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Biomedical subjects

G Scherer

Publications and source records attributed to G Scherer.

At least 127 records · Page 7Linked to original sources
PubMed1988

Pharmacokinetics of nicotine, cotinine, and 3'-hydroxycotinine in cigarette smokers.

The trans-isomer of 3'-hydroxycotinine has recently been identified as a major metabolite of nicotine in urine of cigarette smokers. We, therefore, investigated the pharmacokinetics of 3'-hydroxycotinine in six male smokers after intravenous infusion of nicotine, cotinine, and 3'-hydroxycotinine. Serum concentrations of 3'-hydroxycotinine were lower than those of cotinine throughout the observation period of 60 h after infusion of nicotine or cotinine, whereas the amounts excreted in the urine were similar or higher than those of cotinine. The following means and ranges for the pharmacokinetic parameters were derived from the 3'-hydroxycotinine infusion experiment: half-life (t1/2 beta) = 5.9 (4.2-9.5) h; apparent volume of distribution (Vd) = 0.87 (0.51-1.14) l/kg; total clearance (Cl total) = 1.79 (1.08-2.59) ml/min/kg; renal clearance (Clr) = 1.31 (0.85-1.78) ml/min/kg; percentage of renal clearance (Clr/Cl total) = 75.4 +/- 12.8 (60.3-98.2). The high percentage of renal clearance suggests that further metabolization of this compound is limited. No evidence for a mutagenic activity of 3'-hydroxycotinine or of urine extracts from subjects dosed with hydroxycotinine was found with the S. typhimurium (TA 98) microsome assay.

Adult↗
PubMed1987

Absence of Y-specific DNA sequences in human 46,XX true hermaphrodites and in 45,X mixed gonadal dysgenesis.

A search for Y-specific DNA sequences has been performed in a sample of seven 46,XX true hermaphrodites and one 45,X mixed gonadal dysgenesis case and compared with a sample of 11 XX males. Using six Y-specific DNA probes no hybridization signal was obtained in the hermaphrodite group; in contrast, all XX males gave a positive signal with at least one probe. This difference is statistically highly significant. We conclude that the aetiology of true hermaphroditism is different from that of the XX male syndrome. As all cases of the hermaphrodite group are positive for the serological sex-specific antigen (Sxs) it is concluded that this antigen can be present even in the absence of Y-specific DNA.

DNA↗
PubMed1987

Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1----q22.3 in a patient with tyrosinemia type II.

Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pter----q22.1::q22.3----qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1,MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome.

Alleles↗
PubMed1987

Determination of nicotine and cotinine in human serum and urine: an interlaboratory study.

An interlaboratory study aimed at determining nicotine and cotinine in human serum and urine was carried out. 11 laboratories from 6 countries, all experienced in performing nicotine and cotinine determinations in biological fluids by radioimmunoassay (RIA) and/or gas chromatography (GC) were involved. Each of them received 18 serum and 18 urine samples. The specimens were obtained from 8 smokers and 10 non-smokers; 2 samples from non-smokers were spiked with defined amounts of nicotine and cotinine. All the laboratories distinguished perfectly between the smokers and the non-smokers and according to cotinine levels in serum the laboratories ranked the samples with good agreement. There were systematic differences in the absolute values between the laboratories. The ratios of urinary cotinine concentrations between active and passive smokers differed widely from laboratory to laboratory. The reasons for this are not yet known and necessitate further investigation.

Chromatography, Gas↗
PubMed1987

Hydroxy-phenanthrenes in the urine of non-smokers and smokers.

Urinary hydroxy-phenanthrene (HO-PHE) excretion in non-smokers exposed to environmental tobacco smoke (ETS) is not increased. There is no significant difference in HO-PHE excretion between smokers (S) and non-smokers (NS), though excretion seems to be slightly elevated in smokers. A diet rich in polycyclic aromatic hydrocarbons leads to a rise in urinary HO-PHE excretion as compared to a diet low in polycyclic aromatic hydrocarbons (PAH), coming close to significance. HO-PHE excretion is not correlated with the mutagenic activity in urine.

Diet↗
PubMed1987

Urinary mutagenicity after controlled exposure to environmental tobacco smoke (ETS).

