (1) modifications to KENO-V.a, (2) development of KENO-VI, (3) modifications to the CSAS4 sequence of the SCALE package, and (4) future work on KENO related programs. Minor changes have been made to KENO-V.a, primarily for maintenance. KENO-VI has been developed and will be released soon. A new search type is being developed in SCALE to allow CSAS4 to do a concentration search on a mixture component.

  2. Professional Development.

    ERIC Educational Resources Information Center

    Benson, Chris, Ed.

    2000-01-01

    This serial issue contains 12 articles on the theme of "Professional Development," specifically about how teachers in the Bread Loaf Rural Teacher Network (BLRTN) are fostering their own and each other's development as teachers. The BLRTN consists of approximately 260 rural teachers in Alaska, Arizona, Colorado, Georgia, Kentucky, Mississippi, New…

  3. Collection Development.

    ERIC Educational Resources Information Center

    School Libraries in Canada, 2002

    2002-01-01

    Includes 21 articles that discuss collection development in Canadian school libraries. Topics include digital collections in school library media centers; print and electronic library resources; library collections; collaborative projects; print-disabled students; informing administrators of the importance of collection development; censorship;…

  4. Numerical Development

    ERIC Educational Resources Information Center

    Siegler, Robert S.; Braithwaite, David W.

    2016-01-01

    In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

  5. [Toddler Development.

    ERIC Educational Resources Information Center

    Pawl, Jeree, Ed.

    1991-01-01

    This theme newsletter issue presents seven articles describing toddler behavior and development, services for toddlers, and toddlers with special needs. The first article, "Toddlers: Themes and Variations" (Lois Barclay Murphy and Colleen Small) focuses on variations in toddler development, noting emerging skills, language, and the caregiver role.…

  6. Management Development.

    ERIC Educational Resources Information Center

    1997

    This document contains three papers from a symposium on management development. "LMX (Leader-Member Exchange) Theory, Personality Type, and Management Development" (Janet Z. Burns) reports the results of a study on the similarities and differences in personality type (as outlined in the theories of Carl Jung and Isabel Myers) and its relationship…

  7. Technology development.

    PubMed

    Gomory, R E

    1983-05-01

    In technology development significant advances are as often the result of a series of evolutionary steps as they are of breakthroughs. This is illustrated by the examples of the steam engine and the computer. Breakthroughs, such as the transistor, are relatively rare, and are often the result of the introduction of new knowledge coming from a quite different area. Technology development is often difficult to predict because of its complexity; practical considerations may far outweigh apparent scientific advantages, and cultural factors enter in at many levels. In a large technological organization problems exist in bringing scientific knowledge to bear on development, but much can be done to obviate these difficulties. PMID:17749515

  8. Technology development.

    PubMed

    Gomory, R E

    1983-05-01

    In technology development significant advances are as often the result of a series of evolutionary steps as they are of breakthroughs. This is illustrated by the examples of the steam engine and the computer. Breakthroughs, such as the transistor, are relatively rare, and are often the result of the introduction of new knowledge coming from a quite different area. Technology development is often difficult to predict because of its complexity; practical considerations may far outweigh apparent scientific advantages, and cultural factors enter in at many levels. In a large technological organization problems exist in bringing scientific knowledge to bear on development, but much can be done to obviate these difficulties.

  9. Eye development.

    PubMed

    Baker, Nicholas E; Li, Ke; Quiquand, Manon; Ruggiero, Robert; Wang, Lan-Hsin

    2014-06-15

    The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This article provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens.

  10. Speech Development

    MedlinePlus

    ... W View More… Donate Donor Spotlight Fundraising Ideas Vehicle Donation Volunteer Efforts Speech Development skip to submenu ... Lip and Palate . Bzoch (1997). Cleft Palate Speech Management: A Multidisciplinary Approach . Shprintzen, Bardach (1995). Cleft Palate: ...

  11. Fetal development

    MedlinePlus

    WEEK BY WEEK CHANGES Gestation is the period of time between conception and birth when a baby grows and develops inside ... to the current date. It is measured in weeks. This means that during weeks 1 and 2 ...

  12. Brain Development

    MedlinePlus

    ... new neural connections every second. This growing brain development is influenced by many factors, including a child’s relationships, experiences and environment. Learn more about the crucial role you play ...

  13. Toddler development.

    PubMed

    Colson, E R; Dworkin, P H

    1997-08-01

    The toddler years are ones of exciting and challenging changes in cognitive, affective, and physical growth. Physical growth is particularly remarkable for the child's increasing skills and ability to navigate the environment. Affective development is marked by the push for autonomy and independence and the highly visible nature of the child's temperament or behavioral style. The toddler also enters the wonderful years of imagination and pretend play. Perhaps most noteworthy is the child's dramatic increase in ability to communicate with others through speech and language, as evidence of the progression to symbolic thinking. The dynamic changes in children's development during the toddler years have important implications for child health supervision. Familiarity with toddler development will enable the pediatrician to monitor children's development effectively and to address common, stage-related behaviors with families during anticipatory guidance.

  14. Toddler development.

    PubMed

    Colson, E R; Dworkin, P H

    1997-08-01

    The toddler years are ones of exciting and challenging changes in cognitive, affective, and physical growth. Physical growth is particularly remarkable for the child's increasing skills and ability to navigate the environment. Affective development is marked by the push for autonomy and independence and the highly visible nature of the child's temperament or behavioral style. The toddler also enters the wonderful years of imagination and pretend play. Perhaps most noteworthy is the child's dramatic increase in ability to communicate with others through speech and language, as evidence of the progression to symbolic thinking. The dynamic changes in children's development during the toddler years have important implications for child health supervision. Familiarity with toddler development will enable the pediatrician to monitor children's development effectively and to address common, stage-related behaviors with families during anticipatory guidance. PMID:9255990

  15. EYE DEVELOPMENT

    PubMed Central

    Baker, Nicholas E.; Li, Ke; Quiquand, Manon; Ruggiero, Robert; Wang, Lan-Hsin

    2014-01-01

    The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This chapter provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens. PMID:24784530

  16. Leaf Development

    PubMed Central

    2013-01-01

    Leaves are the most important organs for plants. Without leaves, plants cannot capture light energy or synthesize organic compounds via photosynthesis. Without leaves, plants would be unable perceive diverse environmental conditions, particularly those relating to light quality/quantity. Without leaves, plants would not be able to flower because all floral organs are modified leaves. Arabidopsis thaliana is a good model system for analyzing mechanisms of eudicotyledonous, simple-leaf development. The first section of this review provides a brief history of studies on development in Arabidopsis leaves. This history largely coincides with a general history of advancement in understanding of the genetic mechanisms operating during simple-leaf development in angiosperms. In the second section, I outline events in Arabidopsis leaf development, with emphasis on genetic controls. Current knowledge of six important components in these developmental events is summarized in detail, followed by concluding remarks and perspectives. PMID:23864837

  17. Development risks

    SciTech Connect

    Riedy, M.; Desai, S.

    1996-04-01

    Risks associated with hydropower production development in India are discussed in this article. A project prospectus for the development of India`s estimated 84,044 MW(e) hydropower potential is given which accounts for environmental and regulatory concerns. Regulations issued by the Government of Industry regarding private investment in hydropower are outlined, and additional policies which are expected to be instituted are discussed.

  18. PARENT DEVELOPMENT

    PubMed Central

    Friedman, David Belais

    1957-01-01

    Today's parents tend to be overwhelmed with advice from many sources. In his role as family counselor, the pediatrician must understand and consider the emotional development of parents in relation to their child's development; otherwise, his advice and counsel do not “take” and he becomes tired and frustrated and angry. Parents progress through definite stages of development: Stage 1: Learning the cues—the struggle of the parents to interpret the infant's needs. Stage 2: Learning to accept growth and development—the parent learning to accept some loss of control of the toddler. Stage 3: Learning to separate—the parent learning to allow the child to develop independently. Stage 4: Learning to accept rejection, without deserting—the struggle of the parents not to intrude and yet to be there when needed. Stage 5: Learning to build a new life having been thoroughly discredited by one's teenager—the parent learning to live independently while the teenager struggles to develop his own identity. The pediatrician who is accepting, sensitive and a good listener and who keeps in mind that parents as well as children have capacities for growth and development, will be a potent factor in promoting good parent-child relationships and many times more effective in dealing with the child in health and disease. PMID:13383387

  19. Sustainable development is healthy development.

    PubMed

    Litsios, S

    1994-01-01

    Economic growth has brought with it substantial environmental damage. Nature has been abused and little consideration has been given to the consequences, among them the adverse effects on health. Healthy people are vital for local development that is both economically and ecologically sound. The health sector should be actively involved in the movement for sustainable development. What this would require in practice is considered below, with particular reference to the quality of life in regions of tropical forest.

  20. Sustainable development is healthy development.

    PubMed

    Litsios, S

    1994-01-01

    Economic growth has brought with it substantial environmental damage. Nature has been abused and little consideration has been given to the consequences, among them the adverse effects on health. Healthy people are vital for local development that is both economically and ecologically sound. The health sector should be actively involved in the movement for sustainable development. What this would require in practice is considered below, with particular reference to the quality of life in regions of tropical forest. PMID:8018295

  1. Sustainable Development

    NASA Astrophysics Data System (ADS)

    Schmandt, Jurgen; Ward, C. H.; Marilu Hastings, Assisted By

    2000-04-01

    Demographers predict that the world population will double during the first half of the 21st century before it will begin to level off. In this volume, a group of prominent authors examine what societal changes must occur to meet this challenge to the natural environment and the transformational changes that we must experience to achieve sustainability. Frances Cairncross, Herman E. Daly, Stephen H. Schneider and others provide a broad discussion of sustainable development. They detail economic and environmental, as well as spiritual and religious, corporate and social, scientific and political factors. Sustainable Development: The Challenge of Transition offers many insightful policy recommendations about how business, government, and individuals must change their current values, priorities, and behavior to meet present and future challenges. It will appeal to scholars and decision makers interested in global change, environmental policy, population growth, and sustainable development, and also to corporate environmental managers.

  2. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  3. Sustainable development.

    PubMed

    Dudani, A T

    1996-01-01

    Many attempts have been made over the last decade to define sustainable development (SD). However, it is much easier to describe one's expectations of SD. The discussion over SD grew in the wake of the Brundlandt Commission report, Our Common Future (OCF), which describes SD as a process of change in which resources, the direction of investment, orientation of technological development, and institutional change all enhance the potential to meet human needs today and in the future. The OCF stresses the interrelationship between SD and economic development such that nothing can be at the expense of environmental destruction. Close cooperation is needed at the domestic and international political, social, and economic levels and spheres in order to achieve long-term SD. The author discusses the state of affairs in the US and sustainable agriculture and SD.

  4. Defining "Development".

    PubMed

    Pradeu, Thomas; Laplane, Lucie; Prévot, Karine; Hoquet, Thierry; Reynaud, Valentine; Fusco, Giuseppe; Minelli, Alessandro; Orgogozo, Virginie; Vervoort, Michel

    2016-01-01

    Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory.

  5. Contraceptive Development.

    ERIC Educational Resources Information Center

    Troen, Philip; And Others

    This report provides an overview of research activities and needs in the area of contraceptive development. In a review of the present state, discussions are offered on the effectiveness and drawbacks of oral contraceptives, intrauterine devices, barrier methods, natural family planning, and sterilization. Methods of contraception that are in the…

  6. Spacelab's development

    NASA Astrophysics Data System (ADS)

    Bignier, M.

    1983-11-01

    Significant events in the international cooperation between ESA members and NASA in the development of Spacelab are outlined. The agreement to develop Spacelab in Europe was formalized in a MOU between NASA and ESRO in 1972, and was followed by configuration studies in both Europe and the U.S. It was decided in 1973 that ESA would build the hardware and turn it over to NASA, which would fly Spacelab on the Shuttle and buy a second Spacelab manned module. Once delivered, all responsibility for Spacelab would be transferred to NASA. A total of 10 European countries participated in the design, construction, and testing, performed by a project team of 100 engineers and 40 industrial companies. Design reviews were performed until 1981, in concert with hardware development of both Spacelab and pallets. The Eureca free-flying platform is being developed as a follow-on project, and studies are being conducted for activities in the future, such as participation in a space station.

  7. Flower Development

    PubMed Central

    Alvarez-Buylla, Elena R.; Benítez, Mariana; Corvera-Poiré, Adriana; Chaos Cador, Álvaro; de Folter, Stefan; Gamboa de Buen, Alicia; Garay-Arroyo, Adriana; García-Ponce, Berenice; Jaimes-Miranda, Fabiola; Pérez-Ruiz, Rigoberto V.; Piñeyro-Nelson, Alma; Sánchez-Corrales, Yara E.

    2010-01-01

    Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID:22303253

  8. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  9. New Developments

    ERIC Educational Resources Information Center

    Karlsson-Lohmander, Maelis

    2005-01-01

    A growing number of countries have recognised the importance of high quality early childhood provision for the development of the young child and the impact on economic growth and prosperity. What shapes Early Childhood Education and Care (ECEC) in an expanding Europe of today? Many factors clearly influence policy decisions and program…

  10. Algorithm development

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.; Lomax, Harvard

    1987-01-01

    The past decade has seen considerable activity in algorithm development for the Navier-Stokes equations. This has resulted in a wide variety of useful new techniques. Some examples for the numerical solution of the Navier-Stokes equations are presented, divided into two parts. One is devoted to the incompressible Navier-Stokes equations, and the other to the compressible form.

  11. Gender Development.

    ERIC Educational Resources Information Center

    Golombok, Susan; Fivush, Robyn

    In spite of the loosening ties between reproductive and social roles, the worlds of men and women and boys and girls, are clearly not the same. There is much more to being female or male than the potential to mother or father a child. Gender development does not simply depend on children's relationship with their parents: it results from a complex…

  12. CAREER DEVELOPMENT

    EPA Science Inventory

    The Baltimore Summit Project on Career Development/PERFORMS Enhancement/360 Evaluations for All has made some progress. We have identified the fact that we cannot change the current Pass/Fail PERFORMS system to a tiered system. The current pass/fail system does not have a mechani...

  13. Interorganizational Development.

    ERIC Educational Resources Information Center

    Schermerhorn, John R., Jr.

    1979-01-01

    Interorganizational development is the application of social science knowledge to the creation of planned, systematic and mutually beneficial cooperative relationships between otherwise autonomous organizations. This paper introduces the concept as a means of focusing attention on key action and research issues associated with interorganizational…

  14. Curriculum Development.

    ERIC Educational Resources Information Center

    Karolides, Nicholas J., Ed.; Quinn, Laura, Ed.

    1986-01-01

    Incorporating diverse viewpoints and featuring articles by teachers and administrators on both the university and the elementary-secondary levels, this focused journal issue offers useful practical suggestions and pragmatic guidance for all levels of curriculum development. The articles and their authors are as follows: (1)"Teaching Students to…

  15. New Developments

    ERIC Educational Resources Information Center

    Lohmander, Maelis Karlson; Vandenbroeck, Michel; Pirard, Florence; Peeters, Jan; Alvestad, Marit

    2009-01-01

    New developments and challenges regarding early childhood education (ECE) policy and practice in Norway and in the Flemish and French communities in Belgium are presented in this issue. There are clear differences between the countries when comparing systems they have chosen for ECE. In Belgium, supervision and responsibilities for education,…

  16. Workforce Development.

    ERIC Educational Resources Information Center

    1999

    This document contains four symposium papers on work force development. "Effects of Two Different Learning Paths on School-to-Work Transition" (Esther Van Der Schoot) discusses a Dutch study documenting that the following items make a difference in the school-to-work transition: learning path, curriculum characteristics, individual…

  17. Flower development.

    PubMed

    Alvarez-Buylla, Elena R; Benítez, Mariana; Corvera-Poiré, Adriana; Chaos Cador, Alvaro; de Folter, Stefan; Gamboa de Buen, Alicia; Garay-Arroyo, Adriana; García-Ponce, Berenice; Jaimes-Miranda, Fabiola; Pérez-Ruiz, Rigoberto V; Piñeyro-Nelson, Alma; Sánchez-Corrales, Yara E

    2010-01-01

    Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID:22303253

  18. Envisioning Development

    ERIC Educational Resources Information Center

    Dealtry, Richard

    2004-01-01

    This paper focuses on an important innovative development in new generation corporate university management. It addresses the thematic area of visual learning that is captured in the term "The Art of Minds-eye Management". It reflects upon experiences with groups of managers in enhancing perceptive competencies using visual awareness learning…

  19. Authoritarian Development.

    ERIC Educational Resources Information Center

    Mason, Edward S.

