PubMed Health⌕ Search

Biomedical subjects

M Neugebauer

Publications and source records attributed to M Neugebauer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Prenatal diagnosis of cystic fibrosis.

Cystic fibrosis is the most common autosomal recessive genetic disorder in the Caucasian population (1:2000-1:4000) (Warwick, W. J. (1978) Helv. Paediatr. Acta 33, 117-125). This defect is characterized by chronic obstructive pulmonary disease, pancreatic exocrine insufficiency and abnormally high perspiration electrolytes in most patients (Talamo et al. (1985) In: The metabolic basis of inherited diseases, pp. 1887-1917). The elevated electrolyte level provides the most reliable diagnostic test for cystic fibrosis homozygotes. Although prospects for cystic fibrosis patients have improved, genetically homozygous cystic fibrosis is effectively a lethal disease. Because of the seriousness of the disease, many families with one affected child desire a prenatal diagnosis when a second pregnancy occurs. Despite extensive research, the biochemical basis of cystic fibrosis remains unknown. Secondary effects on microvillar enzymes allow second trimester diagnosis (17-18 weeks of gestation (Brock, D. H. J. (1983) Lancet II, 941-943). First trimester prenatal diagnosis for cystic fibrosis became possible with DNA technology. Application of polymorphic marker loci to problems of prenatal diagnosis and carrier-testing is discussed.

Alkaline Phosphatase↗
PubMed1988

Cystic fibrosis: typing 89 German families with linked DNA probes.

Three hundred and ninety-two subjects from 89 German families were typed for restriction fragment length polymorphisms (RFLPs) detected by the probes pmetH, pmetD, pJ3.11, KM19, and XV2c known to be tightly linked to the cystic fibrosis (CF) gene. The analysis of the predictive value of this typing in individual CF families indicates that the combined use of these probes provides a powerful diagnostic system for both carrier detection and prenatal diagnosis. In 45 families the complete haplotype including all RFLPs was available. Of them 41 (91.1%) were fully informative and 4 were partly informative.

Alleles↗
PubMed1988

Linkage analysis in X-linked ichthyosis (steroid sulfatase deficiency).

Linkage analysis has been carried out in nine unrelated families segregating for X-linked ichthyosis (steroid sulfatase deficiency) using seven polymorphic DNA markers from the distal Xp. Close linkage was found between the disease locus and the loci DXS16, DXS89, and DXS143. In all families except one, Southern hybridization with the human steroid sulfatase cDNA and GMGX9 probes showed a deletion of corresponding loci in affected males. Three patients belonging to the same family had no evident deletion with either of the two above-mentioned probes. None of the other six DNA loci included in the linkage analysis were found to be deleted.

Arylsulfatases↗
PubMed1988

Two different genes for X-linked retinitis pigmentosa.

Linkage analysis was carried out in three large multigenerational kindreds with X-linked retinitis pigmentosa using DNA markers on Xp. About 10% recombination has been found between the retinitis pigmentosa locus (RP2) and the marker locus DXS7, assigned to band Xp11.3, which was reported earlier to be closely linked to RP2 in several independent families. In the kindreds described in this paper, however, RP2 shows close linkage and no recombination with the marker loci OTC and DXS148, both assigned to Xp21, indicating that, contrary to previous linkage studies, there is evidence of an RP locus distal to DXS7. This suggests that X-linked retinitis pigmentosa is genetically heterogeneous, i.e., caused by mutations at different loci.

Female↗
PubMed1988

[Biotransformation of meclozine in the human body].

After oral administration of 1-[(4-chlorophenyl)-phenylmethyl]-4-[3-methylphenyl)-methyl]-piperazine (1, Meclozine) eleven compounds were isolated from human urine and faeces. The structural elucidation of the metabolites was accomplished by comparison of their spectral data with those of the synthetic reference compounds. The metabolites were identified as: Meclozine (1), N-[(4-chlorophenyl)-phenylmethyl]-piperazine (2), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoic acid (3), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzamide] (4), 2-[3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoyl ]-amino- ethanesulphonic acid (5), 3-(4-[(4-chlorophenyl)-3'-hydroxy-4'-methoxyphenylmethyl]-piper azino)- methyl-benzoic acid (6), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N4-oxide (7), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N,N'-dioxide (8), 3-methyl-benzoic acid (9), 3-methyl-hippuric acid (10) and 3-methyl-benzoic acid-glucuronide (11). The structure of compound 11 was confirmed after enzymatic cleavage and identification of the aglycon. A further metabolite was detected, but not identified.

