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Biomedical subjects

G J Price

Publications and source records attributed to G J Price.

At least 19 recordsLinked to original sources
PubMed2005

Ultrasonic intensification of ozone and electrochemical destruction of 1,3-dinitrobenzene and 2,4-dinitrotoluene.

The removal of nitroaromatics from polluted water is difficult due to their high stability to conventional treatment methods. This paper presents a method for the destruction of 1,3-dinitrobenzene and 2,4-dinitrotoluene in aqueous solutions. The compounds are shown to be stable to reaction with ozone, even under ultrasonic activation. The use of ultrasound enhances the rate of electrochemical reduction but the overall rate of reaction is still slow. However, the simultaneous application of ultrasound and ozonation to the electrochemical reaction allows virtually complete destruction of the compounds in short times. The effect is attributed to the ultrasonic enhancement of the electrochemical process giving intermediates that are susceptible to ozone oxidation. While further analytical work is needed to deduce the exact contributions of the various possible degradation mechanisms, the work demonstrates the synergies that can be gained by using combined techniques for the destruction of these difficult compounds.

Dinitrobenzenes↗
PubMed2005

A study to determine whether cavitation occurs around dental ultrasonic scaling instruments.

The aim of this investigation was to determine if cavitation occurred around dental ultrasonic scalers and to estimate the amount of cavitation occurring. Three styles of tip (3 x TFI-10, 3 x TFI-3, 3 x TFI-1) were used, in conjunction with a Cavitron SPS ultrasonic generator (Dentsply, USA), to insonate terephthalic acid solution. The hydroxyl radical, [*OH], concentration, produced due to cavitation from the scaler tips, was monitored by fluorescence spectroscopy. Cavitational activity was enhanced at higher power settings and at longer operating times. The tip dimensions and geometry as well as the generator power setting are both important factors that affect the production of cavitation.

Dental Scaling↗
PubMed2005

Phenotypic changes in mitochondrial membrane potential (Delta psi(m)) during valinomycin-induced depolarisation and apoptosis.

A large body of evidence has implicated mitochondria in control of cell death, where key apoptotic mechanisms involve change in mitochondrial membrane permeability and depolarisation of mitochondrial membrane potential (Delta psi(m)). Assessment of Delta psi(m) is traditionally conducted using the lipophilic cation JC-1 on the flow cytometer or by fluorescent microscopy. Here we assess JC-1 aggregation using the novel tool of digital texture analysis to establish mitochondrial phenotypic changes induced by the K+ ionophore, valinomycin in a unique model comprising SW480 and SW620 cell lines. This provides an opportunity to study these phenomena in the context of colorectal cancer. Valinomycin-induced apoptosis was detected using morphology and analysis of DNA content. Cells were treated with valinomycin, images digitally recorded on a calibrated video photometer and subjected to high resolution digital texture analysis. This demonstrated that the HARAM texture features (Mean of the Haralick texture features) were highly valuable in describing the transition of Delta psi(m) as the cell undergoes apoptosis. In conclusion this study illustrates the potential of texture analysis as a novel and additional technique for quantifying JC-1 aggregation and revealing the spectrum of collapse of Delta psi(m) during apoptosis.

Apoptosis↗
PubMed2004

Does cavitation occur around powered toothbrushes?

AIMS/OBJECTIVES: The aim of this investigation was to determine if cavitational activity occurred around powered toothbrushes using a chemical dosimeter system based on terephthalic acid (TA). MATERIAL AND METHODS: Five powered toothbrushes were used in this investigation: Braun Plaque Remover D8, Braun Oral-B 3D, Philips Jordan Sensiflex HX2520, Sonicare PS-1 and Sonicare Elite HX 7351/02. Each brush head was inserted into a conical flask containing 50 cm3 of aqueous TA solution. Brushes were operated for 10 and 20 min and a cuvette of the solution was placed in a fluorescence spectrometer (Perkin Elmer 3000). The fluorescence emitted at wavelength 425 nm, which is proportional to *OH radical concentration, was monitored. RESULTS: Any cavitational activity that may have been produced by the powered toothbrushes was below the limit of detection of the system (<10(-8) M) for the timescales investigated. CONCLUSIONS: This work has demonstrated that cavitational activity does not occur around powered toothbrushes. Operating the toothbrushes for periods up to 20 min resulted in no cavitational activity being detected.