    1978-01-01

    While modernizing along Western economic lines, developing nations have not adopted Western political forms. But the evolution of democracy in Europe occurred in a different socioeconomic milieu. The authoritarian governments of the Third World, based on nationalism and centralization, may better meet current needs for modernization. (SJL)

  20. Gender Development

    ERIC Educational Resources Information Center

    Owen Blakemore, Judith E.; Berenbaum, Sheri A.; Liben, Lynn S.

    2008-01-01

    This new text offers a unique developmental focus on gender. Gender development is examined from infancy through adolescence, integrating biological, socialization, and cognitive perspectives. The book's current empirical focus is complemented by a lively and readable style that includes anecdotes about children's everyday experiences. The book's…

  1. Construction and evaluation of a novel bifunctional phenylalanine-formate dehydrogenase fusion protein for bienzyme system with cofactor regeneration.

    PubMed

    Jiang, Wei; Fang, Bai-Shan

    2016-05-01

    Phenylalanine dehydrogenase (PheDH) plays an important role in enzymatic synthesis of L-phenylalanine for aspartame (sweetener) and detection of phenylketonuria (PKU), suggesting that it is important to obtain a PheDH with excellent characteristics. Gene fusion of PheDH and formate dehydrogenase (FDH) was constructed to form bifunctional multi-enzymes for bioconversion of L-phenylalanine coupled with coenzyme regeneration. Comparing with the PheDH monomer from Microbacterium sp., the bifunctional PheDH-FDH showed noteworthy stability under weakly acidic and alkaline conditions (pH 6.5-9.0). The bifunctional enzyme can produce 153.9 mM L-phenylalanine with remarkable performance of enantiomers choice by enzymatic conversion with high molecular conversion rate (99.87 %) in catalyzing phenylpyruvic acid to L-phenylalanine being 1.50-fold higher than that of the separate expression system. The results indicated the potential application of the PheDH and PheDH-FDH with coenzyme regeneration for phenylpyruvic acid analysis and L-phenylalanine biosynthesis in medical diagnosis and pharmaceutical field. PMID:26819086

  2. The knowledge gap in expanded newborn screening: survey results from paediatricians in Massachusetts.

    PubMed

    Gennaccaro, M; Waisbren, S E; Marsden, D

    2005-01-01

    Massachusetts currently offers an optional expanded newborn screening programme that tests for 20 biochemical genetic disorders in addition to the mandated newborn screening tests, including phenylketonuria (PKU) and nine other biochemical genetic disorders. We conducted a mail survey of 550 paediatricians listed in the 2000 Massachusetts Healthcare Directory to determine paediatricians' preparedness in discussing expanded newborn screening and its results with families, and to determine in what specific format physicians in Massachusetts would prefer to receive educational materials and updates. Of surveys mailed, 35% (190/550) were returned within the allotted 3 weeks: 25 paediatricians (14%) were unaware of expanded newborn screening; 78 respondents (42%) indicated feeling less than prepared talking about test results with families; 100 paediatricians (54%) indicated a lack of information about metabolic disorders; 134 (73%) preferred information sent in postal mailings, 62 (34%) preferred grand rounds, 60 (33%) preferred educational seminars, and 58 (32%) preferred websites. Other formats receiving preferences of less than 30% included e-mail (27%), phone calls (8%), video (6%), and distance learning (1%). Paediatricians are ill-prepared for expanded newborn screening for biochemical genetic disorders. To address this problem, paediatricians in Massachusetts indicated a preference for unsolicited periodic mailings including short reviews and brochures. PMID:16435173

  3. The evolution of blood-spot newborn screening

    PubMed Central

    Wotton, Tiffany; Wiley, Veronica

    2014-01-01

    Over 50 years after the introduction of a blood-spot newborn screening test using the bacterial-inhibition assay (BIA), blood-spot newborn screening has evolved into complex public service scientific programmes. For several decades, many patients with phenylketonuria (PKU), congenital hypothyroidism (CH), cystic fibrosis (CF) and hemoglobinopathy disorders have benefited from early intervention across the world. In the last 20 years, there have been great changes in laboratory techniques and high-throughput data handling meaning that a huge spectrum of disorders can be identified from an increasing population. This coupled with the fact that there are an increasing number of therapies for specific rare disorders mean that health services may become inundated with complex and expensive demands in the future. Some of these issues have been realised in the implementation of multiplex assay such as electrospray tandem mass spectrometry (MSMS) programmes but will be much more exaggerated if genomic sequencing screening becomes a reality. In this context, the core-principles for implementation of newborn screening tests remain as important today as they have in the past when new tests are considered as part of the blood-spot screening programme. PMID:26835325

  4. Aspartame: review of safety.

    PubMed

    Butchko, Harriett H; Stargel, W Wayne; Comer, C Phil; Mayhew, Dale A; Benninger, Christian; Blackburn, George L; de Sonneville, Leo M J; Geha, Raif S; Hertelendy, Zsolt; Koestner, Adalbert; Leon, Arthur S; Liepa, George U; McMartin, Kenneth E; Mendenhall, Charles L; Munro, Ian C; Novotny, Edward J; Renwick, Andrew G; Schiffman, Susan S; Schomer, Donald L; Shaywitz, Bennett A; Spiers, Paul A; Tephly, Thomas R; Thomas, John A; Trefz, Friedrich K

    2002-04-01

    Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. These findings are reviewed here. The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.

  5. Construction and evaluation of a novel bifunctional phenylalanine-formate dehydrogenase fusion protein for bienzyme system with cofactor regeneration.

    PubMed

    Jiang, Wei; Fang, Bai-Shan

    2016-05-01

    Phenylalanine dehydrogenase (PheDH) plays an important role in enzymatic synthesis of L-phenylalanine for aspartame (sweetener) and detection of phenylketonuria (PKU), suggesting that it is important to obtain a PheDH with excellent characteristics. Gene fusion of PheDH and formate dehydrogenase (FDH) was constructed to form bifunctional multi-enzymes for bioconversion of L-phenylalanine coupled with coenzyme regeneration. Comparing with the PheDH monomer from Microbacterium sp., the bifunctional PheDH-FDH showed noteworthy stability under weakly acidic and alkaline conditions (pH 6.5-9.0). The bifunctional enzyme can produce 153.9 mM L-phenylalanine with remarkable performance of enantiomers choice by enzymatic conversion with high molecular conversion rate (99.87 %) in catalyzing phenylpyruvic acid to L-phenylalanine being 1.50-fold higher than that of the separate expression system. The results indicated the potential application of the PheDH and PheDH-FDH with coenzyme regeneration for phenylpyruvic acid analysis and L-phenylalanine biosynthesis in medical diagnosis and pharmaceutical field.

  6. Oh, Develop

    NASA Technical Reports Server (NTRS)

    Post, Todd

    2003-01-01

    In a mature view of the subject, career development is not simply four years of college or a week at training, culminating in a diploma or a certificate to hang on an office wall. That's why we wanted to take a broad look at career development in this issue of ASK. Take for example, Dr. Gerald Mulenburg s contribution, Fly on the Wall. When Mulenburg and other members of a knowledge-sharing group at Ames were invited to observe an upcoming project review, Mulenburg thought it would be interesting to learn how another project does its reviews. Note that Mulenburg is no fresh out who's never attended a NASA project review. Not only has he been through a fair share of them as the reviewed, he has also been on the other side of the table as a reviewer. This experienced project manager recognizes that at any stage of a career there is room to grow and develop one's repertoire. Too often people associate career development with textbooks and role classroom training, far removed from project life. But classroom training need not be like this, as you'll find in our Special Feature, The Enterprise Project by Wendy Dolci, which sprung out of an APPL Advanced Project Management class in July 2003 at Ames Research Center. In addition to Dolci, some of her classmates contribute to the story. Mike Sander of the Jet Propulsion Laboratory, project manager for the Mars Science Laboratory mission, who provided the assignment on which the story is based, also has a cameo in the story. We think Dolci's story is an inspiring example of what classroom training can be if it's approached imaginatively and made to serve a practical purpose. Another story from Ames, by Frank Larsen, takes a different twist on career development. At the annual Experimental Aircraft Association Fly-in in Oshkosh, Wisconsin, Larsen represented Ames at a NASA booth. While there, Larsen met a colleague from Glenn Research Center. Months later on a project with a quick turnaround, he remembered his colleague from

  7. Adaptive Development

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The goal of this research is to develop and demonstrate innovative adaptive seal technologies that can lead to dramatic improvements in engine performance, life, range, and emissions, and enhance operability for next generation gas turbine engines. This work is concentrated on the development of self-adaptive clearance control systems for gas turbine engines. Researchers have targeted the high-pressure turbine (HPT) blade tip seal location for following reasons: Current active clearance control (ACC) systems (e.g., thermal case-cooling schemes) cannot respond to blade tip clearance changes due to mechanical, thermal, and aerodynamic loads. As such they are prone to wear due to the required tight running clearances during operation. Blade tip seal wear (increased clearances) reduces engine efficiency, performance, and service life. Adaptive sealing technology research has inherent impact on all envisioned 21st century propulsion systems (e.g. distributed vectored, hybrid and electric drive propulsion concepts).

  8. Polarization developments

    SciTech Connect

    Prescott, C.Y.

    1993-07-01

    Recent developments in laser-driven photoemission sources of polarized electrons have made prospects for highly polarized electron beams in a future linear collider very promising. This talk discusses the experiences with the SLC polarized electron source, the recent progress with research into gallium arsenide and strained gallium arsenide as a photocathode material, and the suitability of these cathode materials for a future linear collider based on the parameters of the several linear collider designs that exist.

  9. Professional development

    NASA Astrophysics Data System (ADS)

    Yoon, Jin Hee; Hartline, Beverly Karplus; Milner-Bolotin, Marina

    2013-03-01

    The three sessions of the professional development workshop series were each designed for a different audience. The purpose of the first session was to help mid-career physicists aspire for and achieve leadership roles. The second session brought together students, postdoctoral fellows, and early-career physicists to help them plan their career goals and navigate the steps important to launching a successful career. The final session sought to increase awareness of the results of physics education research, and how to use them to help students-especially women-learn physics better. The presentations and discussions were valuable for both female and male physicists.

  10. Faculty development.

    PubMed

    McLaughlin, Steven A

    2005-04-01

    As emergency medicine faculty, we are called upon to be skilled in a great number of different areas. Residency training prepares us to be knowledgeable clinicians, skillful at procedures, good communicators, and effective at multitasking. Rarely, however, does it prepare us as educators or in the nuances of career advancement in an academic environment. Faculty development is a term used to describe both our growth as clinician-educators and navigation of the tenure and promotion process. An important role of medical student educators is to assist in preparing themselves and the faculty to be good teachers. In addition, we all hope to have successful careers as clinician-educators. The goal of this report is 2-fold: to provide a guide for faculty to advance their skills as educators and to help teaching faculty to advance their academic career. The first section of this report presents an approach to becoming a skilled educator, and the second section focuses on career development as an educator in an academic setting.

  11. Process development

    NASA Technical Reports Server (NTRS)

    Bickler, D. B.

    1985-01-01

    An overview is given of seven process development activities which were presented at this session. Pulsed excimer laser processing of photovoltaic cells was presented. A different pulsed excimer laser annealing was described using a 50 w laser. Diffusion barrier research focused on lowering the chemical reactivity of amorphous thin film on silicon. In another effort adherent and conductive films were successfully achieved. Other efforts were aimed at achieving a simultaneous front and back junction. Microwave enhanced plasma deposition experiments were performed. An updated version of the Solar Array Manufacturing Industry Costing Standards (SAMICS) was presented, along with a life cycle cost analysis of high efficiency cells. The last presentation was on the evaluation of the ethyl vinyl acetate encapsulating system.

  12. Nozzle development

    SciTech Connect

    Dodge, F.T.; Dodge, L.G.; Johnson, J.E.

    1989-06-01

    The objective of this program has been the development of experimental techniques and data processing procedures to allow for the characterization of multi-phase fuel nozzles using laboratory tests. Test results were to be used to produce a single value coefficient-of-performance that would predict the performance of the fuel nozzles independent of system application. Several different types of fuel nozzles capable of handling multi-phase fuels have been characterized for: (a) fuel flow rate versus delivery pressure, (b) fuel-air ratio throughout the fuel spray or plume and the effective cone angle of the injector, and (c) fuel drop- or particle-size distribution as a function of fluid properties. Fuel nozzles which have been characterized on both single-phase liquids and multi-phase liquid-solid slurries include a variable-film-thickness nozzle, a commercial coal-water slurry (CWS) nozzle, and four diesel injectors of different geometries (tested on single-phase fluids only). Multi-phase mixtures includes CWS with various coal loadings, surfactant concentrations, and stabilizer concentrations, as well as glass-bead water slurries with stabilizing additives. Single-phase fluids included glycerol-water mixtures to vary the viscosity over a range of 1 to 1500 cP, and alcohol-water mixtures to vary the surface tension from about 22 to 73 dyne/cm. In addition, tests were performed to characterize straight-tube gas-solid nozzles using two differences size distributions of glass beads in air. Standardized procedures have been developed for processing measurements of spray drop-size characteristics and the overall cross-section average drop or particle size. 43 refs., 60 figs., 7 tabs.

  13. Sampling Development

    PubMed Central

    Adolph, Karen E.; Robinson, Scott R.

    2011-01-01

    Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of the enterprise. This article discusses how to sample development in order to accurately discern the shape of developmental change. The ideal solution is daunting: to summarize behavior over 24-hour intervals and collect daily samples over the critical periods of change. We discuss the magnitude of errors due to undersampling, and the risks associated with oversampling. When daily sampling is not feasible, we offer suggestions for sampling methods that can provide preliminary reference points and provisional sketches of the general shape of a developmental trajectory. Denser sampling then can be applied strategically during periods of enhanced variability, inflections in the rate of developmental change, or in relation to key events or processes that may affect the course of change. Despite the challenges of dense repeated sampling, researchers must take seriously the problem of sampling on a developmental time scale if we are to know the true shape of developmental change. PMID:22140355

  14. Newborn screening for inborn errors of metabolism: a systematic review.

    PubMed

    Seymour, C A; Thomason, M J; Chalmers, R A; Addison, G M; Bain, M D; Cockburn, F; Littlejohns, P; Lord, J; Wilcox, A H

    1997-01-01

    intermediary metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000.(ABSTRACT TRUNCATED) PMID:9483156

  15. Sustainable Development: The Challenge for Community Development.

    ERIC Educational Resources Information Center

    Gamble, Dorothy N.; Weil, Marie O.

    1997-01-01

    Five areas of inquiry shape the sustainable development movement: environmental movement, women's movement, overpopulation concerns, critique of development models, and new indicators of social progress. Community development workers are challenged to prepare local development projects within a sustainable development framework. (SK)

  16. VAP Development: Initiation, Development, Evaluation, and Release

    SciTech Connect

    Jensen, M; Collis, Fast, J; Flynn, C; Mather, J; McFarlane, S; Monroe, J; Sivaraman, C; Xie, S

    2011-02-23

    This white paper provides a plan to formalize the evaluation of newly developed VAPs and a framework for the development of value-added products through four different stages: Initiation, Development, Evaluation, and Release.

  17. Proton injector acceptance tests for a Dielectric Wall Accelerator (DWA):characterisation of Advanced Injection System of Light Ions (AISLI)

    NASA Astrophysics Data System (ADS)

    Peng, S. X.; Ren, H. T.; Xu, Y.; Zhang, T.; Zhao(赵捷), J.; Zhang, A. L.; Guo, Z. Y.; Chen, J. E.

    2014-11-01

    To demonstrate the acceleration capability of a Dielectric Wall Accelerator (DWA), a proton injector has been developed at Peking University (PKU). It is composed of a compact permanent magnet 2.45 GHz Electron Cyclotron Resonance Ion Source (PKU PMECRIS) associated with a LEBT of two electrostatic Einzel lenses [1]. This injector is named as Advanced Injector System of Light Ions (AISLI). The acceptance tests have been performed with a 40 keV-55 mA hydrogen beam successfully passing through a ϕ 10 mm aperture diaphragm. This diaphragm is located 200 mm downstream the plasma emission hole at the location of the future DWA entrance flange. The beam rms emittance reached about 0.10 π mm mrad in pulsed mode. This article describes the AISLI experimental setup, the measurement principle and the obtained beam characteristics.

