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Biomedical subjects

R Koch

Publications and source records attributed to R Koch.

At least 253 records · Page 14Linked to original sources
PubMed1987

Psychoeducational findings among children treated for phenylketonuria.

Early treated phenylketonuric children who maintained a phe-restricted diet through age 10 were compared with those who discontinued the diet after age 6 on standardized tests of intelligence, school achievement, language, and perceptual skills. Mean IQ, reading, and spelling test scores improved between ages 6 and 10 for the on-diet children in comparison to those who were off diet. Mean scores on arithmetic, language, and perceptual skills, however, declined at a uniform rate for both groups. Children with PKU scored significantly lower than did their non-PKU siblings on tests of visual perception and visual-motor skills. We conclude that children with PKU should be maintained on a phe-restricted diet.

Achievement↗
PubMed1987

Pathogenetic significance of venous hyperoxaemia in retinopathy of prematurity.

Ten underweight newborns with severe retinopathy of prematurity (ROP) and 18 newborns with slight changes in the sense of ROP were compared with 66 healthy infants. The distribution of 13 possibly pathogenetically effective features in these 3 groups of patients was studied by means of variance analysis. The greatest significance resulted for multiple blood transfusions and exchange transfusions. From this it was concluded that the toxic oxygen effect on the immature retina was probably more dependent on the venous PO2 (determined by Hb concentration, O2-affinity, arterial PO2, and blood flow) than on the isolated arterial PO2.

Analysis of Variance↗
PubMed1986

The nonclassical insulin binding of insulin receptors from rat liver is due to the presence of two interacting alpha-subunits in the receptor complex.

The binding characteristics of the insulin receptor tetramer (alpha 2 beta 2) and dimer (alpha beta) were examined. Unlabelled insulin enhanced the dilution-induced dissociation only of the receptor tetramer-bound 125I-insulin. Furthermore, when both the receptor forms had been preincubated with anti-receptor-antibodies (B9-antiserum), insulin binding only to the receptor tetramer but not to the dimer was inhibited. However, both oligomers are not immunologically distinct since more than 80% of the two forms were immunoprecipitated by the antiserum. These results suggest that both insulin and anti-receptor-antibodies induce cooperative interactions between the two linked alpha-subunits of the receptor tetramer leading to a decrease in insulin binding of this receptor form.

Affinity Labels↗
PubMed1986

Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria.

We determined the effect on intellectual performance and behavior of the age at which dietary control was lost in 119 10-year-old children with phenylketonuria (PKU) who had started on a diet low in phenylalanine before the age of 65 days. The children's diets were considered to be out of control when their blood phenylalanine concentration persistently exceeded 15 mg per deciliter. The age at which control was lost was the best, and frequently the only, predictor of the child's IQ at the age of 8 or 10 years and of the deficit in the child's IQ as compared with those of his or her unaffected siblings or parents. The age at which control was lost was also the best predictor of the deficit in scores on the Wide Range Achievement Test of children with PKU at the age of eight, as compared with their unaffected siblings, and of behavior problems (Louisville Behavior Checklist). Variables that were not significant included the maximal phenylalanine concentration before dietary therapy, the age at which treatment was started, and the family's coping abilities. The greatest deficiencies in all of these outcomes were observed among children who were out of dietary control before the age of six years. The highest correlation between the IQs of the children with PKU and their respective parents was observed among the children still on the diet at the age of eight years; the lowest, among those who had poor dietary control before the age of six. These findings suggest that phenylalanine restriction should continue after the age of eight years in children with PKU.

Adolescent↗
PubMed1986

Polymorphic DNA haplotypes at the phenylalanine hydroxylase locus in prenatal diagnosis of phenylketonuria.

