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Biomedical subjects

R Hancock

Publications and source records attributed to R Hancock.

At least 19 recordsLinked to original sources
PubMed2006

The genetic influence on bone susceptibility to fluoride.

INTRODUCTION: The influence of genetic background on bone architecture and mechanical properties is well established. Nevertheless, to date, only few animal studies explore an underlying genetic basis for extrinsic factors effect such as fluoride effect on bone metabolism. MATERIALS AND METHODS: This study assessed the effect of increasing fluoride doses (0 ppm, 25 ppm, 50 ppm, 100 ppm) on the bone properties in 3 inbred mouse strains that demonstrate different susceptibilities to developing enamel fluorosis (A/J a "susceptible" strain, 129P3/J a "resistant" strain and SWR/J an "intermediate" strain). Fluoride concentrations were determined in femora and vertebral bodies. Bone mineral density was evaluating through DEXA. Finally, three-point bend testing of femora, compression testing of vertebral bodies and femoral neck-fracture testing were performed to evaluate mechanical properties. RESULTS: Concordant with increasing fluoride dose were significant increases of fluoride concentration in femora and vertebral bodies from all 3 strains. Fluoride treatment had little effect on the bone mineral densities (BMD) in the 3 strains. Mechanical testing showed significant alterations in "bone quality" in the A/J strain, whereas moderate alterations in "bone quality" in the SWR/J strain and no effects in the 129P3/J strain were observed. CONCLUSION: The results suggest that genetic factors may contribute to the variation in bone response to fluoride exposure and that fluoride might affect bone properties without altering BMD.

Animals↗
PubMed2005

Assessment of teeth as biomarkers for skeletal fluoride exposure.

Skeletal fluorosis and dental fluorosis are diseases related to fluoride (F) ingestion. Bone is the largest storage site of F in our body. Therefore, bone F concentrations are considered biomarkers for total F body burden (exposure). However, difficult accessibility limits its use as a biomarker. Thus, a more accessible tissue should be considered and analyzed as a biomarker for total F body burden. The objective of this study, which was divided into two parts, was to evaluate teeth as a biomarker for skeletal F exposure. In part 1 of the study, 70 mice of three different strains (SWR/J, A/J and 129P3/J) were exposed to different levels of water fluoridation (0, 25, 50 and 100 ppm). Bone (femora and vertebrae) and teeth from these mice were then analyzed for F concentration using Instrumental Neutron Activation Analysis (INAA). In part 2 of the study, human teeth (enamel and dentin) and bone from 30 study subjects were collected and analyzed for F concentration using INAA. Study subjects lived in areas with optimum levels of water fluoridation (0.7 and 1 ppm) and underwent therapeutic extraction of their unerupted third molars. The values of bone and teeth F concentration were correlated for parts 1 and 2 of this study. The results showed that in the animal model, where animals were exposed to a wide range of F in their drinking water, tooth [F] correlated with bone [F]. However, no correlation was seen between bone and enamel F concentrations or between bone and dentin F concentrations in the human samples. Therefore, teeth are not good biomarkers for skeletal F exposure in humans when exposure is confined to optimum levels of F in the drinking water.

Adolescent↗
PubMed2005

How does fluoride affect dentin microhardness and mineralization?

Fluoride (F) has been a useful instrument in caries prevention. However, only limited data exist on the effect of its long-term use on dentin mineralization patterns and microhardness. The objective of this study was to evaluate the influence of tooth F concentration ([F]) and dental fluorosis (DF) severity on dentin microhardness and mineralization. We collected 137 teeth in Montreal and Toronto, Canada, and Fortaleza, Brazil, where optimum or suboptimum levels of water F were 0.2 ppm, 1 ppm, and 0.7 ppm, respectively. Teeth were analyzed for DF severity, dentin [F], enamel [F], dentin microhardness, and dentin mineralization. Dentin [F] correlated with DF severity; enamel [F] correlated with dentin microhardness and dentin mineralization; DF severity correlated with dentin microhardness. Genetic factors (e.g., DF severity) and environmental factors (e.g., tooth [F]) influenced the mechanical properties (microhardness) of the teeth, while only the environmental factors influenced their material properties (e.g., mineralization). Fortaleza teeth were harder and less mineralized and presented higher dentin [F] values. Montreal teeth presented lower levels of DF when compared with both Toronto and Fortaleza teeth.

