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Biomedical subjects

P Rice

Publications and source records attributed to P Rice.

At least 37 records · Page 2Linked to original sources

Non-invasive quantification of skin injury resulting from exposure to sulphur mustard and Lewisite vapours.

The severity and progression of skin lesions resulting from exposure to the chemical warfare agents Lewisite (L) and sulphur mustard (SM) have been investigated using the non-invasive biophysical methods of evaporimetry and reflectance spectroscopy in large white pigs in vivo. Erythema (redness) expressed immediately after exposure to L or SM vapours appeared to be related to the lesion severity as demonstrated by histopathological analysis. Skin brightness correlated well with scab formation whereas blueness (cyanosis) did not appreciably alter throughout the study. Rates of transepidermal water loss (TEWL) changed both with occlusion (during vapour exposure) and also mirrored the progression of macroscopic skin injury after 12 h. Whilst no single parameter could be used in isolation to ascertain the severity and subsequent progression of the skin lesions, measurement of erythema, skin brightness and TEWL could provide quantitative, non-invasive methods for determining the efficacy of antidotes or therapies to prevent the toxic effects of chemical warfare agents. However, neither colourimetry or TEWL provided a clinical evaluation of such lesions that were comparable with the prognostic capabilities of laser Doppler imaging.

Animals↗

A rapid biochemical test to aid identification of Mycoplasma mycoides subsp. mycoides small colony (SC) strains.

The ability to utilize maltose, as determined by measurement of oxygen uptake, is used to differentiate Mycoplasma mycoides subsp. mycoides small colony (SC) and M. capricolum subsp. capripneumoniae (all strains negative) from other members of the M. mycoides cluster (M. mycoides subsp. capri, M. mycoides subsp. mycoides large colony (LC), M. capricolum subsp. capricolum; and bovine serogroup 7; 94% of strains positive). Rapid tests for maltose utilizing ability were developed, based on hydrolysis of a chromogenic alpha-glucosidase (maltase) substrate (p-nitrophenyl-alpha-D-glucopyranoside, colourless) to give a brightly coloured product (p-nitrophenol, yellow). On agar plates, colonies of maltose-utilizing strains became coloured within 40 min.

Animals↗

Artemis: sequence visualization and annotation.

SUMMARY: Artemis is a DNA sequence visualization and annotation tool that allows the results of any analysis or sets of analyses to be viewed in the context of the sequence and its six-frame translation. Artemis is especially useful in analysing the compact genomes of bacteria, archaea and lower eukaryotes, and will cope with sequences of any size from small genes to whole genomes. It is implemented in Java, and can be run on any suitable platform. Sequences and annotation can be read and written directly in EMBL, GenBank and GFF format. AVAILABITLTY: Artemis is available under the GNU General Public License from http://www.sanger.ac.uk/Software/Artemis

Databases, Factual↗

Recurrence of hepatitis B after single lung transplantation.

This study describes a patient who developed decompensated liver disease secondary to reactivation of hepatitis B infection 20 months after single lung transplantation following augmentation of immunosuppression to treat allograft rejection. Discussion focuses on the virologic and management issues of this case and reviews the approach taken when considering patients with chronic hepatitis B infection for lung transplantation.

Adult↗

The development of Lewisite vapour induced lesions in the domestic, white pig.

Studies performed in the past in our laboratory have detailed the development of sulphur mustard lesions in the domestic, white pig using small glass chambers to achieve saturated vapour exposure under occluded conditions. We have now used this experimental model to produce cutaneous lesions for detailed histopathological studies following challenge with lewisite. Histological examination of resulting lesions have revealed that although the overall pattern of lesion development is similar to that seen following mustard challenge, the time-course of cellular events is very much compressed. The epidermis showed focal basal cell vacuolation with associated acute inflammation as early as one hour postexposure. Coagulative necrosis of the epidermis and papillary dermis was complete by 24 hours and followed the appearance of multiple coalescent blisters between six and 12 hours post-exposure. At 48 hours, the lesions were full thickness burns with necrosis extending into the deep subcutaneous connective and adipose tissues. The study of lesions beyond 24 hours revealed early epithelial regeneration at the wound edge. The overall spontaneous healing rate of these biologically severe lesions was significantly faster than comparable sulphur mustard injuries and probably reflected a lack of alkylation of DNA and RNA.

Animals↗

Effect of alcohol on the oral mucosa assessed by quantitative cytomorphometry.

