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Biomedical subjects

S A Williams

Publications and source records attributed to S A Williams.

At least 91 records · Page 5Linked to original sources

The diagnostic reliability of clinical dental auxiliaries in caries prevalence surveys--a pilot study.

The Nuffield Report recommended the development of further education and training for dental auxiliary personnel. The extent to which clinical dental auxiliaries might carry out oral assessments is under consideration currently. While other countries have employed clinical dental auxiliaries as examiners in national surveys, there is no evidence to suggest that they are able to perform oral assessments effectively in the United Kingdom. This study aimed to investigate the possibility of using dental hygienists or therapists as examiners in epidemiological surveys. Five dentists and three clinical dental auxiliaries were trained and calibrated together using standardised BASCD training procedures. Forty 5-year-old children in Leeds were recruited to the training and calibration exercise. Data were analysed according to BASCD recommendations. There were no differences in performance between dentists and auxiliaries. All examiners fell within 95 percent confidence limits of the group mean dt, mt, ft and dmft. Mean grouped dmft scores for the benchmark examiner, dentists and auxiliaries were 1.92, 1.84 and 1.92 respectively. Sensitivity values for dentists and auxiliaries ranged from 0.54 to 1.00 and 0.80 to 0.94 respectively. Kappa scores were 0.70 to 0.90 for dentists; and 0.82 to 0.87 for the auxiliaries. It was concluded that the dental hygienists and therapist recruited to this study could be used in epidemiological surveys of caries in 5-year-old children.

Child, Preschool↗

Caries experience, tooth loss and oral health-related behaviours among Bangladeshi women resident in West Yorkshire, UK.

Several studies have reported high levels of caries experience among young Muslim Asian children, but there has been little corresponding information on adult dental health or related health behaviours. This paper presents the results of a questionnaire together with clinical oral findings among first generation Bangladeshi women aged over 25 years. The majority chewed betel quid with tobacco, were of rural origin, used traditional oral hygiene practices and had never visited a dentist. Of the 247 examined, only one was edentulous. A very low level of caries experience was recorded, a mean DFT score of 1.87 at 25-34 years of age, with an average of 1.05 missing teeth. Coronal caries experience was found to be independent of oral hygiene methods, including the use of fluoride toothpaste, or the frequency of betel quid chewing. It was concluded that Bangladeshi adult women have considerably lower levels of caries experience and tooth loss than United Kingdom adults as represented in recent national surveys.

Adult↗

Positron emission tomographic analysis of central 5-hydroxytryptamine2 receptor occupancy in healthy volunteers treated with the novel antipsychotic agent, ziprasidone.

Ziprasidone is a novel antipsychotic agent, with high affinity for dopamine D2 and serotonin (5-HT2) receptors in vitro and in animal models. The goal of this study was to determine the time course of 5-HT2 receptor occupancy (%RO) in healthy humans after a single p.o. dose. Positron emission tomography with the 5-HT2 ligand, [18F]setoperone, was performed in eight male volunteers, in the drug-naive, base-line (BL) state and 4 to 18 hr after ziprasidone (40 mg). Cerebral cortical binding potential [BP, maximum number of available receptors/KD or association rate for specific binding (k3)/dissociation rate for specific binding (k4)] was estimated using the cerebellum as reference. Transport rate from plasma to brain (K1), transport rate from brain to plasma (k2), association rate of nonspecific binding (k5) and dissociation rate of nonspecific binding (k6) were derived by fitting cerebellar time-activity curves to a three-compartment model. Fitting of cortical data to a 4-compartment model with K1/k2, k5 and k6, fixed at cerebellar values, was used to determine k3 and k4. %RO was calculated using the relation: %RO = [(BPBL-BPDRUG)/BPBL] x 100%. At BL, cortical parameter (mean +/- S.E.M) were: K1 = 0.121 +/- 0.0072 ml.min-1.g-1; k2 = 0.0581 +/- 0.004 min-1; k3 = 0.321 +/- 0.0026 min-1; k4 = 0.0957 +/- 0.0059 min-1; k5 = 0.0147 +/- 0.00066 min-1; and k6 = 0.0059 +/- 0.00042 min-1. Ziprasidone did not effect K1, k2, k5 or k6; however, k3 was reduced and k4 was elevated (P < .01). RO was nearly complete at 4 hr after dosing (98%) and remained elevated at 18 hr (46%). Plasma concentrations were well described by a biexponential function and decreased much more rapidly than RO. These results establish that ziprasidone has high potency for blocking 5-HT2 receptors in healthy humans; a potentially important characteristic of atypical antipsychotic agents.

