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Biomedical subjects

U Seidel

Publications and source records attributed to U Seidel.

18 recordsLinked to original sources
PubMed1999

A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin.

OBJECTIVE: Mutation analysis of the acetylcholine receptor (AChR) epsilon subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS). BACKGROUND: The nicotinic AChR of skeletal muscle is a neurotransmitter-gated ion channel that mediates synaptic transmission at the vertebrate neuromuscular junction. Mutations in its gene may cause congenital myasthenic syndromes. A recently described mutation in exon 12 of the AChR epsilon subunit (epsilon1267delG) disrupts the cytoplasmic loop and the fourth transmembrane region (M4) of the AChR epsilon subunit. METHODS: Forty-three CMS patients from 35 nonrelated families were clinically classified as sporadic cases of CMS (group III according to European Neuromuscular Centre consensus) and were analyzed for epsilon1267delG by PCR amplification and sequence analysis. RESULTS: The authors report the complete genomic sequence and organization of the gene coding for the epsilon subunit of the human AChR (accession number AF105999). Homozygous epsilon1267delG was identified in 13 CMS patients from 11 independent families. All epsilon1267delG families were of Gypsy or southeastern European origin. Genotype analysis indicated that they derive from a common ancestor (founder) causing CMS in the southeastern European Gypsy population. Phenotype analysis revealed a uniform pattern of clinical features including bilateral ptosis and mild to moderate fatigable weakness of ocular, facial, bulbar, and limb muscles. CONCLUSIONS: The mutation epsilon1267delG might be frequent in European congenital myasthenic syndrome patients of Gypsy ethnic origin. In general, patients (epsilon1267delG) were characterized by the onset of symptoms in early infancy, the presence of ophthalmoparesis, positive response to anticholinesterase treatment, and the benign natural course of the disease.

Adolescent↗
PubMed1996

Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida.

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1-3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4-9), healthcare professionals (10-12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.

Adolescent↗
PubMed1996

Occurrence of polychlorinated terphenyls (PCTs) in indoor particulate matter.

In the course of a routine investigation concerned with polychlorinated biphenyl (PCB) contamination of dust collected in classrooms of a junior high school, a group of electron capture detector (ECD)-sensitive compounds with high boiling points were found in addition to PCBs. Using gas chromatographic-mass spectrometric techniques, these compounds were identified as polychlorinated terphenyls (PCTs). Additional measurements indicated that the PCTs were present only in particulate matter collected from the tops of fluorescent light frames but not in air samples obtained concomitantly in the classrooms. Attempts to identify the PCT emission source were unsuccessful. A survey of the literature revealed that PCTs are ubiquitously distributed environmental contaminants, although no data on their indoor occurrence have been reported to date. In view of the toxic effects of PCTs, which seem to be as important as those of PCBs, further attention should be given to the possible presence of PCTs in indoor environments.

Air Pollutants↗
PubMed1996

Risk factors for latex allergy in patients with spina bifida.

OBJECTIVE AND METHODS: In order to study risk factors for latex allergy in patients with spina bifida, we investigated 165 patients with spina bifida (mean age 9 years). Besides answering a questionnaire, patients underwent skin-prick testing and determination of specific serum IgE to latex as well as a screening test for specific IgE to environmental allergens. A total of 80 patients (49%) were sensitized to latex according to the presence of specific IgE to latex. RESULTS: Skin-prick tests (SPT) with high ammonia latex milk were performed in 81 of our patients with spina bifida and were positive in 36 patients (46%). Concordance of SPT with specific IgE in serum was good. Nineteen out of 165 patients suffered from a clinically relevant latex allergy: five patients had a history of systemic reactions to latex (e.g. severe bronchospasm, anaphylactic reactions), mostly during surgery. Fourteen patients reported clinical symptoms while inflating a balloon; all these 19 patients were sensitized to latex. Number of operations ranged from one to 26 (mean 5 operations). Concentration of specific IgE to latex in serum correlated well with increasing numbers of operations. Some 32/76 patients (41%) with spina bifida who were sensitized to latex showed an atopic disposition, while 21 out of 81 latex-negative patients (26%) were atopic. Of 300 consecutive sera (mean age of patients 9 years) sent to our laboratory for routine determination of specific IgE, 144 (48%) were positive in terms of specific IgE to environmental allergens, of which 247144 (17%) were sensitized to latex. CONCLUSIONS: From our data we conclude that in order to minimize risk of severe systemic clinical reactions, all patients with spina bifida should be screened for their individual risk of latex allergy to plan preventive measures before operations. Main risk factors for latex allergy seem to be: more than five operations, atopic predisposition, history of clinical symptoms while inflating a balloon, and a sensitization with a CAP-class of > or = 4.

Adolescent↗
PubMed1992

[Irreversible valproate-associated liver failure].

