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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 109 records · Page 6Linked to original sources
PubMed2000

Health professionals' baseline knowledge of oral/pharyngeal cancers.

BACKGROUND: The purpose of this study was to evaluate: self-perceived competency in screening for oral/pharyngeal cancers (OPCs); knowledge about their signs, symptoms, and risk factors; and percentage of patients routinely examined. METHODS: Of 352 health professionals who completed an assessment, a subgroup of 110 physicians and dental providers was identified. Thirty-three of those had advanced training (AT) related to the oral cavity and 77 were primary care physicians (PCPs). RESULTS: Only 7% of the PCPs reported examining 100% of their patients for OPCs. A greater percentage of the PCP group than the AT group felt their knowledge about OPCs was not up to date (p < 0.05) and inaccurately identified common signs and sites of early OPCs. A greater percentage (p < 0.05) of the PCP group also reported the need for additional training. CONCLUSION: These results suggest the need for OPC educational programs aimed toward health care providers without advanced training related to the oral cavity.

Adult↗
PubMed2000

Rapid separation of nitroaromatic compounds by solvating gas chromatography.

Nitroaromatic compounds such as 2,4,6-trinitrotoluene are used in the production of explosive and munitions, and are environmental contaminants as a result of such use. Conventional methods to detect these compounds have relied on liquid and gas chromatography to isolate the individual compounds which may be present at low levels in complex environmental matrices before final detection and identification. A new method, solvating gas chromatography, was used to rapidly separate 8 nitroaromatic compounds, showing improved speed relative to conventional liquid and gas chromatography methods. Solvating gas chromatography allows near real-time detection for these energetic compounds, providing improvements in their detection as environmental contaminants, and as compounds of interest to law enforcement and military organizations.

Chromatography, Gas↗
PubMed2000

Sequencing of the Francisella tularensis strain Schu 4 genome reveals the shikimate and purine metabolic pathways, targets for the construction of a rationally attenuated auxotrophic vaccine.

Francisella tularensis is the etiological agent of tularemia, a serious disease in several Northern hemisphere countries. The organism has fastidious growth requirements and is very poorly understood at the genetic and molecular levels. Given the lack of data on this organism, we undertook the sample sequencing of its genome. A random library of DNA fragments from a highly virulent strain (Schu 4) of F. tularensis was constructed and the nucleotide sequences of 13,904 cloned fragments were determined and assembled into 353 contigs. A total of 1.83 Mb of nucleotide sequence was obtained that had a G+C content of 33.2%. Genes located on plasmids pOM1 and pNFL10, which had been previously isolated from low virulence strains of F. tularensis, were absent but all of the other known F. tularensis genes were represented in the assembled data. F. tularensis Schu4 was able to grow in the absence of aromatic amino acids and orthologues of genes which could encode enzymes in the shikimate pathway in other bacteria were identified in the assembled data. Genes that could encode all of the enzymes in the purine biosynthetic and most of the en- zymes in the purine salvage pathways were also identified. This data will be used to develop defined rationally attenuated mutants of F. tularensis, which could be used as replacements for the existing genetically undefined live vaccine strain.

Bacterial Vaccines↗
PubMed2000

An epidemiological study to establish the prevalence of urinary symptoms and felt need in the community: the Leicestershire MRC Incontinence Study. Leicestershire MRC Incontinence Study Team.

BACKGROUND: The aim of the study was to establish the prevalence of urinary symptoms and felt need in adults. This paper discusses problems with setting thresholds to distinguish cases from non-cases in this field of research. Few studies have provided detailed age- and sex-specific prevalence estimates for felt need in relation to urinary symptoms. METHODS: A cross-sectional postal survey was carried out of 15,904 community-dwelling adults aged 40 years or more registered with general practitioners in Leicestershire. Subjects were selected randomly by household from the Leicestershire Health Authority Register. The postal questionnaire consisted of questions on general health, urinary and bowel symptoms, quality of life, service use and demographic characteristics. RESULTS: Thirty-four per cent of the sample reported clinically significant symptoms. The prevalence and severity of symptoms increased with age. However, only 2 per cent of the sample reported symptoms that were clinically significant, bothersome and socially disabling. CONCLUSION: Urinary symptoms are very common in adults over 40 years of age living in the community. However, symptom-based estimates probably overestimate the level of need for health care in the community. It may be more effective and efficient to target services, in the first instance, on those people who report clinically significant symptoms that are bothersome or socially disabling. A consensus on thresholds and definitions of urinary symptoms is required to standardize clinical and research work and to target services more appropriately.

Adult↗
PubMed2000

Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans.