Adult↗

Cationic lipids reduce time and dose of c-myc antisense oligodeoxynucleotides required to specifically inhibit Burkitt's lymphoma cell growth.

Burkitt's lymphoma is characterized by a translocation of the c-myc gene with one of the immunoglobulin loci which activates overexpression of the c-myc oncogene. Antisense-oligodeoxynucleotides (AS-ODNs) offer the potential to block specific c-myc gene expression within lymphoma cells, but often exhibit a low efficiency of AS-ODN uptake. In this study, a polycationic lipid reagent, Lipofectamine (LFM), was utilized as a vehicle to increase efficiency of delivery, decrease the time needed to observe an inhibitory effect, and decrease the AS-ODN dose. The objective was to develop a more efficient and rapid in vitro AS-ODN strategy to inhibit proliferation of c-myc-dependent lymphoma cells and to test the specificity of Burkitt's lymphoma cell line-directed AS-ODNs for potential use as molecular purging agents in bone marrow transplantation. Proliferation assays were performed to determine the inhibitory effect of the AS-ODNs on two Burkitt's lymphoma cell lines with different chromosomal translocations, Daudi and ST486, in medium containing 8.5 microM LFM. AS-ODNs at a concentration of 0.36 microM induced a significant decrease in proliferation for both cell lines using the specific AS-ODN for each respective translocation. Within 5 h, Daudi responded to its specific AS-ODN/lipid complexes with a 35% decrease in proliferation, compared to cells which received no treatment or Daudi-specific AS-ODN without LFM (P = 0.0001). Daudi showed an insignificant decrease in proliferation when treated with an AS-ODN specific for the ST486 translocation (4%, P = 0.26). ST486 proliferation was decreased by 52% when treated with the specific antisense for ST486 compared to no treatment or ST486-specific AS-ODN without LFM (P < 0.003). Treatment with the AS-ODN specific for Daudi showed an insignificant 4% decrease (P = 0.42). Controls, including sense ODN for structure, reverse AS-ODN for structure and base composition, and AS-ODN without LFM, did not produce a significant change in cells treated with LFM alone or cells receiving no treatment. Clonogenic assays of both Daudi and ST486 treated with their specific AS-ODNs revealed a 50% inhibition of colony formation after the 5 h incubation as compared to no treatment. Confocal laser scanning microscopy verified that cellular uptake of AS-ODN was enhanced by cationic lipids. Immunoblot analysis showed a 63 +/- 5% and a 50 +/- 3% reduction in intracellular c-myc levels for Daudi and ST486, respectively, when their respective AS-ODNs were administered. Normal bone marrow progenitors were unaffected by the ODN/LFM complexes. These results suggest that the specific c-myc AS-ODN/LFM complexes inhibit c-myc-dependent tumor proliferation at an earlier time and at a lower dose compared to no lipid facilitation. This approach may form the basis for utilizing specific AS-ODN/LFM therapy either alone or in a cocktail of other agents as an ex vivo molecular purging approach to autologous stem cell transplantation in Burkitt's lymphoma.

Adult↗

Direct evaluation of electronic coupling mediated by hydrogen bonds: implications for biological electron transfer.