Adolescent↗
PubMed2004

Is fluoride concentration in dentin and enamel a good indicator of dental fluorosis?

Despite some studies correlating dental fluorosis (DF) and fluoride (F) concentration in dental enamel, no information is available about DF and dentin F concentration. Our objective was to determine the correlation between teeth F concentration and DF severity in unerupted human 3rd molars, and the correlation between dentin and enamel F concentrations in the same tooth. Ninety-nine 3rd molars were studied-53 from Fortaleza, Brazil (F water, 0.7 ppm), 22 from Toronto (1.0 ppm), and 24 from Montreal (0.2 ppm). DF severity was evaluated according to the Thylstrup-Fejerskov Index, while F concentration was analyzed by Instrumental Neutron Activation Analysis. DF severity varied between TF0 and TF4, while F concentration ranged between 39 and 550 ppm in enamel and 101 and 860 ppm in dentin. Our results showed correlation between dentin F concentration and DF (r(S) = 0.316, p = 0.001), but no correlation between enamel F concentration and DF (r(S) = 0.154, p = 0.133). No correlation was observed between dentin and enamel F concentrations in the same tooth (r(S) = 0.064, p = 0.536).

Adult↗
PubMed2003

How does fluoride concentration in the tooth affect apatite crystal size?

Despite fluoride's (F) well-documented ability to prevent caries, the effects of F concentrations on enamel and dentin apatite crystals are unknown. The present study examined the hypothesis that tooth F concentration and tooth crystallite size correlate. One hundred human unerupted third molars were studied-53 from Fortaleza-Brazil (F water 0.7 ppm), 23 from Toronto (1.0 ppm), and 24 from Montreal (0.2 ppm). F concentration was analyzed by Neutron Activation Analysis and apatite crystal size by powder x-ray diffraction. A positive correlation between dentin F concentration and enamel crystallite length and width was found. Enamel crystallite length was significantly greater in teeth from Fortaleza than in teeth from Toronto (p = 0.011) and Montreal (p = 0.003). Enamel crystallite widths were significantly greater in Fortaleza teeth compared with those from Toronto (p = 0.020) and Montreal (p < 0.001). No difference in the dentin crystallite size was seen in the 3 regions. Thus, tooth F concentration and crystallite size correlate.

Analysis of Variance↗
PubMed2000

A new look at the nuclear matrix.

The concept of the nuclear matrix, a karyoskeletal structure that serves as a support for the genome and its activities, has stimulated many studies of the association of nuclear components and functions with this structure. However, certain experimental findings are not consistent with the existence of the nuclear matrix in vivo, including our inability to visualise a corresponding structure in intact cells, the demonstrated mobility in vivo of chromatin and messenger ribonucleoprotein particles, which are claimed to be bound to the nuclear matrix, the paradoxical extractability from nuclei in low ionic strength buffers of enzymes that are found in the 2 M NaCl-insoluble matrix, and the extractability, in conditions which reproduce the intranuclear milieu, of regions of DNA (matrix or scaffold attachment regions, MAR/SARs) postulated to be bound to the nuclear matrix in vivo. This review considers the nuclear matrix model in the light of sometimes overlooked evidence that each step in its isolation may cause nuclear components to bind to it by new liaisons that do not exist in vivo. This is illustrated by experiments where nuclear-targeted green fluorescent protein is found in the nuclear matrix, and raises the possibility that MAR/SARs actually bind to DNA-binding proteins or multiprotein complexes, including replicational, transcriptional and processing machinery, and topoisomerases that are incorporated into the nuclear matrix during its preparation. Considering that the nuclear lamina forms a rigid exoskeleton, the necessity for internal skeletal structures is raised; the major roles that macromolecular crowding, phase partitioning, and charge effects are likely to play in organisation of the intranuclear space may provide new models for the compartmentalisation of proteins and functions into different nuclear domains and of chromosomes into territories.

DNA↗
PubMed1999

Outbreak of Escherichia coli O157 infection associated with a music festival.

