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Biomedical subjects

S Woodward

Publications and source records attributed to S Woodward.

At least 55 records · Page 3Linked to original sources

Aphidicolin resistance in herpes simplex virus type I reveals features of the DNA polymerase dNTP binding site.

We describe the mapping and sequencing of mutations within the DNA polymerase gene of herpes simplex virus type 1 which confer resistance to aphidicolin, a DNA polymerase inhibitor. The mutations occur near two regions which are highly conserved among DNA polymerases related to the herpes simplex enzyme. They also occur near other herpes simplex mutations which affect the interactions between the polymerase and deoxyribonucleoside triphosphate substrates. Consequently, we argue in favor of the idea that the aphidicolin binding site overlaps the substrate binding site and that the near-by conserved regions are functionally required for substrate binding. Our mutants also exhibit abnormal sensitivity to another DNA polymerase inhibitor, phosphonoacetic acid. This drug is thought to bind as an analogue of pyrophosphate. A second-site mutation which suppresses the hypersensitivity of one mutant to phosphonoacetic acid (but not its aphidicolin resistance) is described. This second mutation may represent a new class of mutations, which specifically affects pyrophosphate, but not substrate, binding.

Amino Acid Sequence↗

A molluscivorous Conus toxin: conserved frameworks in conotoxins.

We purified and characterized a 27 amino acid toxin from a snail-hunting Conus venom, Conus textile. This toxin causes convulsive-like activity in snails and causes subordinate lobsters to assume an exaggerated dominant posture. The sequence of this peptide is Trp-Cys-Lys-Gln-Ser-Gly-Glu-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp- Gly-Tyr-Cys-Ile-Val-Leu-Val-Cys-Thr. The sequence was confirmed by determining the nucleotide sequence of a cDNA clone coding for the peptide. The conservation of Cys residues compared to the omega-conotoxins from piscivorous Conus venom suggests that toxins from different cone venoms may use only a few "Cys-motifs" as conserved structural backbones for targeting to a variety of receptors in different animals.

Amino Acid Sequence↗

A mapped set of genetic markers for human chromosome 9.

A genetic map of markers for human chromosome 9, spanning a genetic distance of 147 cM in males and 231 cM in females, has been constructed from linkage studies with 19 loci in a large panel of reference families. The markers included four classical systems previously assigned to chromosome 9, and restriction fragment length polymorphisms of two cloned genes, ABL oncogene and argininosuccinase synthetase pseudogene 3 (ASSP3). The remaining 13 marker loci, with an average heterozygosity of 42%, were defined by arbitrary DNA probes newly ascertained from genomic libraries; seven of them were variable number of tandem repeat (VNTR) loci. A subset of 7 of the 19 linked markers is proposed for a primary map that could detect linkage with a genetic defect within the covered region of chromosome 9, provided that at least 45 phase-known meioses were available for study in an affected family.

Cell Line↗

Organogenesis and embryogenesis in mature zygotic embryos of Picea sitchensis.

Differentiation of adventitious buds and somatic embryos from mature zygotic embryos of Picea sitchensis (Bong.) Carr. is described. Adventitious buds were formed on embryos pulse-treated with 250 microM benzyladenine for 2 h and cultured on medium lacking growth regulators. Buds were initiated at different frequencies and sites depending on when the BA-pulsed embryos were transferred to fresh culture medium. Embryogenic callus was formed when the zygotic embryos were cultured on medium containing 10 microM 2,4-dichlorophenoxyacetic acid and 5 microM benzyladenine. Although 50% of the embryos gave rise to embryogenic callus, only 20% of the callus continued to proliferate after subculture. Proliferation of new somatic embryos occurred from both the embryonic region and the suspensor region on previously formed somatic embryos. The pattern for development of adventitious buds and somatic embryos in Picea sitchensis is compared to that in Picea abies under similar culture conditions.

Journal Article↗

VNTR (variable number of tandem repeats) markers show loss of chromosome 17p sequences in human colorectal carcinomas.