Three supramolecular bischromophoric systems featuring zinc(II) and iron(III) porphyrins have been synthesized to evaluate the relative magnitudes of electronic coupling provided by hydrogen, sigma, and pi bonds. Laser flash excitation generates the highly reducing singlet excited state of the (porphinato)zinc chromophore that can subsequently be electron transfer quenched by the (porphinato)iron(III) chloride moiety. Measurement of the photoinduced electron transfer rate constants enables a direct comparison of how well these three types of chemical interactions facilitate electron tunneling. In contrast to generally accepted theory, electronic coupling modulated by a hydrogen-bond interface is greater than that provided by an analogous interface composed entirely of carbon-carbon sigma bonds. These results bear considerably on the analysis of through-protein electron transfer rate data as well as on the power of theory to predict the path traversed by the tunneling electron in a biological matrix; moreover, they underscore the cardinal role played by hydrogen bonds in biological electron transfer processes.

Electron Transport↗

Accuracy and precision of joint space width measurements in standard and macroradiographs of osteoarthritic knees.

OBJECTIVES: To improve the reproducibility and accuracy of joint space width (JSW) measurement as an assessment of cartilage loss in patients with osteoarthritis (OA) of the knee by determining how precision and accuracy of JSW measurement were altered by a computerised method of measurement, correction for radiographic magnification, radiography of the knee in the standing semiflexed view, and high definition macroradiography of the knee in the semiflexed view--taking JSW measurements from standard radiographs of OA knees in the extended view as the standard for comparison. METHODS: Twenty five OA and 10 nonarthritic knees were radiographed in the extended view and minimum JSW was measured manually. Conventional and x5 macroradiographs were taken in the semiflexed view. All radiographs were taken twice on the same day and repeated two weeks later. Automated computerised measurement of minimum JSW was obtained from digitally stored images of all radiographs. RESULTS: For medial compartment JSW measurements, computerised was more accurate than manual, correction for radiographic magnification improved precision and accuracy, measurements in the semiflexed view were more precise and accurate, and macroradiography increased measurement precision. For the lateral compartment JSW measurements, correction for radiographic magnification improved precision and accuracy, and the semiflexed view improved precision only. CONCLUSIONS: Protocols defining radiographic and mensural procedures are essential for quality control of knee radiography in the semiflexed view to permit accurate and reproducible measurement of JSW. Macroradiography provides greater precision of JSW measurement.

Adult↗

The dental health of single male hostel dwellers in Leeds.

Attitudes and behaviour towards oral health among 104 homeless men in Leeds were assessed at interview. Of these, 101 agreed to a subsequent dental examination. The findings confirmed a high level of normative need despite a low level of felt need. Appointments were offered at two local community dental clinics, but the majority of men failed to attend. Appropriate provision of dental care is discussed and recommendations made for future developments.

Adolescent↗

Using Oncology Nursing Society Cancer Chemotherapy Guidelines as a basis for continuing education in rural hospitals.

PURPOSE/OBJECTIVES: To describe a workshop developed to teach nurses caring for patients with cancer in a southern, rural area how to administer chemotherapy in an inpatient or homecare setting. DATA SOURCES: The Oncology Nursing Society (ONS) Cancer Chemotherapy Guidelines and published articles and books. DATA SYNTHESIS: An oncology clinical nurse specialist teaching at a local university developed and presented 10 hours of didactic content and a 6-hour clinical practicum. The workshop was conducted in association with a community hospital, which offered oncology care to patients with cancer in the community. CONCLUSIONS: All nurses who successfully completed the workshop demonstrated improved ability in caring for patients with cancer and in administering chemotherapy. The ONS Cancer Chemotherapy Guidelines provided an excellent outline for the development of an initial course on the science of chemotherapy and management of related symptoms. IMPLICATIONS FOR NURSING PRACTICE: Many nurses work in rural areas where they are expected to provide competent nursing care to a variety of specialized patient populations, yet they have limited access to educational opportunities. A workshop format is feasible and can provide the education necessary for nurses who care for patients with cancer.

