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A Rump

Publications and source records attributed to A Rump.

At least 19 recordsLinked to original sources
PubMed2001

Complex arrangement of genes within a 220-kb region of double-duplicated DNA on human 2q37.1.

Gene duplication events are followed by divergence of initially identical gene copies, due to the subsequent accumulation of mutations. These mutations tend to be degenerative and may lead to either nonfunctionalization or subfunctionalization of the gene copies. Here we report the molecular characterization of a 220-kb genomic DNA fragment from human 2q37.1, in which a double duplication and a partial triplication event has taken place. As a result, this region contains four copies of alkaline phosphatase (P), four copies of the ECEL1 gene (X), two copies of a newly identified gene (N), and two copies of a cholinergic receptor subunit (R), in the order N-P-X-P-X-P-X-N-P-X-R-R. While three of the four ECEL1 copies, one copy of the phosphatase gene and one copy of the newly identified gene have lost their function, three phosphatase gene copies and the two receptor subunits are still functionally active and thus may provide an example for subfunctionalization of duplicated genes.

Alkaline Phosphatase↗
PubMed2000

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Base Sequence↗
PubMed2000

Comparative genome sequence analysis of the Bpa/Str region in mouse and Man.

The progress of human and mouse genome sequencing programs presages the possibility of systematic cross-species comparison of the two genomes as a powerful tool for gene and regulatory element identification. As the opportunities to perform comparative sequence analysis emerge, it is important to develop parameters for such analyses and to examine the outcomes of cross-species comparison. Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region. We identified 11 genes in mouse and 13 genes and two pseudogenes in human. In addition, we compared the mouse and human sequences using pairwise alignment and searches for evolutionary conserved regions (ECRs) exceeding a defined threshold of sequence identity. This approach aided the identification of at least four further putative conserved genes in the region. Comparative sequencing revealed that this region is a mosaic in evolutionary terms, with considerably more rearrangement between the two species than realized previously from comparative mapping studies. Surprisingly, this region showed an extremely high LINE and low SINE content, low G+C content, and yet a relatively high gene density, in contrast to the low gene density usually associated with such regions.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Elevated DNA sequence diversity in the genomic region of the phosphatase PPP2R3L gene in the human pseudoautosomal region.

The evolution, inheritance and recombination rate of genes located in the pseudoautosomal region 1 (PAR1) is exceptional within the human genome. Pseudoautosomal genes are identical on X and Y chromosomes and are not inherited in a sex linked manner. Due to an obligatory recombination event in male meiosis, pseudoautosomal genes are exchanged frequently between X and Y chromosomes. During the isolation, characterization and sequencing of a novel gene PPP2R3L, which was classified by sequence homology as a novel member of the protein phosphatase regulatory subunit families, it became apparent that cosmids of different origin harboring this gene are highly polymorphic between individuals, both at the nucleotide level and in the number.

Amino Acid Sequence↗
PubMed1998

Efficacy of silver-coated medical devices.

Silver coating of medical devices is believed to prevent device-associated infection. Several in-vitro and in-vivo studies, as well as clinical observations on silver-nylon, silver-intramedullary pins, silver oxide Foley catheters and silver-coated vascular prostheses have been performed during the past 30 years. Nevertheless, randomized clinical studies showing efficacy of such coated medical devices in high-risk patient populations are rare, have dealt with very small numbers of patients or are controversial. Physico-chemical, pharmacological and microbiological data explaining the antimicrobial efficacy of silver in prophylaxis of implants are presented here, as well as the scientific background for the established clinical benefits of silver-preparations in burns.

Blood Vessel Prosthesis↗
PubMed1997

Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome.

Growth retardation resulting in short stature is a major concern for parents and due to its great variety of causes, a complex diagnostic challenge for clinicians. A major locus involved in linear growth has been implicated within the pseudoautosomal region (PAR1) of the human sex chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and different rearrangements on Xp22 or Yp11.3. This deletion was not detected in any of the relatives with normal stature or in a further 30 individuals with rearrangements on Xp22 or Yp11.3 with normal height. We have isolated a homeobox-containing gene (SHOX) from this region, which has at least two alternatively spliced forms, encoding proteins with different patterns of expression. We also identified one functionally significant SHOX mutation by screening 91 individuals with idiopathic short stature. Our data suggest an involvement of SHOX in idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients.

Adolescent↗
PubMed1997

Caffeine in saliva after peroral intake: early sample collection as a possible source of error.

