bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observations indicating the nature of the mutation in phenylketonuria
Authors: Choo K. H. , Cotton R. G. H. , Jennings I. G. , Danks D. M. 
Published: June 2005

AbstractRabbit antiserum was prepared against purified normal human liver phenylalanine hydroxylase. This was used to test for cross‐reacting material in crude extracts of livers from patients with classical phenylketonuria (PKU); the samples from patients were two livers obtained at autopsy and a needle biopsy core. None of these enzymically inactive livers contained detectable cross‐reacting material capable of neutralizing antibody activity in double immunodiffusion and/or enzyme inhibition experiments. In an earlier study, no phenylalanine hydroxylase was found in the two autopsy PKU livers by an affinity chromatography method or by the use of a specific antiserum raised against purified monkey liver phenylalanine hydroxylase (Chooet al., 1979a). This evidence suggests that mutations in the PKU patients studied may be regulatory in nature.
Trimethylaminuria
Authors: Spellacy Elizabeth , Watts R. W. E. , Goolamali S. K. 
Published: June 2005

AbstractWe describe the case of an otherwise healthy 7‐year‐old girl whose mother noticed that she intermittently smelt of fish. This was due to the intermittent excretion of trimethylamine which could be precipitated by choline ingestion and by eating fish. Excluding eggs, liver and salt‐water fish from the diet relieved the symptom. After a standard 15g choline load, the child's father, but not her mother, excreted amounts of trimethylamine which were intermediate between those excreted by the patient and normal control subjects.
α‐aminoadipic aciduria: Chemical and enzymatic studies
Authors: Gray R. G. F. , O'Neill E. M. , Pollitt R. J. 
Published: June 2005

AbstractA new case of α‐aminoadipic aciduria had an apparent immunodeficiency and died at the age of 4 months. The urine contained large amounts of α‐aminoadipate and smaller quantities of α‐keto‐ and α‐hydroxyadipate.Post mortem, the highest concentrations of α‐aminoadipate were found in liver and kidney. Enzymatic studies on liver and cultured fibroblasts failed to demonstrate the expected deficiency of α‐aminoadipate aminotransferase, a result perhaps explicable by the presence of cytoplasmic aminotransferase activity.
The use of natural and artificial substrates in the prenatal diagnosis of Krabbe's disease
Authors: Besley G. T. N. 
Published: June 2005

AbstractKrabbe's disease was diagnosed prenatally using cultured amniotic fluid cells and the diagnosis confirmed using fetal brain, liver and cultured fetal skin fibroblasts. The enzyme defect was demonstrated by assay of galactocerebrosidase and lactocerebrosidase I, and by hydrolysis of the chromogenic analogue, 2‐hexadecanoylamino‐4‐nitrophenyl‐β‐D‐galactopyranoside. The relative merits of the three diagnostic methods are discussed.
Threonine dehydratase deficiency: A probable cause of non‐ketotic hyperglycinaemia
Authors: Krieger I. , Booth F. 
Published: June 2005

AbstractA patient with classical symptoms of non‐ketotic hyperglycinaemia (NKH) is presented. Threonine dehydratase was undetectable in a liver autopsy specimen, which was obtained within 1 h of death and immediately frozen at −70 °C. Activities of four marker enzymes were normal. This represents the first documentation of an inborn error of threonine metabolism and a new explanation of NKH.
Analytical procedures for diagnosis of trace element disorders
Authors: Fell G. S. 
Published: June 2005

AbstractTrace element levels in tissues show changes in various diseases including inborn errors of metabolism. Such changes may be primary or secondary due to stress or diseases of the liver and gastrointestinal tract. Measurement of trace elements in these cases may be essential both for diagnostic and therapeutic purposes. Trace element measurements can also be useful in other areas of clinical interest including nutrition, toxicity and therapy with inorganic pharmaceutical agents. The available techniques for measuring trace elements in tissues are summarized and the various problems of each are discussed.
High‐performance liquid chromatographic assay of argininosuccinate: its application in argininosuccinic aciduria and in normal man
Authors: Portolés M. , Rubio V. 
Published: June 2005

AbstractArgininosuccinate (ASA) is determined in a few minutes with little manipulation by reversed phase high‐performance liquid chromatography (HPLC) usingO‐phthaldialdehyde. The two cyclic anhydrides of ASA are not formed during analysis but, if present, can be determined simultaneously. As little as 1 nl urine from a patient with argininosuccinic aciduria was sufficient for analysis; the ASA/creatinine ratio was 50.8 mmol g−1 and daily excretion was 5–7g ASA. We found small amounts of the two anhydrides in the patient's urine and we give factors to estimate, from their peaks, the corresponding amount of ASA. Urine from normal children showed a small acid‐labile (at 100°C) peak at the ASA position, which we tentatively assign to genuine ASA. From this peak <2mg ASAday−1 were excreted in our controls. Procedures for collection and storage of samples and the potential of this method for heterozygote detection are discussed.
Accumulation of [3H]Sialyl‐conjugates in sialidosis (sialidase‐deficient) fibroblasts cultured in the presence of [3H]‐N‐acetylmannosamine
Authors: Scocca J. , Thomas G. H. , Reynolds L. , Miller C. S. 
Published: June 2005