Restriction fragment length polymorphisms (RFLPs) detected in the human genome by means of a cDNA clone of phenylalanine hydroxylase (PAH) segregate concordantly with phenylketonuria (PKU) in several families. To establish the usefulness of these DNA polymorphisms for prenatal diagnosis of PKU the genotypes and chromosomal haplotypes of eight RFLPs at the PAH locus were determined in 46 families, each with one or more affected children. 34 of these families were informative for linkage analysis, giving a maximum probability of 10(9):1 in favour of tight linkage between PKU and the PAH RFLP haplotypes. Thus the deficiency of hepatic PAH in PKU patients is caused by mutations in the PAH gene itself, and the RFLPs could be used effectively for prenatal diagnosis and carrier detection of PKU in affected families. Use of the PKU haplotypes based on these eight RFLPs would establish disease status in approximately 87% of siblings at risk, although three RFLPs alone (detected with the restriction enzymes Pvu II, Xmn I, and EcoR R) are nearly as effective.

Alleles↗
PubMed1986

Characterization of solubilized insulin receptors from rat liver microsomes. Existence of two receptor species with different binding properties.

Insulin receptors were solubilized from rat liver microsomes by the nonionic detergent Triton X-100. After gel filtration of the extract on Sepharose CL-6B, two insulin-binding species (peak I and peak II) were obtained. The structure and binding properties of both peaks were characterized. Gel filtration yielded Stokes radii of 9.2 nm (peak I) and 8.0 nm (peak II). Both peaks were glycoproteins. At 4 degrees C peak I showed optimal insulin binding at pH 8.0 and high ionic strength. In contrast, peak II had its binding optimum at pH 7.0 and low ionic strength, where peak I binding was minimal. For peak I the change in insulin binding under different conditions of pH and ionic strength was due to a change in receptor affinity only. For peak II an additional change in receptor number was found. Both peaks yielded non-linear Scatchard plots under most of the buffer conditions examined. At their binding optima at 4 degrees C the high affinity dissociation constants were 0.50 nM (peak I) and 0.55 nM (peak II). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of peak I revealed five receptor bands with Mr 400 000, 365 000, 320 000, 290 000, and 245 000 under non-reducing conditions. For peak II two major receptor bands with Mr 210 000 and 115 000 were found. The peak II receptor bands were also obtained after mild reduction of peak I. After complete reduction both peaks showed one major receptor band with Mr 130 000. The reductive generation of the peak II receptor together with molecular mass estimations suggest that the peak I receptor is the disulfide-linked dimer of the peak II receptor. Thus, Triton extracts from rat liver microsomes contain two receptor species, which are related, but differ considerably in their size and insulin-binding properties.

Affinity Labels↗
PubMed1986

Use of synthetic oligodeoxynucleotide probes for the isolation of a human cholinesterase cDNA clone.

Cholinesterases are serine esterases that rapidly hydrolyze the neurotransmitter acetylcholine. In humans, cholinesterases exhibit extensive polymorphism in terms of their substrate specificity, sensitivity to selective inhibitors, hydrophobicity, and cellular as well as subcellular localization. It is not yet known whether the various cholinesterase forms originate from different genes or are products of posttranscriptional and posttranslational processing. The extent to which these enzyme forms are homologous in their amino acid sequence is also not known. However, a consensus organophosphate-binding hexapeptide sequence Phe-Gly-Glu-Ser-Ala-Gly was found both in "true" acetylcholinesterase from the electric organ of Torpedo [McPhee-Quigley et al: J Biol Chem 260:12185-12189, 1985] and in "pseudocholinesterase" (butyrylcholinesterase) from human serum [Lockridge: "Cholinesterases--Fundamental and Applied Aspects." New York: de Gruyter pp 5-12, 1984], suggesting that this region in the protein is conserved in all cholinesterases. Based on this common sequence, we prepared synthetic oligodeoxynucleotides and used them as labeled probes to screen a cDNA library from fetal human brain mRNA, cloned in lambda gt10 phages. A cDNA clone of 770 nucleotides in length was isolated. It contains an open reading frame terminating with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala, which includes the consensus hexapeptide used for designing the DNA probe. Furthermore, the sequence of this 12-amino acid peptide is identical to the sequence reported for the organophosphate binding site of human serum pseudocholinesterase [Lockridge: "Cholinesterases--Fundamental and Applied Aspects." New York: de Gruyter, pp 5-12, 1984]. These findings confirm that the isolated clone is indeed part of a human cholinesterase cDNA.

