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Biomedical subjects

F Guttler

Publications and source records attributed to F Guttler.

5 recordsLinked to original sources
PubMed1996

Three prevalent mutations in a patient with phenylalanine hydroxylase deficiency: implications for diagnosis and genetic counselling.

Mutation analysis in a patient with mild hyperphenylalaninaemia showed three distinct base substitutions in exon 12 of the phenylalanine hydroxylase (PAH) gene. All three mutations, R413P, Y414C, and D415N, have previously been described as being independently associated with PAH deficiency. Family studies and independent analysis of the PAH alleles of the patient showed cosegregation of the R413P and Y414C mutations. Data on the ethnic background of the family provide evidence that the R413P mutation has occurred on a PAH allele carrying the Y414C mutation. Using current methods for mutation identification, the presence of two known mutations on a single PAH allele implies the risk of misdiagnosis of PAH deficiency and complicates genetic counselling. Our results stress the need for comprehensive mutation scanning of the PAH gene in diagnostic settings.

Adolescent↗
PubMed1989

Modern techniques of differentiating the various phenotypes of phenylketonuria.

Recognition of various phenylketonuria phenotypes has led to a variety of descriptive terms but classical phenylketonuria (PKU) may be defined as phenylalanine (PA) tolerance of 10-20 mg/kg/day at 5 years. The term 'mild PKU' indicates PA tolerance of 20-50 mg/kg/day whereas children with benign hyperphenylalaninaemia show normal development and are able to eliminate 100 mg/kg within 24 hours. The genetic basis for PKU has been investigated by reverse transcription via mRNA of the genes for phenylalanine hydroxylase (PH) present on chromosome 12q 22-24.1. The resulting complementary DNA sequence has been studied and the normal genes characterized. Following digestion of DNA from PKU patients and their families with restriction endonucleases, haplotype analysis has allowed identification of 12 restriction fragment length polymorphism haplotypes associated with normal and mutant PH alleles. Four haplotypes accounted for 91% of all mutant alleles in the Danish population studied. For heterozygotic parents it is possible to determine the haplotype associated with the normal allele and the mutant allele. Correlation between the different haplotypes and PKU phenotypes has allowed identification of the mutation responsible for classical PKU. Fifty eight per cent of mutant PKU alleles in the Danish population were found to be associated with 2 haplotypes and this is consistent with a founder effect in which the spread of mutant alleles passively follows the spread of these haplotypes in the European population. The phenotypical diversity of PH deficiency arises from multiple mutant alleles. Two mutations account for the majority of classical PKU in Denmark and since 75% of the Danish PKU population are heterozygotes for PH haplotypes, the various phenotypes reflect the composite activity and interactions of gene products from two mutant alleles.

Cloning, Molecular↗
PubMed1976

Impact of Ig-anti-Ig column fractionation on T-lymphocyte functions.

C57Bl/6 anti-Pe15-immune spleen cells were fractionated on immunoglobulin (Ig)-anti-Ig antibody columns in medium containing EDTA or in EDTA-free medium. The antigen-specific cytotoxic potential of immune cells in vitro was only slightly enriched after passage through the columns in the absence of EDTA, whereas immune cells passed through the columns in the presence of EDTA displayed a cytotoxic potential enriched about three times compared with unfractionated cells; this is similar to the enrichment in theta-positive cells. The lack of increase of the cytotoxic potential of immune cells after passage through the columns in the absence of EDTA was shown to be due to the adsorption of subpopulations of cytotoxic T lymphocytes. These cytotoxic cells could be eluted with EDTA-containing medium, and the findings suggest that their adsorption may be mediated via the interaction between cell-bound Fc receptors and the column antigen-antibody complexes.

Animals↗
PubMedDate not supplied

What do doctors know about statistics?

A multiple choice test with nine statistical questions was sent to a random sample of Danish doctors to assess their knowledge of elementary statistical expressions (SD, SE, p less than 0.05, p greater than 0.05 and r). One hundred and forty eight (59 per cent) of 250 doctors answered the questions. The test was also completed by 97 participants in postgraduate courses in research methods, mainly junior hospital doctors. The median number of correct answers was 2.4 in the random sample and 4.0 in the other sample of doctors. It is concluded that the statistical knowledge of most doctors is so limited that they cannot be expected to draw the right conclusions from those statistical analyses which are found in papers in medical journals. Sixty-five per cent of the doctors in the random sample stated that it is very important that this problem is raised.

Biometry↗