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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 19 recordsLinked to original sources
PubMed1992

Chemical contrast in X-ray microscopy and spatially resolved XANES spectroscopy of organic specimens.

The scanning transmission x-ray microscope at the National Synchrotron Light Source has been used to record x-ray absorption near-edge structure (XANES) spectra from 0.01-square-micrometer regions of organic specimens. The spectral features observed reflect the molecular structure of the dominant absorbing atoms and provide the contrast mechanism for high-resolution imaging with chemical sensitivity. This technique was used with x-ray energies near the carbon K absorption edge to identify and map separate phases in various polymer blends and to map the DNA distribution in chromosomes with a spatial resolution of 55 nanometers.

Acrylic Resins↗
PubMed1992

Adolescence and sun protection.

AIM: to examine adolescents' sun behaviours and use of sun protection measures, attitudes to tanning, and awareness of melanoma, in the light of the Cancer Society's Sun-smart campaign in the summer of 1990-1. METHODS: a sample of 345 fourth formers from schools in Auckland, Wellington and Christchurch was surveyed regarding their experiences and beliefs about tanning, and their use of sun protection measures including sunblock lotions, hats and clothing; their knowledge of melanoma and risks for melanoma; and their exposure to the educational campaign and its message. RESULTS: despite relatively high awareness of melanoma as a dangerous form of cancer, a significant proportion of the sample showed high positive attitudes towards tanning and high levels of sun exposure without adequate sun protection. On the positive side, reports of exposure to sources of information about melanoma were correlated with melanoma awareness, which in turn predicted use of sun protection measures. CONCLUSION: the findings suggest that campaigns such as those of the Cancer Society have an important role to play in reducing high levels of sun exposure among adolescents. Continued efforts need to be directed at adolescents to increase the acceptability and use of sun protection measures.

Adolescent↗
PubMed1992

A monomeric von Willebrand factor fragment, Leu-504--Lys-728, inhibits von Willebrand factor interaction with glycoprotein Ib-IX [corrected].

von Willebrand factor interaction with glycoprotein Ib alpha (GPIb alpha) plays a critical role in the initial phase of platelet adhesion at high shear rates, and it may also play a role in platelet thrombus formation in partially occluded arteries. Previous studies have indicated that two peptides, Cys-474--Pro-488 (peptide 153) and Ser-692--Pro-708 (peptide 154), inhibit von Willebrand factor--GPIb alpha interaction. We have expressed a recombinant fragment of von Willebrand factor, Leu-504--Lys-728 [corrected], with a single intrachain disulfide bond linking residues Cys-509--Cys-695 and examined its ability to inhibit von Willebrand factor--GPIb alpha interactions and platelet adhesion at high shear forces. This recombinant fragment, named VCL, inhibits ristocetin-induced, botrocetin-induced, and asialo-von Willebrand factor-induced platelet aggregation and binding to platelets at an IC50 = 0.011-0.260 microM, significantly lower than the IC50 of peptide 153 or 154, IC50 = 86-700 microM. Peptides 153 and 154 did not result in any inhibition of platelet adhesion (IC50 greater than 500 microM). In contrast, VCL inhibited 50% of platelet adhesion at 0.94 microM and at 7.6 microM inhibited greater than 80% of platelet adhesion to human umbilical artery subendothelium at high shear forces. VCL inhibited the contact and spreading of platelets and also caused a marked decrease in thrombus formation. These studies indicate that VCL may be an effective antithrombotic agent in preventing arterial thrombus formation in areas of high shear force.

Amino Acid Sequence↗
PubMed1992

Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator.

Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade, is cleared rapidly in vivo by the liver. Using chemical crosslinking, we have recently identified a plasminogen-activator inhibitor type 1 (PAI-1)-independent t-PA clearance receptor on rat hepatoma MH1C1 cells with a relative molecular mass of approximately 500 kDa. Another recently identified membrane receptor, low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), was also detected on MH1C1 hepatoma cells by using immunoprecipitation with anti-LRP/alpha 2MR antibody. When analyzed by SDS/PAGE, we found the t-PA receptor identified on MH1C1 cells comigrated with the large subunit of LRP/alpha 2MR. The t-PA receptor was immunoprecipitated by an anti-LRP/alpha 2MR antibody after chemical crosslinking of specifically bound 125I-labeled t-PA to its receptor. Through chemical crosslinking studies, we found that t-PA and methylamine-activated alpha 2-macroglobulin could bind to LRP/alpha 2MR simultaneously without competing with one another for binding, suggesting that the two ligands bound to two independent sites on the LRP/alpha 2MR molecule. Furthermore, a 39-kDa protein, which modulates ligand binding to LRP/alpha 2MR, was also found to inhibit t-PA binding to its receptor. These data thus show that the t-PA clearance receptor identified on MH1C1 hepatoma cells is LRP/alpha 2MR.

Animals↗
PubMed1992

Prevention of endocarditis: communication between doctors and dentists.

Successful implementation of guidelines to prevent infective endocarditis (IE) depends upon the dental practitioner being aware of which of his patients are at risk. This was studied by sending a questionnaire to at risk patients and their dentists in the Grampian area. Of 145 respondents (53% response rate) with predisposing cardiac disorders, only 63 reported having seen their dentist in the past 2 years, although for dentate patients 47/61 had seen a dentist in the past 2 years. The dentists of 59 of these cases were then surveyed and replies received in 53 cases. Nineteen had no record of the patient having a cardiac disorder. In only 17 of the remaining cases was information on the cardiac disorder well enough recorded to warrant prophylaxis for at risk procedures. The dentist was usually told of the disorder only by the patient. Sixty-three per cent of dentists felt that communication between them and the patient's doctor was unsatisfactory. It is necessary to improve doctor/patient/dentist communication so that current recommendations on prophylaxis can be implemented to the full. This should be done through the patient's GP or consultant, who should communicate directly with the dentist. Details could also be inserted on warfarin cards and 'cardiac alert cards' expanded.

Anti-Bacterial Agents↗
PubMed1992

GABAB receptor-mediated inhibitory postsynaptic potentials evoked by electrical stimulation and by glutamate stimulation of interneurons in stratum lacunosum-moleculare in hippocampal CA1 pyramidal cells in vitro.

Following micropressure application of glutamate (500 microM) in stratum lacunosum-moleculare (L-M), inhibitory postsynaptic potentials (glut-IPSPs) were recorded in CA1 pyramidal cells. These glut-IPSPs were blocked by tetrodotoxin (1 microM) and, thus, were probably generated by the activation of local interneurons. The effects of pharmacological antagonists on glut-IPSPs and on electrically-evoked early and late IPSPs were assessed in the same cells during the same application of the antagonist. Local application of the GABAB antagonist 2-OH saclofen (1-4 mM) reduced both glut-IPSPs and late IPSPs but not early IPSPs. In contrast, the GABAB antagonist phaclofen (20 mM) reduced late IPSPs but not early IPSPs but not early IPSPs or glut-IPSPs. Early IPSPs were blocked by the GABAA antagonists bicuculline and picrotoxin but late IPSPs and glut-IPSPs were not. Repetitive electrical stimulation depressed early and late IPSPs as well as glut-IPSPs, suggesting that interneurons activated with glutamate were also stimulated electrically. Thus, interneurons in str. lacunosum-moleculare appear to inhibit pyramidal cells via a GABAB receptor-mediated IPSP. The discrepancy in the pharmacological profile of the GABAB glut-IPSPs and of the GABAB late IPSPs may suggest the presence of two GABAB mechanisms in CA1 pyramidal cells.

Animals↗
PubMed1992

Attention deficit disorder and age of onset of problem behaviors.