Estrogens and androgens are essential for the maturation of the ovarian follicle and normal fertility in the female. We have used antibodies specific for both forms of estrogen receptor (alpha [ERalpha] and beta [ERbeta]) and androgen receptor (AR) to investigate the pattern of receptor expression in ovaries obtained from women and from a New World primate, the Common marmoset (Callthrix jacchus). On Western blots, three antibodies directed against different peptides within human ERbeta all recognized recombinant human (h) ERbeta but did not bind to recombinant hERalpha. The ERbeta protein was extracted from human ovary and prostate and marmoset ovary. In marmoset and human ovaries, ERbeta protein was detected in the nuclei of granulosa cells in all sizes of follicle (both before and after formation of the antrum), and it was also detected in thecal cells, corpora lutea, surface epithelium, and stroma. In contrast, ERalpha protein was not detected in the nuclei of granulosa cells in preantral follicles, was low/absent from stromal and thecal cells, but was expressed in granulosa cells of antral follicles and in the surface epithelium. The pattern of expression of AR protein more closely resembled that of ERbeta than ERalpha. In conclusion, three independent antibodies have demonstrated convincingly that ERbeta is expressed in a wide range of cells in the primate ovary. Granulosa cells in preantral follicles could contain ERbeta:beta dimers. In antral follicles, however, ERalpha is also expressed, and the formation of homo- or heterodimers containing ERalpha may influence the pattern of gene activation within these cells.

Amino Acid Sequence↗
PubMed2000

Accessing patient assistance programs to meet clients' medication needs.

The high cost of medication is a barrier to patient compliance. Nurse practitioners can access patient assistance programs to assist low-income clients to obtain medications, empowering them to take action to improve their health. At Health Care Access, a primary care clinic serving low-income, uninsured persons, approximately $150,000 worth of medications were obtained through patient assistance programs in 1997, compared to the total clinic budget of $189,000. Processes for obtaining prescription drugs vary between pharmaceutical companies. An understanding of these types of programs provides nurse practitioners access to these resources for their clients.

Drug Costs↗
PubMed2000

An immunoglobulin G1 monoclonal antibody highly specific to the wall of Cryptosporidium oocysts.

The detection of Cryptosporidium oocysts in drinking water is critically dependent on the quality of immunofluorescent reagents. Experiments were performed to develop a method for producing highly specific antibodies to Cryptosporidium oocysts that can be used for water testing. BALB/c mice were immunized with six different antigen preparations and monitored for immunoglobulin G (IgG) and IgM responses to the surface of Cryptosporidium oocysts. One group of mice received purified oocyst walls, a second group received a soluble protein preparation extracted from the outside of the oocyst wall, and the third group received whole inactivated oocysts. Three additional groups were immunized with sequentially prepared oocyst extracts to provide for a comparison of the immune response. Mice injected with the soluble protein extract demonstrated an IgG response to oocysts surface that was not seen in the whole-oocyst group. Mice injected with whole oocysts showed an IgM response only, while mice injected with purified oocyst walls showed little increase in IgM or IgG levels. Of the additional reported preparations only one, BME (2-mercaptoethanol treated), produced a weak IgM response to the oocyst wall. A mouse from the soluble oocyst extract group yielding a high IgG response was utilized to produce a highly specific IgG(1) monoclonal antibody (Cry104) specific to the oocyst surface. Comparative flow cytometric analysis indicated that Cry104 has a higher avidity and specificity to oocysts in water concentrates than other commercially available antibodies.

Animals↗
PubMed2000

The response regulator PhoP is important for survival under conditions of macrophage-induced stress and virulence in Yersinia pestis.

The two-component regulatory system PhoPQ has been identified in many bacterial species. However, the role of PhoPQ in regulating virulence gene expression in pathogenic bacteria has been characterized only in Salmonella species. We have identified, cloned, and sequenced PhoP orthologues from Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica. To investigate the role of PhoP in the pathogenicity of Y. pestis, an isogenic phoP mutant was constructed by using a reverse-genetics PCR-based strategy. The protein profiles of the wild-type and phoP mutant strains, grown at either 28 or 37 degrees C, revealed more than 20 differences, indicating that PhoP has pleiotrophic effects on gene expression in Y. pestis. The mutant showed a reduced ability to survive in J774 macrophage cell cultures and under conditions of low pH and oxidative stress in vitro. The mean lethal dose of the phoP mutant in mice was increased 75-fold in comparison with that of the wild-type strain, indicating that the PhoPQ system plays a key role in regulating the virulence of Y. pestis.

Animals↗
PubMed2000

Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division.