The effect of alcohol on the oral mucosa was assessed using quantitative cytomorphology applied to smears taken from clinically normal oral mucosa of patients attending an alcohol problem unit and results were compared to a control group (consisting of social and non-drinkers) attending a hospital for routine dental care. Smears were stained using the Papanicolaou method and the nuclear and cell boundaries of 50 randomly selected cells traced and mean areas (NA and CA, respectively) calculated. The average number of units of alcohol consumed were recorded for each group together with relevant blood tests. The alcohol group was further subdivided into "binge" and "regular" drinkers. No significant differences were found between mean NA and mean CA values for these two types of alcohol drinkers, despite a marked difference in weekly units consumed. However, a statistically significant reduction in mean cytoplasmic area (P < 0.001) and mean nuclear area (P < 0.01) was found for the alcohol group when compared to controls. In conclusion, excess alcohol intake may influence results for quantitative oral cytomorphology. Further research is indicated on the relative effects of alcohol (both topical and systemic).

Adult↗

The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids.

1. This study investigated whether the reactive organohalogen gases perfluoroisobutene (PFIB) and phosgene, which cause death by overwhelming pulmonary oedema, affect the surfactant system or type II pneumocytes of rat lung. 2. The progression and type of pulmonary injury in Porton Wistar-derived rats was monitored over a 48 h period following exposure to either PFIB or phosgene (LCt30) by analyzing the inflammatory cells and protein in bronchoalveolar lavage fluid. Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction from lavage fluid. 3. Alterations in the cell population and lung permeability occurred following both gases, indicating that the injury was a permeability-type pulmonary oedema. Changes in the total amount of phospholipid and in the percentage composition of the surfactant were different for the two gases. PFIB produced increases in phosphatidylglycerol and phosphatidylcholine over the first hour, similar to that seen following air exposure, followed by substantial decreases in these phospholipids. Phosgene caused late increases in all phospholipids from 6 h post-exposure. 4. Differences in the response of the surfactant system to exposure to PFIB and phosgene suggest different mechanisms of action at the alveolar surface although the final injurious response is pulmonary oedema for both gases.

Administration, Inhalation↗

Early experience using duplex ultrasonography in the diagnosis of deep venous thrombosis; a prospective evaluation.

Duplex ultrasound is used in many radiology departments as the first line of investigation for symptomatic deep venous thrombosis. Before changing the practice of our department from venography to duplex ultrasonography, we wanted to assess our ability to identify deep venous thrombosis on ultrasound. Thirty-eight patients were investigated for suspected deep venous thrombosis by venography and duplex ultrasound. The results were compared using venography as the 'gold standard'. Duplex ultrasound correctly identified 13 out of 16 limbs with deep venous thrombosis. Four of the 38 duplex ultrasound examinations (11%) were described as inadequate at the time of examination, and when these are excluded from the analysis a sensitivity of 93 %, and specificity of 80 % are achieved. We conclude that there is a significant learning curve when performing duplex ultrasound of the lower limb, and that change-over from venography to ultrasound should include a period during which both examinations are routinely performed.

Adult↗

Diminished CYP2E1 expression and formation of 2-S-glutathionyl acetate, a glutathione conjugate derived from 1,1-dichloroethylene epoxide, in murine lung tumors.

We hypothesized that resistance of lung tumors to the cytotoxic effects of xenobiotics is associated with loss of cytochrome P-450 expression, leading to defective formation of reactive intermediates. To test this hypothesis, we investigated 1,1-dichloroethylene (DCE), a chemical that causes Clara cell damage, in a urethane-induced model of lung tumorigenesis. Lung metabolism of DCE yields 2-S-glutathionyl acetate (conjugate [C]), a glutathione conjugate derived from DCE-epoxide, believed to be the ultimate toxic species. We used immunohistochemistry to investigate CYP2E1 expression in nontumor- and tumor-bearing lung to identify cells capable of generating [C]. CYP2E1 and [C] were colocalized in adjacent tissue sections to determine coincidence between CYP2E1 and [C] in lung cells. CYP2E1 was highly localized to the bronchiolar epithelium of nontumor-bearing lung and in uninvolved tissue of tumor-bearing lung and was concentrated in the Clara cells. In contrast, tumor foci including hyperplasias, adenomas, and carcinomas were deficient in CYP2E1 in both untreated and DCE-treated mice. Immunoreactivity for [C] was also detected in the bronchiolar epithelium in nontumor-bearing lung and uninvolved tissue of tumor-bearing lung of DCE-treated mice and was reduced in hyperplasias, adenomas, or carcinomas. Thus, there was a coincidence between the sites of CYP2E1 expression and [C] formation. Conjugate [C] accumulated only in lung cells in which CYP2E1 was expressed. Histochemical staining for glutathione confirmed its presence in tumor foci. Thus, bioactivation and conjugation of DCE occur in structurally normal tissue from both nontumor- and tumor-bearing lung but was lost in tumor tissue, irrespective of the stage of tumor development.