The influence of collection time on the correlation of caffeine concentrations in saliva and serum was examined in six healthy adults after peroral administration of 5 mg/kg caffeine citrate. Saliva was obtained from three different salivary glands (sublingual, right parotid, and left parotid) and evaluated separately. Caffeine concentrations in saliva and serum samples were determined by high-performance liquid chromatography. There were no differences in the caffeine concentrations in saliva from the three investigated glands (alpha = 0.05). Saliva samples collected earlier than 2 hours after caffeine intake showed higher caffeine concentrations than could be expected from the corresponding serum samples. Gingiva contamination was shown to be responsible for the higher caffeine concentrations in saliva, and it was concluded that saliva is a feasible matrix for therapeutic drug monitoring of caffeine. If caffeine is administered orally, saliva samples should be taken at least 2 hours after caffeine intake. If caffeine-containing beverages are used as the source of caffeine or if subjects do not cooperate by rinsing the mouth of caffeine contamination, an additional 60 minutes should be added before saliva sampling.

Administration, Oral↗
PubMed1997

New antiinfectious biomaterials. Ciprofloxacin containing polyurethanes as potential drug delivery systems to prevent foreign-body infections.

Device related infections are an increasing problem since foreign materials are used in modern medicine. Ciprofloxacin-HCl salt (CAS 86393-32-0) and lipophilic ciprofloxacin-betaine (Bay o 9867) incorporated into polyurethanes by solvent casting technique were studied in order to develop antiinfectious properties of this biomaterial. Drug release rates, bacterial colonization and morphological features of the polymerciprofloxacin combinations were studied and the physico-chemical mechanisms of the delivery were discussed. Ciprofloxacin salt showed a fast initial release rate, whereas ciprofloxacin-betaine was characterized by a more continuous release behaviour. A higher diffusity of the lipophilic ciprofloxacin-betaine in the polymer could be shown as compared to its salt incorporated into the polyurethane. The high initial burst effect of the hydrochloride antibiotic was caused by its high solubility in the elution medium. Bacterial colonization to the antibiotic-loaded polyurethanes was inhibited effectively only by preparations showing a slower but more sustained drug release. Scanning electron microscopy (SEM) demonstrated that the polyurethane-antibiotic combination was most homogenous for ciprofloxacin-betaine. Polyurethane material loaded with ciprofloxacin salt showed crystals at the surface and a granular structure of the polymeric matrix. Crystalline structure of the drug on polymeric surfaces varied with loading concentration and lipophilicity. Physico-chemical similarity of the polymeric material and the antibodies is important for the homogeneity of the polymer-antibiotic combinations. High homogeneity is required for a sustained and prolonged release and effective inhibition of bacterial colonization.

Anti-Infective Agents↗
PubMed1996

Drug delivery concepts for the efficacious prevention of foreign-body infections.

Several classes of antibiotics released from polyurethanes and silicones were examined for their activity against foreign body colonization by coagulase-negative staphylococci. Beta-lactams, gyrase inhibitors, aminoglycosides, macrolides and rifampicin were used as antimicrobials to impregnate or load the polymers. Coating of polymeric surfaces by precipitation or adsorption techniques lead to a lower and shorter drug release as compared to polymeric devices with incorporated antibiotics. Prolonged drug delivery of matrix-loaded polymers exceeding the microenvironmental minimal bactericidal concentrations (mMBC), ensured the prevention of bacterial colonization. In this study, we have been able to demonstrate the usefulness of a reproducible long-time antimicrobial dosage regime from the internal phase of the implant as compared to surface coated polymers. In addition, pharmacodynamic aspects and the potential of bonded antibiotics for inducing adverse effects such as resistance development and allergic reactions are discussed.

Ciprofloxacin↗
PubMed1996

Editing of GluR2 RNA in the gerbil hippocampus after global cerebral ischemia.

Postischemic delayed neuronal death (DND) in CA1 of the gerbil hippocampus is thought to be caused by an abnormal increase of Ca2+ influx into the cell, mediated by excessive activation of glutamate receptors. One subtype of glutamate receptors, the AMPA receptor, is not permeable to calcium ions as long as an edited form of its GluR2 subunit is present. It is possible that global ischemia interferes with the posttranscriptional editing of the GluR2 mRNA and thus leads to calcium influx via the AMPA receptor. In order to test this hypothesis, we examined the extent of GluR2 RNA editing in CA1 and CA3 microdissected from gerbil hippocampus after 5 min of global ischemia and various recirculation intervals. At each interval tested, quality and quantity of mRNA editing in the vulnerable CA1 region were the same as in CA3. Furthermore, postischemic mRNA editing in both hippocampal regions was indistinguishable from editing in untreated control animals. Our results clearly demonstrate that global ischemia does not cause impairment of GluR2 RNA editing, which is thus not responsible for the abnormal calcium permeability of the postischemic cell membrane.

Animals↗
PubMed1991

Tandem arrangement of tRNA(Asp)-encoding genes in Phytophthora spp.

