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Biomedical subjects

J Cowell

Publications and source records attributed to J Cowell.

At least 19 recordsLinked to original sources
PubMed2001

Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome.

Klippel-Trenaunay syndrome (KTS) is a disorder primarily characterized by capillary-venous vascular malformations associated with altered limb bulk and/or length. We report the identification of a balanced translocation involving chromosomes 8q22.3 and 14q13 in a patient with a vascular and tissue overgrowth syndrome consistent with KTS. We demonstrated that translocation t(8;14)(q22.3;q13) arose de novo. These data suggest that a pathogenic gene for a vascular and tissue overgrowth syndrome (KTS) may be located at chromosome 8q22.3 or 14q13. Fluorescence in situ hybridization (FISH) analysis was used to define the breakpoint on chromosome 8q22.3 to a <5-cM interval flanked by markers AFMA082TG9 and GATA25E10, and the 14q13 breakpoint within a 1-cM region between STSs WI-6583 and D14S989. This study provides a framework for the fine-mapping and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13.

Adolescent↗
PubMed2000

The TACC domain identifies a family of centrosomal proteins that can interact with microtubules.

We recently showed that the Drosophila transforming acidic coiled-coil (D-TACC) protein is located in the centrosome, interacts with microtubules, and is required for mitosis in the Drosophila embryo. There are three known human TACC proteins that share a conserved, C-terminal, coiled-coil region with D-TACC. These proteins have all been implicated in cancer, but their normal functions are unknown. We show that all three human TACC proteins are concentrated at centrosomes, but with very different characteristics: TACC1 is weakly concentrated at centrosomes during mitosis; TACC2 is strongly concentrated at centrosomes throughout the cell cycle; and TACC3 is strongly concentrated in a more diffuse region around centrosomes during mitosis. When the C-terminal TACC domain is overexpressed in HeLa cells, it forms large polymers in the cytoplasm that can interact with both microtubules and tubulin. The full-length TACC proteins form similar polymers when overexpressed, but their interaction with microtubules and tubulin is regulated during the cell cycle. At least one of the human TACC proteins appears to increase the number and/or stability of centrosomal microtubules when overexpressed during mitosis. Thus, the TACC domain identifies a family of centrosomal proteins that can interact with microtubules. This may explain the link between the TACC genes and cancer.

Animals↗
PubMed1999

Using care pathways in pressure area management: a pilot study.

Care pathways are a method of managing, delivering and documenting care. A pilot study of a care pathway system in pressure area management was conducted in two clinical areas. Results from this pilot study indicate that the pathway approach to pressure area management is both useful and valid as a means to enhance clinical decision-making and to facilitate comprehensive pressure area management and the completeness of care documentation. Implementation of the pathway requires a facilitator to provide support and education and to monitor and maintain the change process.

Critical Pathways↗
PubMed1996

Incorporation of 35 novel gene transcripts into the physical and genetic map of human chromosome 13.

A panel of somatic cell hybrids carrying a defined set of rearrangements involving chromosome 13 has been used to assign 35 novel gene transcripts regionally. The positions of the chromosome 13 breakpoints in each somatic cell hybrid have previously been defined relative to the Généthon genetic linkage map. As a result, the position of each gene transcript has been determined relative to both the physical and the genetic linkage maps. Analysis of the distribution of these gene transcripts indicates a slight overrepresentation toward locations on the distal long arm of chromosome 13, with no localizations noted in the 13q22-q31 region. Seven of these novel gene transcripts and the gene encoding small ribonucleoprotein U6 have been mapped to YACs known to contain Généthon microsatellite markers, thereby providing further sublocalization relative to the genetic map. The positioning the these gene transcripts within the genetic and physical maps provide candidate genes for disease loci that are being mapped to the same intervals on the chromosome.

Animals↗
PubMed1996

EagI and NotI linking clones from human chromosomes 11 and Xp.

EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability to hybridise with total human DNA and digested with SalI and EcoRI to identify the human insert size and single-copy fragments. The mean (+/- SD) insert sizes of the EagI and NotI clones were 18.3 +/- 3.2 kb and 16.6 +/- 3.6 kb, respectively. Regional localisation of 66 clones (52 EagI, 14 NotI) was achieved using a panel of 20 somatic cell hybrids that contained different overlapping deletions of chromosomes 11 or Xp. Thirty-nine clones (36 EagI, 3 NotI) were localised to chromosome 11; 17 of these were clustered in 11q13 and another nine were clustered in 11q14-q23.1. Twenty-seven clones (16 EagI, 11 NotI) were localised to Xp and 10 of these were clustered in Xp11. The 66 clones were assessed for seven different microsatellite repetitive sequences; restriction fragment length polymorphisms for five clones from 11q13 were also identified. These EagI and NotI clones, which supplement those previously mapped to chromosome 11 and Xp, should facilitate the generation of more detailed maps and the identification of genes that are associated with CpG-rich islands.

Animals↗
PubMed1996

Evaluation of purified UspA from Moraxella catarrhalis as a vaccine in a murine model after active immunization.

Moraxella catarrhalis causes otitis media, laryngitis, and respiratory infections in humans. A high-molecular-weight outer membrane protein from this bacterium named ubiquitous surface protein A (UspA) is present on all isolates. A monoclonal antibody (MAb) to UspA that recognizes a conserved epitope of this protein has been shown to promote pulmonary clearance of bacteria in passively immunized mice. In the present study, M. catarrhalis heterologous isolates were screened by dot blot with a panel of four additional MAbs specific for surface-exposed epitopes of UspA from M. catarrhalis isolate 035E. Three of the MAbs were specific for 035E, and the fourth reacted with 17 (74%) of the 23 isolates tested. Thus, UspA contains highly conserved, semiconserved, and variable surface-exposed epitopes. The UspA was purified from the 035E isolate by ion-exchange and size-exclusion chromatography, formulated with the adjuvant QS-21, and used to immunize BALB/c mice. Upon pulmonary challenge with either 035E or the heterologous isolate TTA24, significantly fewer bacteria were recovered from the lungs of immunized mice 6 h postchallenge than from control mice. The immune sera from mice or guinea pigs contained high titers of antibodies to the homologous isolate and heterologous isolates in a whole-bacterial-cell enzyme-linked immunosorbent assay. Sera against UspA, whether prepared in mice or guinea pigs, had complement-dependent bactericidal activity toward homologous and 11 heterologous M. catarrhalis isolates. These results indicate that the conserved epitopes of the UspA are highly immunogenic and elicit broadly reactive and biologically functional antibodies. UspA may offer protection against M. catarrhalis infections and is being further evaluated as a vaccine candidate.

Animals↗
PubMed1996

The Brn-3a transcription factor gene (POU4F1) maps close to the locus for the variant late infantile form of neuronal ceroid-lipofuscinosis.

We have refined the location of the Brn-3a genomic locus (POU4F1), using somatic cell hybrid analysis, to 13q21.1-->q22. Furthermore, we have shown that two YACs, known to contain the closest marker linked to neuronal ceroidlipofuscinosis (CLN5), also contains the Brn-3a gene. As one of these YACs is only 320 kb long, this localises POU4F1 within the critical region defining the CLN5 locus, and raises the possibility that POU4F1 is a candidate gene for CLN5.

Chromosome Mapping↗
PubMed1993

Insertional inactivation of the WT1 gene in tumour cells from a patient with WAGR syndrome.

The WT1 gene was analysed using DNA from a Wilms' tumour derived from a patient with the WAGR syndrome using single strand conformation polymorphism analysis and polymerase chain reaction sequencing. A 14-bp insertion was found in the intron part of the splice donor site of exon 7 and was a tandem duplication of an upstream exon sequence. This mutation would be expected to disrupt the correct processing of the WT1 mRNA and is predicted to result in a non-functional protein. This observation further supports the role of WT1 in Wilms' tumorigenesis in patients with constitutional 11p13 deletions.