A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate. In combination with a febrile otitis media the child had been periodically restless and lethargic during the last week prior to liver coma. Activity of liver enzymes remained within normal limits up to two days before coma occurred. Analysis of valproate metabolites by gas chromatography/mass spectrometry yielded unusually high concentrations of the di-unsaturated metabolite E,E-2,3'-dien-valproate before and during liver failure. The concentrations of the main metabolites E-2-en-valproate und 3-keto-valproate remained within the usual range found during valproate therapy at steady state. The oxydation products 4-en-valproate and E-2,4-dien-valproate which are formed by alternative pathways and are considered to be hepatotoxic were detected in very low concentrations only. The application of carnitine, of antioxidants thought to improve the capacity of the free radical scavenger system (selen, vitamin E), and of N-acetylcysteine which can detoxify reactive drug metabolites could not prevent the fatal outcome.

Dandy-Walker Syndrome↗
PubMed1990

[High-grade tracheomalacia and tracheal stenosis in congenital esophageal atresia with lower esophagotracheal fistula (Type III b)].

Stenosis and malacia of the trachea wall can provoke chronic stridor and/or chronic bronchitis, but usually stenosis and malacia only exist separately. The finding of an infant born with atresia of the oesophagus and a lower tracheoesophageal fistula which was cured by surgery on the 1st day of life are discussed. During the following 8 months we observed persistent stridor, chronic cough and (4-times) relapsing episodes of respiratory insufficiency ("nearly-sudden-infant-death-syndrome"/NSIDS) due to gastrooesophageal reflux (GER with aspiration) and severe tracheomalacia combined with tracheostenosis and bacterial infections (Pseudomonas aeruginosa). The strategy of therapy for GER and for the tracheal abnormality are discussed.

Esophageal Atresia↗
PubMed1989

Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle.

The human gene encoding the alkali myosin light chains (MLC) 1 and 3 of fast skeletal muscle has been isolated. Two separate start sites for transcription have been identified by S1 analysis of muscle RNA. The nucleotide sequences of both proximal promoter regions have been determined and compared to the corresponding gene regions of other species. Several conserved promoter elements were located within 140 nucleotides upstream of the mRNA cap site, whereas further upstream no homologous sequences were found. Unidirectional 5' deletion mutants of both MLC promoters were used to direct bacterial chloramphenicol acetyltransferase activity in transient transfection assays of muscle and nonmuscle cells. Approximately 120 nucleotides of the MLC1 promoter and 80 nucleotides of the MLC3 promoter were sufficient for the transcriptional activation in primary myotubes and to a lower degree also in fibroblasts and hepatocytes. The preferential expression in muscle cells was not dependent on the conserved MLC consensus sequence, CCTTTTATAG, but it absolutely required the CCAT box or the CAT-like box in the MLC1 and MLC3 promoters, respectively. The weak activity of the MLC1 promoter was markedly enhanced in myotubes when DNA from the 3' gene flanking sequence was included in the chloramphenicol acetyltransferase constructs.

Amino Acid Sequence↗
PubMed1989

The alkali light chains of human smooth and nonmuscle myosins are encoded by a single gene. Tissue-specific expression by alternative splicing pathways.

Human smooth muscle and nonmuscle cells express closely related myosin alkali light chains which are different from the isoforms present in striated muscle tissues. To date no information on the amino acid sequence of these mammalian nonstriated muscle isoforms has been available. We have isolated full-length cDNA clones encoding the nonmuscle (lym4) and smooth muscle (GT6) myosin light chains (MLCs) from cultured human lymphoblasts and heart aorta smooth muscle cells, respectively. Here we present the complete nucleotide sequences for both cDNA clones, together with the deduced amino acid sequences for the peptides. Both cDNAs contain the same open reading frame for 151 amino acids with 5 amino acid differences located in the C terminus. These differences are encoded by a block of 44 nucleotides which is present only in the smooth muscle (SM) mRNA. To identify the human gene coding for the two MLC isoforms, we have isolated and sequenced the nonmuscle (NM)/SM MLC gene, together with several intronless pseudogenes. A single functional gene was found containing 7 exons which are utilized for the coding information of the SM MLC mRNA. In contrast, the NM MLC mRNA does not contain sequences encoded by exon 6 which corresponds to the 44 nucleotides expressed in SM mRNA. This genomic configuration suggests that both the smooth muscle and nonmuscle MLCs in man are generated from the identical primary transcript by alternative splicing pathways taking place in a tissue-dependent manner.

Amino Acid Sequence↗
PubMed1988

A novel human myosin alkali light chain is developmentally regulated. Expression in fetal cardiac and skeletal muscle and in adult atria.