In the course of a prospective longitudinal study, we examined age of onset of behavior problems in a group of boys and girls identified with attention deficit disorder (ADD) at age 11. Onset occurred during the preschool years, by the first year of schooling, or by the end of the second year of school. Onset was strongly related to informant source at age 11, pattern of comorbidity of disorder at age 11, and developmental language, perceptual motor, and IQ measures. Onset by the first year of schooling was particularly related to poor reading skills. By age 15, nearly three-quarters of those with onset of problems before age 6 had one or more DSM-III disorders.

Adolescent↗
PubMed1992

Divergent effects of taxol on tumor necrosis factor-alpha-mediated cytolysis of ovarian carcinoma cells.

OBJECTIVE: Our objective was to study the combined effect of taxol and tumor necrosis factor-alpha on the cytolysis of human ovarian carcinoma cell lines, because taxol has been shown to be active against ovarian carcinoma and has also been shown to increase tumor necrosis factor-alpha release from macrophages. STUDY DESIGN: The combined effect of taxol and tumor necrosis factor-alpha on the cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780, which are sensitive to the cytolytic effect of tumor necrosis factor-alpha in the presence of inhibitors of protein synthesis, was investigated with a 24-hour chromium 51 release assay. RESULTS: At therapeutic concentrations taxol caused a significant increase in tumor necrosis factor-alpha-mediated cytolysis of Caov-3 and A2780 (p < or = 0.05). By contrast, taxol caused a decrease in the tumor necrosis factor-alpha-mediated cytolysis of SK-OV-3 and NIH:OVCAR-3 (p < or = 0.01). CONCLUSION: These results suggest that ovarian carcinomas have a heterogeneous response to the chemotherapeutic effect of taxol.

Carcinoma↗
PubMed1992

Intrauterine growth retardation and blood pressure at age seven and eighteen.

The association between intrauterine growth retardation and blood pressure in middle childhood and early adulthood was examined. At age 7, after adjusting for sex and weight, the differences between normal children and those who had experienced intrauterine growth delay were 0.9 mmHg (95% CI -0.1 to 2.2) for systolic and 0 mmHg (-1.7 to 2.0) for diastolic blood pressure respectively. The differences between the blood pressures of intrauterine growth retarded infants with an appropriate ponderal index and those with a low ponderal index were 4.4 mmHg (-0.9 to 7.9) for systolic, and 3.8 mmHg (0.2 to 7.3) for diastolic blood pressure respectively. At age 18 the differences were much less pronounced. The association between blood pressure and the placental weight was also examined. The evidence from this sample lends weak support to the findings of other studies which suggest that there is an association between factors occurring before or around the time of birth and blood pressure in later life.

Age Factors↗
PubMed1992

The telomeric 60 kb of chromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p.

A telomere YAC clone containing the most distal 115 kb of chromosome arm 4p has been previously isolated. This clone is of particular interest as it spans a potential candidate region for the Huntington disease gene. The YAC was subcloned into a phage vector, and a high-resolution restriction map extending to within 13 kb of the telomere was constructed. In situ hybridization of the YAC to human metaphase spreads gives a peak of hybridization on 4pter but also an increase in the number of signals close to several other telomeres. Where possible, these results were investigated further by the hybridization of probes from the YAC to somatic cell hybrids containing single human chromosomes. This analysis indicates that the most telomeric 60 kb of chromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p. The extent of this homology makes it less likely that the mutation for Huntington's disease is located within the telomere YAC clone.

Animals↗
PubMed1992

Defining a therapeutic dose of peripheral blood stem cells.

Peripheral blood stem cells (PBSC) are now used extensively to provide rapid and durable hematopoietic reconstitution following supralethal myeloablative therapies. A major clinical issue is the quantitation of the cells responsible for reconstitution. We review here published reports of transplants using the measurement of mononuclear cells and granulocyte-macrophage colony-forming units (CFU-GM) to quantitate PBSC. In addition, we present data from three institutions where hematopoietic recovery is correlated with doses of CFU-GM or CD34+ cells. These data suggest doses of 20 x 10(4) CFU-GM or 2 x 10(6) CD34+ cells/kg body weight that provide rapid engraftment of neutrophils and platelets.