Restriction fragment length polymorphisms at 53 autosomal loci were screened for heterozygosity in 40 colorectal cancer patients. The DNA pattern in constitutional versus tumor/polyp tissue was compared. More than half of the markers tested were of the VNTR (variable number of tandem repeats) type, giving the patient panel a higher informational content, since the frequency of individuals heterozygous for a particular marker is increased. Loss of alleles was revealed in 40% of the tumors from constitutionally heterozygous patients at the chromosome 17p loci, identified by the markers YNH37 and YNZ22. Similar losses were also detected on other autosomes, but at a significantly lower frequency. Our results suggest that hemi/homozygosity of 17p alleles plays a role in the development of a major subset of colorectal carcinomas. Similar observations regarding other autosomal loci may be interpreted as random losses in these tumors, or they may indicate loci important to minor clinical subclasses of colon carcinomas.

Carcinoma↗

The gene for familial polyposis coli maps to the long arm of chromosome 5.

The inherited genetic defect in adenomatous polyposis has been localized to a small region on the long arm of chromosome 5. Sixteen DNA marker loci were used to construct a linkage map of the chromosome. When five kindreds segregating a gene for adenomatous polyposis coli were characterized with a number of the markers, significant linkage was found between one marker and the disease gene. Linkage analysis determined the location of the defective gene within a primary genetic map of chromosome 5.

Chromosome Mapping↗

Further linkage data on cystic fibrosis: the Utah Study.

We reported earlier complete linkage between cystic fibrosis and an RFLP of the met proto-oncogene revealed by the probe pmetH. Another clone, pmetD, detects another polymorphism with the TaqI restriction enzyme. Further linkage studies, now involving 22 families, have confirmed the tight linkage of cystic fibrosis to the MET and D7S8 loci. Significant allelic association was found between CF and allelic series defined by the pmetH probe.

Alleles↗

Legislation for smoking control in Western Australia.

This historical analysis of public issues relating to smoking control in Western Australia examines relevant Western Australian state and Australian federal laws, their introduction, and their consequences. Public and political support and opinion led by the health professions resulted in two attempts to legislate against all forms of cigarette advertising in 1982 and 1983. Both attempts failed, and public support for such measures has been seen to be affected by the campaigns mounted in opposition by the tobacco and advertising industries. Other smoking control measures which have been successfully introduced in 1983 and 1984 are higher tobacco taxes and a comprehensive coordinated public education and information programme. The activities associated with the legislative initiatives resulted in a greatly increased level of community awareness of the dangers of smoking and acceptance of the need for some action on this major health problem.

Advertising↗

Bereavement counselling after sudden infant death.

Of 14 families who suffered a sudden infant death, eight were followed up intensively over several months and offered individual counselling, parents' group meetings, and interviews with doctors as a way of helping them come to terms with their feelings of loss. Five couples accepted short term support from their health visitor, and one refused help. Many families experienced considerable stress including marital conflict, difficulties with surviving children, and anxiety about future children becoming victims of the sudden infant death syndrome. It was concluded that medical social workers, health visitors, hospital paediatricians, general practitioners, and parent self help groups are in key positions to help. The success of such help is likely to depend on the confidence that each helper has that his or her contribution will be valued by the bereaved family.

Counseling↗

On comprehension across the adult lifespan.

To test whether healthy elderly subjects develop language comprehension strategies to compensate for decreases in pure-tone audition, we tested 128 healthy subjects aged 30-79 on two tasks: (1) Comprehension materials from the Boston Diagnostic Aphasia Examination (Goodglass and Kaplan, 1972) presented over babble noise with and without the speaker's face visible; and (2) the Kalikow et al. (1977) Speech Perception in Noise test, which assesses the effect of semantic predictability on sentence-final word intelligibility. Whereas, as predicted, overall performance decreased with advancing age, it appeared, unexpectedly, that older and younger adults were equally affected by the absence of visual input and the absence of semantic predictability.

Adult↗

Changes in cerebral lateralization in aging.

To determine whether there is increasing left hemispheric lateralization for language with age and whether the right hemisphere is selectively impaired with advanced age, we tested 96 right-handed people aged 25-80 yr on verbal and non-verbal matching tasks presented tachistoscopically. Task difficulties was equalized by adjusting exposure durations. Exposure duration, error laterality and response latency laterality were analyzed. Typical field effects as well as age-related slowing and sex by task interactions were observed. However, no systematic age-related changes in lateralization were apparent.

Adult↗