  18. Improving spatial representation of soil moisture by integration of microwave observations and the temperature-vegetation-drought index derived from MODIS products

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Ling, Ziwei; Wang, Yang; Zeng, Hui

    2016-03-01

    The microwave observations of land surface soil moisture have been widely used for studying environmental change at large spatial scales. However, the coarse spatial resolution of the products limits their local-scale applications. In this paper, we developed a new method, which integrates the coarse spatial resolution soil moisture derived from microwave sensors and the temperature-vegetation-drought-index (TVDI) derived from the Moderate-resolution Imaging Spectroradiometer (MODIS) products, to spatially downscale soil moisture data from 25-km resolution to 1-km resolution. First, we assessed the quality of the remotely sensed soil moisture by comparing their values with field measured soil moisture at three temporal scales and two spatial scales. Second, we analyzed the robustness of the developed approach namely the PKU method by comparing its performance with the results of three published methods (i.e., the triangle-based method, the Merlin method, and the UCLA method) at the Magqu soil moisture monitoring network located in the northeastern Tibetan grasslands. The modeling results showed that by integrating the contextual information from the relatively fine spatial resolution MODIS products, spatial soil moisture representations were significantly improved. The PKU method produced the most accurate spatially disaggregated soil moisture among the four methods. In conclusion, the PKU method developed in this study is a practical and efficient approach for improving spatial representations of the coarse spatial resolution soil moisture data derived from microwave remote sensors. Within the PKU method, our refined method for estimating the parameters of the dry-edge outperforms the traditional method.

  19. Developed-developing country partnerships: Benefits to developed countries?

    PubMed Central

    2012-01-01

    Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  20. Developed-developing country partnerships: benefits to developed countries?

    PubMed

    Syed, Shamsuzzoha B; Dadwal, Viva; Rutter, Paul; Storr, Julie; Hightower, Joyce D; Gooden, Rachel; Carlet, Jean; Bagheri Nejad, Sepideh; Kelley, Edward T; Donaldson, Liam; Pittet, Didier

    2012-06-18

    Developing countries can generate effective solutions for today's global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed--this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  1. Developed-developing country partnerships: benefits to developed countries?

    PubMed

    Syed, Shamsuzzoha B; Dadwal, Viva; Rutter, Paul; Storr, Julie; Hightower, Joyce D; Gooden, Rachel; Carlet, Jean; Bagheri Nejad, Sepideh; Kelley, Edward T; Donaldson, Liam; Pittet, Didier

    2012-01-01

    Developing countries can generate effective solutions for today's global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed--this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  2. App Development Paradigms for Instructional Developers

    ERIC Educational Resources Information Center

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

  3. Faculty Development as Human Resource Development.

    ERIC Educational Resources Information Center

    Mathis, B. Claude

    Faculty development is distinguished in this speech from the business model of human resource development on numerous issues including the fact that human resource development in business and industry values productivity, and higher education is not committed to making money. Faculty development is more concerned with the growth of individuals…

  4. Entrepreneurial Intentions in Developing and Developed Countries

    ERIC Educational Resources Information Center

    Iakovleva, Tatiana; Kolvereid, Lars; Stephan, Ute

    2011-01-01

    Purpose: This study proposes to use the Theory of Planned Behaviour to predict entrepreneurial intentions among students in five developing and nine developed countries. The purpose is to investigate whether entrepreneurial intention and its antecedents differ between developing and developed countries, and to test the theory in the two groups of…

  5. What Is Development?

    ERIC Educational Resources Information Center

    Astle, Alec

    1989-01-01

    Reviews inequalities in development, a topic in the New Zealand Form Six Geography Syllabus. Explains the different perspectives from which to approach development: academic, ideological, political, or personal. Considers the various meanings of development to less developed countries. (GG)

  6. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  7. Developing New Academic Developers: Doing before Being?

    ERIC Educational Resources Information Center

    Kensington-Miller, Barbara; Brailsford, Ian; Gossman, Peter

    2012-01-01

    A small group of new academic developers reflected on their induction into the profession and wondered if things could have been done differently. The researchers decided to question the directors of three tertiary academic development units about how they recruited new developers, what skills and competences they looked for and how they inducted…

  8. Clean development mechanism: Perspectives from developing countries

    SciTech Connect

    Sari, Agus P.; Meyers, Stephen

    1999-06-01

    This paper addresses the political acceptability and workability of CDM by and in developing countries. At COP-3 in Kyoto in 1997, the general position among developing countries changed from strong rejection of joint implementation to acceptance of CDM. The outgrowth of CDM from a proposal from Brazil to establish a Clean Development Fund gave developing countries a sense of ownership of the idea. More importantly, establishing support for sustainable development as a main goal for CDM overcame the resistance of many developing countries to accept a carbon trading mechanism. The official acceptance of CDM is not a guarantee of continued acceptance, however. Many developing countries expect CDM to facilitate a substantial transfer of technology and other resources to support economic growth. There is concern that Annex I countries may shift official development assistance into CDM in order to gain carbon credits, and that development priorities could suffer as a result. Some fear that private investments could be skewed toward projects that yield carbon credits. Developing country governments are wary regarding the strong role of the private sector envisioned for CDM. Increasing the awareness and capacity of the private sector in developing countries to initiate and implement CDM projects needs to be a high priority. While private sector partnerships will be the main vehicle for resource transfer in CDM, developing country governments want to play a strong role in overseeing and guiding the process so that it best serves their development goals. Most countries feel that establishment of criteria for sustainable development should be left to individual countries. A key issue is how CDM can best support the strengthening of local capacity to sustain and replicate projects that serve both climate change mitigation and sustainable development objectives.There is support among developing countries for commencing CDM as soon as possible. Since official commencement must

  9. Quantitative fluorescence detection of phenylalanine in blood spots on filter paper

    NASA Astrophysics Data System (ADS)

    Li, Yuezhi; Liu, Fengjun; Wang, Xuemin; Xu, Gang

    2007-11-01

    Phenylketonuria is a genetic disease, which causes the metabolization disorder of phenylalanine, this disorder would damage the neural system of infants as a result of the accumulation of phenylalanine in blood. Therefore, it is of great importance to diagnose and treat phenylketonuria as early as possible for newborns. The aim of this paper is to develop a fluorescence detection system to measure blood phenylalanine concentration of new-born infants. In this design, a high luminance ultraviolet LED is used for excitation source, and a kind of bifurcated optical fiber assembly is applied for conduction of light. The excitation source is filtered and coupled into quartz fibers of the bifurcated fiber assembly for conduction of light to excite the fluorescence of phenylalanine in blood sample. The collected fluorescence is transmitted along the glass fibers of the assemblies and coupled to a photomultiplier tube. The fluorescence is filtered with 470~500 nm band-pass filter to subdue scattered excitation light and to limit the spectral width of the detected fluorescence. By the comparison with a standard instrument, the new system with low power consumption, low cost and small size is also proven sensitive and accurate, which meets the demand of clinical phenylketonuria screening.

  10. Methods for the identification of mutations in the human phenylalanine hydroxylase gene using DNA probes

    SciTech Connect

    Woo, S.L.C.; Dilella, A.G.

    1990-10-23

    This patent describes a method of detecting a mutation in a phenylalanine hydroxylase gene of human genomic DNA. Also described is an automated method of detecting PKU affected, PKU helerozgotes and normals in fetal to adult human samples.

  11. FPG Child Development Institute

    MedlinePlus

    ... Development, Teaching, and Learning The Frank Porter Graham Child Development Institute will partner with Zero to Three to ... Education October 4, 2016 More Frank Porter Graham Child Development Institute The University of North Carolina at Chapel ...

  12. Curriculum Development: Teacher Involvement in Curriculum Development

    ERIC Educational Resources Information Center

    Alsubaie, Merfat Ayesh

    2016-01-01

    In order for curriculum development to be effective and schools to be successful, teachers must be involved in the development process. An effective curriculum should reflect the philosophy, goals, objectives, learning experiences, instructional resources, and assessments that comprise a specific educational program ("Guide to curriculum…

  13. Developing Teachers: Improving Professional Development for Teachers

    ERIC Educational Resources Information Center

    Coe, Robert; Aloisi, Cesare; Higgins, Steve; Major, Lee Elliot

    2015-01-01

    This document is a summary of the report "What Makes Great Teaching". It argues that improved teacher ­development will positively impact on pupil attainment, particular those from disadvantaged backgrounds. "Developing Teachers" presents five policy recommendations which have been signed by 17 of Britain's leading headteachers…

  14. Developing New Models for Collection Development.

    ERIC Educational Resources Information Center

    Stoffle, Carla J.; Fore, Janet; Allen, Barbara

    1999-01-01

    Discusses the need to develop new models for collection development in academic libraries, based on experiences at the University of Arizona. Highlights include changes in the organizational chart; focusing on users' information goals and needs; integrative services; shared resources; interlibrary loans; digital technology; and funding. (LRW)

  15. SIRU development. Volume 1: System development

    NASA Technical Reports Server (NTRS)

    Gilmore, J. P.; Cooper, R. J.

    1973-01-01

    A complete description of the development and initial evaluation of the Strapdown Inertial Reference Unit (SIRU) system is reported. System development documents the system mechanization with the analytic formulation for fault detection and isolation processing structure; the hardware redundancy design and the individual modularity features; the computational structure and facilities; and the initial subsystem evaluation results.

  16. Ceramic brush seals development

    NASA Technical Reports Server (NTRS)

    Howe, Harold

    1994-01-01

    The following topics are discussed in this viewgraph presentation: ceramic brush seals, research and development, manufacturing, brazed assembly development, controlling braze flow, fiber selection, and braze results.

  17. Education and Development: A Developing Theme

    NASA Astrophysics Data System (ADS)

    Brock-Utne, Birgit

    2002-03-01

    The following article is based on an analysis of selected examples from the approximately 2500 main articles that have been published in the International Review of Education ( IRE) since its inception in 1931 until the fall of 2001. The scope of the topic is education within developing countries and the promotion of such education by industrialised countries and development agencies. After an introduction on the growth of the concern over education and development over seven decades of the journal, three themes are looked at in some more detail: (1) The discussion on nationalism versus internationalism in education, a theme that bears clear relevance to the field "Education and Development" and has been with the journal from its inception but on which one finds more emphasis in the earlier volumes. (2) The language of instruction in developing countries. This theme has also been with the journal from its inception and it is still much debated. (3) The effects of external aid on the education sector in developing countries. Though massive economic aid in the form of grants or loans to the education sector in developing countries is of more recent nature external influence on the education sector has been there since colonial times.

  18. Geothermal development opportunities in developing countries

    SciTech Connect

    Kenkeremath, D.C.

    1989-11-16

    This report is the proceedings of the Seminar on geothermal development opportunities in developing countries, sponsored by the Geothermal Division of the US Department of Energy and presented by the National Geothermal Association. The overall objectives of the seminar are: (1) Provide sufficient information to the attendees to encourage their interest in undertaking more geothermal projects within selected developing countries, and (2) Demonstrate the technological leadership of US technology and the depth of US industry experience and capabilities to best perform on these projects.

  19. Value Conflicts in Computing Developments: Developed and Developing Countries.

    ERIC Educational Resources Information Center

    Kling, Rob

    1983-01-01

    This paper examines the value conflicts engendered by computing developments in two different institutional settings: electronic funds transfer systems and instructional computing in primary and secondary schools. While specific values depend upon culture and upon the character of the particular institutional setting studied, these two cases serve…

  20. LGBT Career Development

    ERIC Educational Resources Information Center

    Gedro, Julie

    2007-01-01

    In this paper, I would like to open a conversation with my HRD colleagues about the issues related to Lesbian, Gay, Bisexual and Transgender (LGBT) career development. This paper provides some insights about LGBT career development, analyzing the factors that distinguish LGBT career development from heterosexual career development.

  1. Agile Software Development

    ERIC Educational Resources Information Center

    Biju, Soly Mathew

    2008-01-01

    Many software development firms are now adopting the agile software development method. This method involves the customer at every level of software development, thus reducing the impact of change in the requirement at a later stage. In this article, the principles of the agile method for software development are explored and there is a focus on…

  2. Leadership Development. Symposium 12.

    ERIC Educational Resources Information Center

    2000

    Three presentations are provided from the Academy of Human Resource Development (HRD) 2000 Conference Proceedings. "Leadership Development: A Review of the Theory and Literature" (Susan A. Lynham) has four parts that analyze the leadership development process: the present state of the available body of knowledge on leadership development; core…

  3. Developing Local Community Leaders.

    ERIC Educational Resources Information Center

    Dyer, Delwyn A.; Williams, Oscar M.

    The successful development of local leaders is the goal of leadership training and community development. Development involves defining and developing leadership. Although leader-centered leadership offers few chances of meeting the maintenance needs of the group as a whole, shared leadership allows the group to join in the decision-making…

  4. Energy Sources and Development.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with energy sources and development. Its objective is for the student to be able to discuss energy sources and development related to the historical perspective, biological development, current aspects, and future expectations…

  5. Directions in Staff Development

    ERIC Educational Resources Information Center

    Brew, Angela, Ed.

    This collection of readings is intended to provide a source book on best practices in staff development in higher education within a British context. The 13 papers are grouped into three parts: part 1 presents the educational development tradition which has focused on development of staff as teachers; part 2 considers development of staff in…

  6. Aspartame intolerance.

    PubMed

    Garriga, M M; Metcalfe, D D

    1988-12-01

    Aspartame is a food additive marketed under the brand name Nutrasweet. Aspartame is a white, odorless, crystalline powder and consists of two amino acids, L-aspartic acid and L-phenylalanine. It is 180 times as sweet as sugar. The Food and Drug Administration (FDA) first allowed its use in dry foods in July 1981 and then approved its use in carbonated beverages in July 1983. It has subsequently been approved for use in a number of materials including multivitamins, fruit juices, stick-type confections, breath mints, and iced tea. The FDA requires the statement "phenylketonurics: contains phenylalanine" on labels of food products containing aspartame because individuals with phenylketonuria (PKU) must restrict their intake of phenylalanine. Aspartame is judged to be free of long-term cancer risks. Aspartame is not stable under certain conditions including baking and cooking, and prolonged exposure to acid conditions. In such situations it loses its sweetness. Products formed from aspartame include its component amino acids (phenylalanine and aspartic acid), methanol, and diketopiperazine (DKP). Animal studies show DKP to be nontoxic. Methanol occurs in small amounts and does not exceed that formed during consumption of many foods including fresh fruits and vegetables. FDA's Center for Food Safety and Applied Nutrition (CFSAN) monitors aspartame's safety in part through reports of adverse reactions. After aspartame was approved for use in carbonated beverages, the FDA received an increased number of reports concerning adverse reactions related to aspartame. The Centers for Disease Control (CDC) reviewed these reports, which included complaints of neurologic, gastrointestinal, andallergic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Chemical probe development versus drug development.

    PubMed

    Jackson, Michael R

    2013-01-01

    Phosphatases as a class of proteins have recently attracted significant attention from the pharmaceutical industry. As our knowledge of this diverse family of proteins has grown, the relationship between phosphatases and human disease has clearly been established, with model systems proving much validation for the potential of some members of this family to be candidate drug targets. This, coupled with the fact that there have been a flood of successful drug development efforts over the past 10 years targeting protein kinases, has led some to propose that phosphatases as a class of enzymes might be equally as rich a source of drug targets as kinases. However to date there remain relatively few molecules targeting protein phosphatases in clinical development. This is less a reflection of their importance in key processes associated with disease, but rather seems to reflect inherent issues with developing drugs for many members of this family. This seems especially so for intracellular phosphatases where the development of selective, potent cell penetrant molecules with good drug-like properties has proven a formidable challenge. This chapter provides a brief outline of the two major processes that have resulted in the existing armament of chemical modulators of protein phosphatases, namely, chemical probe development and drug development. These two processes initially seem to be rather similar and while they do overlap, the stated goals of the two approaches at project initiation are distinct. PMID:23860644

  8. Chemical probe development versus drug development.

    PubMed

    Jackson, Michael R

    2013-01-01

    Phosphatases as a class of proteins have recently attracted significant attention from the pharmaceutical industry. As our knowledge of this diverse family of proteins has grown, the relationship between phosphatases and human disease has clearly been established, with model systems proving much validation for the potential of some members of this family to be candidate drug targets. This, coupled with the fact that there have been a flood of successful drug development efforts over the past 10 years targeting protein kinases, has led some to propose that phosphatases as a class of enzymes might be equally as rich a source of drug targets as kinases. However to date there remain relatively few molecules targeting protein phosphatases in clinical development. This is less a reflection of their importance in key processes associated with disease, but rather seems to reflect inherent issues with developing drugs for many members of this family. This seems especially so for intracellular phosphatases where the development of selective, potent cell penetrant molecules with good drug-like properties has proven a formidable challenge. This chapter provides a brief outline of the two major processes that have resulted in the existing armament of chemical modulators of protein phosphatases, namely, chemical probe development and drug development. These two processes initially seem to be rather similar and while they do overlap, the stated goals of the two approaches at project initiation are distinct.

