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Biomedical subjects

E Schmidt

Publications and source records attributed to E Schmidt.

At least 127 records · Page 7Linked to original sources
PubMed1995

Determinants of cord-blood IgE concentrations in 6401 German neonates.

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P < 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (> 0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P < 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.

Adrenal Cortex Hormones↗
PubMed1995

[Hearing screening within the scope of pediatric U5 preventive examination: can diagnosis be improved by use of a parent questionnaire?].

OBJECTIVE: Assessment of a) the efficacy of hearing loss screening in baby check-ups at the age of 6 to 8 months b) the efficiency and efficacy using parent questionnaires about hearing loss risk factors and parents' concern about the child's hearing as part of baby check-up. METHODS: The analyses are based on 7282 baby check-ups carried out in 47 pediatricians' offices in the Düsseldorf area from July 1991 to March 1993: 3385 of these check-ups were performed in the traditional manner (period A; July 1, 1991, to January 1, 1992; 3897 check-ups involved parent questionnaires (period B June 1, 1992, to March 31, 1993). All children who failed the tests and a random sample of those who had passed the test when tested in the traditional manner, were offered extensive hearing assessment. RESULTS: In period A, 4.3% of the children failed the test as compared to 21.7% with the first version of the questionnaire and 14.3% with a revised questionnaire in period B. Compliance to the offer of extensive hearing assessment was unsatisfactory (53% in period A and 63% in period B). The first extensive hearing examination failed to distinguish healthy children from children with probable sensorineural hearing loss in about 30% of the patients, mainly because of glue ear. One child with sensorineural hearing loss was identified by the screening in period A as compared to six children in period B. CONCLUSIONS: 1) The systematic use of parent questionnaires in baby check-ups at ages 6 to 8 months is likely to increase the efficacy of the screening. 2) The efficiency of the questionnaires currently in use, however, needs to be improved and can be improved with the data from the study. 3) The compliance with extensive hearing testing in children who have failed the screening test must be improved. 4) Due to the high prevalence of conductive hearing loss in this age group, treatment of potential glue ear problems is mandatory before referral for extensive testing for sensorineural hearing loss.

Deafness↗
PubMed1994

Thiol ligation of two zinc atoms to a class I tRNA synthetase: evidence for unshared thiols and role in amino acid binding and utilization.

Class I tRNA synthetases generally contain a characteristic N-terminal catalytic core joined to a C-terminal domain that is idiosyncratic to the enzyme. The closely related class I Escherichia coli methionyl- and isoleucyl-tRNA synthetases each have a single zinc atom coordinated to ligands contained in the catalytic domain. Isoleucyl-tRNA synthetase has a second, functionally essential, zinc bound to ligands at the C-terminal end of the 939 amino acid polypeptide. Recent evidence suggested that this structure curls back and interacts directly or indirectly with the active site. We show here by X-ray absorption spectroscopy that the average Zn environment contains predominantly sulfur ligands with a Zn-S distance of 2.33 A. A model with eight coordinated thiolates divided between two Zn(Cys)4 structures best fit the data which are not consistent with a thiolate-bridged Zn2(Cys)6 structure joining the C-terminal end with the N-terminal active site domain. We also show that zinc bound to the N-terminal catalytic core is important specifically for amino acid binding and utilization, although a direct interaction with zinc is unlikely. We suggest that, in addition to idiosyncratic sequences for tRNA acceptor helix interactions incorporated into the class-defining catalytic domain common to class I enzymes, the architecture of at least some parts of the amino acid binding sites may differ from enzyme to enzyme and include motifs that bind zinc.

Amino Acids↗
PubMed1994

Mutational isolation of a sieve for editing in a transfer RNA synthetase.

Editing reactions are essential for the high fidelity of information transfer in processes such as replication, RNA splicing, and protein synthesis. The accuracy of interpretation of the genetic code is enhanced by the editing reactions of aminoacyl transfer RNA (tRNA) synthetases, whereby amino acids are prevented from being attached to the wrong tRNAs. Amino acid discrimination is achieved through sieves that may overlap with or coincide with the amino acid binding site. With the class I Escherichia coli isoleucine tRNA synthetase, which activates isoleucine and occasionally misactivates valine, as an example, a rationally chosen mutant enzyme was constructed that lacks entirely its normal strong ability to distinguish valine from isoleucine by the initial amino acid recognition sieve. The misactivated valine, however, is still eliminated by hydrolytic editing reactions. These data suggest that there is a distinct sieve for editing that is functionally independent of the amino acid binding site.

Adenosine Triphosphate↗
PubMed1994

Sustained attention in adult phenylketonuria: the influence of the concurrent phenylalanine-blood-level.