Calpains are a family of Ca(2+)-dependent intracellular cysteine proteases, including the ubiquitously expressed micro- and m-calpains. Both mu- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4). The physiological roles and possible functional distinctions of mu- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murine Capn4 eliminated both mu- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.

Animals↗
PubMed2000

Prevalence and impact of urinary symptoms among community-dwelling stroke survivors.

BACKGROUND AND PURPOSE: To establish prevalence of urinary symptoms among community-dwelling stroke survivors and how these symptoms affected lives of these survivors compared with a nonstroke population. METHODS: The present study was a community-based postal survey in Leicestershire community, UK (that excluded institutional settings), that was designed to track stroke, urinary, and bowel symptoms and the effect of such symptoms on relationships, social life, daily activities, and overall quality of life. Subjects included 14 600 people who were living in the community and </=40 years of age, randomly selected from the Leicestershire Health Authority Register. RESULTS: A 70% response rate was achieved with the return of 10 226 questionnaires. Prevalence of reported stroke was 4% (n=423). Prevalence of urinary symptoms was 34% (n=3197). Overall, stroke survivors had a higher prevalence of symptoms than the nonstroke population (64% to 32%, respectively). These symptoms were reported to have more of an effect on the lives of the stroke survivors compared with the nonstroke population even when adjusted for age and sex differences. This reported impact was not related to the stroke per se but to the severity of the urinary symptoms. CONCLUSIONS: These data show a high prevalence of urinary symptoms among community-dwelling stroke survivors. These symptoms were reported to have considerable impact on the lives of stroke survivors, which needs to be taken into account in future research and clinical practice.

Adult↗
PubMed2000

Physician prescribing of anorexigenics for weight loss in Salt Lake County, Utah.

The objective of this survey of primary care physicians in Salt Lake County, Utah, was to determine how many of these providers were prescribing anorexigenics (antiobesity drugs) and to evaluate their knowledge of side effects and drug interactions. A confidential survey was sent to 377 family practice, internal medicine, and obstetrics-gynecology physicians, of whom 236 (62.5%) responded. Of those who answered the survey completely, 146 (65.2%) prescribed anorexigenics to 5,107 patients. Family practice physicians, male physicians less than 40 years old, and internal medicine physicians less than 40 years old prescribed anorexigenics more frequently than their counterparts. Female physicians (vs male) and female family practice physicians (vs male family practice physicians) reported a higher proportion of psychiatric comorbidity among patients for whom they prescribed the drugs. Respondents had limited knowledge of side effects and drug interactions of anorexigenics. Better understanding of physicians' prescribing patterns of these agents is relevant for current and future optimal treatment of obesity.

Adult↗
PubMed2000

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-beta (TGFbeta)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of beta-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

Amino Acid Sequence↗
PubMed2000

Characterization and outcome of "hard to mobilize"' lymphoma patients undergoing autologous stem cell transplantation.

A "hard to mobilize" patient was defined as one in whom >or= 1x10(6) CD 34+ cells/kg cannot be obtained after two consecutive large volume aphereses. Forty-four consecutive Hodgkin's and non-Hodgkin's lymphoma patients who underwent autologous peripheral blood stem cell (PBSC) transplant treatment between June 1996 and June 1998 were included in this study. Twenty-one patients (48%) met the definition of "hard to mobilize" (Group I). All the rest of the patients (n=23) were the good mobilizers (Group II). The initial mobilization protocol for most patients was 10 microg/kg of G-CSF alone for both groups. For Group I, 7/21 (33%) patients were unable to achieve a minimal dose of >or= 1x10(6) CD34+ cells/kg even after a second mobilization attempt and/or bone marrow (BM) harvest (n=5). Overall, 11/21 (52%) required an additional mobilization and/or BM harvest. Only 3/21 (14%) patients were able to meet the target cell dose of >or= 2.5x10(6) CD34+ cells/kg (median of 4 apheresis). In contrast, 87% of Group II achieved the target dose with a median of 2 aphereses. Predictors of poor mobilization were greater than two prior treatment regimens (p=0.038) and the WBC count (<25,000/microL) on the first day of apheresis (p=0.053). Nineteen patients in Group I and all Group II completed treatment with a median time to engraftment of ANC>500/microl of 12 and 11 days, and platelet >20x10(3)/microl of 31 and 13 days, respectively. Outcome analysis revealed that 6/19 patients in Group I died of relapse within one year from transplant compared with only 2/23 of Group II who died of relapse (p=0.005, log rank test). There were no treatment related deaths in either group. Independent predictive features for "hard to mobilize" patients are a lack of significant increase in WBC count on the first day of apheresis and the number of prior treatment regimens. Poor mobilization appears to predict a worse outcome after autografting for lymphoma patients.