Antineoplastic Agents↗

Dentists' perceptions of difficulties encountered in providing dental care for British Asians.

British Asians represent a substantial proportion of the population in some parts of the United Kingdom, yet many fail to use dental services regularly. This study aimed to investigate dentists' concerns about providing care for this client group. Following a pilot study, a postal questionnaire was sent to general dental practitioners and community dental officers working in seven family health services authority localities. Of 1546 questionnaires circulated, 639 (41 per cent) were returned. The language barrier was most frequently identified as a major impediment to care (78 per cent), followed by patients' understanding of treatment proposed (67 per cent), while 64 per cent found difficulty obtaining medical histories. Only 20 per cent considered that gaining consent for treatment was a problem. Other issues concerned attendance as casual patients (65 per cent) and, in terms of treatment provided, difficulties with preventive (77 per cent), periodontal (66 per cent) and orthodontic care (27 per cent). The proportion of dentists identifying barriers to care reflected the English-speaking abilities of different Asian populations. Compared with the high percentage mentioning language, understanding and medical history, the small proportion of dentists who thought that consent was of concern suggests that concepts of consent may need to be questioned. Despite the low response rate, the high proportion of respondents identifying these issues implies that the present position may put patients' health at risk, restrict treatment options and offer a potential for litigation. Future initiatives to overcome barriers to appropriate care must address the perspectives of dentists treating British Asians, as well as that of the client group.

Attitude of Health Personnel↗

Breast feeding, bottle feeding and dental caries in Kuwait, a country with low-fluoride levels in the water supply.

A study was carried out in Kuwait, a country with low levels of fluoride in the water supplies, to determine the prevalence and extent of caries in early childhood, and enquire into associated factors. Mothers of pre-schoolchildren were interviewed, and their children aged 18 to 48 months received a dental examination. Of the 227 children examined, 107 (47 per cent) were caries free, and 41 (18%) had five or more dmf teeth. 'Nursing caries', affecting at least two maxillary incisors, was seen in 19 per cent of the sample. Breast fed children were significantly more likely to be caries free than those who were bottle fed from birth, although 'nursing caries' was positively associated with the practice of breast feeding at night 'at will' after 6 months of age (P < 0.01). Bottle fed children were more likely to develop caries, including 'nursing caries', particularly when the practice was continued to an older age. It was concluded that 'nursing caries' constitutes a significant dental health problem in Kuwait.

Bottle Feeding↗

Molecular biology and cytogenetics of non-Hodgkin's lymphoma in children.

Molecular analysis, combined with cytogenetic studies of proto-oncogenes and tumor suppressor genes, has provided insight into the pathogenesis of non-Hodgkin's lymphoma. Characterization of these malignancies at the molecular level will aid in developing more sensitive detection methods for earlier and more accurate diagnosis. Thus, genetic rearrangements provide highly specific molecular markers for monitoring malignant cells. Additionally, a more detailed understanding of the precise, molecular steps leading to malignant transformation will facilitate the development of more specific and, perhaps, less toxic therapies.

Blotting, Southern↗

Structure-function relationships in the 47-kDa antenna protein and its complex with the photosystem II reaction center core: insights from picosecond fluorescence decay kinetics and resonance Raman spectroscopy.