Amino Acid Sequence↗
PubMed1986

Maternal phenylketonuria.

Pregnant women with untreated phenylketonuria (PKU) with blood phenylalanine levels greater than 1200 mumol/L usually give birth to offspring with congenital birth defects, including microcephaly, cardiac defects and mental retardation. According to Mabry and Levy, hyperphenylalaninaemic (HPA) women with blood phenylalanine levels between 600 and 1200 mumol/L also have an increased risk to their offspring. To study this problem further, the National Institute of Child Health and Human Development has established a collaborative study for 7 years to elucidate a proper treatment programme for these women.

Adult↗
PubMed1986

Oestrogenic and antioestrogenic actions in a series of triphenylbut-1-enes: modulation of prolactin synthesis in vitro.

The oestrogenic and antioestrogenic activities of a series of substituted derivatives of 1,1,2 triphenylbut-1-ene have been determined using primary cultures of rat pituitary gland cells to monitor prolactin synthesis in vitro. The relative binding affinity of the agonists for the oestrogen receptor was consistent with their oestrogenic potency. Bis para substitution at C1 of 1,1,2 triphenylbut-1-ene with either phenolic or acetoxy groups produced partial agonists. The antioestrogenic properties were reversible by the incubation of cells with increasing concentrations of oestradiol. The results lend support to a hypothetical single binding site model of oestrogen action, based upon an adaptation of Belleau's macromolecular perturbation theory.

Alkenes↗
PubMed1985

Temperature dependence of verapamil action.

Ca2+-tolerant ventricular myocytes from adult rats were electrically stimulated. The maximal contraction frequency (fm) was determined at different temperatures. In drug-free Tyrode solution, fm follows the Arrhenius equation from 7 to 39.5 degrees C. However, verapamil introduces a discontinuity around 27 degrees C into the Arrhenius plot of fm. Above this transition temperature the calcium antagonist lowers fm more pronouncedly than below. Below, a tenfold higher concentration is needed for the same relative effect as at 37 degrees C. It is argued that this finding might be important in cardiac surgery when calcium antagonists are used for cardioplegia at deep hypothermia.

Animals↗
PubMed1985

Successful adjustment to society by adults with phenylketonuria.

The study shows that most individuals between 16 and 25 years of age with PKU appear to function in a productive manner in society. Although they have not become professional men and women, they can acquire jobs of a skilled or semiskilled nature and perform them satisfactorily. The majority seemed content with their jobs and happy with the way their lives were progressing, although only 23% were financially independent. Of the patients interviewed, the majority had made friendships and appeared to keep them without much trouble. The majority of the patients would not tell their friends that they had PKU. The reason for this was that they felt uncomfortable acknowledging that they had this disorder.

Adolescent↗
PubMed1985

Structure-activity relationships of estrogens.

The last 50 years has seen an exponential rise in the published reports about estrogen action. The model to describe the early events in the mechanism of action of estrogens via the estrogen receptor is updated in this paper to incorporate some of the recent data on the subcellular localization of the receptor. New evidence suggests that the receptor is a nuclear protein, so it appears that estrogens must first diffuse into the nuclear compartment to initiate estrogen action via the receptor complex. This review traces the development of potent estrogenic compounds by the study of their structure-activity relationships. Studies of structure-activity relationships in vivo using Allen Doisy or 3-day uterine weight tests can provide much valuable information, but the assays suffer from the complex problems of pharmacokinetics and metabolic transformation. Studies in vitro using primary cultures of rat pituitary or uterine cells to assay the ability of a compound to induce prolactin synthesis or progesterone receptor synthesis, respectively, can provide essential information about the structural requirements for a compound to produce estrogenic effects. Nevertheless, it should be pointed out that studies in vivo are required to determine whether a compound is metabolically activated to an estrogen. Estrogen receptor binding models are presented to describe the changes in a molecule that will predict high affinity for the ligand and agonist, partial agonist and antagonist properties of the ligand-receptor complex. Most estrogenic pesticides and phytoestrogens comform to the predictions of the estrogen receptor binding model.

Animals↗