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G Knapp

Publications and source records attributed to G Knapp.

At least 37 records · Page 2Linked to original sources
PubMed1985

Frameshift suppressor mutations outside the anticodon in yeast proline tRNAs containing an intervening sequence.

Extragenic suppressors of +1 frameshift mutations in proline codons map in genes encoding two major proline tRNA isoacceptors. We have shown previously that one isoacceptor encoded by the SUF2 gene (chromosome 3) contains no intervening sequence. SUF2 suppressor mutations result from the base insertion of a G within a 3'-GGA-5' anticodon, allowing the tRNA to read a 4-base code word. In this communication we describe suppressor mutations in genes encoding a second proline tRNA isoacceptor (wild-type anticodon 3'-GGU-5') that result in a novel mechanism for translation of a 4-base genetic code word. The genes that encode this isoacceptor include SUF7 (chromosome 13), SUF8 (chromosome 8), trn1 (chromosome 1), and at least two additional unmapped genes, all of which contain an intervening sequence. We show that suppressor mutations in the SUF7 and SUF8 genes result in G-to-U base substitutions at position 39 that disrupted the normal G . C base pairing in the last base pair of the anticodon stem adjacent to the anticodon loop. These anticodon stem mutations might alter the size of the anticodon loop and permit the use of a 3'-GGGU-5' sequence within the loop to read 4-base proline codons. Uncertainty regarding the exact structure of the mature suppressor tRNAs results from the possibility that anticodon stem mutations might affect sites of intervening sequence removal. The possible role of the intervening sequence in the generation of mature suppressor tRNA is discussed. Besides an analysis of suppressor tRNA genes, we have extended previous observations of the apparent relationship between tRNA genes and repetitive delta sequences found as solo elements or in association with the transposable element TY1. Hybridization studies and a computer analysis of the DNA sequence surrounding the SUF7 gene revealed two incomplete, inverted delta sequences that form a stem and loop structure located 165 base pairs from the 5' end of the tRNA gene. In addition, sequences beginning 164 base pairs from the 5' end of the trn1 gene also exhibit partial homology to delta. These observations provide further evidence for a nonrandom association between tRNA genes and delta sequences.

Anticodon↗
PubMed1984

Transfer RNA splicing in Saccharomyces cerevisiae: defining the substrates.

The primary sequences of all the tRNA precursors which contain intervening sequences and which accumulate in the Saccharomyces cerevisiae rnal mutant are presented. A combination of DNA and RNA sequence analysis has led to elucidation of the primary sequence of four hitherto uncharacterized precursors. The location of the intervening sequence has in all cases been unambiguously determined by analysis of the intermediates in the splicing reaction. Secondary structures based upon the tRNA cloverleaf are shown for all the tRNA precursors and discussed with respect to common recognition by the yeast splicing endonuclease.

Base Sequence↗
PubMed1983

Introduction of plasma indomethacin level monitoring and evaluation of an effective threshold level in very low birth weight infants with symptomatic patent ductus arteriosus.

First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI2 and PGE2, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.

Ductus Arteriosus, Patent↗
PubMed1983

Aortic flow velocity curves in the diagnosis and the followup of symptomatic patent ductus arteriosus in preterm infants during therapeutic interventions.

In preterm infants, persistent ductus arteriosus (PDA) fails to close soon after birth and becomes symptomatic (sPDA) in about 40% of the infants, causing cardio-respiratory deterioration by a left-to-right shunt across the PDA. Aortic run-off of blood, predominantly occurring during ventricular diastole, causes an abnormal diastolic retrograde aortic blood flow. This aortic reverse flow can be assessed semi-quantitatively in a noninvasive way, using continuous-wave Doppler-ultrasonography. An increased ratio (R/F ratio) of the abnormal retrograde aortic blood flow (R) related to the normal forward flow (F) in the aorta indicates presence of sPDA in preterm infants. The R/F ratio was assessed in 30 premature infants, including 13 cases without sPDA, and 17 infants with sPDA--in 12 of them before and after surgical ligation of PDA, in five concomitantly to pharmacological closure of PDA by the application of indomethacin. The R/F ratio was low in all infants without sPDA and in infants following surgical ligation of PDA. On the other hand, a high R/F ratio was found in all patients with sPDA before specific treatment. During indomethacin-induced closure of PDA the R/F ratio decreased continuously, whereas it remained high in infants with sPDA not responding to indomethacin treatment.

Aorta, Thoracic↗
PubMed1981

Stereospecific determination of D-thyroxin and L-thyroxin in serum.

A new method for separate determination of D-thyroxin and L-thyroxin in the serum was applied to study the response of serum levels of these isomers and of radioimmunologically determined total T3, total T4, free T4 and TSH upon administration of 2, 4 and 6 mg of a highly purified D-thyroxin preparation in six male patients with diffuse nontoxic goiter. D- and L-thyroxin are determined separately following extraction of the hormone from the serum and formation of diastereomeric dipeptides. The separation and final determination are accomplished by means of ion-pair chromatography on reversed-phase columns using an iodine-selective catalytic detector. A significant decrease in TSH takes place during the 3-days observation period. The values of D-T4, total T3 and free T4 are highest 4 hours after administration of the tablets and get to be to initial values after 24 hours. L-T4 shows no significant change. A direct suppressive effect of D-T4 on the pituitary gland may therefore be assumed as the cause of the suppression of TSH secretion.

Adult↗
PubMed1981

[Serum levels od D-thyroxine in euthyroidism and hypothyroidism (author's transl)].

