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Biomedical subjects

D Schnabel

Publications and source records attributed to D Schnabel.

29 records · Page 2Linked to original sources
PubMed1992

Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.

Sphingolipid activator proteins (SAPs) are small, nonenzymic glycoproteins that stimulate lysosomal degradation of various sphingolipids. SAP-1, SAP-2, and two additional potential activator proteins are derived from a common precursor by proteolytic processing. A severe case of sphingolipid storage disease that led to death within 16 weeks was attributed to a possible total deficiency of the SAPs generated by this gene (Harzer, K., Paton, B. C., Poulos, A., Kustermann-Kuhn, B., Roggendorf, W., Grisar, T., and Popp, M. (1989) Eur. J. Pediatr. 149, 31-39). Analysis of the SAP precursor cDNA from the patient and his fetal sibling showed an A to T transversion in the initiation codon. Allele-specific oligonucleotide hybridization revealed that both parents are heterozygous carriers for this mutation. In pulse-chase experiments using antisera raised against SAP-1 or SAP-2, no cross-reacting material could be detected in the patients' fibroblasts.

Alleles↗
PubMed1992

[Thoracoscopic treatment of spontaneous pneumothorax using fibrin pleurodesis].

In 33 patients with a recurrent spontaneous pneumothorax, a thoracoscopic pleurodesis with fibrin glue was performed under local anesthesia. During an average postoperative observation period of 4 years the relapse frequency was 39% (13 cases). In these cases thoracotomy was performed and a new relapse of pneumothorax occurred in 3 patients (23%): Application of thoracoscopy with fibrin glue pleurodesis should only be applied in those patients without large emphysema vesicles and without large coalescences. Under these conditions the relapse frequency could be reduced to 26%. The thoracoscopic treatment of recurrent pneumothorax by using fibrin glue and local anesthesia in well selected patients is an alternative procedure to thoracotomy.

Adolescent↗
PubMed1991

A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB.

GM2-gangliosidoses are neurological disorders caused by a genetic deficiency of either the beta-hexosaminidase A or the GM2 activator, a glycolipid binding protein. In a patient with an immunologically proven GM2 activator protein deficiency, A T412----C transition (counted from A of the initiation codon) was found in the coding sequence, which results in the substitution of Arg for the normal Cys107 in the mature GM2 activator protein. The remainder of the coding sequence remained entirely normal.

Base Sequence↗
PubMed1991

Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein.

Full-length cDNAs coding for the human GM2-activator protein has been isolated and characterized, and its genomic structure studied in two overlapping clones in lambda-EMBL-4 isolated from a human brain genomic library. Two different cDNAs were found that were identical to the 5'-terminus to nt 1311 (counted from the A of the initiation codon, ATG) including the entire protein coding sequence. However, they were entirely dissimilar in the 3'-non-coding sequences. The genomic clones covered 94% of the full-length cDNA sequence. Three introns were found. The last exon spans contiguously the carboxyl terminus of the protein and the entire 3'-untranslated region of one of the two cDNAs with different 3'-ends. The origin of the 3'-portion of the other cDNA clone is not clear at this time.

Base Sequence↗
PubMed1991

Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease.

The lysosomal degradation of glucosylceramide requires the hydrolase, glucosylceramide-beta-glucosidase and a sphingolipid activator protein (Gaucher factor, SAP-2, saposin C). Genetic defects in either of these lysosomal proteins cause phenotypically similar disorders in man, the Gaucher disease. SAP-2 originates from a gene which generates a mRNA that codes for four homologous proteins. In a patient with an immunologically proven SAP-2 deficiency a G1154----T transversion (counted from A of the initiation codon ATG) was found in the mRNA of the SAP-2 precursor which results in the substitution of Phe for Cys385 in the mature SAP-2. The rest of the coding sequence remained entirely normal.

Base Sequence↗
PubMed1991

The organization of the gene for the human cerebroside sulfate activator protein.

The organization of 14 exons covering 97% of the cDNA sequence of human cerebroside sulfate activator protein precursor has been determined from two overlapping EMBL-4 human genomic clones extending over 17 kb. All exons and exon/intron splice junctions and five introns were sequenced. Exon 8 consists of only 9 bp and is involved in alternative splicing which generates three different mRNAs of cerebroside sulfate activator precursor.