AbstractSkin fibroblasts from normal individuals and a patient with the infantile form of sialidosis were cultured for up to 72h in medium containing [3H]‐N‐acetylmannosamine. The sialidosis fibroblasts consistently accumulated more labeled compound(s) than the control cells, i.e. 37–88% more cpm per mg protein. Precipitation of sonicates of these cells with 10% trichloracetic acid, TCA, demonstrated that the excess radioactivity in the sialidosis fibroblasts was in one or more TCA soluble compounds. There was no detectable difference in the amount of label in the TCA insoluble material.The TCA soluble, labeled, material from the sialidosis and the control fibroblasts was separated, isolated and purified on AG1‐X8, QAE Sephadex A‐25 and Bio‐Gel P‐4 chromatography columns. Analysis of the isolated material showed the excess radioactivity in the sialidosis fibroblasts to be due to increased levels of [3H]sialic acid covalently bound to a variety of anionic sialyl conjugates. These compounds have been separated and partially purified.Finally, acid hydrolysis and chromatographic analysis of the TCA insoluble fractions showed that greater than 80% of the label in this material was also due to [3H]sialic acid. There was no detectable difference between the control and the sialidosis patient in the amount of label in this fraction.
A method for enrichment of hybrid somatic cells: Complementation studies in certain lysosomal enzymopathies
Authors: Nelson P. V. , Carey W. F. 
Published: June 2005

AbstractAn improved method, which combines a number of published techniques, is described for the polyethyleneglycol‐induced fusion of mononuclear human skin fibroblasts in the presence of phytohaemagglutinin‐P and for the subsequent isolation of polynuclear cells by Ficoll gradient sedimentation. Enriched cultures contain between 60 and 75% multinucleated cells and may be maintained in culture without fetal calf serum for up to 14 days without significant overgrowth by the few contaminating mononuclear parental cells. Complementation appears not to occur between GM1 gangliosidosis and mucopolysaccharidosis, type VIB (Morquio) cell strains; this experimental observation provides support for the earlier hypothesis that the mutations for these conditions are allelic. Earlier observations that complementation does not occur between selected phenotypic variants (viz., neuronopathic forms and those without neurological involvement) of sphingomyelin storage (Niemann‐Pick) disease or Gaucher's disease are confirmed.
Transient hyperphenylalaninaemia with a high neopterin to biopterin ratio in urine
Authors: Takahashi T. , Kodama S. , Nishio H. , Takumi T. , Matsuo T. , Hase Y. , Sawada Y. 
Published: June 2005

AbstractA case of transient hyperphenylalaninaemia with a maturational delay of dihydropteridine synthesis is described. With the Guthrie test, the patient showed a blood phenylalanine level of 38 mg dl−1, which had fallen to a normal value without a phenylalanine restricted diet by 3 months of age. The neopterin level and the neopterin to biopterin ratio in the patient's urine were very high at 19 days of age. The blood phenylalanine level did not decrease when tetrahydrobiopterin (2.5 mg kg−1) was administered at 19 days of age, while administration of tetrahydrobiopterin (7.5 mg kg−1) at 20 days of age had decreased the blood phenylalanine level to 50% of the preloading level after 24 h. The oral phenylalanine loading test showed the pattern of classic phenylketonuria (PKU) at 15 days of age, but it showed the normal pattern at 1 year 8 months of age.
The Evolving Role of Endoscopic Treatment for Bleeding Esophageal Varices
Authors: Krige J. E. J. , Shaw J. M. , Bornman P. C. 
Published: June 2005

AbstractThe treatment of acute and recurrent variceal bleeding is best accomplished by a skilled, knowledgeable, and well‐equipped team using a multidisciplinary integrated approach. Optimal management should provide the full spectrum of treatment options including pharmacologic therapy, endoscopic treatment, interventional radiologic procedures, surgical shunts, and liver transplantation. Endoscopic therapy with either band ligation or injection sclerotherapy is an integral component of the management of acute variceal bleeding and of the long‐term treatment of patients after a variceal bleed. Variceal eradication with endoscopic ligation requires fewer endoscopic treatment sessions and causes substantially less esophageal complications than does injection sclerotherapy. Although the incidence of early gastrointestinal rebleeding is reduced by endoscopic ligation in most studies, there is no overall survival benefit relative to injection sclerotherapy. Simultaneous combined ligation and sclerotherapy confers no advantage over ligation alone. A sequential staged approach with initial endoscopic ligation followed by sclerotherapy when varices are small may prove to be the optimal method of reducing variceal recurrence. Overall, current data demonstrate clear advantages for using ligation in preference to sclerotherapy. Ligation should therefore be considered the endoscopic treatment of choice in the treatment of esophageal varices.
Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine
Authors: Bagley Elena E , Chieng Billy C H , Christie MacDonald J , Connor Mark 
Published: June 2005