We have isolated cDNA recombinant phages encoding the embryonic isoform of the myosin alkali light chain (MLC1emb) from a human fetal skeletal muscle library. The cDNA clones were detected by their weak cross-hybridization to a human MLC1F and MLC3F cDNA clone. Nucleotide sequence analysis of the complete cDNA (GT14) revealed an open reading frame for 197 amino acids. The derived protein sequence constitutes the first structural information on this myosin isoform of any organism. Remarkable structural similarities to other alkali MLC polypeptides, particularly to those of the slow-muscle type, are evident. Under conditions of high stringency, the GT14 clone hybridized to an abundant mRNA species in fetal ventricular muscle and adult atrial muscle, whereas in fetal skeletal muscle only a very weakly hybridizing mRNA component was detected. These mRNAs were indistinguishable by size and the thermal stability of their hybrids formed with the DNA insert of clone GT14. We therefore conclude that identical mRNA is expressed in these tissues, presumably transcribed from the same gene. According to its pattern of mRNA expression, the novel MLC isoform described here was designated as "embryonic and atrial myosin light chain" (MLC1emb/A) in reference to its developmental stage-specific and tissue-specific appearance in embryonic skeletal muscle, fetal ventricle and adult atrium.

Adult↗
PubMed1988

Alkali myosin light chains in man are encoded by a multigene family that includes the adult skeletal muscle, the embryonic or atrial, and nonsarcomeric isoforms.

A set of cDNA clones coding for alkali myosin light chains (AMLC) was isolated from fetal human skeletal muscle. Nucleotide sequence analysis and RNA expression patterns of individual clones revealed related sequences corresponding to (i) fast fiber type MLC1 and MLC3; (ii) the embryonic MLC that is also expressed in fetal ventricle and adult atrium (MLCemb); and (iii) a nonsarcomeric MLC isoform that is found in all nonmuscle cell types and smooth muscle. The AMLC gene family in man comprises unique copies for MLC1, MLC3 and MLCemb, and multiple copies for the nonsarcomeric MLC genes. The gene coding for MLC1 and MLC3 is located on human chromosome 2.

Amino Acid Sequence↗
PubMed1987

The prognostic value of EEG patterns in epilepsies with infantile spasms.

By scoring EEG patterns (hypsarrhythmia = 10, absence of sleeping patterns = 10, focal epileptic discharge = 5, general-treatment or in whom infantile spasms never disappeared even during ACTH. A low voltage EEG did not have any ending ACTH therapy free of seizures showed lower scores compared to those infants relapsing after the end of ACTH treatment or in whom infantile spasms never disappeared even during ACTH. A low voltage EED did not have any prognostic significance. Using EEG scores it might be possible to separate non-responders and responders after 3 weeks of ACTH therapy, thus shortening ACTH treatment in non-responding infants.

Adrenocorticotropic Hormone↗
PubMed1986

The repeated sequences (incB) preceding the protein E gene of plasmid mini-F are essential for replication.

At the XhoI site (45.08F) of plasmid mini-F a deletion of 649 bp was generated employing exonuclease Bal31. By this deletion nucleotide sequences functioning as origin II and the four 19 bp direct repeats constituting the incB region in front of the E protein gene were removed from the plasmid. Analysis of proteins radioactively labelled in Escherichia coli mini-cells indicated that all mini-F encoded proteins are expressed. However, the plasmid carrying the deletion was not capable of replicating from the primary origin (origin I, 42.6F). Recently a smaller deletion at the XhoI site (45.08F) of about 300 bp, removing only the region functioning as origin II and replicating from origin I, was described by Tanimoto and Iino (1984, 1985). The data presented suggest that the incB repeats are essential for the initiation of replication from origin I, and possibly also from origin II, and seem not to be engaged in the autoregulation of E protein expression.

Bacterial Proteins↗
PubMedDate not supplied

Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity.

Of a cohort of 470 epileptic patients in whom valproate (VPA) serum metabolites had been measured, 170 subjects without symptoms or signs of hepatic side effects were chosen as a reference group to establish the usual metabolic pattern. A wide interindividual variation of VPA metabolite concentrations was noted. Infants receiving VPA monotherapy and comedication with other antiepileptic drugs (AEDs) showed lower concentrations of the potential hepatotoxin 4-ene-VPA than did older children. In 11 patients with early symptoms and signs of possible fatal VPA-associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients). Reversible or irreversible fulminant liver failure had occurred in 5 children. Three of the 4 children with a fatal outcome had massive lactic acidosis. In all patients with probable VPA-associated hepatotoxicity, some aspects of VPA metabolism differed distinctly from that of the reference group, but the inter-individual profile of metabolites varied considerably, even in the subgroup of 4 children who died. Impairment of VPA beta-oxidation and increase of metabolites of alternative metabolic pathways (omega- and omega 1-hydroxylation, dehydrogenation reactions) were the most frequent findings. Increased values of 2-n-propyl-4-pentenoic acid metabolite of VPA (4-ene-VPA), could be detected only in 1 of the 5 patients with fulminant liver failure and in one other child with a slight hepatic dysfunction, indicating that this VPA metabolite is not the decisive hepatotoxin or indicator of hepatotoxicity. Because we cannot distinguish between benign and life-threatening hepatic adverse reactions on the basis of VPA metabolites, all identified changes are considered secondary to an as-yet-unknown primary metabolic event. The most toxic compound could be VPA itself, which may unmask an inborn or an acquired metabolic defect in the processing of fatty acids.

Chemical and Drug Induced Liver Injury↗