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Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

At least 307 records · Page 17Linked to original sources
PubMed1991

Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3.

As part of the search for the Huntington disease (HD) gene we have cloned and sequenced 34 kb of genomic DNA containing the full-length gene for the beta-subunit of the human cGMP phosphodiesterase (beta-cGMP PDE). This gene is localized to 4p16.3 about 700 kb proximal to the 4p telomere and represents the most telomeric gene characterized on 4p to date. We show that this gene is comprised of 22 exons spanning approximately 43 kb of genomic DNA. We also provide 400 bp immediately 5' to the putative initiator methionine and 700 bp of 3' flanking sequences. Northern blot analysis of several human tissues revealed a highly abundant 3.5 kb transcript and a minor signal of 4.5 kb in retinal tissue. Alignment of the deduced amino acid sequence to the previously identified beta-subunits of the cGMP PDEs of mouse and cow demonstrates highly significant similarities and, therefore, confirms the identity of the cloned gene. A defect in the beta-subunit of the cGMP PDE gene has been shown recently to be the cause for the retinal degeneration in the rd mouse. The cloning of the human homolog and the knowledge of its genomic organization with exon/intron boundaries will allow rapid assessment of the role of this gene in the causation of human retinopathies.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

[The status of immunity against poliomyelitis. The 5th cooperative study of the German Union to Control Viral Diseases, Inc].

Neutralizing antibodies against poliovirus types 1, 2 and 3 were determined in the serum samples, supplied by 11 virological institutes, from 3,341 subjects of different ages living in the western part of the Federal Republic of Germany. The 3 poliovirus types were found in all age groups, with a seroprevalence of at least 80%. Although antibodies against the 3 types of poliovirus in the age-groups up to 30 years were demonstrated more frequently than in the previous years in which samples had been examined (1969, 1972, 1978 and 1983), 33% of subjects over 40 years (this age-group had not previously been tested) did not have complete immunity against all 3 poliovirus types. For this reason immunization against poliomyelitis should continue to be recommended when indicated, especially before travels to regions where the disease is endemic.

Age Factors↗
PubMed1991

Sensitive determination of free and plasma protein-bound dipyridamole by high-performance liquid chromatography.

For many years dipyridamole (DP) has been used in the treatment of hypertension as a vasodilator, but recently it has been recognised as an anti-platelet aggregation agent and to potentiate anti-metabolite activity. A rapid and sensitive (20 nM) procedure for the determination of free and protein-bound DP in plasma, using reversed-phase high-performance liquid chromatography on an Ultrasphere XL ODS (3 microns) column (70 mm x 4.6 mm I.D.) with ultraviolet detection (280 nm), is reported. Free and bound DP were separated using ultrafiltration. Concentrations of DP between 0.1 and 10 microM were measured in plasma with a relative standard deviation of less than 9.6%. The subsequent determination of DP levels in patients orally administered 450 mg per day showed that DP binding to plasma protein is higher than 90%.

Administration, Oral↗
PubMed1991

Intrachromosomal location of the telomeric repeat (TTAGGG)n.

Eukaryotic telomeres are specialized DNA-protein structures that are thought to ensure chromosomal stability and complete replication of the chromosome ends. All telomeres which have been studied consist of a tandem array of G-rich repeats which seem to be sufficient for telomere function. Originally, the human telomeric repeat (TTAGGG)n was assumed to be exclusively located at the very end of all human chromosomes. More recent evidence, however, suggests an extension into proterminal regions. Very little is known about the interstitial distribution of telomeric repeats. Here we present evidence for the presence of (TTAGGG)n repeats in internal loci on the long and short arms of different human chromosomes. In addition, we studied the genomic organization of these repeats in more detail and discuss possible functions of interstitial telomeric repeats in the human genome.

Base Sequence↗
PubMed1991

Identification of multiple CpG islands and associated conserved sequences in a candidate region for the Huntington disease gene.

The HD locus has been assigned to 4p16.3 distal to the DNA segment D4S10. However, the precise location of this gene is still unknown. At least three regions, together encompassing more than 3.5 Mb of DNA, can still be considered as candidate regions for the HD gene. Our efforts are directed toward the cloning and the complete characterization of one of these regions. Thus far we have cloned 460 kb of DNA in contiguously overlapping cosmids distal to D4S111 and have developed a detailed long-range restriction map orienting the contig within the terminal region of 4p16.3. We characterized 15 CpG-rich islands defined by tightly clustered rare cutter restriction sites for the enzymes NotI, BssHII, EagI, NruI, and SacII. In addition, we show that the sequences associated with the CpG-rich islands detect cross-species conservation. The detailed genetic analysis of the 460-kb contig provides a framework for the identification of genes, which can be assessed for the characteristics expected for the HD gene.