The effect of concurrent phenylalanine levels (Phe-level) on sustained attention was tested in a group of 19 early treated adult PKU patients. Mean age was 20.5 years; WAIS IQs were in the normal range (M = 109.3). Phe-levels were manipulated in a high-low-high design by reintroduction of a strict phenylalanine-reduced diet for 4 to 5 weeks between test time 1 and 2 and returning to usual diet between test time 2 and 3. A control group of 20 healthy subjects, mean age 20.7 years was tested twice. Results of a sustained attention task are presented. In adult PKU patients with high concurrent Phe-levels, sustained attention is significantly impaired and reaction times are prolonged. In the low Phe-level condition, performance improved significantly. Nevertheless, the PKU group did not reach the level of performance of the control group. Results are not influenced by IQ and suggest a sustained attention deficit in adult PKU patients that varies according to the concurrent Phe-level. The partial reversibility of the deficits provides support for the hypothesis that biochemical mechanisms rather than structural changes of the brain underlie the relationship between concurrent Phe-level and sustained attention.

Adolescent↗
PubMed1994

Psychopathology of patients treated early for phenylketonuria: results of the German collaborative study of phenylketonuria.

At the age of 13 years, 60 adolescents, suffering from phenylalaninemia due to hydroxylase deficiency, and their mothers were simultaneously investigated with a standardized psychiatric interview in order to determine the adolescents' psychiatric status. Forty symptoms related to emotional disorders, antisocial and conduct disorders, hyperkinetic syndromes, and specific symptoms like psychophysiological pains, enuresis, encopresis, tics, stereotypies, and eating disorders were examined. Severity level was rated as undisturbed, mild, moderate, and severe disturbance. Comparison with a representative sample of 191 age mates revealed a double rate of moderate disturbances for the PKU sample. There was no association between severity level and sex as well as mean phenylalanine level during the first 13 years of the patients' lives. No PKU specific diagnosis could be determined. WISC-R-IQ below 90 was associated with a threefold risk of more severe disturbance and patients with more than three adverse familial circumstances had a 50% chance of getting a psychiatric diagnosis. It is concluded that the observed disturbances result from stress associated more with the chronic condition than with the increased phenylalanine level.

Adolescent↗
PubMed1994

Challenge with high concentrations of cyclic AMP induces transient changes in the cytosolic free calcium concentration in Dictyostelium discoideum.

Dictyostelium discoideum cells use cyclic AMP (cAMP) for chemotactic signaling as well as for differentiation. The precise regulation of the cytosolic Ca2+ concentration ([Ca2+]i) seems to play a key role for both processes. We performed single cell measurements of [Ca2+]i in amoebae that were starved in suspension for various times and scrape-loaded with the Ca2+ indicator fura-2. Stimulation of cells with cAMP at the concentration required to induce gene expression (> or = 100 microM) elicited a global transient increase in [Ca2+]i that depended on the presence of external Ca2+. Both vegetative and aggregation-competent cells displayed a rise in [Ca2+]i, with aggregation-competent cells responding more often than vegetative cells. Basal [Ca2+]i in the presence of Ca2+ was high in vegetative cells and declined during development; the cAMP-induced rise in [Ca2+]i was higher and lasted longer in vegetative cells than in aggregative cells. The addition of 2'-deoxy-cAMP, which binds to the cAMP receptor, induced an increase in [Ca2+]i, whereas the membrane-permeant analogue 8-bromo-cAMP that has a low affinity for the receptor but activates cAMP-dependent protein kinase had no effect. This indicates that the change in [Ca2+]i is mediated by the cell surface cAMP receptor. Since HC85 mutant cells, which lack the G alpha 2 subunit of the G-protein that couples the receptor to phospholipase C, also responded to stimulation with cAMP, the Ca2+ influx does not seem to be triggered by the phosphoinositide signaling cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function.

Some smokers have an accelerated loss of lung function, possibly due to a chronic bronchial inflammation in which granulocytes are involved. Eosinophil cationic protein (ECP) and lactoferrin (LF) are granule proteins in the eosinophil and neutrophil granulocyte, respectively. We wanted to investigate the relationship of serum (s) ECP and LF concentrations to smoking history and lung function alteration. This partly cross-sectional and partly prospective study included 98 nonatopic smokers and 31 lifetime nonsmokers. As participants in a smoking cessation programme, 50 of the 98 smokers ceased smoking for > or = 1 year. Smoking history, lung function and blood samples were obtained at the start of the study, and smokers and ex-smokers also gave blood samples 3, 6 and 12 months later. s-ECP and s-LF were elevated in smokers compared to people who had never smoked. s-ECP was linearly associated with daily cigarette consumption and forced expiratory volume in one second (FEV1) residuals. In a multiple linear regression analysis, low s-ECP and high s-LF were associated with decreased FEV1 residuals. s-ECP and s-LF together accounted for 10.2% of the variation in FEV1 residuals. After smoking cessation, s-ECP and s-LF decreased within 6 months. s-ECP and s-LF are raised in smokers, and may serve as indicators of granulocyte activation. We speculate that they might contribute to prediction of accelerated lung function loss in smokers, but this question needs further investigation in a prospective study.

