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Biomedical subjects

A Olsen

Publications and source records attributed to A Olsen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Homology-driven assembly of a sequence-ready mouse BAC contig map spanning regions related to the 46-Mb gene-rich euchromatic segments of human chromosome 19.

Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.

Animals↗
PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗
PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Comparison of human genetic and sequence-based physical maps.

Recombination is the exchange of information between two homologous chromosomes during meiosis. The rate of recombination per nucleotide, which profoundly affects the evolution of chromosomal segments, is calculated by comparing genetic and physical maps. Human physical maps have been constructed using cytogenetics, overlapping DNA clones and radiation hybrids; but the ultimate and by far the most accurate physical map is the actual nucleotide sequence. The completion of the draft human genomic sequence provides us with the best opportunity yet to compare the genetic and physical maps. Here we describe our estimates of female, male and sex-average recombination rates for about 60% of the genome. Recombination rates varied greatly along each chromosome, from 0 to at least 9 centiMorgans per megabase (cM Mb(-1)). Among several sequence and marker parameters tested, only relative marker position along the metacentric chromosomes in males correlated strongly with recombination rate. We identified several chromosomal regions up to 6 Mb in length with particularly low (deserts) or high (jungles) recombination rates. Linkage disequilibrium was much more common and extended for greater distances in the deserts than in the jungles.

Female↗
PubMed2001

A study of risk factors for intestinal helminth infections using epidemiological and anthropological approaches.

This study. conducted in Kisumu District, Kenya, identified important risk factors for infection with intestinal helminths using traditional epidemiological methods. This was combined with a rapid assessment study using qualitative methods, which focused on sanitation practices and local illness perceptions. The multiple logistic regression analysis revealed that the absence of latrines was a significant predictor for hookworm infection with an odds ratio (OR) of 1.9. The analysis also revealed that households without soap had a 2.6 times higher risk of being infected with Ascaris lumbricoides compared with households where soap was available, and that the number of inhabitants living in a household was a significant predictor for infections with hookworms (OR=3.2). Furthermore, the presence of children of 5 years and under in the household was a predictor for infection with A. lumbricoides (OR=2.7), while the absence of this age group was a predictor for hookworm infection (OR=3.8). The qualitative part of the study revealed that people did not consider worms as a serious health threat, but as a nuisance. Among the population. latrines were seen as beneficial because they were believed to prevent disease, to provide privacy and to keep the environment free of faeces. Handwashing was done many times a day but usually not with soap, which was mainly used when bathing or washing the whole body. Many inhabitants in a household or the presence of children of 5 years and under were never mentioned as being a disadvantage, and these elements would therefore be difficult to include in a control strategy. Since the lack of latrines and of soap were identified as risk factors for infection, while latrines, soap and medicine were seen as assets by the population, it is suggested that helminth control interventions should be concentrated within these areas in this particular society.

Age Distribution↗
PubMed2001

Chickens and pigs as transport hosts for Ascaris, Trichuris and Oesophagostomum eggs.

Ten chickens and 2 pigs were fed non-embryonated eggs of Ascaris suum, Trichuris suis and Oesophagostomum dentatum. Each chicken was fed approximately 15,000 eggs of each parasite species while approximately 300,000 eggs were given to each of the pigs. After passage in chickens 8.3% of O. dentatum eggs were recovered in faeces compared to 61.1% and 38.4%, 49.1% and 30.3%, 41.6% of A. suum and T. suis eggs, respectively. After passage in pigs the percentages were respectively. After embryonation in the laboratory, 1,000 eggs of each parasite species having passed through chickens or pigs or having been kept in the laboratory as controls were fed to groups of 6 pigs to check the infectivity. The number of A. suum recovered from pigs was similar in the 3 groups with 34.0, 52.8 and 41.8%, respectively. The recovery of T. suis in the pig passage group was 54.0% which was significantly lower than the recovery in the chicken passage group (81.8%) and the laboratory group (88.0%). The number of O. dentatum recovered was not significantly different among the 3 experimental groups, the percentage recovery being 30.5, 9.2 and 28.5%, respectively. One explanation for the lower infectivity of T. suis in the pig passage group may be that the eggs have been sublethally damaged through their passage. The results demonstrate that chickens and pigs can act as transport hosts for A. suum, T. suis and O. dentatum, and it is highly probable that these domestic animals are able to act also as transport hosts for the human parasite equivalents. This will have important consequences for the environmental and behavioural strategies in human helminth control

Animals↗
PubMed2000

Cloning of human Ca2+ homoeostasis endoplasmic reticulum protein (CHERP): regulated expression of antisense cDNA depletes CHERP, inhibits intracellular Ca2+ mobilization and decreases cell proliferation.