Animals↗
PubMed1991

In vitro combination of high dose busulfan with radiotherapy on medulloblastoma cells: additive effect without potentiation.

The aim of this in-vitro study was to evaluate the combination of busulfan with radiotherapy on TE-671 human medulloblastoma cells since unexpected clinical toxicity of busulfan was reported during the treatment of brain tumors, suggesting a possible radiopotentiation. The cytotoxicity of busulfan was determined by using colony forming assays, and doses inducing growth inhibitions of 10, 20 and 50% were selected to be tested in association: 6, 12 and 32 mumol/l for busulfan and 0.5, 1 and 3 Gy for irradiation. All possible combinations were considered within this frame and the results showed that the combination of busulfan with radiotherapy exerted an additive effect without potentiation.

Busulfan↗
PubMed1991

A low-copy repeat located in subtelomeric regions of 14 different human chromosomal termini.

Two cosmid clones, cG1A3 and cG1A6, containing large blocks of a telomeric repeat sequence, (TTAGGG)n, were isolated independently. Restriction mapping and fingerprinting studies suggested that cosmid cG1A6 is entirely contained within cG1A3. Competitive in situ hybridization localized cG1A3 to 14 different human telomeres and one internal site at 2q14----q21, indicating the presence of a subtelomeric low-copy repeat within this cosmid.

Base Sequence↗
PubMed1991

Linkage disequilibrium and modification of risk for Huntington disease.

The major limitation in performing predictive testing for Huntington disease (HD) is the unavailability of DNA from crucial family members. In our program approximately 20% (36/183) of persons have been excluded from predictive testing because of this reason. The major aim of this study was to examine whether data derived from linkage disequilibrium could modify risk analysis for persons at risk for HD. As a first step, we assessed whether the previously reported linkage disequilibrium between alleles recognized by probe pBS674E-D at locus D4S95 remained significant in a much larger data set. A total of 1,150 chromosomes from 622 individuals--200 affected and 422 unaffected--from 118 families were assessed. Significant haplotype association was detected with AccI and MboI RFLPs at the locus D4S95, with all the families (P = .00003), as well as for a subset from the United Kingdom (P = .0037). Data derived from linkage disequilibrium studies using D4S95 modifies the risk for HD, especially in persons of U.K. descent. Utilization of this approach for risk modification of HD awaits both validation of these data and additional information concerning ethnic-specific alleles at the D4S95 locus.

Adult↗
PubMed1991

N-nitrosoalkanolamines in cosmetics.

A method has been developed for the determination of the N-nitrosoalkanolamines, N-nitrosodiethanolamine (NDELA) and N-nitrosobis(2-hydroxypropyl)amine (NDHPA) in cosmetics. In model systems, we studied nitrosation of the most relevant precursors by NaNO2, by the preservatives Bronopol and Bronidox and by nitric oxides. Secondary amines were most rapidly nitrosated, and Bronopol, Bronidox and atmospheric nitric oxides appeared to be the most relevant nitrosating agents. In order to remove the most important sources of contamination, the Federal Health Office issued an official recommendation to producers to avoid use of secondary amines in cosmetics (March, 1987). Analysis of cosmetics taken from the German market 6-18 months later showed that only 19/126 samples were contaminated with NDELA (12-235 micrograms/kg or NDHPA (40-215 micrograms/kg). The results reflect a strong downward trend in contamination.

Carcinogens↗
PubMed1991

[Therapy of diabetes mellitus in childhood and adolescence. Goals, evaluation criteria and results].

We report on the results of longterm treatment of 466 children and adolescents with Type I diabetes (IDDM) between 1980 to 1989. Of these, in, 1989, 240 patients, aged 1 to 20 years, were under continuous treatment, 168 (70%) with CT and 72 (30%) with ICT. For 112 of 466 patients (24%) the medians of all measured HBA1c values were calculated to be less than or equal to 7.7%, for 53% between 7.8 and 9.6%, and for 24% greater than or equal to 9.7%. The respective percentages for the ICT patients were found to be 32, 48, and 20%. Medical treatment was accompanied by the continuous offer of education and psychosocial support. In order to reduce the risks for secondary vascular complications, good glycemic control is important in particular during postpubertal years. Therefore children and adolescents need support to obtain both, the acceptance of their disease and the individual responsibility necessary to endure any intensified treatment regimen. Furthermore, the effects of any therapeutic approach should not be measured by glycated haemoglobin only, but in particular by the young subject's individual development and his gain in courage to go on.