  9. Hanford Site Development Plan

    SciTech Connect

    Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

    1993-05-01

    The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP`s primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans.

  10. Modeling Tourism Sustainable Development

    NASA Astrophysics Data System (ADS)

    Shcherbina, O. A.; Shembeleva, E. A.

    The basic approaches to decision making and modeling tourism sustainable development are reviewed. Dynamics of a sustainable development is considered in the Forrester's system dynamics. Multidimensionality of tourism sustainable development and multicriteria issues of sustainable development are analyzed. Decision Support Systems (DSS) and Spatial Decision Support Systems (SDSS) as an effective technique in examining and visualizing impacts of policies, sustainable tourism development strategies within an integrated and dynamic framework are discussed. Main modules that may be utilized for integrated modeling sustainable tourism development are proposed.

  11. Hanford Site Development Plan

    SciTech Connect

    Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J. ); Yancey, E.F. )

    1990-01-01

    The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs.

  12. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-07-28

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  13. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2005-01-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  14. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2005-04-30

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  15. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  16. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2004-04-30

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  17. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2002-07-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  18. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2001-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  19. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2001-07-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  20. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    SciTech Connect

    Kathryn Baskin

    2003-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts.

  1. Developing the plan

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The basic sequence in the planning development process is discussed. Alternative ways of satisfying estimated needs, and the selection of an alternative are described along with the development of a plan to implement the selected alternative.

  2. Book Development in Bangladesh.

    ERIC Educational Resources Information Center

    Rabbi, Fazle

    1982-01-01

    Describes the historical development of book production in Bangladesh and discusses the situation in Bangladesh with regard to the economics of publishing, the relationship between publishing and library development, book distribution, copyright and translation, and book experts. (Author/JL)

  3. The Developing Brain.

    ERIC Educational Resources Information Center

    Schatz, Carla J.

    1992-01-01

    Discusses neural activity and stimulation crucial in fetal brain development and the formation of the mind. Focuses on activity-dependent remodeling related to development of the visual system and retinal activity. (MCO)

  4. Robotic Lander Development Project

    NASA Video Gallery

    The Robotic Lander Development Project at the Marshall Center is testing a prototype lander that will aid in the design and development of a new generation of small, smart, versatile robotic lander...

  5. Development and Environment.

    ERIC Educational Resources Information Center

    Dubhashi, P. R.

    1994-01-01

    Review of environmental issues in India concludes that educational institutions can contribute to sustainable development by promoting understanding of the ecosystem; assessing a community's natural wealth; developing strategies; and promoting participation in environmental preservation projects. (SK)

  6. Gammasphere software development

    SciTech Connect

    Piercey, R.B.

    1993-01-01

    Activities of the nuclear physics group are described. Progress was made in organizing the Gammasphere Software Working Group, establishing a nuclear computing facility, participating in software development at Lawrence Berkeley, developing a common data file format, and adapting the ORNL UPAK software to run at Gammasphere. A universal histogram object was developed that defines a file format and provides for an objective-oriented programming model. An automated liquid nitrogen fill system was developed for Gammasphere (110 Ge detectors comprise the sphere).

  7. Essays on Child Development in Developing Countries

    ERIC Educational Resources Information Center

    Humpage, Sarah Davidson

    2013-01-01

    This dissertation presents the results of three field experiments implemented to evaluate the effectiveness of strategies to improve the health or education of children in developing countries. In Guatemala, community health workers at randomly selected clinics were given patient tracking lists to improve their ability to remind parents when their…

  8. Science and Development

    ERIC Educational Resources Information Center

    Auger, Pierre

    1973-01-01

    The relation between science and socioeconomic development in both developed and developing countries is discussed. The interdependence of pure and applied science, technology and finance, knowledge and tradition, and national, regional, and world-wide efforts in behalf of progress are characterized. (BL)

  9. Evaluating Instructional Development Programmes.

    ERIC Educational Resources Information Center

    Knapper, Christopher K.

    The effectiveness of instructional development evaluation programs is assessed. It is suggested that although it is a basic tenet in instructional development that teaching improvement is closely linked to effective evaluation, it is ironical that most instructional development programs have themselves been evaluated only superficially, if at all.…

  10. Folk Media in Development.

    ERIC Educational Resources Information Center

    Instructional Technology Report, 1975

    1975-01-01

    This issue is dedicated to folk media. Using Indonesia for his case study, Dr. Nat Colletta analyzes traditional culture as a medium for development. Juan Diaz Bordenave expresses doubts about adapting folk media to development objectives; Susan Hostetler and Arthur Gillette report on uses of the theater to promote development objectives; and…

  11. Mechanisms in Plant Development

    SciTech Connect

    Hake, Sarah

    2013-08-21

    This meeting has been held every other year for the past twenty-two years and is the only regularly held meeting focused specifically on plant development. Topics covered included: patterning in developing tissues; short and long distance signaling; differentiation of cell types; the role of epigenetics in development; evolution; growth.

  12. Moral Development in Adolescence

    ERIC Educational Resources Information Center

    Hart, Daniel; Carlo, Gustavo

    2005-01-01

    Themes in the papers in this special issue of the "JRA" on moral development are identified. We discuss the intersection of moral development research with policy concerns, the distinctive qualities of moral life in adolescence that warrant investigation, the multiple connotations of "moral", the methods typical of moral development research, and…

  13. Language and Psychological Development.

    ERIC Educational Resources Information Center

    Gleason, Jean Berko

    Input language may have an effect on child development that goes far beyond language development alone. Language is the medium by which children acquire at least a portion of their sex role and social class or group characteristics, world view, and emotional and psychological well-being. Existing theories of psychological development ignore…

  14. Developing Large CAI Packages.

    ERIC Educational Resources Information Center

    Reed, Mary Jac M.; Smith, Lynn H.

    1983-01-01

    When developing large computer-assisted instructional (CAI) courseware packages, it is suggested that there be more attentive planning to the overall package design before actual lesson development is begun. This process has been simplified by modifying the systems approach used to develop single CAI lessons, followed by planning for the…

  15. Cultural Energy & Grassroots Development.

    ERIC Educational Resources Information Center

    Kleymeyer, Charles D.

    1992-01-01

    Discusses how cultural vitality drives successful community development. Links cultural, community, and environmental values. Examines successes and failures of programs attempting to link culture and development in Panama, Ecuador, and Colombia. Examines role of cultural self-examination for creating new development paradigm. Examines prospects…

  16. Human Resource Development.

    ERIC Educational Resources Information Center

    Mensel, R. Frank

    The contradictions of campus management are examined in this speech and applied to the problems of human resource development. The author suggests that human resource development cannot be considered fully without taking into account the state of the institution and institutional development. Since human resources represents 75 percent or more of…

  17. Teachers as Course Developers.

    ERIC Educational Resources Information Center

    Graves, Kathleen, Ed.

    The collection of essays on teachers as course developers is designed to help teachers understand how to develop courses or modify existing ones using their own experience and the experiences and theories of others. It attempts to capture this process through the stories of six teachers who have developed courses. Each narrative focuses on a…

  18. Bilingualism and Cognitive Development.

    ERIC Educational Resources Information Center

    Caraballo, Jose N.

    Research on the effects of bilingualism on cognitive development is reviewed, and two complementary models of bilingualism are developed to account for research results. It is suggested that research since 1960 shows a positive relationship between bilingualism and cognitive development, at least for some types of bilingualism. The advantage or…

  19. Marketing Human Resource Development.

    ERIC Educational Resources Information Center

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  20. Curriculum Development in Geomorphology.

    ERIC Educational Resources Information Center

    Gregory, Kenneth J.

    1988-01-01

    Examines the context of present curriculum development in geomorphology and the way in which it has developed in recent years. Discusses the content of the geomorphology curriculum in higher education and the consequences of curriculum development together with a consideration of future trends and their implications. (GEA)

  1. PHOTOGRAPHIC FILM DEVELOPER

    DOEpatents

    Berry, F.G.

    1958-06-24

    S>An improved photographic developer is presented having very high energy development fine grain characteristics and a long shelf life. These characteristics are obtained by the use of aminoacetic acid in the developer, the other constituents of which are: sodium sulfite, hydroquinone, sodiunn borate, boric acid and potassium bromide, 1-phenyl-3-pyrazolidone.

  2. HRD Professional Development.

    ERIC Educational Resources Information Center

    1998

    This document contains four papers from a symposium on professional development of human resource development (HRD) professionals. "Lifelong Learning and Performance: The Role of Key Qualifications in Human Resource Development" (Simone J. van Zolingen, Wim J. Nijhof) argues that, besides being of interest to employers, key qualifications are also…

  3. Prodder's Development Annual, 1988.

    ERIC Educational Resources Information Center

    van der Kooy, R. J. W., Ed.

    This collection of reports examines the current state of development in southern Africa, in general, and in South Africa, in particular. The introduction, "A Development Perspective of Southern Africa" (R. J. W. van der Kooy), briefly reviews the history of southern African development, and discusses purposes, approaches, and progress. Sixteen…

  4. World Development Report 1984.

    ERIC Educational Resources Information Center

    World Bank, Washington, DC.

    This report, seventh in a series of annual publications, examines the relationship between population change and development, showing why continuing rapid population growth in developing countries is likely to mean a lower quality of life for millions of people. The first part of the report concludes that the economies of developing countries can…

  5. Collection Development Project.

    ERIC Educational Resources Information Center

    Nuby, Mary

    Undertaken to provide data on the current status of collection development in selected academic libraries, this study also analyzed the structure of the collection development function at Chicago Academic Library Council (CALC) institutions and outlined a formal collection development policy for Chicago State University's Douglas Library.…

  6. Student Development as Theory.

    ERIC Educational Resources Information Center

    Rogers, Russell R.

    Student development theory has been adopted as the guiding theoretical framework of the student affairs profession. Unfortunately this adoption has largely occurred without a critical analysis of the concept of student development as a gestalt. A case can be made that for the most part the theories of student development are logically coherent in…

  7. Staff Development Content Delivery.

    ERIC Educational Resources Information Center

    Dillon, Elizabeth A.

    1979-01-01

    Question clusters related to staff development content delivery are used to develop programs that will result in more productive professional development. The questions determine the focus of programs, analyze the target audience, discuss the selection of delivery modes, and identify future directions. (JMF)

  8. Molecular biology of development

    SciTech Connect

    Davidson, E.H.; Firtel, R.A.

    1984-01-01

    This book is a compilation of papers presented at a symposium on the molecular biology of development. Topics discussed include: cytoplasmic localizations and pattern formations, gene expression during oogenesis and early development, developmental expression of gene families molecular aspects of plant development and transformation in whole organisms and cells.

  9. Development Communication Report, 1993.

    ERIC Educational Resources Information Center

    Bosch, Andrea, Ed.

    1993-01-01

    The three 1993 issues of the newsletter "Development Communication Report" focus on the use of communication technologies in developing countries to educate the people about various social issues as well as the field of development communication itself. Agricultural communication is the theme of the first issue which contains the following…

  10. Management Development Study.

    ERIC Educational Resources Information Center

    Department of Transportation, Washington, DC.

    This document reports on a management development study within the Department of Transportation (DOT). The aim of the study was to develop a systematic approach to management development for military and civilian personnel. A variety of methods was used to gather data including having DOT staff members gather the information to be passed on to the…

  11. Educating for Career Development.

    ERIC Educational Resources Information Center

    Tennyson, W. Wesley; And Others

    Basic career needs, management tasks, objectives, human development rationale, and implementation strategies for a career development education program are discussed in terms of the Minnesota Career Development Curriculum (CDC) project. Oriented toward teachers and counselors, the document contains six chapters: (1) The Challenge, presenting an…

  12. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  13. Renewable energy project development

    SciTech Connect

    Ohi, J.

    1996-12-31

    The author presents this paper with three main thrusts. The first is to discuss the implementation of renewable energy options in China, the second is to identify the key project development steps necessary to implement such programs, and finally is to develop recommendations in the form of key issues which must be addressed in developing such a program, and key technical assistance needs which must be addressed to make such a program practical.

  14. Fusion development and technology

    SciTech Connect

    Montgomery, D.B.

    1992-01-01

    This report discusses the following: superconducting magnet technology; high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies--aries; ITER physics: alpha physics and alcator R D for ITER; lower hybrid current drive and heating in the ITER device; ITER superconducting PF scenario and magnet analysis; ITER systems studies; and safety, environmental and economic factors in fusion development.

  15. Exploration Technology Development & Demonstration

    NASA Video Gallery

    Chris Moore delivers a presentation from the Exploration Technology Development & Demonstration (ETDD) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX....

  16. Avionics advanced development strategy

    NASA Technical Reports Server (NTRS)

    Dyer, D.

    1990-01-01

    Discussed here is the problem of how to put together an integrated, phased, and affordable avionics advanced development program that links and applies to operational, evolving, and developing programs/vehicles, as well as those in the planning phases. Collecting technology needs from individual programs/vehicles and proposed technology items from individual developers usually results in a mismatch and something that is unaffordable. A strategy to address this problem is outlined with task definitions which will lead to avionics advanced development items that will fit within an overall framework, prioritized to support budgeting, and support the scope of NASA space transportations needs.

  17. Infectious diarrhea in developed and developing countries.

    PubMed

    Cheng, Allen C; McDonald, Jay R; Thielman, Nathan M

    2005-10-01

    Diarrhea from gastrointestinal infection remains a common problem. In industrialized countries, management is aimed at reducing morbidity and defining groups that may benefit from further investigation. Most infectious diarrhea is self-limiting and only requires supportive management. Viral agents are increasingly recognized as causative agents of epidemic and sporadic diarrhea. In developing countries, diarrhea is a major cause of mortality in children. Oral rehydration therapy, guided by a clinical assessment of the degree of dehydration, is cheap, simple, and effective and remains the mainstay of management of infant diarrhea. Controversies focus on the optimal formulation of oral rehydration solution. A vaccine against rotavirus has the potential to save millions of lives worldwide.

  18. Halbach Magnetic Rotor Development

    NASA Technical Reports Server (NTRS)

    Gallo, Christopher A.

    2008-01-01

    The NASA John H. Glenn Research Center has a wealth of experience in Halbach array technology through the Fundamental Aeronautics Program. The goals of the program include improving aircraft efficiency, reliability, and safety. The concept of a Halbach magnetically levitated electric aircraft motor will help reduce harmful emissions, reduce the Nation s dependence on fossil fuels, increase efficiency and reliability, reduce maintenance and decrease operating noise levels. Experimental hardware systems were developed in the GRC Engineering Development Division to validate the basic principles described herein and the theoretical work that was performed. A number of Halbach Magnetic rotors have been developed and tested under this program. A separate test hardware setup was developed to characterize each of the rotors. A second hardware setup was developed to test the levitation characteristics of the rotors. Each system focused around a unique Halbach array rotor. Each rotor required original design and fabrication techniques. A 4 in. diameter rotor was developed to test the radial levitation effects for use as a magnetic bearing. To show scalability from the 4 in. rotor, a 1 in. rotor was developed to also test radial levitation effects. The next rotor to be developed was 20 in. in diameter again to show scalability from the 4 in. rotor. An axial rotor was developed to determine the force that could be generated to position the rotor axially while it is rotating. With both radial and axial magnetic bearings, the rotor would be completely suspended magnetically. The purpose of this report is to document the development of a series of Halbach magnetic rotors to be used in testing. The design, fabrication and assembly of the rotors will be discussed as well as the hardware developed to test the rotors.