Seven persons who attended the Glastonbury Music Festival were infected with Vero cytotoxin-producing Escherichia coli O157 and an eighth person had serological evidence of infection. Cases were reported from different parts of England. Patients were interviewed by telephone about clinical symptoms, festival attendance, camping details, food history, water exposure, and contact with mud and animals. The interviews identified no common food source, differing use of water sources and widely dispersed camping sites. Escherichia coli O157 strains from seven persons and from a cow belonging to a herd that had previously grazed the site all belonged to phage type 2 and possessed genes for Vero cytotoxin 2. Drug resistance and DNA-based tests showed that six patients were infected with strains indistinguishable from each other and from the bovine isolate. The most likely vehicle of infection was mud contaminated with Escherichia coli O157 from infected cattle.

Adult↗
PubMed1998

DNA loop domains in a 1.4-Mb region around the human hprt gene mapped by cleavage mediated by nuclear matrix-associated topoisomerase II.

We have mapped the positions in a approximately 1.4-Mb region of genomic DNA around the human hprt gene which are accessible in vivo to cleavage by topoisomerase II associated with the nuclear matrix. These positions, which are interpreted as the boundaries of DNA loop domains, were mapped in K562 cells by examining the truncation of rare-cutter restriction fragments separated by pulsed field gel electrophoresis after topoisomerase II-mediated cleavage, using seven linked markers mapped in this region as probes for indirect end-labeling. Eleven cleavage positions were detected and were interpreted as defining ten loop domains of lengths between 70 and 210 kb (average approximately 135 kb); the hprt gene resides in a 150-kb loop domain. Loop domain boundaries coincided with three of the fifteen deletion breakpoints mapped in a 600-kb sector of this region in human lymphocytes, within the limits of resolution of pulsed field gel electrophoresis; this correlation was not statistically significant.

Cell Nucleus↗
PubMed1998

The Bradyrhizobium japonicum noeD gene: a negatively acting, genotype-specific nodulation gene for soybean.

Bradyrhizobium japonicum strain USDA 110 is restricted for nodulation by soybean genotype PI 417566. We previously reported the identification of a USDA 110 Tn5 mutant, strain D4.2-5, that had the ability to overcome nodulation restriction conditioned by PI 417566 (S. M. Lohrke, J. H. Orf, E. Martínez-Romero, and M. J. Sadowsky, Appl. Environ. Microbiol. 61:2378-2383, 1995). In this study, we report the cloning and characterization of the negatively acting DNA region mutated in strain D4.2-5 that is involved in the genotype-specific nodulation of soybean. The Tn5 integration site was localized to a 5.2-kb EcoRI fragment isolated from wild-type USDA 110 genomic DNA. Saturation Tn5 mutagenesis of this 5.2-kb region and DNA homogenitization studies indicated that a 0.9-kb DNA region was involved in the genotype-specific nodulation of PI 417566. A single open reading frame (ORF) of 474 nucleotides, encoding a predicted protein of 158 amino acids, was identified within this region by DNA sequencing. This ORF was named noeD. Computer comparisons with available data bases revealed no significant similarities between the noeD DNA or predicted amino acid sequence and any known genes or their products. However, comparisons done with the region upstream of noeD revealed a high degree of similarity (about 76% similarity and 62% identity) to the N-terminal regions of the Rhizobium leguminosarum bv. viciae and R. meliloti nodM genes, which have been postulated to encode a glucosamine synthase. Southern hybridization analysis indicated that noeD is not closely linked to the main or auxiliary nodulation gene clusters in B. japonicum and that both nodulation-restricted and -unrestricted B. japonicum serogroup 110 strains contain a noeD homolog. High-performance liquid chromatography and fast atom bombardment-mass spectrometry analyses of the lipo-chitin oligosaccharide (LCO) nodulation signals produced by an noeD mutant showed a higher level of acetylation than that found with wild-type USDA 110. These results suggest that specific LCO signal molecules may be one of the factors influencing nodulation specificity in this symbiotic system.

Amino Acid Sequence↗
PubMed1997

Induction of magnetic resonance-visible lipid in a transformed human breast cell line by tetraphenylphosphonium chloride.