Blood Proteins↗
PubMed1994

Personality characteristics in patients with phenylketonuria treated early.

In the course of the German Collaborative PKU Study, the results of the Personality Questionnaire for Children (PFK 9-14) of 58 10-y-old patients treated early for phenylketonuria were analyzed. The main message of our data is that patients with phenylketonuria who were treated early and strictly did not show a higher risk for severe emotional and behavioral maladjustment compared with healthy controls at the age of 10 y. The patients were characterized only by "less masculinity of attitudes." Because no significant correlations were observed between the quality of dietary control and the results of the questionnaire, the noticed personality characteristic of the patients could be interpreted as a psychosocial consequence of the chronic disease.

Child↗
PubMed1993

Dominant lethality by expression of a catalytically inactive class I tRNA synthetase.

Alignment-guided mutagenesis was used to create an inactive, but toxic, aminoacyl-tRNA synthetase. An Asp-96-->Ala (D96A) replacement in the nucleotide binding fold of the class I Escherichia coli isoleucyl-tRNA synthetase inactivates the enzyme without disrupting its competence for binding isoleucine tRNA. Expression of plasmid-encoded mutant enzyme in a cell with a wild-type ileS chromosomal allele resulted in cell death. Introduction of a second K732T substitution previously shown to weaken tRNA binding gives an inactive D96A/K732T double mutant. Expression of the double mutant is not lethal to E. coli. D96A but not the double mutant significantly inhibited in vitro charging of isoleucine tRNA by the wild-type enzyme. The results suggest a dominant tRNA binding-dependent arrest of cell growth caused by a reduction in the pool of a specific tRNA. Specific tRNA binding drugs may have therapeutic applications for treatment of microbial pathogens.

Amino Acid Sequence↗
PubMed1993

Genotype-phenotype correlations in phenylketonuria.

Genotyping of the phenylalanine hydroxylating system offers a new way of characterizing patients with phenylalanine hydroxylase (PAH) deficiency. This paper investigates the power of genotyping as a parameter for differential diagnosis and as a measure of the risk factor of brain damage in well-treated patients with phenylketonuria (PKU). Thirty-three PKU patients were followed up over 9 years and the quality of dietary treatment, plasma phenylalanine (phe) in the newborn period before treatment and intellectual outcome at the age of 9 years were measured and correlated with the predicted residual activity (PRA) of the phe hydroxylase system as estimated from mutation analysis of the PAH gene. Patients were grouped in group Ia (PRA = 0%), group Ib (PRA = 5-15%) and group II (PRA > or = 25% of the normal activity). Mean plasma phe levels in the newborn in group Ia were 37.9 +/- 6.5 (2296 +/- 394), in group Ib 40.8 +/- 15.9 (2472 +/- 963) and in group II 16.2 +/- 4.2 (981 +/- 254) mg/dl (mumol/l). Difference in mean plasma values of groups Ia and Ib on the one hand and group II on the other were highly significant (P < 0.0001). No difference could be seen between groups Ia and Ib. There was a higher mean IQ at the age of 9 years in group II (97.4 +/- 5.4) in comparison with groups Ia (92.7 +/- 12.8) and Ib (85.0 +/- 14.4). The difference between group Ib and group II was significant (P < 0.040).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1993

Role of cytochrome P4502D6 in the metabolism of brofaromine. A new selective MAO-A inhibitor.

The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, selective MAO-A inhibitor, has been assessed in poor (PM) and extensive (EM) metabolizers of debrisoquine. Compared to EM, PM had significantly longer t1/2 (136%) and larger AUC(0-infinity) (110%) of the parent compound brofaromine and a lower Cmax (69%) and AUC (0-72 h) (40%) of its O-desmethyl metabolite. The mean metabolite/substrate ratio (based on urine excretion) was about 6-times greater in EM than in PM. Treatment with quinidine converted all EM into phenocopies of PM. All pharmacokinetic parameters of brofaromine and O-desmethyl-brofaromine in EM treated with quinidine were similar to those of untreated PM, including the metabolite/substrate ratio. Quinidine treatment of PM did not alter the pharmacokinetics of brofaromine or of its metabolite, nor the metabolite/substrate ratio. The results indicate a role for the debrisoquine type of oxidation polymorphism in the O-demethylation and pharmacokinetics of brofaromine.

Adult↗