Abnormalities, Multiple↗
PubMed1993

A somatic cell hybrid map of human chromosome 13.

We have constructed a chromosome 13 somatic cell hybrid map using seven cell lines: PGMEA6, a hybrid containing the entire chromosome 13, and six hybrids containing various deletions of chromosome 13 (BARF7, PPF22, KBF11, KSF39, CF25, and CF27). We have mapped 80 markers that define 10 regions of chromosome 13 with respect to 10 breakpoints in the mapping panel; these regions range in size from 4 to 24 Mb, with an average size of 8 Mb. The 80 markers sublocalized on our mapping panel include 10 Alu-PCR clones, 6 of which were converted to sequence-tagged sites; 40 (CA)n repeat-containing clones, 27 of which are microsatellite PCR markers; 8 (AAAG)n repeat-containing PCR markers, 1 two-allele PCR marker, 4 genes or expressed sequences, and 17 anonymous DNA probes. This low-resolution physical map can be used as a backbone map for more refined physical mapping using radiation hybrids or yeast artificial chromosomes.

Animals↗
PubMed1991

GABAergic-serotonergic interactions in regulating lordosis.

The GABAB agonist, baclofen, causes a dose-dependent decrease in lordosis, and this effect is attenuated following hypothalamic serotonin, (5-HT) lesions. Baclofen administration is associated with decreased 5-HT activity in the medial preoptic (mPOA) and ventromedial nuclei and enhanced 5-HT activity in the midbrain central gray, and with enhanced norepinephrine activity in the mPOA. Interactions between gamma-aminobutyric acid (GABA) and 5-HT may, therefore, be important for the activation of lordosis.

5,7-Dihydroxytryptamine↗
PubMed1991

Loss of heterozygosity for chromosome region 11p15 in Wilms' tumours is not related to HRAS gene transforming mutations.

Although a candidate Wilms' tumour gene--WT1--has been identified in chromosome region 11p13, there is strong evidence from loss of heterozygosity studies suggesting that a second relevant gene is present in region 11p15. The Harvey-Ras proto-oncogene also lies in this region. In other types of tumours mutations in RAS genes have been associated with the development and/or progression of a number of tumour types. We therefore analysed the sequence of the Ras oncogene for possible mutations in six Wilms' tumours showing loss of heterozygosity for chromosome region 11p15. No tumour analysed showed HRAS sequence mutations. We conclude that loss of heterozygosity at 11p15 does not implicate HRAS mutations in the molecular pathogenesis of Wilms' tumour.

Base Sequence↗
PubMed1988

Homozygous deletion of a DNA marker from chromosome 11p13 in sporadic Wilms tumor.

A random DNA fragment, probe p2.3 (locus D11S87), was cloned from the 11p13 region between a translocation breakpoint associated with familial aniridia and another translocation breakpoint associated with childhood T-cell leukemia. The D11S87 locus maps between the catalase (CAT) locus and the beta subunit of follicle stimulating hormone (FSHB). The D11S87 locus is deleted in a Wilms tumor patient with a constitutional deletion of 11p and in a case of sporadic Wilms tumor (WiT-13) apparently with normal karyotype. In the WiT-13 tumor both maternal and paternal chromosomes 11 are retained; D11S87 is deleted homozygously and FSHB hemizygously. These results suggest two mutational events resulting in homozygous deletion in this patient. The D11S87 homozygous deletion was also demonstrated in WiT-13 nude mouse heterotransplants and in fibroblast-like cell line derived from the primary tumor. The minimum size of the deletion was estimated to be 30 kb as determined by cosmid screening and hybridization. As homozygous deletions in the 11p13 region have not been previously reported for sporadic Wilms tumors, these findings place the D11S87 locus within or approximate to the Wilms tumor gene.

Blotting, Southern↗
PubMed1988

Computer matching of oligonucleotide patterns on electrophoretic gels: an application to the epidemiology of cytomegalovirus.

A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission. The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs. The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.

Algorithms↗