We report the fluorescence decay kinetics and the vibrational properties of chlorophyll a bound to the 47-kDa antenna protein (CP47) of spinach photosystem II. The chlorophyll fluorescence of CP47 samples decays with four lifetimes (tau = 75.8 ps, 1.05 ns, 3.22 ns, and 5.41 ns). The 75.8-ps and 3.22-ns components are associated with chlorophyll a bound to relatively intact centers, the 1.05-ns component corresponds to chlorophyll bound to centers that are slightly perturbed, and the the 5.41-ns phase probably originates from centers that are severely denatured. The resonance Raman spectrum of CP47 at 441.6 nm (this work) and at 406.7 nm [de Paula, J. C., Ghanotakis, D. F., Bowlby, N. R., Dekker, J. P., Yocum, C. F., & Babcock, G. T. (1990) in Current Research in Photosynthesis (Baltscheffsky, M., Ed.), Vol. I, pp 643-646, Kluwer Academic Publishers, Dordrecht, The Netherlands] shows heterogeneity in the C = O stretching region. This part of the spectrum monitors the environment of the keto group at position 9 of the chlorophyll a molecule. We show that several structurally distinct pools of chlorophyll a are bound to CP47. Four of these may be distinguished by their C9 = O stretching frequencies (nu C = O = 1670, 1688, 1693, and 1701 cm-1). By analyzing the resonance enhancement pattern of these modes, we ascribe the 1693-cm-1 vibration to denatured centers. Of the remaining populations, we propose that the 1670-cm-1 vibration is consistent with a hydrogen bond between the C9 = O group of chlorophyll a and the protein. We elaborate on the role of this chromophore-protein interaction in the mechanism of energy transfer within the 47-kDa antenna protein.

Chlorophyll↗

Cloning and analysis of a constitutive heat shock (cognate) protein 70 gene inducible by L-glutamine.

An intronless gene encoding a protein of 652 amino acid residues with an M(r) of 71,266, showing between 79% and 59% identity in nucleotide sequence with heat shock protein 70 (HSP 70) genes of Bremia lactucae (a parasitic Oomycete of lettuce) and a wide range of organisms that include humans, was isolated from the nonparasitic Oomycete Achlya klebsiana. While the gene appears to be constitutively expressed, L-glutamine augmented its expression particularly under conditions of nutritional stress. L-Glutamine enhanced the transcription of a 2.4-kilobase poly(A)+ RNA simultaneously in the same way as it elevated the cellular level of the HSP 70-like protein. A polyclonal antibody (affinity-purified) raised in rabbit against the purified monomeric (M(r) 120,000) form of an NAD-specific glutamate dehydrogenase (Yang, B., and LéJohn, H.B. (1994) J. Biol. Chem. 269, 4506-4512) immunoprecipitated the HSP 70-like protein, and it was used to study the kinetics of induction of this stress-related protein and the effect of proteinase inhibitors on its metabolism. By using as probes four partial length cDNA clones, nine overlapping DNA fragments of the organism's genome carrying the HSP 70-like protein gene were isolated from a genomic library. The nucleotide sequence of the gene, including its boundaries, was determined by using these genomic clones. The 5'-untranslated boundary of the gene displayed the classical nucleotide arrangement of heat shock elements as well as CCAAT and TATA box motifs. Within the coding region are the typical conserved amino acid heat shock protein signatures 1 and 2 at the predicted locations. By primer extension and S1 nuclease protection mapping system, we estimated that the gene is probably transcribed into a message of 2.2 kilobases.

Amino Acid Sequence↗

Construction of cDNA libraries from limiting amounts of material.

The use of cDNA libraries has become increasingly widespread as new techniques for library construction and analysis have become available. In recent years, interest in cell-type or stage-specific gene expression has necessitated the construction of cDNA libraries from very small numbers of cells. Recent advances in techniques of RNA isolation, cDNA synthesis, library construction, and the use of the polymerase chain reaction have made this a realistic goal.

Animals↗

Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer sequences.