  19. Population, environment and development.

    PubMed

    Karkal, M

    1994-06-01

    Western development models label subsistence economies, which do not participate in the market economy on a grand scale and do not consume commodities produced for and distributed through the market, to be poor. Yet, subsistence does not always indicate a low quality of life. The Western development process has destroyed wholesome and sustainable lifestyles. In India, the Green Revolution caused many small farmers to lose their land. In comparison to traditional economies, industrial economies have longer technological chains dependent on higher energy and resource inputs and exclude large numbers of people without power to buy goods. Further, they generate new and artificial needs, necessitating increased production of industrial goods and services. They erode resource bases for survival. This erosion is marginalizing people who were traditionally in nature's economy. Developed countries did not deliver 0.15% of their GNP to development projects in developing countries as promised. The US made population growth in these countries its cause. The UN and other multinational agencies during 1962-1972, at the US's request, began to support population and family planning programs in developing countries. These countries opposed the 1st draft at the 1974 Bucharest Population Conference, but by the conference in Mexico City, most supported the need for family planning. Yet, the US politicized this conference and had a greater say in the recommendations than did developing countries. Structural adjustments and external debt repayments required of developing countries in the 1980s set them back. In fact, the number of developing countries increased from 31 to 42. The UN recognizes the right to development, but social inequalities are barriers to this right. If environmental degradation continues, poverty will only increase. Women's groups are playing a great role in preparations for the International Conference on Population and Development in Cairo in September 1994. PMID

  20. Population, environment and development.

    PubMed

    Karkal, M

    1994-06-01

    Western development models label subsistence economies, which do not participate in the market economy on a grand scale and do not consume commodities produced for and distributed through the market, to be poor. Yet, subsistence does not always indicate a low quality of life. The Western development process has destroyed wholesome and sustainable lifestyles. In India, the Green Revolution caused many small farmers to lose their land. In comparison to traditional economies, industrial economies have longer technological chains dependent on higher energy and resource inputs and exclude large numbers of people without power to buy goods. Further, they generate new and artificial needs, necessitating increased production of industrial goods and services. They erode resource bases for survival. This erosion is marginalizing people who were traditionally in nature's economy. Developed countries did not deliver 0.15% of their GNP to development projects in developing countries as promised. The US made population growth in these countries its cause. The UN and other multinational agencies during 1962-1972, at the US's request, began to support population and family planning programs in developing countries. These countries opposed the 1st draft at the 1974 Bucharest Population Conference, but by the conference in Mexico City, most supported the need for family planning. Yet, the US politicized this conference and had a greater say in the recommendations than did developing countries. Structural adjustments and external debt repayments required of developing countries in the 1980s set them back. In fact, the number of developing countries increased from 31 to 42. The UN recognizes the right to development, but social inequalities are barriers to this right. If environmental degradation continues, poverty will only increase. Women's groups are playing a great role in preparations for the International Conference on Population and Development in Cairo in September 1994.

  1. Supporting Character Development.

    ERIC Educational Resources Information Center

    Janas, Monica; Nabors, Martha C.

    2002-01-01

    Identifies strategies early childhood educators can use to create an environment that encourages character development in young children. Provides reflective checklists for specific areas of character development and character education addressed: (1) content; (2) communication; (3) clarification; (4) community; (5) critical thinking; (6) context;…

  2. Developing Fact Sheets.

    ERIC Educational Resources Information Center

    Weiler, Robert M.

    1998-01-01

    Presents an assignment that allows preservice health educators to learn how to develop fact sheets for communicating health information. The process of developing fact sheets involves selecting a topic, selecting a target audience, researching the topic, writing the message, constructing the draft, and pretesting the product. Strategies for…

  3. Language and Development.

    ERIC Educational Resources Information Center

    Crooks, Tony, Ed.; Crewes, Geoffrey, Ed.

    A selection of papers presented at an international conference on the role of language in economic and social development includes: "Changing Paradigms: The Project Approach" (John McGovern); "Team Development of ELT Projects: A Case Study" (William M. Martin, Lynn P. Balabanis); "The Roles of Insiders and Outsiders in Evaluating English Language…

  4. Youth Development: Maori Styles

    ERIC Educational Resources Information Center

    Ware, Felicity; Walsh-Tapiata, Wheturangi

    2010-01-01

    Despite the innovative approach of the Youth Development Strategy Aotearoa and the applicability of its Rangatahi Development Package, the diverse realities and experiences of Maori youth are still presenting unique challenges to national policy in Aotearoa New Zealand. A Maori youth research approach that utilised a combination of action research…

  5. South Korea's Economic Development.

    ERIC Educational Resources Information Center

    Ihm, Chon-Sun

    1988-01-01

    Examines South Korea's economic development from being one of the poorest nations in the world in the 1950s to becoming a "rising giant" in international trade. Surveys the path to growth, the reasons for success, and problems and new challenges facing the country as it seeks developed nation status. (GEA)

  6. Developing Environmental Study Areas.

    ERIC Educational Resources Information Center

    Wert, Jonathan M.

    This publication is designed to help the teacher in developing environmental study areas. Numerous examples of study areas, including airports, lakes, shopping centers, and zoos, are listed. A current definition of environmental study areas is given and guidelines for their development and identification are included. The appendix, which comprises…

  7. Understanding Teacher Development.

    ERIC Educational Resources Information Center

    Hargreaves, Andy, Ed.; Fullan, Michael G., Ed.

    The 12 chapters in this book interpret teacher development in relation to self-development, teacher reflection, teacher biographies, cultures of teaching, teacher careers, teachers' work, gender identity, and classroom practice. The collection begins with an introductory chapter (Andy Hargreaves and Michael G. Fullan) and continues with 11…

  8. Technical Assistance to Developers

    SciTech Connect

    Rockward, Tommy; Borup, Rodney L.; Garzon, Fernando H.; Mukundan, Rangachary; Spernjak, Dusan

    2012-07-17

    This task supports the allowance of technical assistance to fuel-cell component and system developers as directed by the DOE. This task includes testing of novel materials and participation in the further development and validation of single cell test protocols. This task also covers technical assistance to DOE Working Groups, the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Driving Research and Innovation for Vehicle efficiency and Energy sustainability (U.S. Drive) Fuel Cell Technology Team. Assistance includes technical validation of new fuel cell materials and methods, single cell fuel cell testing to support the development of targets and test protocols, and regular advisory participation in other working groups and reviews. This assistance is made available to PEM fuel cell developers by request and DOE Approval. The objectives are to: (1) Support technically, as directed by DOE, fuel cell component and system developers; (2) Assess fuel cell materials and components and give feedback to developers; (3) Assist the DOE Durability Working Group with the development of various new material durability Testing protocols; and (4) Provide support to the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Fuel Cell Technology Team. FY2012 specific technical objectives are: (1) Evaluate novel MPL materials; (2) Develop of startup/ shutdown protocol; (3) Test the impact of hydrophobic treatment on graphite bi-polar plates; (4) Perform complete diagnostics on metal bi-polar plates for corrosion; and (5) Participate and lead efforts in the DOE Working Groups.

  9. Communication for Rural Development.

    ERIC Educational Resources Information Center

    Fraser, Colin

    1984-01-01

    These reflections emerging from the Food and Agriculture Organization's long involvement in communication for development focus on lack of physical communication infrastructures accommodating development work; human dimension; more systematic media use; use of educational radio and portable video recorders; political considerations; and need for…

  10. Developing Our Water Resources

    ERIC Educational Resources Information Center

    Volker, Adriaan

    1977-01-01

    Only very recently developed as a refined scientific discipline, hydrology has to cope with a complexity of problems concerning the present and future management of a vital natural resource, water. This article examines available water supplies and the problems and prospects of water resource development. (Author/MA)

  11. Action in Development

    ERIC Educational Resources Information Center

    von Hofsten, Claes

    2007-01-01

    It is argued that cognitive development has to be understood in the functional perspective provided by actions. Actions reflect all aspects of cognitive development including the motives of the child, the problems to be solved, and the constraints and possibilities of the child's body and sensorimotor system. Actions are directed into the future…

  12. Early Developments, 1998.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    1998-01-01

    This document consists of the two 1998 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. In the Spring 1998 issue, articles highlight the Center's diverse cross-cultural projects and global research, training and…

  13. Steps in Intrauterine Development.

    ERIC Educational Resources Information Center

    Barra, H. Gensini; And Others

    1996-01-01

    Recognizing the importance of health care during the perinatal period, the topic for this issue of "Children in the Tropics" is prenatal development; this issue is intended for health educators for use in educating their clients about prenatal development, health care during pregnancy, labor and delivery, and the needs of the mother and neonate…

  14. Development Communication Report, 1992.

    ERIC Educational Resources Information Center

    Development Communication Report, 1992

    1992-01-01

    The four issues of the quarterly newsletter contained in this document focus on the use of communication technologies in developing countries to educate the people about various social issues as well as the field of development communication itself. Environment and communication is the theme of the first issue, which includes articles on…

  15. Early Developments, 2002.

    ERIC Educational Resources Information Center

    Winton, Pam, Ed.; Buysse, Virginia, Ed.

    2002-01-01

    This document consists of the three 2002 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center (FPG) at the University of North Carolina at Chapel Hill. Articles in the Winter 2002 issue highlight some current work at FPG on factors that enhance or inhibit social and…

  16. Update on World Development.

    ERIC Educational Resources Information Center

    Social Education, 1996

    1996-01-01

    Summarizes a wealth of statistical information concerning the economic development and debt for a number of developing nations. Includes statistics on the gross national product growth of Cote d'lvoire, Guatemala, Malaysia, Korea, Colombia, and Nigeria, as well as, the gross domestic product growth and debt service for Latin America, Africa, and…

  17. Development of IVF Children.

    ERIC Educational Resources Information Center

    van Balen, Frank

    1998-01-01

    Examines physical and psychological development of children conceived through in vitro fertilization (IVF), focusing on questions related to risk of congenital defects or mental retardation and impact on the parent-child relationship. Concludes that no serious problems have arisen concerning the physical and psychological development of IVF…

  18. Personnel Training and Development.

    ERIC Educational Resources Information Center

    Campbell, John P.

    A comprehensive review of the literature on organizational training and development is undertaken in this report. Developments in learning, motivation, and attitude theory are discussed, with particular attention being paid to the theory and techniques of behavior modification and to General Systems Theory. Computer-assisted instruction and…

  19. Adolescent Development: Workshop II.

    ERIC Educational Resources Information Center

    Keng, Chiam Heng; And Others

    Workshops concerning adolescent development explored problems of adolescents, schooling and adolescence, preparation for adulthood, leisure and recreation, as well as values, culture, and change in relation to the development of youth. The discussion of adolescents' problems identified major problem areas, (emphasizing problems of communicating…

  20. Early Developments, 2000.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    2000-01-01

    This document consists of the three 2000 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. Articles in the spring 2000 issue focus on a follow-up study of the Abecedarian Project, children of depressed mothers,…

  1. Successful Community Development Strategies.

    ERIC Educational Resources Information Center

    Johnson, Thomas G.

    This paper sketches several successful community economic development programs that have implications for rural education. Case studies are used to discuss community characteristics that contribute to development success. In Virginia, a Community Certification Program offers statewide business recruitment services to communities that meet program…

  2. Information for Agricultural Development.

    ERIC Educational Resources Information Center

    Kaungamno, E. E.

    This paper describes the major international agricultural information services, sources, and systems; outlines the existing information situation in Tanzania as it relates to problems of agricultural development; and reviews the improvements in information provision resources required to support the process of agricultural development in Tanzania.…

  3. Facilitating Cognitive Development.

    ERIC Educational Resources Information Center

    Schwebel, Milton

    1985-01-01

    Human cognition research is shifting away from the importance of IQ and is emphasizing the stimulation and acceleration of a child's mental development. The emerging field of instructional psychology is trying to facilitate cognitive development. Current experimental programs--a university-school project in Belgium and a family project in…

  4. Developing Sustainable Leadership

    ERIC Educational Resources Information Center

    Davies, Brent, Ed.

    2007-01-01

    Developing and sustaining leaders is a major challenge for all those involved in education today. This book contains a collection of essays from recognized authors to provide insights, frameworks and ideas on how to sustain school leaders and develop values-based leadership. It also offers guidance on countering short-term management solutions,…

  5. Rural Development Strategies.

    ERIC Educational Resources Information Center

    Sears, David W., Ed.; Reid, J. Norman, Ed.

    This book seeks to provide a basis for reexamining rural development policy by presenting comprehensive and current information on the effectiveness of various rural policy approaches. An introduction that defines development terminology and discusses changing policy needs is followed by 13 chapters that represent the best recent research…

  6. Theme: International Development.

    ERIC Educational Resources Information Center

    Martin, Robert A.; And Others

    1989-01-01

    Consists of seven articles focusing on international agricultural education. Topics discussed include (1) international curriculum development, (2) programs for rural youth, (3) experiential training in international agriculture, (4) university/high school global exchange, (5) international development, and (5) the Association of International…

  7. Graphite technology development plan

    SciTech Connect

    1986-07-01

    This document presents the plan for the graphite technology development required to support the design of the 350 MW(t) Modular HTGR within the US National Gas-Cooled Reactor Program. Besides descriptions of the required technology development, cost estimates, and schedules, the plan also includes the associated design functions and design requirements.

  8. PLATO Courseware Development Procedures.

    ERIC Educational Resources Information Center

    Mahler, William A.; And Others

    This is an exploratory study of methods for the preparation of computer curriculum materials. It deals with courseware development procedures for the PLATO IV computer-based education system, and draws on interviews with over 100 persons engaged in courseware production. The report presents a five stage model of development: (1) planning, (2)…

  9. Hemovigilance in developing countries.

    PubMed

    Ayob, Yasmin

    2010-01-01

    Hemovigilance like quality systems and audits has become an integral part of the Blood Transfusion Service (BTS) in the developed world and has contributed greatly to the development of the blood service. However developing countries are still grappling with donor recruitment and efforts towards sufficiency and safety of the blood supply. In these countries the BTS is generally fragmented and a national hemovigilance program would be difficult to implement. However a few developing countries have an effective and sustainable blood program that can deliver equitable, safe and sufficient blood supply to the nation. Different models of hemovigilance program have been introduced with variable success. There are deficiencies but the data collected provided important information that can be presented to the health authorities for effective interventions. Hemovigilance program modeled from developed countries require expertise and resources that are not available in many developing countries. Whatever resources that are available should be utilized to correct deficiencies that are already apparent and obvious. Besides there are other tools that can be used to monitor the blood program in the developing countries depending on the need and the resources available. More importantly the data collected should be accurate and are used and taken into consideration in formulating guidelines, standards and policies and to affect appropriate interventions. Any surveillance program should be introduced in a stepwise manner as the blood transfusion service develops.

  10. Child Development through Literature.

    ERIC Educational Resources Information Center

    Landau, Elliott D., Ed.; And Others

    This volume is an attempt to provide literature that will enhance through vicarious experience and emotional involvement the adult's understanding of the principles of child development. The selections are organized into categories and cross-indexed with most of the standard texts in child development and psychology. It is divided into ten major…

  11. Character and Moral Development.

    ERIC Educational Resources Information Center

    Denton, Johnnie

    1997-01-01

    Reflects on the ways in which children develop character as well as ways to foster moral development in elementary education communities. Includes a brief discussion of Robert Coles' documentation of moral intelligence in children, and lists several ways to aid the moral life of children in Montessori classrooms. (EV)

  12. Staff Development Program.

    ERIC Educational Resources Information Center

    Cherry Creek School District 5, Englewood, CO.