The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ‐opioid receptor (MOP) regulation of voltage‐gated calcium channel currents (ICa) and G‐protein‐activated K channel currents (GIRK) in PAG neurons from CMT mice.
Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception.
Voltage clamp recordings were made of ICa in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr‐D‐Ala‐Gly‐N‐Me‐Phe‐Gly‐ol enkephalin) inhibited ICa in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of ICa by the GABAB agonist baclofen was not altered by CMT.
Met‐enkephalin‐activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered.
These data demonstrate that CMT‐induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit ICa and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.

British Journal of Pharmacology (2005) 146, 68–76. doi:10.1038/sj.bjp.0706315
Red cell pyruvate kinase deficiency: molecular and clinical aspects
Authors: Zanella Alberto , Fermo Elisa , Bianchi Paola , Valentini Giovanna 
Published: June 2005

SummaryRed cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non‐spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life‐threatening neonatal anaemia and jaundice necessitating exchange transfusions. Erythrocyte PK is synthesized under the control of the PK‐LR gene located on chromosome 1. To date, more than 150 different mutations in the PK‐LR gene have been associated with PK deficiency. First attempts to delineate the biochemical and clinical consequences of the molecular defect were mainly based on the observation of the few homozygous patients and on the analysis of the three‐dimensional structure of the enzyme. More recently, the comparison of the recombinant mutants of human red cell PK with the wild‐type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.
Headache and Intermittent Claudication of the Jaw In Temporal Arteritis
Authors: HORTON BAYARD T. 
Published: June 2005

SYNOPSIS‐ABSTRACTTHE PHYSICIAN should beware of headache in the senior citizen. It may forebode, among many things, the insidious onset of temporal arteritis, a disease that can be easily overlooked in its early stages. Temporal arteritis occurs exclusively in older persons. The average age of the first 105 patients carefully studied at the Mayo Clinic was 69.1 years. Danger lurking behind the headache of temporal arteritis is of far greater magnitude than that in any other type of headache. Loss of vision can occur at any time during the course of the illness, and has occurred in a high percentage of cases. Loss of vision, if it occurs, is always permanent. A high degree of suspicion on the part of the physician will lead to an early diagnosis, and thus, if treatment is promptly instituted, to the prevention of blindness. To the medical profession, the real challenge of temporal arteritis is to fide the patient through the illness without the loss of vision.
SITE CONTROL OF HAZARDOUS WASTE FACILITIES
Authors: Wells Donald T. 
Published: June 2005

Although it controls disposal of hazardous wastes, the Resource Conservation and Recovery Act of 1976 leaves the details of site selection and control to the states.Twelve states have passed site selection laws, but their implementation shows that there are problems still to be worked out. Georgia's law, which goes beyond those of many other states by providing for eminent domain, still has not fully resolved difficulties of state‐local relations, liability, and representation of the public.
POLICY EVALUATION AND PROGRAM TERMINATION
Authors: DeLeon Peter 
Published: June 2005

One example of treating the policy process as an integrated process is the relationship between policy evaluation and policy termination.Policy and program terminations are seen as having three rationales: cost reductions, programmatic inefficiencies, and political ideology. The third appears to be the most important. Even so, formal program evaluation is increasingly critical to the termination exercise. This has important policy implications for both the professional evaluation community and those who have program termination responsibilities.
FIELD NETWORK RESEARCH IN POLICY EVALUATION
Authors: Dommol Paul R. , Hall John Stuart 
Published: June 2005

The field‐network evaluation studies (FNES) approach to policy evaluation research seeks to overcome deficiencies of small‐sample case study method and of the large‐sample survey research approach. Methodologically, FNES uses many of the familiar techniques of both these approaches interviews, data collection and analysis, limited sampling, field observation, and document analysis. The crucial difference is sample size. The FNES approach using a middle‐range sample of 50 to 60 research sites has the advantages of the case study method in being able to provide an in depth account of a program and how it operates, and is sufficiently flexible to permit a shift in the analytical framework as the research proceeds thus overcoming the inflexibility of the instruments of survey research.Seven major studies employing the FNES approach have been carried out or are underway in the United States of America. The principal components of the methodology are a network of university‐based field associates and a central management group. The field associates collect the information and the data using a uniform analytical framework and reporting form. The central staff aggregates these analyses into a single report that cuts across the sample. This approach and the use of a middle‐range sample make it possible to draw generalizable conclusions based on the national experience, and also provide sufficient detail to differentiate policy impacts among the sample jurisdictions.
POLITICAL CONDITIONS MOTIVATING LEGISLATORS' USE OF POLICY INFORMATION
Authors: Webber David J. 
Published: June 2005