We have cloned a region of repetitive DNA from the phytopathogenic fungus, Phytophthora parasitica. The cloned region consists of 17 highly homologous units arranged in tandem. The consensus sequence is 562 bp long and carries the information for a tRNA(Asp). All sequence motifs required for efficient RNA polymerase III transcription are present, and the tRNA derived from the nucleotide sequence is able to form a complete cloverleaf structure with high homology to previously characterized tRNA(Asp) molecules. The isolated tRNA(Asp) gene cluster is located at a distance of 20 kb from the TRP1 gene of P. parasitica. It comprises about 0.1% of the total genomic DNA. Similar clusters were detected in four other Phytophthora species.

Base Sequence↗
PubMed1988

Nucleotide sequence of a 24,206-base-pair DNA fragment carrying the entire nitrogen fixation gene cluster of Klebsiella pneumoniae.

The complete nucleotide sequence (24,206 base-pairs) of the Klebsiella pneumoniae gene region for nitrogen fixation (nif) is presented. Coding regions corresponding to the 19 known nif genes (including nifW and nifZ) could be identified. An additional open reading frame of 216 base-pairs, called nifT, was detected between nifK and nifY. Search for transcriptional signal structures revealed some unusual features: (1) several possible NifA-binding motifs are present in the intergenic regions between nifJ and nifH as well as between nifX and nifU; (2) a perfect NifA-binding motif, preceding the nifENX promoter, is located within an inverted repeat structure; (3) structures resembling the consensus nif promoter are found within the coding regions of nifW and nifZ and, together with a NifA-binding motif, in nifN. Typical rho-independent termination structures were detected only downstream from the nifHDKTY and the nifBQ operons. Analysis of the deduced amino acid sequences revealed the presence of two Cys-X2-Cys-X2-Cys-X3-Cys-Pro clusters in the pyruvate-flavodoxin oxidoreductase NifJ. This arrangement of cysteine residues is normally present only in ferredoxins. A high degree of homology between the two gene products (NifE and NifN) involved in iron-molybdenum cofactor biosynthesis and the two nitrogenase component I structural proteins (NifD and NifK) was found. All four proteins are characterized by the conserved motif His-Gly-X2-Gly-Cys, which may play a role in binding the iron-molybdenum cofactor.

Amino Acid Sequence↗
PubMed1987

[173 cases of insulin-induced hypoglycemia admitted to the hospital].

From 1980 to 1985, 120 insulin-dependent diabetics were admitted to the emergency department of the Cantonal Hospital, Basle, for altogether 173 severe hypoglycemic attacks. Relating these numbers to a total of 700 insulin-dependent diabetics in Basle, this means an hypoglycemia incidence of 4.2 per 100 treatment years. The principal causes were: dietary error or increased physical activity (43.7%); increase in daily insulin dose by the patient or his doctor (14.6%); and other illnesses, mostly involving the gastrointestinal tract (10.9%). Age and duration of insulin treatment were risk factors for the occurrence of hypoglycemic episodes. Thus, comparing patients at the Cantonal Hospital with or without hypoglycemia, there were significantly more hypoglycemic attacks (p less than 0.05) in the group of patients aged over 60 years or who had been treated with insulin for more than ten years. Average daily dose of insulin was about the same in both groups (35.8 U daily with hypoglycemia; 39.6 U without). Regardless of the daily number of injections, hypoglycemia occurred most frequently between 10 and 13 h and before the evening meal between 17 and 19 h.

Adult↗
PubMed1986

[The relatively frequent incidence of severe sulfonylurea-induced hypoglycemia in the last 25 years in Switzerland. Results of 2 surveys in Switzerland in 1969 and 1984].

In 1969 and 1984 all emergency wards in Switzerland were asked to report on the incidence of severe episodes of hypoglycemia (HE) during treatment with sulfonylureas. Each of the two surveys referred to a ten-year period (period A 1960-1969, period B 1975-1984). The number of HE reported was 78 for period A and 116 for period B. The number of diabetics treated with sulfonylurea preparations was established on the basis of tablet consumption, which amounted to 35,000 in period A and 47,500 in period B. The incidence of hypoglycemia in each period was comparable (period A 0.22, and period B 0.24 per 1000 patient years), but differed with regard to the sulfonylurea preparations used. In period A hypoglycemic episodes occurred more frequently under chlorpropamide than under tolbutamide and carbutamide. In period B the incidence of episodes under chlorpropamide and glibenclamide was comparable, but was significantly higher than under tolbutamide and glibornuride. The risk of hypoglycemia occurring is thus significantly higher under glibenclamide and chlorpropamide than under glibornuride and tolbutamide. 6.5% of HE were fatal in period A, compared with 4.3% in period B. Advanced age proved to be a risk factor in HE: 77% of patients with HE were over 69 years of age, whereas only 50% of all diabetics treated with sulfonylurea preparations were in this age group. Further risk factors were impaired renal function (21%) and possible drug interactions (27%). There was less likelihood of recurrence of a hypoglycemic episode in period B than in period A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