Amino Acid Sequence↗
PubMed1991

Individualization of theophylline dosage: a Bayesian method evaluated in patients with once-daily dosing.

A Bayesian drug dosing program was prospectively evaluated in 16 hospitalized patients with obstructive respiratory disease treated with a novel sustained-release preparation Euphylong. Theophylline was given as a single evening dose. By means of the Bayesian method, the early morning peak was predicted from a steady-state theophylline serum level determined at 8:00 a.m. The prediction errors were in all cases within a clinically acceptable range (mean prediction error +/- standard deviation: -0.2 +/- 1.3 mg/L). The results were compared with predictions based on steady state theophylline serum levels at 8:00 p.m. The prediction errors observed were on average greater than the prediction errors based on the serum levels at 8:00 a.m. (-0.6 +/- 2.5 mg/L). These findings suggest that the Bayesian method is useful for dosage predictions in patients treated once a day with Euphylong.

Adult↗
PubMed1990

[Dose titration with Euphylong following prior determination of serum concentration in the steady state].

Euphylong is a theophylline preparation with new galenic slow-release design (micropellets in a capsule), developed for daily single-dose administration in the evening. It has been shown that the majority of patients with bronchial asthma, chronic obstructive bronchitis or emphysema who receive a single evening dose of Euphylong have a theophylline serum concentration that remains within the therapeutic range for 24 hours when the theophylline serum concentration measured at 8 a.m. under steady-state conditions is found to lie within the therapeutic range.

Adult↗
PubMed1989

Effect of recombinant human growth hormone on urinary 15N-nitrogen balance in girls with Turner syndrome as compared to children with growth hormone deficiency.

15N-nitrogen balances before and on human growth hormone (hGH) were studied in 13 girls with Turner syndrome (TS) aged 4.4-16 (median 13.2) years (45,X0 or equivalent, no X0/XX mosaicism, no estrogen replacement). The results were compared with those reported from 9 patients with growth hormone deficiency (GHD). The TS patients received subcutaneous hGH doses of 2 x 3 (group A, n = 6), 3 x 2 (group B, n = 3), or 2 x 6 (group C, n = 4) IU/m2 on consecutive days. The mean 15N dose given to the patients of groups A and C was higher (13.6 mg/kg) than that given to those of group B (2.7 mg/kg). The lower hGH doses in the first two groups induced small positive mean 15N balance changes (+0.6 +/- 0.6 mg/kg 15N, group A; +0.03 mg/kg, group B). The higher hGH dose in group C caused a more marked mean balance change (+3.0 mg/kg 15N) comparable to that in GHD patients (+3.2 mg/kg). Individual variation of response, however, was larger in patients with TS than in those with GHD. With low and high hGH doses, there were responders and nonresponders. It is concluded from this pilot study in a small number of cases that 15N balance studies might be potentially useful to choose the appropriate hGH dose for long-term treatment in TS patients.

Adolescent↗
PubMed1989

[Treatment of nocturnal bronchial asthma].

To date, the pathogenesis of nocturnal bronchiale asthma has not been completely clarified. For the treatment of nocturnal asthma that fails to respond to beta-2-sympathomimetics or inhalative glucocorticosteroids, theophylline in a delayed release form or delayed-release oral beta-2-sympathomimetics are available. In a double-blind crossover study, 10 patients with nocturnal or early-morning bronchial asthma were treated for one week with theophylline 390-900 mg daily (1/3 of the total dose being given in the morning, 2/3 in the evening) and one week with terbutaline 15 mg daily (7.5 mg in the morning and 7.5 mg in the evening). No significant differences were observed with respect to the measured peak flow values in the night and early morning. However, those receiving terbutaline more frequently required the additional application of inhalative beta-2-sympathomimetics for respiratory distress. Thus, the sustained-release form of theophylline is the more suitable drug for the treatment of nocturnal bronchial asthma. As a further study revealed, the sole administration of a sustained-release form of theophylline in the evening suffices. In the future, apart from theophylline in a delayed-release form, inhalative beta-2-sympathomimetics with a long-term effect will play an important role in the treatment of nocturnal breathing disorders.

Adolescent↗