20 non-smokers on a defined diet low in polycyclic aromatic hydrocarbons (PAH) were exposed to environmental tobacco smoke (ETS) in an unventilated room for 8 h. The urinary mutagenicity in the 24-h urine samples as tested with the Salmonella (TA98) microsome assay did not significantly increase after exposure to either 10 ppm CO or 20-25 ppm CO. We conclude that exposure of non-smokers to ETS does not lead to an increase in their urinary mutagenicity, provided the exposure conditions are within a realistic range.

Adult↗
PubMed1987

Tyrosine aminotransferase and chymotrypsinogen B are linked to haptoglobin on human chromosome 16q: comparison of genetic and physical distances.

The loci for haptoglobin (HP) and tyrosine aminotransferase (TAT) are known to reside at 16q22. Chymotrypsinogen B (CTRB), which is syntenic with TAT and HP on mouse chromosome 8, has also been assigned to human chromosome 16 but has not been mapped regionally. A linkage analysis was carried out in 13 informative families using RFLPs for these three markers. For CTRB, two TaqI RFLPs with a polymorphism information content of 0.60 derived from haplotype frequencies are described. The most likely order of loci, deduced from triple informative crosses, and their map distances, obtained by pair-wise linkage analysis, are HP-7 cM-TAT-9 cM-CTRB. By pulsed-field gel electrophoresis, a physical map covering more than 2000 kb was constructed. A maximum physical distance of about 700 kb was obtained for HP and TAT, which contrasts with the genetic distance of 7 cM (approximate confidence limits 2-18 cM). CTRB is at least 800 kb away from these two markers.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

Evidence for the presence of testicular tissue and Sxs antigen in the absence of Y-derived sequences.

Eleven XX males and seven XX true hermaphrodites have been tested for the presence of Y-derived DNA sequences using six different probes. All eleven XX males were positive with at least one of the probes but none of the seven true hermaphrodites could be shown to possess any Y-DNA. Using a new sensitive test for serologically sex-specific (Sxs) antigen, we found that, despite their apparent lack of Y-DNA, the XX true hermaphrodites were positive for their expression of the Sxs antigen.

DNA↗
PubMed1986

A 45,X male with a Yp/18 translocation.

A patient described as a 45,X male (Forabosco et al. 1977) was examined for the presence of Y-specific DNA by using various probes detecting restriction fragments from different regions of the Y chromosome. Positive hybridization signals were obtained for Yp fragments only. In situ hybridization with two different probes, pDP31 and the pseudoautosomal probe 113F, led to a clear assignment of the Yp sequences to the short arm of one chromosome 18. Cytogenetically, the presence of all of Yp including the Y centromere on 18p could be demonstrated replacing a segment of similar size of 18p. Thus, the Y/18 translocation chromosome is dicentric structurally, but it was shown to be monocentric functionally with the no. 18 centromere active. Gene dosage studies with the probe B74 defining a sequence at 18p11.3 demonstrated a single dose of this sequence in the patient. In agreement with these observations, the patient shows clinical signs of the 18p-syndrome. It is concluded that in XO males in general, the X is of maternal origin while the maleness is due to a de novo Y/autosome translocation derived from the father. Depending on the nature of the autosomal deficiency caused by the Y/autosome translocation, the patient may have congenital malformations.

Child↗
PubMed1986

Regional localisation of X chromosome short arm probes.

Nine human X chromosome-specific clones have been isolated by screening an X-chromosomal genomic library with fetal muscle cDNA. Five of the clones have been localised to the short arm and four to the long arm. The short arm probes have been regionally assigned using a panel of somatic cell hybrids. They have been mapped further using a series of DNA samples from male patients with different deletions of the region Xp21, and having complex phenotypes including Duchenne muscular dystrophy. The use of these probes in the mapping of the short arm of the X chromosome is discussed.

Chromosome Banding↗
PubMed1986

Assignment of the human tyrosine aminotransferase gene to chromosome 16.

The liver enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5) catalyzes the rate-limiting step in the catabolic pathway of tyrosine. Deficiency in TAT enzyme activity underlies the autosomally inherited disorder tyrosinemia II (Richner-Hanhart syndrome). Using a human TAT cDNA clone as hybridization probe, we have determined the chromosomal location of the TAT structural gene by Southern blot analysis of DNAs from a series of human X rodent somatic cell hybrids. The results assign the TAT gene to human chromosome 16.