Antigens, CD↗
PubMed1992

DSM-III disorders from age 11 to age 15 years.

Although research into the continuity of disorder from childhood to adolescence is sparse, results from both longitudinal and cross sectional studies suggest that the prevalence of disorder increases for girls but may remain more stable for boys. In this paper, the methodologies of two assessment phases of the Dunedin longitudinal study have been equated to estimate the continuity of DSM-III disorder from ages 11 to 15. Although the overall prevalence of disorder doubled between the ages, this was primarily because of an increase in nonaggressive conduct disorder and major depressive episode. The sex ratios in disorder had largely reversed from a male predominance at 11 to a female predominance at 15. In terms of persistence, over 40% of those with disorder at age 11 were also identified at age 15. However, over 80% of those identified with disorder at 15 did not have a history of disorder at 11. Significant sex differences were also found in the continuity of internalizing and externalizing disorders, with externalizing disorders showing more continuity for boys, and internalizing for girls. Logistic regression models were employed to evaluate the roles family background, academic and social competence, and early histories of behavior problems may play in the determination of disorder continuity.

Adolescent↗
PubMed1992

Acquired resistance in Arabidopsis.

Acquired resistance is an important component of the complex disease resistance mechanism in plants, which can result from either pathogen infection or treatment with synthetic, resistance-inducing compounds. In this study, Arabidopsis, a tractable genetic system, is shown to develop resistance to a bacterial and a fungal pathogen following 2,6-dichloroisonicotinic acid (INA) treatment. Three proteins that accumulated to high levels in the apoplast in response to INA treatment were purified and characterized. Expression of the genes corresponding to these proteins was induced by INA, pathogen infection, and salicylic acid, the latter being a putative endogenous signal for acquired resistance. Arabidopsis should serve as a genetic model for studies of this type of immune response in plants.

Amino Acid Sequence↗
PubMed1992

NMDA-receptor-independent long-term potentiation.

Although NMDA-R-dep LTP in the hippocampus has received much attention, it is clear that many types of LTP do not involve NMDA receptors. While early studies of NMDA-R-indep LTP were done in invertebrates, an NMDA-R-indep LTP is also seen in at least three excitatory pathways of the hippocampus. There would appear to be quite diverse mechanisms of induction of NMDA-R-indep LTP, although in most cases there is evidence, or at least a suggestion, that Ca2+ is involved. At the hippocampal CA3 MF synapse, activation of voltage-gated Ca2+ channels has been proposed as a trigger for LTP induction, and this may also be the case for certain types of LTP at the SC synapse in CA1 (25, 40). The modulation of both MF LTP and Ca2+ channels by beta-adrenoreceptor and muscarinic agonists suggests that specifically the L-type channel is critical for MF LTP induction. L-type Ca2+ channels may also be involved in NMDA-R-indep LTP at SC synapses (6, 40). Clearly more work is needed to test these possibilities. In addition, it will be interesting to discover whether voltage-gated Ca2+ channels play a role in LTP in other areas of the brain such as the cerebral cortex and amygdala (24).

Animals↗
PubMed1992

The origin of water and urea sampled at bronchoalveolar lavage in asthmatic and control subjects.

Bronchoalveolar lavage (BAL) urea has been advocated as a denominator that might allow for the dilution of the pulmonary epithelial lining fluid sampled at BAL, and so provide a meaningful method of expressing BAL data. We investigated the origin of water and urea sampled at BAL in five asthmatic and five control subjects using radiolabeled urea injected intravenously 5 min before BAL. Labeled BAL urea was found to be fully equilibrated with that in the bloodstream. A strong relationship was found between influx of radiolabeled water and radiolabeled urea from blood to BAL fluid, suggesting that urea sampled at BAL may be derived predominantly from an acute movement from the bloodstream into the BAL aspirate. We conclude that urea is an inappropriate denominator for the expression of BAL results, and that the fluid and solute dynamics that occur during BAL are both complex and variable.

Adult↗