Proton magnetic resonance spectroscopy (1H MRS) and DNA flow cytometry were used to monitor the effects of the cationic lipophilic phosphonium salt and potential antineoplastic agent tetraphenylphosphonium chloride (TPP) on the transformed human breast cell line HBL-100. TPP treatment for 48 hr was cytostatic at low concentrations and cytotoxic at higher concentrations with an IC50 of 55 microM as measured by Trypan blue exclusion. At micromolar concentrations, TPP caused a significant increase in the methylene MR signal arising from mobile lipid as measured by the ratio of the lipid CH2 peak height to either the CH3 peak height (internal referencing) or the peak height for p-aminobenzoic acid (PABA) as an external reference in a co-axial capillary within the sample. Over the same concentration range, TPP caused a slowing of passage through S phase as demonstrated by a significant depletion of cells in G2/M phase with a concurrent but non-significant increase in cells in S. Time-dependent increases in MR-visible lipid were observed with 2 microM TPP treatment, and the removal of TPP from the culture medium caused no significant reduction in mobile lipid. Two-dimensional 1H-1H COSY spectra of TPP-treated HBL-100 cells revealed concentration-dependent increases in cross-peak volume ratios arising from lipid acyl chains relative to both internal (lysine, polyamines) and external (PABA) standards. Increases in choline and glycerophosphocholine cross-peak volume ratios were observed, indicating that the catabolism or rearrangement of phospholipids may be responsible for the observed MR-visible lipid increases.

Adult↗
PubMed1997

Distribution of topoisomerase II-mediated cleavage sites and relation to structural and functional landmarks in 830 kb of Drosophila DNA.

The pattern of sites for cleavage mediated by topoisomerase II was determined in 830 kb of cloned DNA from the Drosophila X chromosome, with the objectives of comparing it with mapped structural and functional landmarks and examining if the correlations with such landmarks reported in individual loci can be generalized to a region approximately 100 times longer. The relative frequencies of topoisomerase II cleavage sites in 247 restriction fragments from 67 clones were quantified by hybridization with probes prepared from DNA fragments which abutted all cleavage sites in each clone, selected through the covalently bound topoisomerase II subunit; the specificity and quantitative nature of this method were demonstrated using a plasmid DNA model. The 12 restriction fragments with strong nuclear scaffold attachment (SAR) activity, of which seven possess autonomous replication (ARS) activity, show statistically strong coincidence or contiguity ( P </=0.11) with regions of high topoisomerase II cleavage site frequency. These regions show no correlation with repetitive sequence or A/T or C/G content and some extend over >10 kb; their sensitivity is therefore unlikely to be due to alternating purine-pyrimidine repeats or regions of Z conformation, which are preferred motifs. The hypothesis that they possess intrinsic curvature is consistent with the similarity of their length and spacing to regions of predicted curvature in the 315 kb DNA of Saccharomyces cerevisiae chromosome III and with the reported strong binding preference of topoisomerase II for curved DNA. The topoisomerase II cleavage pattern in this DNA further shows that its relationships to functional properties seen in individual loci, especially to MAR/SAR and ARS activity and to the restricted accessibility of DNA to topoisomerase II in vivo, can be generalized to much longer regions of the genome.

Animals↗
PubMed1997

Clinical experience with a balloon-tipped urethral insert for stress urinary incontinence.

A balloon-tipped urethral insert for control of urinary incontinence in women has undergone clinical trials and has been accepted for clinical use by the U.S. Food and Drug Administration. On the basis of results of a multicenter clinical trial, it was concluded that the device provides a safe and effective option for management of genuine stress incontinence and mild mixed incontinence in women. This article reviews appropriate patient selection, education, and training to optimize patient acceptance and efficacy of this urinary control insert.

Adult↗
PubMed1996

Tetraphenylphosphonium chloride induced MR-visible lipid accumulation in a malignant human breast cell line.