This paper is the first large-scale molecular phylogenetic study on filarial parasites (family Onchocercidae) which includes 16 species of 6 genera: Brugia beaveri Ash et Little, 1962, B. buckleyi Dissanaike et Paramananthan, 1961; B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson et Heisch, 1958) Buckley, 1960; B. timori Partono et al, 1977; Wuchereria bancrofti (Cobbold, 1877) Seurat, 1921: W. kalimantani Palmieri. Purnomo, Dennis and Marwoto, 1980: Mansonella perstans (Manson, 1891) Eberhard et Orihel, 1984; loa loc, Stiles, 1905; Onchocerca volvulus (Leuckart, 1983) Railliet er Henry, 1910; O. ochengi Bwangamoi, 1969; O. gutturosa Neumann, 1910; Dirofilaria immitis (Leidy, 1856) Railliet e Henry, 1911; Acanthocheilonema viteae (Krepkogorskaya, 1933) Bain, Baker et Chabaud, 1982 and Litomosoides sigmodontis Chandler, 1931. 5S rRNA gene spacer region sequence data were collected by PCR, cloning and dideoxy sequencing. The 5S rRNA gene spacer region sequences were aligned and analyzed by maximum parsimony algorithms, distance methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the robustness of the different phylogenetic reconstructions. The data indicated that 5S spacer region sequences are highly conserved within species yet differ significantly between species. Spliced leader sequences were observed in all of the 5S rDNA spacers with no sequence variation, although flanking region sequence and length heterogeneity was observed even within species. All of the various tree-building methods gave very similar results. This study identified four clades which are strongly supported by bootstrap analysis the Brugia clade; the Wuchereria clade; the Brugia-Wuchereria clade and the Onchocerca clade. The analyses indicated that L. sigmodontis and A. viteae may be the most primitive among the 16 species studied. The data did not show any close relationship between Loa loa and D. immitis presently classified in the same subfamily, and the constitution of the Dirofilariinae subfamily is questionable.

Algorithms↗

Molecular phylogenetic studies on Brugia filariae using Hha I repeat sequences.

This paper is the first molecular phylogenetic study on Brugia parasites (family Onchocercidae) which includes 6 of the 10 species of this genus: B. beaveri Ash et Little, 1964; B. buckleyi Dissanaike et Paramananthan, 1961: B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson er Heisch, 1958) Buckley, 1960 and B. timori Partono et al., 1977. Hha l repeat sequences are 322 nucleotides long, highly repeated, tandemly arranged and unique to the nuclear genomes of the genus Brugia. Hha l repeat sequence data was collected by PCR, cloning and dideoxy sequencing. The Hha l repeat sequences were aligned and analyzed by maximum parsimony algorithms, distance methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the robustness of the different phylogenetic reconstructions. The data indicated that the Hha l repeat sequences are highly conserved within species yet differ significantly between species. The various tree-building methods gave identical results. Bootstrap analyses on the Hha l repeat sequence data set identified at least two clades: the B. pahangi-B. beaveri clade and the B. malayi-B. timori-B. buckleyi clade; the first clade includes parasites of carnivores from Asia and America; the second includes species from primates and lagomorphs from Asiatic region. It was also noted that the Hha l repeat sequences obtained from B. malayi were identical to those obtained from B. timori, indicating very recent speciation.

Algorithms↗

NPR genes, which are negatively regulated by phytochrome action in Lemna gibba L. G-3, can also be positively regulated by abscisic acid.

We have found that NPR1 and NPR2, two genes from Lemna gibba L. G-3 that can be negatively regulated by phytochrome action, can also be positively regulated by the plant hormone abscisic acid (ABA). Both genes were responsive to low concentrations of exogenous ABA; an increase in NPR1 RNA could be detected in response to concentrations as low as 10 nM. We have also tested phytochrome responsiveness of 5' promoter-deletion constructs of one of these genes, NPR1, in transient assays utilizing particle bombardment. This analysis demonstrated that DNA sequences important for phytochrome regulation are present downstream of -198 from the transcription start site. A response to ABA treatment could also be observed in the transient assay system. When intact plants were placed in darkness, there was an increase in ABA levels as well as increased levels of NPR1 and NPR2 RNA.

Abscisic Acid↗