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Biomedical subjects

T A Smith

Publications and source records attributed to T A Smith.

At least 91 records · Page 5Linked to original sources
PubMed1995

Using a Delphi Technique in a needs assessment for an innovative approach to advanced general dentistry education.

The University of Kentucky College of Dentistry has been awarded a $500,000 grant to develop and test a university-based educational program leading to a graduate certificate in Advanced General Dentistry, by the use of "extended campus" and distance learning methods. As an aid in developing this curriculum, dentists in general practice in non-urban Kentucky were asked about their educational needs. A Delphi Technique approach to this assessment was adopted. Forty dentists in general practice in non-urban areas in eastern and southern Kentucky were sent four mailings in which they rated or re-rated 65 topics for inclusion in the curriculum. A total of 59 topics were voted to be essential or desirable for the curriculum, 40 of them by a 2/3 majority. The Delphi Technique was workable for involving students in curriculum design. The curriculum produced by this method has also proven to be attractive to the dentists and their colleagues.

Curriculum↗
PubMed1994

Evaluation and replication of impact damage to bicycle helmets.

A group of 72 impacted bicycle helmets were collected, primarily from manufacturers with a crash replacement policy that encourages the return of damaged helmets. Each damaged helmet was thoroughly inspected and measured to determine the construction details and collision damage. Laboratory replication tests were then performed on selected samples using exemplar helmets to determine impact velocity and peak headform aceleration. The predominant impact location was the front left quarter and the replication studies indicate that the majority of impacts took place on flat surfaces from drop heights of 1 meter or less. Overall, it is evident that a large number of bicycle helmet users who have benefited from the use of a bicycle helmet, and future bicycle helmet standards must incorporate the protective requirements of this unique group.

Accidents, Traffic↗
PubMed1994

Mutations in a signal sequence for the thylakoid membrane identify multiple protein transport pathways and nuclear suppressors.

The apparatus that permits protein translocation across the internal thylakoid membranes of chloroplasts is completely unknown, even though these membranes have been the subject of extensive biochemical analysis. We have used a genetic approach to characterize the translocation of Chlamydomonas cytochrome f, a chloroplast-encoded protein that spans the thylakoid once. Mutations in the hydrophobic core of the cytochrome f signal sequence inhibit the accumulation of cytochrome f, lead to an accumulation of precursor, and impair the ability of Chlamydomonas cells to grow photosynthetically. One hydrophobic core mutant also reduces the accumulation of other thylakoid membrane proteins, but not those that translocate completely across the membrane. These results suggest that the signal sequence of cytochrome f is required and is involved in one of multiple insertion pathways. Suppressors of two signal peptide mutations describe at least two nuclear genes whose products likely describe the translocation apparatus, and selected second-site chloroplast suppressors further define regions of the cytochrome f signal peptide.

Amino Acid Sequence↗
PubMed1994

Attitudes toward marriage and premarital sexual activity of college freshmen.

In order to explore the relationship between attitudes toward marriage and premarital sexual activity, 143 male and 198 female college freshmen were administered a general information questionnaire and a modified version of Hill's (1951) Favorableness of Attitudes Toward Marriage Scale. It was found that females had more favorable attitudes toward marriage than did males. It was also found that virgins had more favorable attitudes toward marriage than nonvirgins who had multiple sex partners. Scores for nonvirgins who had only one sex partner fell between those for virgins and nonvirgins who had multiple sex partners. The interaction of gender and group status (i.e., virgins, nonvirgins with only one partner, and nonvirgins with multiple partners) was not significant.

Adolescent↗
PubMed1993

Levels of anti-pneumococcal antibodies in young children in Papua New Guinea.

Anti-pneumococcal polysaccharide antibody (anti-PPS) levels were measured in 153 serum samples collected from children aged between 2 and 47 months living in the highlands of Papua New Guinea (PNG). Fifty-seven of the samples were collected during acute episodes of lower respiratory tract infection (ALRI). Total IgA and IgG increased steadily with age; however, no association was found between the levels of these antibodies and the health status of the child. Total IgM levels showed little relationship to the age of the child but under 12 months of age levels were somewhat higher on average in children with pneumonia. For most of eight pneumococcal serotypes tested, specific IgG levels were found to decline rapidly in the first 6-8 months, reaching a minimum at approximately 12 months of age. Serotype 3 was exceptional in having very low titres in the youngest children. A separate analysis of 24 cord sera suggested that antibodies to this serotype do not usually cross the placenta in PNG. Children with pneumonia tended to have lower levels of specific IgG than healthy controls of the same age. Specific anti-PPS IgA levels were found to increase steadily with age, but were not associated with health status.

Age Factors↗
PubMed1993

Proliferative behaviour of an oestrogen sensitive rat mammary tumour: evidence for a paracrine interaction between tumour and stroma.