Equipment Design↗
PubMed2003

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

Bayes Theorem↗
PubMed2002

Expert system support using a Bayesian belief network for the classification of endometrial hyperplasia.

Accurate morphological classification of endometrial hyperplasia is crucial as treatments vary widely between the different categories of hyperplasia and are dependent, in part, on the histological diagnosis. However, previous studies have shown considerable inter-observer variation in the classification of endometrial hyperplasias. The aim of this study was to develop a decision support system (DSS) for the classification of endometrial hyperplasias. The system used a Bayesian belief network to distinguish proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. These diagnostic outcomes were held in the decision node. Four morphological features were selected as diagnostic clues used routinely in the discrimination of endometrial hyperplasias. These represented the evidence nodes and were linked to the decision node by conditional probability matrices. The system was designed with a computer user interface (CytoInform) where reference images for a given clue were displayed to assist the pathologist in entering evidence into the network. Reproducibility of diagnostic classification was tested on 50 cases chosen by a gynaecological pathologist. These comprised ten cases each of proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. The DSS was tested by two consultant pathologists, two junior pathologists and two medical students. Intra- and inter-observer agreement was calculated following conventional histological examination of the slides on two occasions by the consultants and junior pathologists without the use of the DSS. All six participants then assessed the slides using the expert system on two occasions, enabling inter- and intra-observer agreement to be calculated. Using unaided conventional diagnosis, weighted kappa values for intra-observer agreement ranged from 0.645 to 0.901. Using the DSS, the results for the four pathologists ranged from 0.650 to 0.845. Both consultant pathologists had slightly worse weighted kappa values using the DSS, while both junior pathologists achieved slightly better values using the system. The grading of morphological features and the cumulative probability curve provided a quantitative record of the decision route for each case. This allowed a more precise comparison of individuals and identified why discordant diagnoses were made. Taking the original diagnoses of the consultant gynaecological pathologist as the 'gold standard', there was excellent or moderate to good inter-observer agreement between the 'gold standard' and the results obtained by the four pathologists using the expert system, with weighted kappa values of 0.586-0.872. The two medical students using the expert system achieved weighted kappa values of 0.771 (excellent) and 0.560 (moderate to good) compared to the 'gold standard'. This study illustrates the potential of expert systems in the classification of endometrial hyperplasias.

Bayes Theorem↗
PubMed2000

Magnetic resonance imaging of spinal plasmacytoma.

AIM: To describe the magnetic resonance imaging (MRI) features of spinal plasmacytoma. MATERIALS AND METHODS: The clinical records and MRI findings in six patients (five men, one woman; age range 41-61 years) with histologically proven plasmacytoma of the spine were reviewed. All studies included sagittal T1- and T2-weighted spin-echo sequences and axial T1-weighted spin-echo sequences. Intravenous gadolinium DTPA was administered in four cases. RESULTS: MRI showed a characteristic appearances in four cases of low signal intensity curvilinear areas within the vertebra or cortical irregularity. CONCLUSION: Recognition of these imaging features can initiate the appropriate investigation as the commonest differential diagnosis for such lesions is metastasis.Shah, B. K. (2000). Clinical Radiology55, 439-445.

Adult↗
PubMed1997

Measurement of radical production as a result of cavitation in medical ultrasound fields.

This paper describes the use of the terephthalate dosimeter to measure the threshold and extent of cavitation arising from medical ultrasound sources at high frequencies. Significant hydroxyl radical production was noted from a physiotherapy source and low level activity was also detected when using a pulsed, diagnostic type transducer system. The effect of sound intensity and the type of field is described. The possibility of using polymer degradation to monitor the cavitation is also discussed.

Calibration↗
PubMed1997

Cell-specific regulation of mRNAs for IGF-I and IGF-binding proteins-4 and -5 in streptozotocin-diabetic rat kidney.

Streptozotocin (STZ)-induced diabetes in the rat causes early renal enlargement preceded by a transient elevation in IGF-I content and an increase in IGF-I tissue binding. The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. In diabetes, IGFBP-1 mRNA showed markedly increased expression in distal tubules, collecting ducts and thick ascending limbs of Henle (TALs). IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. There was no difference between control and insulin-treated kidneys. These complex changes suggest possible involvement of the IGF/IGFBP system in the early stages of diabetic renal hypertrophy.

Animals↗
PubMed1996

Frequent clones of p53-mutated keratinocytes in normal human skin.