    This document lists staff development components in the Cherry Creek Schools of metropolitan Denver. A brief overview stresses that the establishment of the office of the Director of Staff Development in the Cherry Creek Schools reflects a recognition of the need for more active participation of local school districts as well as all interested…

  13. Adolescent Development Reconsidered.

    ERIC Educational Resources Information Center

    Gilligan, Carol

    1987-01-01

    Emphasizes necessity of reconsideration of adolescent development, for these reasons: the view of childhood has changed; females have not been systematically studied; theories of cognitive development favor mathematical and scientific thinking over the humanities; and because the psychology of adolescence is anchored in separation and independence…

  14. Leadership and Management Development.

    ERIC Educational Resources Information Center

    1996

    This document contains four papers presented at a symposium on leadership and management development moderated by Mark Porter at the 1996 conference of the Academy of Human Resource Development (AHRD). "Expanding Formative Experiences: A Critical Dimension of Leadership Deportment" (Gary D. Geroy, Jackie L. Jankovich) advocates focusing leadership…

  15. Child Development Guide.

    ERIC Educational Resources Information Center

    Richardson, J. Lynne; Garfield, Nancy

    The Education for Parenthood Child Development Guide is designed to encourage Girl Scouts to choose various activities relating to: observing and working with children; drawing conclusions based on their own experiences and evidence; choosing their own activities and projects; collecting their own evidence on child development; creating projects…

  16. Jamaica: A Development Perspective.

    ERIC Educational Resources Information Center

    Scott, Rosalind; And Others

    Jamaica is known mainly as a tourist playground and the home of Reggae music. This Jamaican teaching unit dispels stereotypes and shows Jamaica for what it really is--an economically-troubled, developing nation. The unit illustrates the challenges this island nation is facing in its struggle toward economic development. Contents are: Teacher…

  17. Development Communication Report, 1991.

    ERIC Educational Resources Information Center

    Development Communication Report, 1991

    1991-01-01

    The four 1991 issues of the newsletter "Development Communication Report" are primarily concerned with the use of communication technologies in developing countries to educate the people. Evaluation is the theme of the first issue, which contains the following articles: "Evaluating Communication Programs: Means and Ends,""Making a Splash: How…

  18. Handbook of Moral Development

    ERIC Educational Resources Information Center

    Killen, Melanie; Smetana, Judith

    2006-01-01

    The psychological study of moral development has expanded greatly, both in terms of the diversity of theoretical perspectives that are represented in the field, as well as in the range of topics that have been studied. This "Handbook of Moral Development" represents the diversity and multidisciplinary influences on current theorizing about the…

  19. Brain Structure and Development.

    ERIC Educational Resources Information Center

    Teyler, T.J.; Chiaia, N.

    1983-01-01

    Considers basic biology of brain, what is known of how it operates, and something of how it develops. Discusses properties of neurons and specialized regions of the brain in linguistic and higher order processing skills, as well as genetic and environmental influences on brain development. (CMG)

  20. Development. Courier No. 26.

    ERIC Educational Resources Information Center

    ASPBAE Courier Service, 1982

    1982-01-01

    This journal contains a series of articles dealing with the theme of development in Asia and rural Indonesia. Included in the journal are the following articles: "Nonformal Education in Rural Areas of Developing Countries," by members of the Rural Project Team from the Centre for Continuing Education at Australian National University; "Application…

  1. Strengthening Evaluation for Development

    ERIC Educational Resources Information Center

    Ofir, Zenda

    2013-01-01

    Although some argue that distinctions between "evaluation" and "development evaluation" are increasingly superfluous, it is important to recognize that some distinctions still matter. The severe vulnerabilities and power asymmetries inherent in most developing country systems and societies make the task of evaluation…

  2. Sandia microelectronics development

    SciTech Connect

    Weaver, H.T.

    1997-02-01

    An overview of the operations of Sandia`s Microelectronics Development Lab (MDL) is to develop radiation hardened IC, but techniques used for IC processing have been applied to a variety of related technologies such as micromechanics, smart sensors, and packaging.

  3. Industry and Instructional Development.

    ERIC Educational Resources Information Center

    Wallington, Clint

    This chapter examines the current state of instructional development (ID) in business and industry, emphasizing the differences between ID in industry and in education. The competency studies of both the American Society for Testing and Development (ASTD) and the Association for Educational Communications and Technology (AECT) are considered, and…

  4. [Population Growth and Development].

    ERIC Educational Resources Information Center

    Clausen, A. W.

    Rapid population growth as a central development problem, the proper domain of government in reducing population growth, and effective measures which can be taken to reduce fertility are examined. Rapid population growth puts a brake on development because it exacerbates the difficult choice between higher consumption now and the investment needed…

  5. Developing Higher Level Thinking

    ERIC Educational Resources Information Center

    Limbach, Barbara; Waugh, Wendy

    2010-01-01

    This paper identifies an interdisciplinary, five-step process, built upon existing theory and best practices in cognitive development, effective learning environments, and outcomes-based assessment. The "Process for the Development of Higher Level Thinking Skills" provides teachers with an easy to implement method of moving toward a more…

  6. Data Centric Development Methodology

    ERIC Educational Resources Information Center

    Khoury, Fadi E.

    2012-01-01

    Data centric applications, an important effort of software development in large organizations, have been mostly adopting a software methodology, such as a waterfall or Rational Unified Process, as the framework for its development. These methodologies could work on structural, procedural, or object oriented based applications, but fails to capture…

  7. Professional Development & Student Achievement.

    ERIC Educational Resources Information Center

    Kroeger, Marianne, Ed.; Blaser, Stephanie, Ed.; Raack, Lenaya, Ed.; Cooper, Cinder, Ed.; Kinder, Ann, Ed.

    2000-01-01

    Professional development is viewed from several perspectives--time, funding, planning, and student outcomes--and includes both an urban and a rural story. This issue provides a special pullout section designed as a checklist to help guide professional development planning activities. The following articles are included: "Perspectives on Managing…

  8. Reference Model Development

    SciTech Connect

    Jepsen, Richard

    2011-11-02

    Presentation from the 2011 Water Peer Review in which principal investigator discusses project progress to develop a representative set of Reference Models (RM) for the MHK industry to develop baseline cost of energy (COE) and evaluate key cost component/system reduction pathways.

  9. Women and World Development.

    ERIC Educational Resources Information Center

    Tinker, Irene, Ed.; Bramsen, Michele Bo., Ed.

    The book presents background papers and an overview of the proceedings of the American Association of Science Seminar on Women in Development held in Mexico City in June 1975. The objectives of the seminar were to show how and why development programs fail to reach women and to emphasize the waste of human potential that has resulted. An…

  10. Black Community Development.

    ERIC Educational Resources Information Center

    Harris, William M.

    This published dissertation discusses the community development process as applied to urban black ghettoes. It provides extensive documentation on the many issues, concepts, and procedures in the field of community development. The method employed in collecting the data is a through review of existing literature in the topical areas for relevance…

  11. Physical Development: Thinking Physically

    ERIC Educational Resources Information Center

    Strickland, Erik

    2005-01-01

    Children grow and develop physically according to their own experiences, characteristics, and abilities. Physical development is so important and the environment should allow each child to find her space in the sunshine. This can be done by: (1) creating the right outdoor environment; (2) allowing children time to use it; (3) encouraging movement…

  12. Developing Successful Global Leaders

    ERIC Educational Resources Information Center

    Training, 2011

    2011-01-01

    Everyone seems to agree the world desperately needs strong leaders who can manage a global workforce and all the inherent challenges that go with it. That's a big part of the raison d'etre for global leadership development programs. But are today's organizations fully utilizing these programs to develop global leaders, and, if so, are they…

  13. Advice for Developing Scholars

    ERIC Educational Resources Information Center

    Kiewra, Kenneth A.

    2008-01-01

    This commentary offers advice for developing scholars culled from this volume's contributors, research on talent development in educational psychology and other domains, and my own experiences as an educational psychologist and journal editor. The advice includes: a) follow your bliss, b) spend and create time, c) build collaborative…

  14. Wind Economic Development (Postcard)

    SciTech Connect

    Not Available

    2011-08-01

    The U.S. Department of Energy's Wind Powering America initiative provides information on the economic development benefits of wind energy. This postcard is a marketing piece that stakeholders can provide to interested parties; it will guide them to the economic development benefits section on the Wind Powering America website.

  15. Guidance for Total Development.

    ERIC Educational Resources Information Center

    Van Hoose, William H.

    Elementary guidance, deriving much of its content from the developmental phenomena of middle childhood, is viewed as the maximization of human potentiality in the total range of the population. Included in the list of elementary school guidance objectives are (1) aiding academic development, (2) helping children develop health self-concepts, (3)…

  16. Astronomy for African development

    NASA Astrophysics Data System (ADS)

    Govender, Kevindran

    2011-06-01

    In recent years there have been a number of efforts across Africa to develop the field of astronomy as well as to reap benefit from astronomy for African people. This presentation will discuss the case of the SALT (Southern African Large Telescope) Collateral Benefits Programme (SCBP) which was set up to ensure societal benefit from astronomy. With African society as the target, the SCBP has embarked on various projects from school level education to public understanding of science to socio-economic development, the latter mainly being felt in the rural communities surrounding the South African Astronomical Observatory (home to SALT). A development plan for ``Astronomy in Africa'' will also be discussed. This plan has been drawn up with input from all over Africa and themed ``Astronomy for Education''. The Africa case stands as a good example for the IYA cornerstone project ``Developing Astronomy Globally'' which focuses on developing regions.

  17. Aggressive development plans

    SciTech Connect

    McCandless, D.H.

    1993-11-01

    Hydropower developments are capital-intensive, are subject to uncertainty in water availability, and have a somewhat higher construction-cost risk than thermal projects. However, a developer who selects an attractive site, arranges a good financial package, and designs and constructs a well-conceived hydropower project can earn an attractive long-term return while providing a dependable, low-cost source of energy to consumers. In the Philippines, many attractive hydropower sites are now available. As demonstrated by the attendance at the US Trade and Development Agency-sponsored Symposium on Power Development and Investment Opportunities in the Philippines, in Washington, D.C., on Sept. 21 and 22, 1993, there is a growing interest in private hydropower. Following its successful record in implementing thermal private power developments, the Philippines now offers many attractive opportunities to exploit its tremendous potential in the hydropower sector.

  18. Developing biomedical ontologies collaboratively.

    PubMed

    Noy, Natalya F; Tudorache, Tania; de Coronado, Sherri; Musen, Mark A

    2008-01-01

    The development of ontologies that define entities and relationships among them has become essential for modern work in biomedicine. Ontologies are becoming so large in their coverage that no single centralized group of people can develop them effectively and ontology development becomes a community-based enterprise. In this paper we present Collaborative Protégé-a prototype tool that supports many aspects of community-based development, such as discussions integrated with ontology-editing process, chats, and annotation of changes. We have evaluated Collaborative Protégé in the context of the NCI Thesaurus development. Users have found the tool effective for carrying out discussions and recording design rationale. PMID:18998901

  19. Xenopus pancreas development.

    PubMed

    Pearl, Esther J; Bilogan, Cassandra K; Mukhi, Sandeep; Brown, Donald D; Horb, Marko E

    2009-06-01

    Understanding how the pancreas develops is vital to finding new treatments for a range of pancreatic diseases, including diabetes and pancreatic cancer. Xenopus is a relatively new model organism for the elucidation of pancreas development, and has already made contributions to the field. Recent studies have shown benefits of using Xenopus for understanding both early patterning and lineage specification aspects of pancreas organogenesis. This review focuses specifically on Xenopus pancreas development, and covers events from the end of gastrulation, when regional specification of the endoderm is occurring, right through metamorphosis, when the mature pancreas is fully formed. We have attempted to cover pancreas development in Xenopus comprehensively enough to assist newcomers to the field and also to enable those studying pancreas development in other model organisms to better place the results from Xenopus research into the context of the field in general and their studies specifically. Developmental Dynamics 238:1271-1286, 2009. (c) 2009 Wiley-Liss, Inc.

  20. Quality Development in Education

    NASA Astrophysics Data System (ADS)

    Panetsos, Spiros; Zogopoulos, Anastasios; Tigas, Odysseas; Gubaidullina, Albina

    The article suggests that people involved in quality development need a specific competence, called quality literacy, in order to successfully improve learning processes. Quality literacy is viewed as a set of competencies that are needed for professional quality development. Quality literacy emphasizes the importance of professionalism as a necessary component for quality development, in addition to structural quality management models. Quality development is a co-production between learners and their learning environment. This means that the educational process can only be influenced and optimized through participation and not steered externally. Quality strategies cannot, therefore, guarantee a high quality of learning processes but rather aim at professionalisation of the educational process. This article suggests participation and negotiation between educational participants (clients and providers) as a main condition for quality development.

  1. Normal psychomotor development.

    PubMed

    Cioni, Giovanni; Sgandurra, Giuseppina

    2013-01-01

    "Psychomotor" development refers to changes in a child's cognitive, emotional, motor, and social capacities from the beginning of life throughout fetal and neonatal periods, infancy, childhood, and adolescence. It occurs in a variety of domains and a wide range of theories makes understanding children's development a challenging undertaking. Different models have tried to interpret the origins of human behavior, the pattern of developmental changes over time, and the individual and contextual factors that could direct child development. No single theory has been able to account for all aspects of child development, but each of them may contribute an important piece to the child development puzzle. Although theories sometimes disagree, much of their information is complementary rather than contradictory. The knowledge of child typical development and related theories and models is greatly useful for clinical practice, leading to recognition of developmental disorders and the ways in which they can be approached and treated. In this chapter, traditional and more modern concepts around functional development of psychomotor abilities are reported, firstly more in general and then specifically in the motor domain. PMID:23622146

  2. Liga developer apparatus system

    DOEpatents

    Boehme, Dale R.; Bankert, Michelle A.; Christenson, Todd R.

    2003-01-01

    A system to fabricate precise, high aspect ratio polymeric molds by photolithograpic process is described. The molds for producing micro-scale parts from engineering materials by the LIGA process. The invention is a developer system for developing a PMMA photoresist having exposed patterns comprising features having both very small sizes, and very high aspect ratios. The developer system of the present invention comprises a developer tank, an intermediate rinse tank and a final rinse tank, each tank having a source of high frequency sonic agitation, temperature control, and continuous filtration. It has been found that by moving a patterned wafer, through a specific sequence of developer/rinse solutions, where an intermediate rinse solution completes development of those portions of the exposed resist left undeveloped after the development solution, by agitating the solutions with a source of high frequency sonic vibration, and by adjusting and closely controlling the temperatures and continuously filtering and recirculating these solutions, it is possible to maintain the kinetic dissolution of the exposed PMMA polymer as the rate limiting step.

  3. Textile technology development

    NASA Technical Reports Server (NTRS)

    Shah, Bharat M.

    1995-01-01

    The objectives of this report were to evaluate and select resin systems for Resin Transfer Molding (RTM) and Powder Towpreg Material, to develop and evaluate advanced textile processes by comparing 2-D and 3-D braiding for fuselage frame applications and develop window belt and side panel structural design concepts, to evaluate textile material properties, and to develop low cost manufacturing and tooling processes for the automated manufacturing of fuselage primary structures. This research was in support of the NASA and Langley Research Center (LaRc) Advanced Composite Structural Concepts and Materials Technologies for Primary Aircraft Structures program.

  4. Space station structures development

    NASA Technical Reports Server (NTRS)

    Teller, V. B.

    1986-01-01

    A study of three interrelated tasks focusing on deployable Space Station truss structures is discussed. Task 1, the development of an alternate deployment system for linear truss, resulted in the preliminary design of an in-space reloadable linear motor deployer. Task 2, advanced composites deployable truss development, resulted in the testing and evaluation of composite materials for struts used in a deployable linear truss. Task 3, assembly of structures in space/erectable structures, resulted in the preliminary design of Space Station pressurized module support structures. An independent, redundant support system was developed for the common United States modules.

  5. Thermal Protection Materials Development

    NASA Technical Reports Server (NTRS)

    Selvaduray, Guna; Cox, Michael

    1998-01-01

    The main portion of this contract year was spent on the development of materials for high temperature applications. In particular, thermal protection materials were constantly tested and evaluated for thermal shock resistance, high-temperature dimensional stability, and tolerance to hostile environmental effects. The analytical laboratory at the Thermal Protection Materials Branch (TPMB), NASA-Ames played an integral part in the process of materials development of high temperature aerospace applications. The materials development focused mainly on the determination of physical and chemical characteristics of specimens from the various research programs.

  6. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  7. Microsystem product development.

    SciTech Connect

    Polosky, Marc A.; Garcia, Ernest J.

    2006-04-01

    Over the last decade the successful design and fabrication of complex MEMS (MicroElectroMechanical Systems), optical circuits and ASICs have been demonstrated. Packaging and integration processes have lagged behind MEMS research but are rapidly maturing. As packaging processes evolve, a new challenge presents itself, microsystem product development. Product development entails the maturation of the design and all the processes needed to successfully produce a product. Elements such as tooling design, fixtures, gages, testers, inspection, work instructions, process planning, etc., are often overlooked as MEMS engineers concentrate on design, fabrication and packaging processes. Thorough, up-front planning of product development efforts is crucial to the success of any project.