Serum levels of D-thyroxine (D-T4) and L-thyroxine (L-T4) were determined by use of a newly developed method for the stereospecific determination of these isomers in 8 patients with diffuse non-toxic goiter and 2 hypothyroid patients following administration of increasing doses of D-thyroxine. During the 3-day observation period a significant decrease of serum-TSH takes place. D-T4 levels are highest 4 hours after administration of the tablets and approach basal values within 24 hours in euthyroid as well as hypothyroid patients. Serum half life of D-T4 was 5.7 hours on the average in the euthyroid group and was markedly prolonged in hypothyroidism. L-T4 levels show no significant changes. Since the D-T4 preparation used, contained only very little amounts of the L-isomer, it may be assumed that D-T4 exerts a direct suppressive effect on the pituitary TSH secretion, as evidenced by the observed significant decrease in basal and TRH-stimulated TSH serum levels.

Adult↗
PubMed1980

[Investigations concerning the mechanism of contrast damage. The significance lipophilia (author's transl)].

The damaging action on vascular endothelia of meglumin iothalamate and of meglumin ioxitalamate was tested on the rat aorta. Ioxitalamate was significantly better tolerated than iothalamate. The octanol-water-partition coefficient of various contrast media was evaluated by assessing the iodine content of the octanol phase after mixing. The coefficients found were about 100 fold lower than the coefficients computed by Levitan and Rapoport. The significance of the octanol-water-partition coefficient for endothelial injuries caused by contrast media is disputed.

Blood Vessels↗
PubMed1980

[Therapy of salmonella enteritis with special reference to lactulose (author's transl)].

Excretion of Salmonellae in two groups of outpatients with Salmonellae is discussed. In one group of 51 adults, a total of 30 different serotypes were isolated. These patients were treated with lactulose and after four weeks the organisms had been eliminated in 68.6%. In a group of 23 adults receiving no treatment whatsoever, 56.5% were still excreting the organism after four weeks. Of the 64 in-patients studied, 37 received various antibiotics, 14 lactulose and in 13 only the symptoms were treated. The length of the excretion period was longer for the group receiving antibiotics (four weeks after onset of illness 67.8% were still excreting the organism). Treatment with lactulose, however, resulted in a shorter period of excretion for these patients. Special aspects of the various groups - e.g. age structure, pattern of infecting organisms - are reported in detail.

Adult↗
PubMed1979

Splicing of yeast tRNA precursors: a two-stage reaction.

Soluble extracts of S. cerevisiae splice tRNA precursors which contain intervening sequences. The reaction goes to completion and requires ATP for the production of mature sequence tRNA. In the absence of ATP, half-tRNA molecules accumulate. Similar half-tRNA molecules appear as kinetic intermediates and accumulate if splicing is inhibited with pure, mature tRNA. Half-tRNA molecules have been purified. These half-tRNAs are efficiently ligated in an ATP-dependent reaction that is inhibited by added mature tRNA. The product of ligation is the expected mature sequence tRNA. The excised intervening sequence has also been identified. These results suggest an enzymatic mechanism for splicing which involves two independent steps.

Adenosine Triphosphate↗
PubMed1979

Splicing of yeast tRNA precursors: structure of the reaction intermediates.

The intermediates of the yeast tRNA splicing reaction have been characterized. The intervening sequence is excised as an unique linear molecule. It has 5'-hydroxyl and 3'-phosphate termini. Correspondingly, the half-tRNA molecules are shown to have a 3'-phosphate terminus on the 5' half and 5'-hydroxyl terminus on the 3' half. These isolated halves have been shown to be active in the ligation step of tRNA splicing. Removal of the 3'-phosphate from the 5' half eliminates the ability of the 5' half to participate in ligation.

Base Sequence↗
PubMed1978

Transcription and processing of intervening sequences in yeast tRNA genes.

Genes for yeast tRNATyr and tRNAPhe have been sequenced (Goodman, Olson and Hall, 1977; Valenzuela et al., 1978) which contain additional nucleotides (intervening sequences) within the middle of the gene that are not present in the mature tRNA. We have isolated precursors to rRNATyr and tRNAPhe from a yeast temperature-sensitive mutant (at the rna1 locus) which accumulates only certain precursor tRNAs at the nonpermissive temperature. The tRNATyr and tRNAPhe precursors were analyzed by oligonucleotide mapping; they each contain the intervening sequence and fully matured 5' and 3' termini. Furthermore, these precursors were used as substrates to search for an enzymatic activity which can remove the intervening sequences and religate the ends. We have shown that wild-type yeast contains such an activity, and that this activity specifically removes the intervening sequences to produce mature-sized RNAs.

Base Sequence↗
PubMed1978

Child abuse. Its relationship to birthweight, apgar score, and developmental testing.

Fifty-two abused and 23 nonabused children from a low socioeconomic group were studied with respect to birthweight, five-minute Apgar score, and developmental quotients. An association was found between low Apgar scores, low birthweight, poor performance on developmental testing, and child abuse. Furthermore, it was found that among children with normal birthweights, abused children tended to have lower Apgar scores and significantly lower developmental quotients. This study suggests that among this group of children, abuse and subsequent poor performance may be related not only to the socioeconomic status of the children but also to the characteristics the child brings to the parent-child relationship and to the abusive environment.

Apgar Score↗
PubMed1976

[Short forms of a short psychopathological intelligence test (author's transl)].

Even short tests can still be materially shortened when they are intended to provide rough information. An example of a short intelligence test shows that considerable reductions are permissible when the procedure is intended to classify subjects into IQ groups of roughly "under 100" or "over 100". Also division into three as below average, average and above average level of intelligence is possible, and also division into four grades. If about 85% accuracy is satisfactory, a three-problem test is sufficient. For grading into three and four parts, six and nine problems, respectively may be adequate.

Adult↗