A monoclonal antibody which blocks InsP(3)-induced Ca(2+) release from isolated endoplasmic reticulum was used to isolate a novel 4.0 kb cDNA from a human erythroleukaemia (HEL) cell cDNA expression library. A corresponding mRNA transcript of approx. 4.2 kb was present in all human cell lines and tissues examined, but cardiac and skeletal muscle had an additional transcript of 6.4 kb. The identification in GenBank(R) of homologous expressed sequence tags from many tissues and organisms suggests that the gene is ubiquitously expressed in higher eukaryotes. The gene was mapped to human chromosome 19p13.1. The cDNA predicts a 100 kDa protein, designated Ca(2+) homoeostasis endoplasmic reticulum protein (CHERP), with two putative transmembrane domains, multiple consensus phosphorylation sites, a polyglutamine tract of 12 repeats and regions of imperfect tryptophan and histadine octa- and nona-peptide repeats. In vitro translation of the full-length cDNA produced proteins of M(r) 128000 and 100000, corresponding to protein bands detected by Western blotting of many cell types. CHERP was co-localized in HEL cells with the InsP(3) receptor by two-colour immunofluorescence. Transfection of HEL cells with antisense cDNA led to an 80% decline in CHERP within 5 days of antisense induction, with markedly decreased intracellular Ca(2+) mobilization by thrombin, decreased DNA synthesis and growth arrest, indicating that the protein has an important function in Ca(2+) homoeostasis, growth and proliferation.

Amino Acid Sequence↗
PubMed1999

N(6)-Furfuryladenine, kinetin, protects against Fenton reaction-mediated oxidative damage to DNA.

N(6)-Furfuryladenine (kinetin) has been shown to have anti-ageing effects on several different systems including plants, human cells in culture, and fruitflies. Since most of the experimental data point toward kinetin acting as an antioxidant both in vitro and in vivo, and since much evidence supporting a causal role of oxidative damage in ageing is accumulating, we tested the antioxidant properties of kinetin directly. Using 8-oxo-2'deoxyguanosine (8-oxo-dG) in calf thymus DNA as a marker for oxidative damage, we demonstrate that kinetin significantly (P < 0.005) protects the DNA against oxidative damage mediated by the Fenton reaction. Kinetin inhibited 8-oxo-dG formation in a dose-dependent manner with a maximum of 50% protection observed at 100 microM kinetin.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

RalA requirement for v-Src- and v-Ras-induced tumorigenicity and overproduction of urokinase-type plasminogen activator: involvement of metalloproteases.

Overproduction of urokinase-type plasminogen activator (uPA) and metalloproteases (MMPs) is strongly correlated with tumorigenicity and with invasive and metastatic phenotypes of human and experimental tumors. We demonstrated previously that overproduction of uPA in tumor cells is mediated by a phospholipase D (PLD)- and protein kinase C-dependent mechanism. The oncogenic stimulus of v-Src and v-Ras results in the activation of PLD, which is dependent upon the monomeric GTPase RalA. We have therefore investigated whether RalA plays a role in uPA and MMP overproduction that is observed in response to oncogenic signals. We report here that NIH3T3 cells transformed by both v-Src and v-Ras, constitutively overproduce uPA and that expression of a dominant negative RalA mutant (S28N) blocks overproduction of uPA in both the v-Src-and v-Ras-transformed cells. v-Src and v-Ras also induced an upregulation of the activity of MMP-2 and MMP-9 as detected by zymograms, however only the v-Src induction correlated with MMP protein levels detected by Western blot analysis. The dominant negative RalA mutant blocked increased MMP-2 and 9 overproduction induced by v-Src, but not the increased activity of MMP-2 and 9 induced by v-Ras. And, consistent with a role for the RalA/PLD pathway in mitogenesis and tumor development, the dominant negative RalA mutant completely blocked tumor formation by v-Src- and v-Ras-transformed NIH3T3 cells injected subcutaneously in syngeneic mice. The data presented here implicate RalA and PLD as signaling mediators for tumor formation and protease production by transformed cells.

3T3 Cells↗
PubMed1999

Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations.