While “research utilization” literature has focused on the limited use of policy research by policymakers, there has been l i t t l e attention directed at legislators1 use of policy research o r the importance of the decisionmaking context in explaining policy research use.Relying on the research utilization literature and the legislative behavior literature, this paper examines the legislative setting as it relates to policy information use, and it outlines the conditions under which policy information might be used by legislators. Specifically, two types of legislator information searches are discussed–the constituent service search and policy formulating search. While there are many obstacles to policy information use–including cognitive and organizational ones–this paper focuses only on political conditions and political obstacles relating to legis‐ lators' use of policy information.
“THE LONG AND VIOLENT PULL”: SCIENCE FUNDING AND POLICY RESEARCH
Authors: Johansen Elaine 
Published: June 2005

Books reviewed in this article.Claude E. Barfield. Science Policy from Ford to Reagan: Continuity and Change.D.B.T. Kallen et al. (Eds.) Social Science Research and Public Policy‐Making: A ReappraisalDavid Meister. Behavioral Research and Government Policy: Civilian and Defense R & D
GOVERNMENT PRODUCTIVITY, EFFECTIVENESS, AND PUBLIC POLICY
Authors: Herzik Eric B. 
Published: June 2005

Marc Holzer and Stuart S. Nagel (editors). 1984. Productivity and Public Policy. George W. Downs and Patrick D. Larkey. 1986. The Search for Government Efficiency: From Hubris to Helplessness Elaine Morley. 1986. A Practitioner's Guide to Public Sector Productivity Improvement. Richard H. Silkman and Dennis R. Young with the assistance of Robert Lipp. 1985. Subsidizing Inefficiency: A Study of State Aid and Local Government Productivity.
IMPACTS OF THE FARM FINANCIAL CRISIS OF THE 1980s ON RESOURCES AND POVERTY IN AGRICULTURALLY DEPENDENT COUNTIES IN THE UNITED STATES
Authors: Murdock Steve H. , Leistritz F. Larry , Hamm Rita R. 
Published: June 2005

The farm financial crisis of the 1980s has had a major effect on agriculturally dependent areas in the United States. The crisis has resulted in a large proportion of producers leaving agriculture, in a substantial decline in the number of rural businesses, and in the support for rural service bases. Although extensively analyzed, the crisis' impacts on resources and poverty have not been adequately evaluated.This paper examines such impacts using parameters derived from USDA data and from extensive surveys of producers, business operators, and employees in rural communities. The results show effects on populations, services, and income that could lead to a substantial increase in the rates of poverty in these counties.The paper concludes that the crisis, if left unaddressed, may result in a long‐term loss of economic opportunities, accentuated rates of poverty, and reduced potential for economic development in agriculturally dependent areas in the United States.
The Nurse Practitioner's Role in Helping Patients Achieve Lipid Goals with Statin Therapy
Authors: Mason Carol M. 
Published: June 2005

PurposeTo discuss the merits of statins in achieving lipid goals and the role of nurse practitioners (NPs) in improving adherence to medical regimens with the goals of improving patient outcomes, reducing cardiovascular disease (CVD) risk within the population at large, and enhancing patients’ ability to reach their individual goals.Data sourcesOriginal research articles, journal articles, professional association practice guidelines.ConclusionsDespite extensive research clearly documenting the relation between lowering low‐density lipoprotein cholesterol (LDL‐C) and decreasing rates of cardiovascular events and deaths, lipid‐lowering therapy is not being aggressively managed to achieve optimal lipid levels and CVDs remain the leading cause of death among adults in the United States. Contributing factors include lack of patient adherence with prescribed therapy, absence of dose titration when needed, and suboptimal follow‐up. Two pathways to improving compliance are the following: first, use of a starting dose of a more efficacious statin to allow more patients to reach their LDL‐C goal and, second, more effective primary care programs with NPs as team leaders who can assess and diagnose patients, then develop individual treatment plans and follow‐up with patients to ensure that their lipid goals are met.Implications for practiceNPs are well suited to manage patients with hypercholesterolemia. The NP can bridge all aspects of care for the patient by overseeing assessment and treatment of cardiovascular risk factors, including elevated levels of LDL‐C, initiating pharmacotherapy when needed, and establishing for each patient an individualized program that features education, support, and follow‐up.