The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles. These clones, 60-3000 cells in size, are present at frequencies exceeding 40 cells per cm2 and together involve as much as 4% of the epidermis. In sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin. We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells. These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to cancer.

Adult↗
PubMed1996

Mutagenesis studies of interleukin-8. Identification of a second epitope involved in receptor binding.

Interleukin-8 (IL-8) is a dimeric, C-X-C chemokine, produced by a variety of cells and which elicits proinflammatory responses from the neutrophil. As a prelude to drug design, we have investigated the interactions between IL-8 and its receptor by preparing a number of single-site mutants of IL-8 and determining their activity in receptor-binding and functional assays. In order to define the binding surface as precisely as possible, we have used chemical shifts obtained from nuclear magnetic resonance spectroscopy to screen mutant proteins for structural changes which affect regions of the IL-8 surface remote from the site of mutation. In addition to a previously recognized sequence, Glu4-Leu5-Arg6 in the N-terminal peptide, we have identified a second epitope comprising a contiguous group of non-sequential, solvent-exposed, hydrophobic residues, Phe17, Phe2l, Ile22, and Leu43. These two receptor-binding regions are separated by over 20 A in the IL-8 structure and are important both for receptor binding and function. In addition, we have shown through the production of a covalently linked IL-8 dimer, that subunit dissociation is not necessary for biological activity.

Amino Acid Sequence↗
PubMed1996

The use of a metal detector to locate ingested metallic foreign bodies in children.

OBJECTIVE: A pilot study to assess whether modern metal detectors can reduce unnecessary radiation in searching for ingested metallic foreign bodies. METHODS: Over a one year period, 20 children presenting to an accident and emergency department with suspected metallic foreign body ingestion were studied. Using an Adams Electronics AD15 metal detector, the radiographer recorded the location of metallic foreign bodies on a pictorial representation of neck, chest, and abdomen. The child then had plain radiographs of abdomen, chest, and neck in sequential order until the foreign body was located. RESULTS: In seven cases neither metal detector nor radiography revealed a foreign body (true negatives). In the remaining 13 cases where metal detection was positive, subsequent radiography or faecal search was also positive (true positives). The 13 foreign bodies were coins (8), gold ring (1), ball bearing (1), screw (1), staple (1), and washer (1). All were in the stomach or proximal small bowel on radiography except for one coin in the right iliac fossa. CONCLUSIONS: The detector can demonstrate ingested metallic foreign bodies reliably in children, thereby reducing unnecessary irradiation.

Child↗
PubMed1995

Localization of mRNAs for insulin-like growth factor binding proteins 1 to 6 in rat kidney.

Insulin-like growth factor-I (IGF-I) is a peptide growth factor whose activity is modulated by interaction with the family of six IGF binding proteins (IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. We have used in situ hybridization to localize mRNAs for the IGFBPs in rat kidney. Messenger RNAs for all six IGFBPs were detected, each with a distinctive distribution. IGFBP-1 mRNA was expressed in the distal nephron, from the thick ascending limb of the loop of Henle to the cortical collecting ducts. IGFBP-2 mRNA expression was confined to epithelial cells of the glomeruli and the thin limbs of the loop of Henle. IGFBP-3 mRNA was localized to the cortical interstitium while IGFBP-4 was the only IGFBP mRNA found in the proximal tubule. IGFBP-5 mRNA, the most abundant and widely distributed of the IGFBP mRNAs in the kidney, occurred in the glomerular mesangium and the medullary interstitium as well as in the epithelial cells of the distal nephron. IGFBP-6 mRNA, the least abundant, was expressed mainly in fibroblasts associated with renal blood vessels and the ureter. This heterogeneous distribution of the IGFBPs may enable IGF action to be regulated by multiple factors in a site-specific manner.

Animals↗
PubMed1995

Technical note: measurement of collapse cavitation in ultrasound fields.

This note describes a method for the measurement of hydroxyl free radical concentration due to collapse acoustic cavitation in medical ultrasound fields using aqueous terephthalic acid (TA) solution. An enclosed cylindrical chamber with acoustically transparent membranes at either end was used. Control of cavitation activity was achieved by seeding the solution with polystyrene microspheres to provide cavitation centres. Insonation experiments using unseeded TA previously exposed to air gave very variable results, sometimes detecting cavitation activity and at other times detecting nothing, under the same exposure conditions. Introduction of polystyrene microsphere seeds into the TA enabled it to detect reproducibly levels of cavitation activity at least one order of magnitude higher than in unseeded solutions. An experiment using the seeded TA in a standing wave ultrasound field, set up using a brass reflecting plate, demonstrated that the presence of a standing wave inhibited the measured cavitation yield.