An oestrogen-sensitive rat mammary tumour (OES HR1) has been grown in normal female rats and in female and male rats supplemented with oestrone. In some rats, after the tumour was established, both exogenous and endogenous sources of oestrogen were removed--a treatment which inhibited further growth of the tumour. The proliferative characteristics of the tumours were measured by injecting the rats with deoxybromouridine (BrdU) 4 h before removing the tumour. Extracted nuclei were reacted with anti-BrdU and the labelling index and DNA content measured by flow cytometry. A correlation between the number of (diploid) host cells present and the number of (aneuploid) tumour cells in S-phase of the cell cycle was observed. This result suggests that there are paracrine interactions between tumour and host cells. We also observed that, on oestrogen ablation, the labelling index was significantly reduced while the percentage of cells in S-phase changed far less. The demonstration that there are cells in S-phase which are not proliferating highlights a possible problem with the measurement of proliferation in human tumours from a DNA histogram.

Aneuploidy↗
PubMed1993

Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice.

Gene therapy strategies designed to combat haemophilia B, caused by defects in clotting factor IX, have so far concentrated on ex vivo approaches. We have now evaluated adenoviral vector-mediated expression of human factor IX in vivo. Injection of the vector Av1H9B, which encodes human factor IX cDNA, into the tail veins of mice resulted in efficient liver transduction and plasma levels of human factor IX that would be therapeutic for haemophilia B patients. However, levels slowly declined to baseline by nine weeks and were not re-established by a second vector injection. These results address both the advantages and obstacles to the use of adenoviral vectors for treatment of haemophilia B.

Adenoviruses, Human↗
PubMed1993

Assessing patient pain during dental laser treatment.

Patients reported little or no pain during or after treatment with a dental laser. With many people reporting fear of pain as their chief reason for not seeking dental care, lasers may offer a more acceptable treatment technique.

Adolescent↗
PubMed1992

An Arabidopsis serine/threonine kinase homologue with an epidermal growth factor repeat selected in yeast for its specificity for a thylakoid membrane protein.

A number of molecules have recently been described that effect the correct transport and assembly of cytoplasmically synthesized proteins to cellular membranes. To identify proteins that bind or modify other proteins during the process of membrane translocation, we developed a yeast selection scheme that employs the yeast transcriptional activator GAL4. This selection facilitates the isolation of cDNAs that encode proteases and binding proteins for known target peptide sequences. We report the isolation of an Arabidopsis cDNA encoding a polypeptide that can interact with the amino terminus of a ligh-harvesting chlorophyll a/b-binding protein (LHCP), a cytoplasmically synthesized protein that is integral to the chloroplast thylakoid membrane. The cDNA was selected in yeast from an Arabidopsis expression library for its ability to inhibit a transcriptional activator GAL4-LHCP fusion protein, but not inhibit native GAL4 protein. The LHCP amino-terminal sequences included in the fusion protein are known to regulate LHCP biogenesis and function. The Arabidopsis cDNA encodes a 595-amino acid protein with at least two functional domains, one with similarity to the family of protein-serine/threonine kinases and another that contains an epidermal growth factor repeat. The identification of an EGF repeat in Arabidopsis indicates that the motif is conserved between the plant and animal kingdoms. Hybridization studies indicate that this gene is likely to be present in other genera of plants. Its mRNA is detected in green leaves but not in other plant tissues or in etiolated plants. The specificity in yeast and the expression pattern in plants together are suggestive of a role for this protein kinase in the assembly or regulation of LHCP.

Amino Acid Sequence↗
PubMed1992

The Malaria Vaccine Epidemiology and Evaluation Project of Papua New Guinea: rationale and baseline studies.

The range of possible malaria vaccines, against different species of Plasmodium and various stages in the life cycle of the parasite in both human host and mosquito vector, is reviewed. The importance, in a malaria-endemic area, of protection by a malaria vaccine against disease rather than infection is emphasized, and the ways by which disease prevention may be achieved are discussed. Mechanisms of production and presentation of vaccines are considered, including the importance of appropriate and more effective adjuvants. The variety of immune responses to malaria is set out and linked to both human and plasmodial genetic factors. Host genetics may also modify susceptibility to malaria through mechanisms which are not immunological. There is a need for entomological studies of the Anopheles vectors, especially but not only in preparation for transmission-blocking vaccines. This overall complexity justifies a multidimensional approach to epidemiology and field-site preparation. An iterative procedure is proposed for initial field evaluation, through adult male volunteers to community studies in immune adults and then to semi-immune school children, before evaluation in the principal target population of nonimmune young children. The outcome variables for epidemiological evaluation are specified. After this brief review of malaria vaccines, the baseline studies being undertaken by the Malaria Vaccine Epidemiology and Evaluation Project of the Papua New Guinea Institute of Medical Research in the Wosera area of East Sepik Province are discussed in some detail, and their rationale linked to the range and complexity of the malaria vaccines that have been reviewed. These studies are described under the headings of their principal components of epidemiology, parasitology, immunology, genetics and entomology.

Animals↗
PubMed1992

Age at menarche and associated nutritional status variables in Karimui and Daribi census divisions of Simbu Province.