Adolescent↗
PubMed1990

On the validity of Shannon-information calculations for molecular biological sequences.

The usefulness of information-theoretic measures of the Shannon-Weaver type, when applied to molecular biological systems such as DNA or protein sequences, has been critically evaluated. It is shown that entropy can be re-expressed in dimensionless terms, thereby making it commensurate with information. Further, we have identified processes in which entropy S and information H change in opposite directions. These processes of opposing signs for delta S and delta H demonstrate that while the Second Law of Thermodynamics mandates that entropy always increases, it places no such restrictions on changes in information. Additionally, we have developed equations permitting information calculations, incorporating conditional occurrence probabilities, on DNA and protein sequences. When the results of such calculations are compared for sequences of various general types, there are no informational content patterns. We conclude that information-theoretic calculations of the present level of sophistication do not provide any useful insights into molecular biological sequences.

Animals↗
PubMed1990

[Petechiae, microhematuria, colic-like abdominal pain].

A 46-year-old patient was referred because of recurring bouts of abdominal colics, petechiae and an accompanying nephropathy. The clinical setting pointed towards a cryoglobulinemia, proved by serum cryoprecipitation and electrophoresis and classified as type II. The primary disease was a low-grade non-Hodgkin lymphoma involving bone-marrow and liver. A renal biopsy showed a proliferative glomerulonephritis. Treatment with prednisone and chlorambucil led to improvement of renal function, and the patient became asymptomatic.

Colic↗
PubMed1990

Characterization and organization of DNA sequences adjacent to the human telomere associated repeat (TTAGGG)n.

We present a strategy for the cloning of DNA sequences adjacent to the tandemly repeated DNA sequence (TTAGGG)n. Sequence analysis of 14 independently isolated clones revealed the presence of non-repetitive sequences immediately adjacent to or flanked by blocks of the simple repeat (TTAGGG)n. In addition, we provide sequence information on two previously undescribed tandemly repeated sequences, including a 9 bp repeat and a modification of the (TTAGGG)n repeat. Using different mapping approaches six sub-clones, free of the TTAGGG repeat, were assigned to a single human chromosome. Moreover, in situ hybridization mapped one of these subclones, G2 - 1H, definitively to the telomeric band on chromosome 4q. However, Bal 31 insensitivity suggests a location in a more subterminal region. All the (TTAGGG)n-adjacent unique sequences tested are highly conserved among primates but are not present in other mammalian species. Identification and mapping of TTAGGG-adjacent sequences will provide a refined insight into the genomic organization of the (TTAGGG)n repeat. The isolation of chromosome specific TTAGGG-adjacent sequences from subtelomeric regions of all human chromosomes will serve as important end points for the genetic maps and will be useful for the molecular characterization of chromosomal rearrangements involving telomeres.

Base Sequence↗
PubMed1990

Targeting of a lysosomal membrane protein: a tyrosine-containing endocytosis signal in the cytoplasmic tail of lysosomal acid phosphatase is necessary and sufficient for targeting to lysosomes.

Lysosomal acid phosphatase (LAP) is synthesized as a transmembrane protein with a short carboxy-terminal cytoplasmic tail of 19 amino acids, and processed to a soluble protein after transport to lysosomes. Deletion of the membrane spanning domain and the cytoplasmic tail converts LAP to a secretory protein, while deletion of the cytoplasmic tail as well as substitution of tyrosine 413 within the cytoplasmic tail against phenylalanine causes accumulation at the cell surface. A chimeric polypeptide, in which the cytoplasmic tail of LAP was fused to the ectoplasmic and transmembrane domain of hemagglutinin is rapidly internalized and tyrosine 413 of the LAP tail is essential for internalization of the fusion protein. A chimeric polypeptide, in which the membrane spanning domain and cytoplasmic tail of LAP are fused to the ectoplasmic domain of the Mr 46 kd mannose 6-phosphate receptor, is rapidly transported to lysosomes, whereas wild type receptor is not transported to lysosomes. We conclude that a tyrosine containing endocytosis signal in the cytoplasmic tail of LAP is necessary and sufficient for targeting to lysosomes.

Acid Phosphatase↗