Free Radical Scavengers↗
PubMed1990

Complete sequence of human vinculin and assignment of the gene to chromosome 10.

We have determined the complete sequence of human vinculin, a cytoskeletal protein associated with cell-cell and cell-matrix junctions. Comparison of human and chicken embryo vinculin sequences shows that both proteins contain 1066 amino acids and exhibit a high level of sequence identity (greater than 95%). The region of greatest divergence falls within three 112-amino acid repeats spanning residues 259-589. Interestingly, nematode vinculin lacks one of these central repeats. The regions of human vinculin that are N- and C-terminal to the repeats show 54% and 61% sequence identity, respectively, to nematode vinculin. Southern blots of human genomic DNA hybridized with short vinculin cDNA fragments indicate that there is a single vinculin gene. By using a panel of human-rodent somatic cell hybrids, the human vinculin gene was mapped to chromosome 10q11.2-qter.

Amino Acid Sequence↗
PubMed1989

Primary sequence and domain structure of chicken vinculin.

We have determined the complete sequence of chick vinculin from two overlapping cDNA clones. The vinculin mRNA consists of 262 bp of 5' untranslated sequence, an open reading frame of 3195 bp (excluding the initiation codon) and a long 3' untranslated sequence (greater than 2 kb). Chick vinculin contains 1066 amino acid residues, and has a deduced molecular mass of 116,933 Da. Analysis of the domain structure of vinculin shows that the molecule can be cleaved by V8 proteinase into a 90 kDa globular head and a 32 kDa tail region, the latter of which could further be cleaved into a 27 kDa polypeptide. The 90 kDa globular head contains the N-terminus of vinculin, three 112-residue repeats (residues 259-589), and extends to approximately residue 850. Gel overlay experiments show that it also contains a binding site for the cytoskeletal protein talin. The talin-binding domain was further localized to the N-terminal 398 amino acid residues of the protein by expression in vitro of this region from a vinculin cDNA cloned into the Bluescript SK+ vector. The head and tail domains are apparently separated by a proline-rich region that contains V8-proteinase-cleavage sites and a candidate tyrosine (822)-phosphorylation site. Secondary-structure prediction suggests that the head and tail domains contain alpha-helical regions separated by short stretches of turn/coil. Comparison of the chick with a partial human sequence reveals that vinculin is a highly conserved protein. In chickens Southern-blot analysis is consistent with a single vinculin gene, and it is therefore likely that vinculin, and its higher-molecular-mass isoform termed metavinculin, arise through alternative splicing.

Amino Acid Sequence↗
PubMed1989

Identification of a talin binding site in the cytoskeletal protein vinculin.

Binding of the cytoskeletal protein vinculin to talin is one of a number of interactions involved in linking F-actin to cell-matrix junctions. To identify the talin binding domain in vinculin, we expressed the NH2-terminal region of the molecule encoded by two closely similar, but distinct vinculin cDNAs, using an in vitro transcription translation system. The 5' Eco RI-Bam HI fragment of a partial 2.89-kb vinculin cDNA encodes a 45-kD polypeptide containing the first 398 amino acids of the molecule. The equivalent restriction enzyme fragment of a second vinculin cDNA (cVin5) lacks nucleotides 746-867, and encodes a 41-kD polypeptide missing amino acids 167-207. The radiolabeled 45-kD vinculin polypeptide bound to microtiter wells coated with talin, but not BSA, and binding was inhibited by unlabeled vinculin. In contrast, the 41-kD vinculin polypeptide was devoid of talin binding activity. The role of residues 167-207 in talin binding was further analyzed by making a series of deletions spanning this region, each deletion of seven amino acids contiguous with the next. Loss of residues 167-173, 174-180, 181-187, 188-194, or 195-201 resulted in a marked reduction in talin binding activity, although loss of residues 202-208 had much less effect. When the 45-kD vinculin polypeptide was expressed in Cos cells, it localized to cell matrix junctions, whereas the 41-kD polypeptide, lacking residues 167-207, was unable to do so. Interestingly, some deletion mutants with reduced ability to bind talin in vitro, were still able to localize to cell matrix junctions.

Amino Acid Sequence↗