  8. Overview of NDE development

    SciTech Connect

    McClung, R.W.

    1992-12-31

    Nondestructive examination technology is an important part of the CTAHE program. Development and application of advanced NDT are being performed by several ceramics producers, engine fabricators, research and development organizations and NDT companies. Advanced and improved techniques are being studied for examination of ceramics at all stages of fabrication from the starting raw materials through intermediate stages, to the final finished product. The very small size of critical flaws [e.g., 50--100 {mu}m (0.002--0.004 in)] in the finished product adds to the challenge of development. This paper will provide an overview of some of the studies and results.

  9. Photovoltaic development in Argentina

    SciTech Connect

    Godfrin, E.M.; Duran, J.C.; Frigerio, A.; Moragues, J.A.

    1994-12-31

    A critical assessment of the photovoltaic program in Argentina is presented. Research and development activities on photovoltaic cells as well as industrial and technological development are still in the initial stages. Activities accomplished by the Atomic Energy Commission (CNEA) and the Institute of Technology Development for the Chemical industry (INTEC) are briefly described. The evolution of photovoltaic installations in Argentina is analyzed and accumulative data up to 1993 are given. A summary of the potential market for photovoltaic systems in the short and medium term is presented.

  10. Furlable spacecraft antenna development

    NASA Technical Reports Server (NTRS)

    Oliver, R. E.; Wilson, A. H.

    1972-01-01

    The development of large furlable spacecraft antennas using conical main reflectors is described. Two basic antenna configurations which utilize conical main reflectors have been conceived and are under development. In the conical-Gregorian configuration each ray experiences two reflections in traveling from the feed center to the aperture plane. In the Quadreflex (four reflection) configuration, each ray experiences four reflections, one at each of two subreflector surfaces and two at the main conical reflector surface. The RF gain measurements obtained from 6-ft and 30-in. models of the conical-Gregorian and Quadreflex concepts respectively were sufficiently encouraging to warrant further development of the concepts.

  11. CNS development: an overview

    NASA Technical Reports Server (NTRS)

    Nowakowski, R. S.; Hayes, N. L.

    1999-01-01

    The basic principles of the development of the central nervous system (CNS) are reviewed, and their implications for both normal and abnormal development of the brain are discussed. The goals of this review are (a) to provide a set of concepts to aid in understanding the variety of complex processes that occur during CNS development, (b) to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and (c) to provide a basis for understanding how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

  12. Speakeasy software development

    NASA Astrophysics Data System (ADS)

    Baskinger, Patricia J.; Ozarow, Larry; Chruscicki, Mary C.

    1993-08-01

    The Speakeasy Software Development Project had three primary objectives. The first objective was to perform Independent Verification and Validation (IV & V) of the software and documentation associated with the signal processor being developed by Hazeltine and TRW under the Speakeasy program. The IV & V task also included an analysis and assessment of the ability of the signal processor software to provide LPI communications functions. The second objective was to assist in the enhancement and modification of an existing Rome Lab signal processor workstation. Finally, TASC developed project management support tools and provided program management support to the Speakeasy Program Office.

  13. Imaging in drug development.

    PubMed

    Nairne, James; Iveson, Peter B; Meijer, Andreas

    2015-01-01

    Imaging has played an important part in the diagnosis of disease and development of the understanding of the underlying disease mechanisms and is now poised to make an impact in the development of new pharmaceuticals. This chapter discusses the underlying technologies that make the field ready for this challenge. In particular, the potentials of magnetic resonance imaging and functional magnetic resonance imaging are outlined, including the new methods developed to provide additional information from the scans carried out. The field of nuclear medicine has seen a rapid increase in interest as advances in radiochemistry have enabled a wide range of new radiotracers to be synthesised. PMID:25727706

  14. Element-ary Development.

    ERIC Educational Resources Information Center

    Schamp, Homer W., Jr.

    1989-01-01

    Describes the historic development of the periodic table from the four-element theory to the Lavoisier's table. Presents a table listing the old and new names of chemicals and the Lavoisier's table of elements. Lists two references. (YP)

  15. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  16. The Career Development Workshop

    ERIC Educational Resources Information Center

    Marsh, P. J.

    1973-01-01

    This article describes a career planning workshop for managers and its purpose is to support and accelerate the process of individual development without organizational coercion or manipulation. (Author/RK)

  17. Developing Friendship and Intimacy.

    ERIC Educational Resources Information Center

    Maslow, Abraham H.

    1991-01-01

    Presents previously unpublished paper written by Abraham Maslow in April 1968 in which Maslow speculates on the issue that society had become pathologically individualistic and needed to develop better means of facilitating close relationships among people. (Author/ABL)

  18. Physics for development

    NASA Astrophysics Data System (ADS)

    Chetty, Nithaya; Connell, Simon; Bawa, Ahmed C.

    2007-11-01

    South Africa has recognized the importance of science in the development of its society, in moving away from its apartheid past and striving to eradicate poverty. Opportunities abound in its growing programme of physics research.

  19. Advanced Hydrogen Turbine Development

    SciTech Connect

    Marra, John

    2015-09-30

    Under the sponsorship of the U.S. Department of Energy (DOE) National Energy Technology Laboratories, Siemens has completed the Advanced Hydrogen Turbine Development Program to develop an advanced gas turbine for incorporation into future coal-based Integrated Gasification Combined Cycle (IGCC) plants. All the scheduled DOE Milestones were completed and significant technical progress was made in the development of new technologies and concepts. Advanced computer simulations and modeling, as well as subscale, full scale laboratory, rig and engine testing were utilized to evaluate and select concepts for further development. Program Requirements of: A 3 to 5 percentage point improvement in overall plant combined cycle efficiency when compared to the reference baseline plant; 20 to 30 percent reduction in overall plant capital cost when compared to the reference baseline plant; and NOx emissions of 2 PPM out of the stack. were all met. The program was completed on schedule and within the allotted budget

  20. Patterns of gender development.

    PubMed

    Martin, Carol Lynn; Ruble, Diane N

    2010-01-01

    A comprehensive theory of gender development must describe and explain long-term developmental patterning and changes and how gender is experienced in the short term. This review considers multiple views on gender patterning, illustrated with contemporary research. First, because developmental research involves understanding normative patterns of change with age, several theoretically important topics illustrate gender development: how children come to recognize gender distinctions and understand stereotypes, and the emergence of prejudice and sexism. Second, developmental researchers study the stability of individual differences over time, which elucidates developmental processes. We review stability in two domains-sex segregation and activities/interests. Finally, a new approach advances understanding of developmental patterns, based on dynamic systems theory. Dynamic systems theory is a metatheoretical framework for studying stability and change, which developed from the study of complex and nonlinear systems in physics and mathematics. Some major features and examples show how dynamic approaches have been and could be applied in studying gender development.

  1. Managing Ada development

    NASA Technical Reports Server (NTRS)

    Green, James R.

    1986-01-01

    The Ada programming language was developed under the sponsorship of the Department of Defense to address the soaring costs associated with software development and maintenance. Ada is powerful, and yet to take full advantage of its power, it is sufficiently complex and different from current programming approaches that there is considerable risk associated with committing a program to be done in Ada. There are also few programs of any substantial size that have been implemented using Ada that may be studied to determine those management methods that resulted in a successful Ada project. The items presented are the author's opinions which have been formed as a result of going through an experience software development. The difficulties faced, risks assumed, management methods applied, and lessons learned, and most importantly, the techniques that were successful are all valuable sources of management information for those managers ready to assume major Ada developments projects.

  2. ECOSYSTEM GROWTH AND DEVELOPMENT

    EPA Science Inventory

    Thermodynamically, ecosystem growth and development is the process by which energy throughflow and stored biomass increase. Several proposed hypotheses describe the natural tendencies that occur as an ecosystem matures, and here, we consider five: minimum entropy production, maxi...

  3. REGIONAL MANUFACTURING TECHNICAL DEVELOPMENT

    SciTech Connect

    EASON, H.A.

    1997-02-21

    This project covers four CRADAS (Cooperative Research and Development Agreements) which were initiated in 1991 and 1993. The two CRADAS with the state of Tennessee and the state of Florida were to provide technical assistance to small manufacturers in those states and the CRADA with the Tennessee Technology Foundation was to engage in joint economic development activities within the state. These three CRADAS do not fit the traditional definition of CRADAS and would be administered by other agreement mechanisms, today. But in these early days of technology transfer efforts, the CRADA mechanism was already developed and usable. The CRADA with Coors Ceramics is a good example of a CRADA and was used to develop nondestructive testing technology for ceramic component inspection. The report describes the background of this project, its economic impact, and its benefits to the U. S. Department of Energy.

  4. NASA Balloon Technology Developments

    NASA Technical Reports Server (NTRS)

    Fairbrother, D. A.

    2004-01-01

    The National Aeronautics and Space Administration (NASA) Balloon Program has been, and will continue to be, committed to improving the capabilities of balloons to support science missions. Fundamental to vehicle improvement is a program of technology development that will enable improved flight performance throughout the next decade. The program s technology thrust areas include: materials, vehicle design & development, structural analysis, operations & support systems, performance modeling and planetary balloons. Building on the foundations of the 18-year research and development program, a technology roadmap has been generated which identifies specific areas of interest to NASA and the vision of future developments. The major components of the roadmap are: vehicle systems, balloon-craft systems, operational and safety support systems, and planetary vehicles. Current technology activities include nanocomposite balloon films, a new balloon designed to lift 3600 kgs to 36 km, a balloon rotation rate study and Mars pumpkin balloon investigations. The technology roadmap, as well as specific projects and recent advancements, will be presented.

  5. Fiber Optics Instrumentation Development

    NASA Technical Reports Server (NTRS)

    Chan, Patrick Hon Man; Parker, Allen R., Jr.; Richards, W. Lance

    2010-01-01

    This is a general presentation of fiber optics instrumentation development work being conducted at NASA Dryden for the past 10 years and recent achievements in the field of fiber optics strain sensors.

  6. Cascade Distillation System Development

    NASA Technical Reports Server (NTRS)

    Callahan, Michael R.; Sargushingh, Miriam; Shull, Sarah

    2014-01-01

    NASA's Advanced Exploration Systems (AES) Life Support System (LSS) Project is chartered with de-veloping advanced life support systems that will ena-ble NASA human exploration beyond low Earth orbit (LEO). The goal of AES is to increase the affordabil-ity of long-duration life support missions, and to re-duce the risk associated with integrating and infusing new enabling technologies required to ensure mission success. Because of the robust nature of distillation systems, the AES LSS Project is pursuing develop-ment of the Cascade Distillation Subsystem (CDS) as part of its technology portfolio. Currently, the system is being developed into a flight forward Generation 2.0 design.

  7. Infant - newborn development

    MedlinePlus

    ... infant responds to rocking and changes of position LANGUAGE DEVELOPMENT Crying is a very important way to communicate. By the baby's third day of life, mothers can tell their own baby's cry from that ...

  8. Normal growth and development

    MedlinePlus

    ... and development can be divided into four periods: Infancy Preschool years Middle childhood years Adolescence Soon after ... child's age. Healthy eating habits should begin during infancy. This can help prevent diseases such as high ...

  9. Environments for Development

    ERIC Educational Resources Information Center

    Grabinski, C. Joanne

    2005-01-01

    This chapter considers Robert Kegan's concept of holding environments, as well as six steps necessary for creation of new or adaptation of existing learning environments that facilitate adult development across the life course.

  10. Space Development Grid Portal

    NASA Technical Reports Server (NTRS)

    Vaziri, Arsi

    2004-01-01

    This viewgraph presentation provides information on the development of a portal to provide secure and distributed grid computing for Payload Operations Integrated Center and Mission Control Center ground services.

  11. NASA balloon technology developments

    NASA Astrophysics Data System (ADS)

    Fairbrother, D. A.

    The National Aeronautics and Space Administration (NASA) Balloon Program has been, and will continue to be, committed to improving the capabilities of balloons to support science missions. Fundamental to vehicle improvement is a program of technology development that will enable improved flight performance throughout the next decade. The program's technology thrust areas include: materials, vehicle design & development, structural analysis, operations & support systems, performance modeling and planetary balloons. Building on the foundations of the 18-year research and development program, a technology roadmap has been generated which identifies specific areas of interest to NASA and the vision of future developments. The major components of the roadmap are: vehicle systems, ballooncraft systems, operational and safety support systems, and planetary vehicles. Current technology activities include nanocomposite balloon films, a new balloon designed to lift 3600 kgs to 36 km, a balloon rotation rate study and Mars pumpkin balloon investigations. The technology roadmap, as well as specific projects and recent advancements, will be presented.

  12. Developments in Color Micrographics.

    ERIC Educational Resources Information Center

    Hourdajian, Ara

    1983-01-01

    Summarizes recent progress in color micrographics, which has centered about the corporate development of new microfilms whose capacities for reproducing and sustaining color image far exceed those of their predecessors. (Author/EJS)

  13. JPRS report, nuclear developments

    SciTech Connect

    1991-03-28

    This report contains articles concerning the nuclear developments of the following countries: (1) China; (2) Japan, North Korea, South Korea; (3) Bulgaria; (4) Argentina, Brazil, Honduras; (5) India, Iran, Pakistan, Syria; (6) Soviet Union; and (7) France, Germany, Turkey.

  14. Motivating Your Development Staff.

    ERIC Educational Resources Information Center

    Henderson, Nancy

    1996-01-01

    Suggestions for motivating institutional advancement staff at colleges and universities include nonfinancial motivators (such as appreciation, team building, empowerment, professional development opportunities, flexibility, and formal recognition) and financial rewards (such as bonuses and merit pay). (DB)

  15. Patterns of Gender Development

    PubMed Central

    Martin, Carol Lynn; Ruble, Diane N.

    2013-01-01

    A comprehensive theory of gender development must describe and explain long-term developmental patterning and changes and how gender is experienced in the short term. This review considers multiple views on gender patterning, illustrated with contemporary research. First, because developmental research involves understanding normative patterns of change with age, several theoretically important topics illustrate gender development: how children come to recognize gender distinctions and understand stereotypes, and the emergence of prejudice and sexism. Second, developmental researchers study the stability of individual differences over time, which elucidates developmental processes. We review stability in two domains—sex segregation and activities/interests. Finally, a new approach advances understanding of developmental patterns, based on dynamic systems theory. Dynamic systems theory is a metatheoretical framework for studying stability and change, which developed from the study of complex and nonlinear systems in physics and mathematics. Some major features and examples show how dynamic approaches have been and could be applied in studying gender development. PMID:19575615

  16. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  17. NASA DEVELOP students

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA DEVELOP students at Stennis Space Center recently held a midterm review with George Crozier, who serves as a science adviser to the team. The team also was joined by Jamie Favors of the Mobile (Ala.) County Health Department DEVELOP Team; Cheri Miller, the team's NASA adviser; and Kenton Ross, a team science adviser. Students participating in the meeting included: Lauren Childs, Jason Jones, Maddie Brozen, Matt Batina, Jenn Frey, Angie Maki and Aaron Brooks. The primary purpose of the meeting was to update Crozier on the status of the team's work for the summer 2008 term and discuss plans for the fiscal year 2009 project proposal. This included discussion of a possible project to study the effects of hurricanes on the Florida panhandle. DEVELOP is a NASA-sponsored, student-led, student-run program focused on developing projects to help communities.

  18. Advanced Interconnect Development

    SciTech Connect

    Yang, Z.G.; Maupin, G.; Simner, S.; Singh, P.; Stevenson, J.; Xia, G.

    2005-01-27

    The objectives of this project are to develop cost-effective, optimized materials for intermediate temperature SOFC interconnect and interconnect/electrode interface applications and identify and understand degradation processes in interconnects and at their interfaces with electrodes.

  19. Developments in Serials: 1977

    ERIC Educational Resources Information Center

    James, John R.

    1978-01-01

    Discusses issues and developments relating to several aspects of serials, including economics and acquisitions; bibliographic control; automation; education; serials literature and bibliographies; and copyrights. A bibliography is included. (Author/MBR)

  20. Geoscientists for international development

    USGS Publications Warehouse

    Hastings, David A.

    1980-01-01

    Professional societies are usually concerned with the advancement of scientific knowledge, but a relative newcomer to the international scene has a different focus - geoscience development in the Third World. David Hastings, a member of AGID, explains.