Actuarial Analysis↗
PubMed2000

Regulation and developmental expression of the divalent metal-ion transporter in the rat brain.

Divalent metal ion transporter 1 (DMT1) is a recently identified metal-ion transporter that appears to mediate the absorption of iron in the intestine. DMT1 mRNA is also present in discrete areas of the brain. In this study, we examined the expression of DMT1 mRNA in developing rat brain. DMT1 mRNA was found by in situ hybridization in the striatum, cortex, hippocampus and cerebellum. During development, DMT1 mRNA was found in Purkinje and granule cells in the cerebellum at post-natal day (PND) 14 and PND 30. DMT1 mRNA was also expressed in the external granular layer of the cerebellum at PND 14. No change in the level of DMT1 mRNA was observed by Northern analysis in the cerebellum at different ages between PND 1 and 21. DMT1 was found by Northern analysis in cultures of rat astrocytes. Activation of protein kinase C increased the expression of DMT1 in kidney epithelial cells but not astrocytes from newborn rats. Because DMT1 is expressed in a wide variety of types of cells, we suggest that it plays an important role in metal homeostasis in the brain.

Animals↗
PubMed2000

Effect of 3 medicaments on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions.

OBJECTIVE: The purpose of this study was to determine the effect of retraction cord medicaments (aluminum chloride, ferric sulfate, and ferric subsulfate/ferric sulfate) on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions. METHOD AND MATERIALS: Polyvinyl siloxane impressions were made of standardized metal dies (American Dental Association [ADA] specification No. 19) treated with 1 of the 3 retraction cord medicaments. Dimensional accuracy was evaluated by comparing the average length of a line in the impressions to the standard die. Surface detail reproduction was evaluated by viewing the impressions under low-angle illumination at x10 magnification. Reproduction was considered satisfactory if 2 of 3 horizontal lines were reproduced continuously. The dies were also evaluated under the microscope before the impression was made. RESULTS: The medicaments did not significantly effect the dimensional accuracy; mean shrinkage was within ADA guidelines in the treatment groups. All of the medicaments had an adverse effect on surface detail reproduction. These effects were statistically significant compared to the untreated control. CONCLUSION: Although the changes in dimensional accuracy were within ADA guidelines, the surface detail reproduction was modified such that the impression would be considered clinically unacceptable. For optimal results, care must taken to remove all traces of these retraction cord medicaments prior to recording of a polyvinyl siloxane impression.

Aluminum Chloride↗
PubMed1999

tRNA prefers to kiss.

Six RNA aptamers that bind to yeast phenylalanine tRNA were identified by in vitro selection from a random-sequence pool. The two most abundantly represented aptamers interact with the tRNA anticodon loop, each through a sequence block with perfect Watson-Crick complementarity to the loop. It was possible to truncate one of these aptamers to a simple hairpin loop that forms a classical 'kissing complex' with the anticodon loop. Three other aptamers have nearly complete complementarity to the anticodon loop. The sixth aptamer has two sequence blocks, one complementary to the tRNA T loop and the other to the D loop; this aptamer binds better to a mutant tRNA that disrupts the normal D-loop/T-loop tertiary interaction than to the wild-type tRNA. Selection of complements to tRNA loops occurred despite an attempt to direct binding to tertiary structural features of tRNA. This serves as a reminder of how special the RNA-RNA interactions are that are not based on complementarity. Nonetheless, these aptamers must present the tRNA complement in some special structural context; the simple single-strand complement of the anticodon loop did not bind tRNA effectively.

Anticodon↗
PubMed1999

Th cells and Th2 responses can develop in the absence of MHC class II-CD4 interactions.

In this paper, we address the question whether CD4 and MHC class II expression are necessary for the development of the T helper lineage during thymocyte maturation and for activation-induced Th2 responses. To bypass the CD4-MHC class II interaction requirements for positive selection and activation, we used mice that are doubly transgenic for CD8 and for the MHC class I-restricted TCR F5. This transgene combination leads to MHC class I-dependent maturation of CD4 lineage cells. Upon activation, these CD4 lineage T cells secrete IL-4 and give help to B cells but show no cytotoxic activity. Remarkably, neither MHC class II nor CD4 expression are necessary for the generation and helper functions of these cells. This suggests that under normal conditions, coreceptor-MHC interactions are necessary to ensure the canonical combinations of coreceptor and function in developing thymocytes, but that they do not determine functional commitment. Our results also imply that expression of the CD4 gene does not influence, but is merely associated with the decision to establish the T helper program. In addition, we show that activation through TCR-MHC class I interactions can induce Th2 responses independently of CD4 and MHC class II expression.

Animals↗