Biotransformation↗
PubMed1988

[The biotransformation of fenetylline].

After oral administration of 3,7-dihydro-1,3-dimethyl-7-2 [(1-methyl-2-phenylethyl)-amino-ethyl]-1H-purine-2,6-dione (fenetylline, Captagon), 7 new metabolites could be detected in urine besides 4 known substances. The metabolites were identified by gas chromatography (GC) and by comparison of the mass spectra (MS) of metabolites with those of authentic reference compounds using a combined GC/MS method.

Adult↗
PubMed1987

Autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Linkage analysis has been carried out in 11 kindreds with autosomal recessive polycystic kidney disease (ARPKD) using the genetic marker 3'HVR, closely linked (theta = 0.05) to the gene of the autosomal dominant type. Close linkage (theta less than or equal to 0.20) between the locus of the marker and that of ARPKD can be excluded. These data strongly suggest that the loci for the autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Alleles↗
PubMed1987

A comprehensive search for segregation distortion in HLA.

Segregation distortion, the non-Mendelian segregation of gametes, has been well documented among diverse groups of organisms. These cases are characterized by extreme segregation ratios found only in males. Previous reports have suggested the existence of segregation distortion operating in the HLA system of humans, a tightly linked complex of genes which regulates the immune system. In mice, some alleles of the T/t complex, which is linked to H-2 (the HLA homologue of mice), cause extreme segregation distortion in wild mice populations. Here we report on the examination of a large body of pedigree data on non-diseased families, scored for the alleles of five HLA region loci. We searched for segregation distortion on the basis of five different models of inheritance: allelic, haplotypic, genotypic, diffuse occurrence in families, and autosomal effects on the sex ratio. There was no clear evidence for segregation distortion. In particular, the possibility of extreme levels of segregation distortion was firmly rejected in the populations examined, thus reducing the likelihood of common distortion-causing HLA associated haplotypes in our species.

Alleles↗
PubMed1987

[Isolation of chlorphenoxamine metabolites in human urine and their identification].

After the administration of chlorphenoxamine (2-[1-(4-chlorophenyl)-1-phenylethoxy]-N,N-dimethylethanamine++ +, Systral) (I) the following compounds have been detected in human urine. They were identified as chlorphenoxamine (I), N-demethyl-chlorphenoxamine (II), chlorphenoxamine-N-oxide (III), 1-(4-chlorophenyl)-l-phenylethanol (IV), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethanol (V), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethene (VI), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethanol (VII), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethene (VIII), 2-[1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethoxy]-N-methyl-ethanamine (IX) and 2-[1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl-ethoxy]- N-methylethanamine (X). The compounds IV, V, VI, VII, VIII, IX and X were also found to be excreted as conjugates. It cannot be excluded that the compounds VI and VIII are artefacts.

Adult↗
PubMed1986

[Cleavage of 2-phenylpropan-1-ol and 2-phenylpropan-2-ol-glucuronide, 2 metabolites of isopropylbenzol (Cumol)].

The behaviour of 2-phenyl-1-propanol (I) and 2-phenyl-2-propanol (II) and their glucuronides with HCl has been investigated. While I shows a high acidic constancy, II undergoes a partial conversion into 2-phenylpropane (III) which itself yields numerous products. The glucosidic bond of glucuronide I is quantitatively split by 10.0% HCl, whereby an aglucone yield of nearly 100% is obtained. The second glucuronide behaves otherwise: the recovery of II is very low (only 40% to 45%) with HCl concentrations of 1.0%-20.0%, although with 1.0% HCl 100% of the glucuronide is hydrolysed.

1-Propanol↗
PubMed1985

[Cleavage of synthetic pentazocine glucuronide with hydrochloric acid].

It has been reported before that pentazocine (I) and pentazocine-glucuronide (II) form an artifact (III) by the addition of water to the double bond in the presence of HCl. This reaction leads to different results concerning the investigation of the rate of hydrolysis of II and the recovery of I. The glucuronide was quantitatively hydrolyzed by 20% HCl, but yielded only 15% of I (about 64% was detected as III). With 5% HCl the rate of hydrolysis only amounted to 40%-43%, whereas I yielded 31% (only 9% was recovered as III). The best III yield was obtained with a HCl concentration of 17.5%.

Chemical Phenomena↗