The effect of the cationic lipophilic phosphonium salt tetraphenylphosphonium chloride (TPP) on a human malignant breast cell line, DU4475, was monitored with proton nuclear magnetic resonance (1H MRS). TPP caused a dose- and time- dependent increase in resonances arising from MR-visible lipid as measured by the CH2/CH3 ratio in the 1-dimensional 1H MR spectrum. Two-dimensional MRS identified increases in the glycerophosphocholine/lysine cross-peak ratio and corresponding decreases in the phosphocholine/lysine ratio in a dose- dependent fashion in TPP-treated cells. Lipid metabolic changes are discussed in the light of other MR experiments, and the data indicate that accumulation of MR-visible lipids may arise from the rearrangement of phospholipids accompanying mitochondrial destruction or from the catabolism of phospholipids associated with early events in the cytotoxic process.

Antineoplastic Agents↗
PubMed1996

Structure and conformational changes of DNA topoisomerase II visualized by electron microscopy.

Type II DNA topoisomerases, which create a transient gate in duplex DNA and transfer a second duplex DNA through this gate, are essential for topological transformations of DNA in prokaryotic and eukaryotic cells and are of interest not only from a mechanistic perspective but also because they are targets of agents for anticancer and antimicrobial chemotherapy. Here we describe the structure of the molecule of human topoisomerase II [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3] as seen by scanning transmission electron microscopy. A globular approximately 90-angstrom diameter core is connected by linkers to two approximately 50-angstrom domains, which were shown by comparison with genetically truncated Saccharomyces cerevisiae topoisomerase II to contain the N-terminal region of the approximately 170-kDa subunits and that are seen in different orientations. When the ATP-binding site is occupied by a nonhydrolyzable ATP analog, a quite different structure is seen that results from a major conformational change and consists of two domains approximately 90 angstrom and approximately 60 angstrom in diameter connected by a linker, and in which the N-terminal domains have interacted. About two-thirds of the molecules show an approximately 25 A tunnel in the apical part of the large domain, and the remainder contain an internal cavity approximately 30 A wide in the large domain close to the linker region. We propose that structural rearrangements lead to this displacement of an internal tunnel. The tunnel is likely to represent the channel through which one DNA duplex, after capture in the clamp formed by the N-terminal domains, is transferred across the interface between the enzyme's subunits. These images are consistent with biochemical observations and provide a structural basis for understanding the reaction of topoisomerase II.

Adenosine Triphosphate↗
PubMed1996

Modulation of MR-visible mobile lipid levels by cell culture conditions and correlations with chemotactic response.

A transformed murine fibroblast cell line has been used to assess which criteria govern the appearance of a lipid pool that is mobile on the MR time scale. A high-resolution proton MR signal arising from neutral lipids, including triglyceride and cholesteryl esters, has previously been associated with membrane events in stimulated, transformed and malignant cells. We report that the attenuation of cellular proliferation by confluence or low pH caused significant increases in MR-visible lipid and that the lipid signal could be amplified at high density by the removal of serum. A significant decrease in chemotactic response accompanied the culture of cells at high density, but chemotactic response was not generally linked to alteration of the lipid signal. The appearance of the signal was also not correlated with the proportion of cells in any phase of the cell cycle. Significant changes in the MR-visible pools of the lipid metabolites choline, phosphocholine and glycerophosphocholine were measured under the culture conditions employed with 2D MRS and suggest that MR-visible lipid may arise from the catabolism of phospholipids.

Animals↗
PubMed1996

Mapping of genomic DNA loop organization in a 500-kilobase region of the Drosophila X chromosome by the topoisomerase II-mediated DNA loop excision protocol.

The recently developed procedure of chromosomal DNA loop excision by topoisomerase II-mediated DNA cleavage at matrix attachment sites (S. V. Razin, R. Hancock, O. Iarovaia, O. Westergaard, I. Gromova, and G. P. Georgiev, Cold Spring Harbor Symp. Quant. Biol. 58:25-35, 1993; I. I. Gromova, B. Thompsen, and S. V. Razin, Proc. Natl. Acad. Sci. USA 92:102-106, 1995) has been employed for mapping the DNA loop anchorage sites in a 500-kb region of the Drosophila melanogaster X chromosome. Eleven anchorage sites delimiting 10 DNA loops ranging in size from 20 to 90 kb were found within this region. Ten of these 11 anchorage sites colocalize with previously mapped scaffold attachment regions. However, a number of other scaffold attachment regions are found to be located in loop DNA.

Animals↗