Animals↗
PubMed1985

Isolation, characterization and chromosomal mapping of the mouse tyrosine aminotransferase gene.

The tyrosine aminotransferase (TAT) gene is expressed in a tissue and developmental-specific manner. In addition, this gene is regulated by glucocorticoid and polypeptide hormones and its expression is affected when a regulatory region near the albino locus of the mouse is deleted. In order to allow studies of the molecular effects of these deletion mutations we have isolated and characterized the mouse TAT gene. The gene is 9.2 x 10(3) bases in length and consists of 12 exons which give rise to a 2.3 x 10(3) base long messenger RNA. The DNA sequence at the 5' end of the gene was determined and compared with the corresponding sequence of the rat tyrosine aminotransferase gene. The sequence comparison showed extensive homology over the entire region sequenced. In addition, DNA: DNA heteroduplex studies between the mouse and rat tyrosine aminotransferase genes revealed that this homology extends over the entire gene and its flanking sequences. The mouse tyrosine aminotransferase gene has been mapped distal to the serum esterase-1 locus on mouse chromosome 8, using a restriction fragment length polymorphism between two mouse species. Since the albino deletions are located on mouse chromosome 7, the assignment of the TAT gene to chromosome 8 suggests that a regulatory factor(s) affecting TAT gene expression acts in trans.

Animals↗
PubMed1985

Urinary hydroxyproline excretion in smokers, non-smokers and passive smokers.

The hydroxyproline/creatinine ratio in urine was investigated in 200 cigarette smokers, 199 pipe and/or cigar smokers and 24 non-smokers. For cigarette smokers a statistically significant positive correlation is found between this ratio and daily cigarette consumption, COHb, serum cotinine and nicotine excretion in urine. This smoking-related increase in the hydroxyproline/creatinine ratio is, for the most part or completely, due to the fact that creatinine urine concentrations inversely correlate with the smoke uptake variables. Neither pipe and/or cigar smoking nor passive smoke exposure of non-smokers seem to affect the hydroxyproline/creatinine ratio. A seasonal influence is found in these studies as well as in two experiments with limited numbers of subjects: the hydroxyproline/creatinine ratio is higher in winter than in summer for both smokers and non-smokers. Our data do not favour the idea that measuring hydroxyproline/creatinine ratios in urine is an accurate method of investigating early effects of smoking, passive smoking and air pollution in man.

Adolescent↗
PubMed1984

Cloning of SV40 genomes from human brain tumors.

From two human brain tumors SV40 genomes were isolated by recombinant DNA techniques. The SV40 genome cloned from a human meningioma DNA was shown to be indistinguishable from wild-type SV40. In contrast, the SV40 genome cloned from a human astrocytoma proved to be a nonviable deletion mutant with a truncated early region removing most of the large T-coding region. In addition, this mutant also carries a tandem duplication of an intact origin of replication.

Astrocytoma↗
PubMed1984

Hydroxyproline excretion in urine of smokers and passive smokers.

Urinary hydroxyproline excretion was investigated in 125 male cigarette smokers, 194 male pipe and/or cigar smokers, and 24 male nonsmokers. Hydroxyproline excretion was calculated either as hydroxyproline/creatinine ratio or as body surface-standardized amounts of hydroxyproline excreted in urine sampled during day, during night, or over 24 hr. The association of hydroxyproline excretion with smoke uptake variables such as daily cigarette consumption, carboxyhemoglobin, serum cotinine, and nicotine in urine and with self-reported passive smoking exposure in nonsmokers was analyzed. The hydroxyproline/creatinine ratio was found to be unsuitable as a measure of hydroxyproline excretion since creatinine urine concentrations correlate inversely with smoke uptake in cigarette and pipe/cigar smokers. The amount of hydroxyproline excreted in 24-hr urine and standardized for body surface was not significantly associated with smoke uptake in pipe/cigar smokers or exposure to passive smoking in nonsmokers. In cigarette smokers the situation appeared similar, although the results were less clear-cut. The data do not favor the premise that measuring urinary hydroxyproline excretion is an accurate method of investigating a lung-damaging effect of smoking, passive smoking, or air pollution.

Adult↗