Age at menarche was estimated from data on 310 girls and young women living in Karimui and Daribi census divisions of Simbu Province in 1987. The area has high malnutrition rates among children under five years of age and short adult female stature suggesting that onset of menses should be late. However, other work has shown young ages at the birth of first children and high overall fertility rates among women. The prediction of age at menarche from adult female height is not valid for this population; the actual age at which 50% of girls had commenced menstruating is approximately one and a half years earlier, at 15.8 years, than the predicted age. The nutritional status variables investigated and found to be associated with the age at menarche are height, weight and triceps skinfold thickness. At any given age girls whose nutritional status was better, particularly in terms of weight, were more likely to have commenced menstruation. Menarche appears to be followed closely by onset of reproductive function, with the age at the birth of first children estimated at 17.2 years. A consequence of early entry into reproduction, particularly for girls in areas where undernutrition is common, is a period of considerable nutritional stress during adolescence. Intervention programs should consider this and target these groups for additional health, family planning and nutritional advice.

Adolescent↗
PubMed1991

Direct selection for sequences encoding proteases of known specificity.

We have developed a simple genetic selection that could be used to isolate eukaryotic cDNAs encoding proteases that cleave within a defined amino acid sequence. The selection was developed by using the transcription factor GAL4 from Saccharomyces cerevisiae as a selectable marker, a cloned protease from tobacco etch virus (TEV), and an 18-amino acid TEV protease target sequence. In yeast, TEV protease cleaves its target even when the target is fused to internal regions of the GAL4 protein. This cleavage separates the DNA binding domain from the transcription activation domain of GAL4, rendering it transcriptionally inactive. The proteolytic cleavage can be detected phenotypically by the inability of cells to metabolize galactose. Cells expressing the TEV protease can also be selected on the suicide substrate 2-deoxygalactose. DNA binding studies show that the TEV protease decreases the activity of the GAL4/target fusion protein. Because another protease target sequence of 55 amino acids can be inserted into GAL4 without any loss of transcriptional activity, this assay offers the opportunity to use high-efficiency cDNA cloning and expression vectors to select coding sequences of other proteases from various species. The assay could also be used to help define both target specificities and functional domains of proteases.

Base Sequence↗
PubMed1991

The effect of intra-tumour heterogeneity on the distribution of phosphorus-containing metabolites within human breast tumours: an in vitro study using 31P NMR spectroscopy.

The concentration of phosphorus-containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue. The degree of lymphoid infiltrate, necrotic fraction and tumour cell and normal tissue fraction were determined on sections taken from each of the tumour samples. In four of the tumours there was a very high degree of variation between samples in the absolute concentration of metabolites. Three of these tumours showed a high degree of intra-tumour variation in the distribution of tumour cells and of normal tissue. The other two tumours were relatively homogeneous with respect to both tumour cellularity and the distribution of phosphorus-containing metabolites. Samples from normal breast tissue was found to contain only low concentrations of phosphorus-containing metabolites. However one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds. The effect of time delay between resection and freezing on the levels of metabolites in human breast tumours was also examined.

Breast↗
PubMed1991

A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism.

An in vivo 31P NMR spectrum was obtained from each of four human breast tumours. The phosphomonoester and phosphodiester region of each spectrum consisted of a broad peak. Chemical extracts from samples of each of the tumours obtained at resection were examined on a high field strength NMR system. The phosphomonoester region in the spectrum from each extract resolved into three peaks consisting of phosphocholine, phosphoethanolamine and a nucleoside monophosphate. The phosphodiester region resolved into two components, glycerophosphorylcholine and glycerophosphorylethanolamine. Comparing the in vivo and in vitro data from each tumour showed that the contribution of phosphodiester was much lower in the in vitro spectra. We believe this to be a consequence of phospholipid, which would not appear in the aqueous extract, contributing to the phosphodiester peak in vivo.

Breast Neoplasms↗
PubMed1991

The phosphocholine and glycerophosphocholine content of an oestrogen-sensitive rat mammary tumour correlates strongly with growth rate.

An oestrogen sensitive rat mammary tumour was grown in two groups of female and one group of male hooded rats. The male group and one of the female groups were supplemented with oestrogen. The tumours grew most rapidly in the female supplemented group. When the tumours reached 1.5 cm in diameter they were harvested and the cell cycle distribution and number of cells actively synthesising DNA (bromodeoxyuridine (BrdU) labelling index) determined in each case. Chemical extracts were prepared from each tumour and the concentration of phosphorus-containing metabolites determined using high resolution NMR spectroscopy. The concentration of phosphocholine was found to correlate strongly with the number of cells in S-phase and the number of cells labelled with BrdU, whilst a highly significant negative correlation was observed between these two parameters and glycerophosphocholine. The concentration of phosphoethanolamine did not correlate with either of these measures of proliferation rate. The concentration of glycerophosphorylethanolamine showed a weak negative correlation with the number of cells in S-phase.

Animals↗