  1. Child Development & Behavior Topics

    MedlinePlus

    ... Children about September 11th Talking to Kids about War and Terrorism Tantrums: Behavior Problems Tantrums Podcast Teen ... Video Games Back to top W Walking Safety Water and Pool Safety Welcome to Your Child: Development ...

  2. Mandible and Tongue Development

    PubMed Central

    Parada, Carolina; Chai, Yang

    2016-01-01

    The tongue and mandible have common origins. They arise simultaneously from the mandibular arch and are coordinated in their development and growth, which is evident from several clinical conditions such as Pierre Robin sequence. Here, we review in detail the molecular networks controlling both mandible and tongue development. We also discuss their mechanical relationship and evolution as well as the potential for stem cell-based therapies for disorders affecting these organs. PMID:26589920

  3. Development of TOPS

    NASA Astrophysics Data System (ADS)

    Tanaka, Yoshiyuki; Tsugiishi, Shigemi

    The off-line patent and utility model information management system at Teijin Ltd. had been developed and operated since 1980. To achieve efficient business management through office automation and to get ready for easy access to electronic document delivery so-called Paperless project being developed by Japan Patent Office, the system was reviewed and new online system was constructed in 1985. The paper describes its details.

  4. Mammalian development in space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  5. Solar energy emplacement developer

    NASA Technical Reports Server (NTRS)

    Mortensen, Michael; Sauls, Bob

    1991-01-01

    A preliminary design was developed for a Lunar Power System (LPS) composed of photovoltaic arrays and microwave reflectors fabricated from lunar materials. The LPS will collect solar energy on the surface of the Moon, transform it into microwave energy, and beam it back to Earth where it will be converted into usable energy. The Solar Energy Emplacement Developer (SEED) proposed will use a similar sort of solar energy collection and dispersement to power the systems that will construct the LPS.

  6. Mandible and Tongue Development.

    PubMed

    Parada, Carolina; Chai, Yang

    2015-01-01

    The tongue and mandible have common origins. They arise simultaneously from the mandibular arch and are coordinated in their development and growth, which is evident from several clinical conditions such as Pierre Robin sequence. Here, we review in detail the molecular networks controlling both mandible and tongue development. We also discuss their mechanical relationship and evolution as well as the potential for stem cell-based therapies for disorders affecting these organs.

  7. UV curable materials development

    SciTech Connect

    Parker, B.G.

    1996-12-01

    Adhesives, coatings, and inks were selected for evaluation based on literature search and possible production applications. A differential photocalorimeter was used to measure degree of cure and allow prediction of optimum processing conditions. UV cure equipment were characterized and the ability to size equipment to specific materials cure needs established. Adhesion tests procedures were developed for the adhesives and solvent resistance testing procedures developed for the coatings and inks.

  8. Remediation Technology Collaboration Development

    NASA Technical Reports Server (NTRS)

    Mahoney, John; Olsen, Wade

    2010-01-01

    This slide presentation reviews programs at NASA aimed at development at Remediation Technology development for removal of environmental pollutants from NASA sites. This is challenging because there are many sites with different environments, and various jurisdictions and regulations. There are also multiple contaminants. There must be different approaches based on location and type of contamination. There are other challenges: such as costs, increased need for resources and the amount of resources available, and a regulatory environment that is increasing.

  9. Development of Portable Detectors

    SciTech Connect

    2006-12-01

    The purpose of this Cooperative Research and Development Agreement (CRADA) between UT-Battelle, LLC (the “Contractor”) and Sense Holdings, Inc. (the “Participant”) was for the development of hand-held detectors with high sensitivity and selectivity for the detection of explosives, toxic industrial chemicals and materials, and other materials of interest for security applications. The two parties built a series of demonstration and prototype handheld sensors based upon micoelectromechanical systems (MEMS) with electronic readout.

  10. Space Network Devices Developed

    NASA Technical Reports Server (NTRS)

    Jones, Robert E.

    2004-01-01

    The NASA Glenn Research Center through a contract with Spectrum Astro, Inc., has been developing space network hardware as an enabling technology using open systems interconnect (OSI) standards for space-based communications applications. The OSI standard is a well-recognized layered reference model that specifies how data should be sent node to node in a communications network. Because of this research and technology development, a space-qualifiable Ethernet-based network interface card (similar to the type found in a networked personal computer) and the associated four-port hub were designed and developed to flight specifications. During this research and development, there also have been many lessons learned for determining approaches for migrating existing spacecraft architectures to an OSI-network-based platform. Industry has recognized the benefits of targeting hardware developed around OSI standards such as Transmission Control Protocol/Internet Protocol (TCP/IP) or similar protocols for use in future generations of space communication systems. Some of these tangible benefits include overall reductions in mission schedule and cost and in system complexity. This development also brings us a step closer to the realization of a principal investigator on a terrestrial Internet site being able to interact with space platform assets in near real time. To develop this hardware, Spectrum Astro first conducted a technology analysis of alternatives study. For this analysis, they looked at the features of three protocol specifications: Ethernet (IEEE 802.3), Firewire (IEEE 1394), and Spacewire (IEEE 1355). A thorough analysis was performed on the basis of criteria such as current protocol performance and suitability for future space applications. Spectrum Astro also projected future influences such as cost, hardware and software availability, throughput performance, and integration procedures for current and transitive space architectures. After a thorough analysis

  11. Cradle Enhanced UI Development

    NASA Technical Reports Server (NTRS)

    Jentsch, Samuel

    2016-01-01

    This summer I have been working in the EDI (Exploration, Development, and Integration) office. The primary goal of my office is to facilitate the integration, cooperation, and communication between programs, projects and departments throughout the agency. The majority of my efforts has been focused on Cradle, a requirements management and systems engineering tool. This tool is utilized by teams throughout NASA to plan and track the development of a variety of ongoing projects.

  12. Seals Flow Code Development

    NASA Technical Reports Server (NTRS)

    1991-01-01

    In recognition of a deficiency in the current modeling capability for seals, an effort was established by NASA to develop verified computational fluid dynamic concepts, codes, and analyses for seals. The objectives were to develop advanced concepts for the design and analysis of seals, to effectively disseminate the information to potential users by way of annual workshops, and to provide experimental verification for the models and codes under a wide range of operating conditions.

  13. Disability and global development.

    PubMed

    Durocher, Joan; Lord, Janet; Defranco, Allison

    2012-07-01

    The United States invests billions of taxpayer dollars each year into foreign assistance programs that foster international diplomacy and development directed toward improving the quality of life for people around the world. These programs develop economies and combat poverty, promote democracy and governance, build new infrastructure, advance and protect human rights, among other development goals. The United States cannot effectively accomplish the goals of foreign assistance programs unless it undertakes measures to ensure that the programs are accessible to and inclusive of people with disabilities. The United States has been a leader in advancing the rights of people with disabilities and must continue to promote disability rights through its international development work. Overseas economic development will not be successful unless people with disabilities are included. Because of the significant number of people with disabilities in developing countries, if they are not included, the very economic growth the United States is trying to foster will be hindered. The goals of democracy and governance programs cannot be achieved without the inclusion of people with disabilities. In many countries, domestic law contains blatant discriminatory provisions for people with disabilities that undermine access to justice and full participation in society. The provisions that discriminate against people with disabilities include arbitrary exclusions in electoral codes, sweeping plenary guardianship laws with no due-process protections, discriminatory banking practices, and inaccessible court proceedings. National disability legal frameworks remain underdeveloped throughout the world. PMID:22726852

  14. Business Development Corporation, Inc.

    SciTech Connect

    Jasek, S.

    1995-12-31

    Business Development Corporation, Inc., is a company specializing in opportunity seeking and business development activities in the {open_quotes}new{close_quotes} post communist Central and Eastern Europe, with particular emphasis on the Republics of Poland and Slovakia. The company currently focuses its expertise on strategic investing and business development between Central Europe and the United States of America. In Poland and Slovakia, the company specializes in developing large scale energy and environmental {open_quotes}infrastructure{close_quotes} development projects on the federal, state, and local level. In addition, the company assists large state owned industries in the transformation and privatization process. Business Development Corporation has assisted and continues to assist in projects of national importance. The staff of experts advise numerous large Polish and Slovak companies, most owned or in the process of privatization, on matters of restructuring, finance, capital structure, strategic parternships or investors, mergers, acquisitions and joint ventures with U.S. based firms. The company also assists and advises on a variety of environmental and energy matters in the public and private sector.

  15. Trilinos developers SQE guide :

    SciTech Connect

    Willenbring, James Michael; Heroux, Michael Allen

    2013-05-01

    The Trilinos Project is an effort to develop algorithms and enabling technologies within an object-oriented software framework for the solution of large-scale, complex multi-physics engineering and scientific problems. A new software capability is introduced into Trilinos as a package. A Trilinos package is an integral unit and, although there are exceptions such as utility packages, each package is typically developed by a small team of experts in a particular algorithms area such as algebraic preconditioners, nonlinear solvers, etc. The Trilinos Developers SQE Guide is a resource for Trilinos package developers who are working under Advanced Simulation and Computing (ASC) and are therefore subject to the ASC Software Quality Engineering Practices as described in the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan: ASC Software Quality Engineering Practices Version 3.0 document [1]. The Trilinos Developer Policies webpage [2] contains a lot of detailed information that is essential for all Trilinos developers. The Trilinos Software Lifecycle Model [3] defines the default lifecycle model for Trilinos packages and provides a context for many of the practices listed in this document.

  16. SEDSAT-1 Technology Development

    NASA Technical Reports Server (NTRS)

    Maier, Mark W.; Wells, B. Earl

    1996-01-01

    The Students for the Exploration and Development of Space Satellite (SEDSAT-1) is an ambitious project to design, build, and fly a generally-accessible low-cost satellite which will 1) act as a technology demonstration to verify the suitability of novel optical, battery, microprocessor, and memory hardware for space flight environments, (2) to advance the understanding of tether dynamics and environmental science through the development of advanced imaging experiments, (3) to act as a communication link for radio amateurs, and (4) to provide graduate and undergraduate students with a unique multi-disciplinary experience in designing complex real-world hardware/software. This report highlights the progress made on this project during the time period from January 2, 1996 to June 1, 1996 at the end of which time the SEASIS 0.7 version software was completed and integrated on the SEASIS breadboard, a functional prototype of the Panoramic Annual Lenses (PAL) camera was developed, the preferred image compression technique was selected, the layout of the SEASIS board was begun, porting of the SCOS operating system to the command data system (CDS) board was begun, a new design for a tether release mechanism was developed, safety circuitry to inhibit tether cutting was developed and prototyped, material was prepared to support a comprehensive safety review of the project which was held at Johnson Space Center (JSC) (which was personally attended by one of the Principal Investigators), and prototype ground software was developed.

  17. GCS component development cycle

    NASA Astrophysics Data System (ADS)

    Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos; Pi, Marti

    2012-09-01

    The GTC1 is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). First light was at 13/07/2007 and since them it is in the operation phase. The GTC control system (GCS) is a distributed object & component oriented system based on RT-CORBA8 and it is responsible for the management and operation of the telescope, including its instrumentation. GCS has used the Rational Unified process (RUP9) in its development. RUP is an iterative software development process framework. After analysing (use cases) and designing (UML10) any of GCS subsystems, an initial component description of its interface is obtained and from that information a component specification is written. In order to improve the code productivity, GCS has adopted the code generation to transform this component specification into the skeleton of component classes based on a software framework, called Device Component Framework. Using the GCS development tools, based on javadoc and gcc, in only one step, the component is generated, compiled and deployed to be tested for the first time through our GUI inspector. The main advantages of this approach are the following: It reduces the learning curve of new developers and the development error rate, allows a systematic use of design patterns in the development and software reuse, speeds up the deliverables of the software product and massively increase the timescale, design consistency and design quality, and eliminates the future refactoring process required for the code.

  18. Disability and global development.

    PubMed

    Durocher, Joan; Lord, Janet; Defranco, Allison

    2012-07-01

    The United States invests billions of taxpayer dollars each year into foreign assistance programs that foster international diplomacy and development directed toward improving the quality of life for people around the world. These programs develop economies and combat poverty, promote democracy and governance, build new infrastructure, advance and protect human rights, among other development goals. The United States cannot effectively accomplish the goals of foreign assistance programs unless it undertakes measures to ensure that the programs are accessible to and inclusive of people with disabilities. The United States has been a leader in advancing the rights of people with disabilities and must continue to promote disability rights through its international development work. Overseas economic development will not be successful unless people with disabilities are included. Because of the significant number of people with disabilities in developing countries, if they are not included, the very economic growth the United States is trying to foster will be hindered. The goals of democracy and governance programs cannot be achieved without the inclusion of people with disabilities. In many countries, domestic law contains blatant discriminatory provisions for people with disabilities that undermine access to justice and full participation in society. The provisions that discriminate against people with disabilities include arbitrary exclusions in electoral codes, sweeping plenary guardianship laws with no due-process protections, discriminatory banking practices, and inaccessible court proceedings. National disability legal frameworks remain underdeveloped throughout the world.

  19. Fuel cell development for transportation: Catalyst development

    SciTech Connect

    Doddapaneni, N.; Ingersoll, D.

    1996-12-31

    Fuel cells are being considered as alternative power sources for transportation and stationary applications. The degradation of commonly used electrode catalysts (e.g. Pt, Ag, and others) and corrosion of carbon substrates are making commercialization of fuel cells incorporating present day technologies economically problematic. Furthermore, due to the instability of the Pt catalyst, the performance of fuel cells declines on long-term operation. When methanol is used as the fuel, a voltage drop, as well as significant thermal management problems can be encountered, the later being due to chemical oxidation of methanol at the platinized carbon at the cathode. Though extensive work was conducted on platinized electrodes for both the oxidation and reduction reactions, due to the problems mentioned above, fuel cells have not been fully developed for widespread commercial use. Several investigators have previously evaluated metal macrocyclic complexes as alternative catalysts to Pt and Pt/Ru in fuel cells. Unfortunately, though they have demonstrated catalytic activity, these materials were found to be unstable on long term use in the fuel cell environment. In order to improve the long-term stability of metal macrocyclic complexes, we have chemically bonded these complexes to the carbon substrate, thereby enhancing their catalytic activity as well as their chemical stability in the fuel cell environment. We have designed, synthesized, and evaluated these catalysts for O{sub 2} reduction, H{sub 2} oxidation, and direct methanol oxidation in Proton Exchange Membrane (PEM) and aqueous carbonate fuel cells. These catalysts exhibited good catalytic activity and long-term stability. In this paper we confine our discussion to the initial performance results of some of these catalysts in H{sub 2}/O{sub 2} PEM fuel cells, including their long-term performance characteristics as well as CO poisoning effects on these catalysts.

  20. Develop a Model Component

    NASA Technical Reports Server (NTRS)

    Ensey, Tyler S.

    2013-01-01

    During my internship at NASA, I was a model developer for Ground Support Equipment (GSE). The purpose of a model developer is to develop and unit test model component libraries (fluid, electrical, gas, etc.). The models are designed to simulate software for GSE (Ground Special Power, Crew Access Arm, Cryo, Fire and Leak Detection System, Environmental Control System (ECS), etc. .) before they are implemented into hardware. These models support verifying local control and remote software for End-Item Software Under Test (SUT). The model simulates the physical behavior (function, state, limits and 110) of each end-item and it's dependencies as defined in the Subsystem Interface Table, Software Requirements & Design Specification (SRDS), Ground Integrated Schematic (GIS), and System Mechanical Schematic.(SMS). The software of each specific model component is simulated through MATLAB's Simulink program. The intensiv model development life cycle is a.s follows: Identify source documents; identify model scope; update schedule; preliminary design review; develop model requirements; update model.. scope; update schedule; detailed design review; create/modify library component; implement library components reference; implement subsystem components; develop a test script; run the test script; develop users guide; send model out for peer review; the model is sent out for verifictionlvalidation; if there is empirical data, a validation data package is generated; if there is not empirical data, a verification package is generated; the test results are then reviewed; and finally, the user. requests accreditation, and a statement of accreditation is prepared. Once each component model is reviewed and approved, they are intertwined together into one integrated model. This integrated model is then tested itself, through a test script and autotest, so that it can be concluded that all models work conjointly, for a single purpose. The component I was assigned, specifically, was a