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal recessive disorder that is caused by mutations in the recently discovered nephrin gene, NPHS1 (AF035835). The disease, which belongs to the Finnish disease heritage, exists predominantly in Finland, but many cases have been observed elsewhere in Europe and North America. The nephrin gene consists of 29 exons spanning 26 kb in the chromosomal region 19q13.1. In the present study, the genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were screened for the presence of mutations in the gene. A total of 32 novel mutations, including deletions; insertions; nonsense, missense, and splicing mutations; and two common polymorphisms were found. Only two Swedish and four Finnish patients had the typical Finnish mutations: a 2-bp deletion in exon 2 (Finmajor) or a nonsense mutation in exon 26 (Finminor). In seven cases, no mutations were found in the coding region of the NPHS1 gene or in the immediate 5'-flanking region. These patients may have mutations elsewhere in the promoter, in intron areas, or in a gene encoding another protein that interacts with nephrin.

Amino Acid Sequence↗
PubMed1998

Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1.

Amyloid-precursor-like protein 1 (APLP1) is a membrane-associated glycoprotein, whose gene is homologous to the APP gene, which has been shown to be involved in the pathogenesis of Alzheimer's disease. APLP1 is predominantly expressed in brain, particularly in the cerebral cortex postsynaptic density. The genomic organization of mouse APLP1 has been determined, and the human gene has been mapped to chromosomal region 19q13.1. In the present study, the entire sequence of human APLP1 has been determined from a cosmid clone, and the genomic structure has been determined. The gene is 11.8 kb long and contains 17 exons. We have previously mapped the gene for congenital nephrotic syndrome (CNF) to the APLP1 region, to the vicinity of marker D19S610 located between markers D19S191 and DS19608. APLP1 is the only known gene in the vicinity of the marker D19S610. Because of its location and the proposed interference of amyloid with basement membrane assembly, APLP1 has been considered a candidate gene for CNF. All exon regions of the gene were amplified by the polymerase chain reaction and sequenced from DNA of CNF patients. No differences were observed between CNF patients and controls, suggesting that mutations in APLP1 are not involved in the etiology of CNF.

Adult↗
PubMed1998

Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome.

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the kidney filtration barrier.

Amino Acid Sequence↗
PubMed1998

Typhaea stercorea (Coleoptera: Mycetophagidae), a carrier of Salmonella enterica serovar Infantis in a Danish broiler house.

In December 1994, Salmonella enterica serovar Infantis (S. Infantis) was accidentally introduced into a Danish broiler house by stocking an S. Infantis-infected broiler flock of 39,900 day-old chicks. At the time of the study, the infection had persisted through 6 broiler cycles. Typhaea stercorea (L.), the hairy fungus beetle, was found in large quantities inside and around the broiler house. Various attempts to control the beetle had failed; T. stercorea had been uncontrollable on the farm since Alphitobius diaperinus (Panzer), the lesser mealworm, was eradicated approximately 10 yr earlier. We investigated the ability of T. stercorea to act as a carrier of S. Infantis in the broiler house between 2 broiler cycles. We examined the empty, cleaned, and disinfected broiler house for S. Infantis 3 d before stocking the 7th broiler flock, and S. Infantis was isolated from the beetles only. Of 20 singly examined T. stercorea, 9 (45%) were S. Infantis positive. A rapid spread of the infection was seen in the 7th broiler flock; 100% of the culled chicks were S. Infantis positive 3 d after stocking. Under experimental conditions chicks were observed eating beetles, and when 5 d-old, specified pathogen-free chicks were fed with S. Infantis-positive T. stercorea collected from the broiler house, all 5 chicks became infected in 4 d. We conclude that T. stercorea may act as a potential carrier of S. Infantis between successive broiler cycles.

Animal Feed↗
PubMed1997

Human synaptotagmin V (SYT5): sequence, genomic structure, and chromosomal location.

We have determined the sequence, genomic structure, and chromosomal location of the human synaptotagmin V (SYTV) gene. The human SYTV gene encodes a 386-amino-acid product which is 91% identical to rat Syt V. The human SYTV open reading frame is interrupted by seven introns which can be alternatively spliced. Human SYTV was found to lie very close to SYTIII on chromosome 19q13.4 by PCR analysis of somatic cell hybrid DNA and by DNA hybridization to arrayed cosmids of the chromosome 19 metric physical map. This provides the first report of linked synaptotagmin genes.

Amino Acid Sequence↗