Adenoma↗

Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells.

Recent data suggest that sepsis stimulates macrophage apoptosis (Ao) with subsequent induction of macrophage dysfunction. Nuclear factor-kappaB (NFkappaB) activation has been linked to Ao in either a pro- or antiapoptotic role. Glucans are biological response modifiers which exert antisepsis activity. This investigation examined the effect of (1-3)-beta-D-glucan receptor binding by a high affinity ligand on Ao and NFkappaB activation in U937 cells in the presence or absence of LPS. A high affinity glucan ligand (IC50 = 23 nM) activated NFkappaB, but did not induce Ao or significantly alter LPS induced U937 Ao. These data indicate that: i) modulation of the macrophage (1-3)-beta-D-glucan receptor stimulates NFkappaB; ii) does not induce Ao or significantly diminish LPS induced Ao and iii) activation of the U937 FAS receptor does not alter the relative Ao responses in glucan and LPS treated cells.

Antibodies↗

The use of laser Doppler imaging as an aid in clinical management decision making in the treatment of vesicant burns.

Vesicants are a group of chemicals recognised, under the terms of the Chemical Weapons Convention, as potential chemical warfare agents whose prime effect on the skin is to cause burns and blistering. Experience of the clinical management of these injuries is not readily available and therefore an accurate assessment of the severity of the lesion and extent of tissue involvement is an important factor when determining the subsequent clinical management strategy for such lesions. This study was performed to assess the use of laser Doppler imaging (LDI) as a noninvasive means of assessing wound microvascular perfusion following challenge with the vesicant agents (sulphur mustard or lewisite) by comparing the images obtained with histopathological analysis of the lesion. Large white pigs were challenged with sulphur mustard (1.91 mg cm(-2)) or lewisite (0.3 mg.cm(-2)) vapour for periods of up to 6 h At intervals of between 1 h and 7 days following vesicant challenge, LDI images were acquired and samples for routine histopathology were taken. The results from this study suggest that LDI was: (i) a simple, reproducible and noninvasive means of assessing changes in tissue perfusion, and hence tissue viability, in developing and healing vesicant burns; (ii) the LDI images correlates well with histopathological assessment of the resulting lesions and the technique was sufficiently sensitive enough to discriminate between skin lesions of different aetiology. These attributes suggest that LDI would be a useful investigative tool that could aid clinical management decision making in the early treatment of vesicant agent-induced skin burns.

Animals↗

Transmission of cervical cancer-associated human papilloma viruses from mother to child.

There is now compelling evidence that persistent infection with certain types of human genital papillomaviruses (HPV) may, after many years, lead to cervical cancer. However, HPV have been detected in asymptomatic women, infants and children. Several studies have demonstrated that infants can acquire high-risk HPV infections from their mothers at birth. Thus, the traditional view that cervical-cancer associated HPV infections are primarily sexually transmitted needs to be re-assessed. Accordingly, the role of mother to child transmission of cancer-associated HPVs may need to be investigated further. These facts are pertinent to those developing prophylactic vaccines to prevent high-risk HPV infections and cervical carcinoma.

Child↗

Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS.

We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia test, also called the CMV direct antigen test (DAT), in the management of patients with advanced human immunodeficiency virus (HIV) infection; we studied all patients who had pp65 assays between 8 September 1995 and 30 August 1996. Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests were negative in 16 patients, of whom 12 have not developed CMV end-organ disease after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4 patients had previously treated CMV disease. Eleven patients had positive tests: 4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow up and 2 have remained disease-free. This test has a positive predictive value of 43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65 antigenaemia assay can be performed in a standard virology laboratory avoiding the problems associated with polymerase chain reaction (PCR), a result is available within 5 h, and it is semi-quantifiable. However, a large prospective study is required to determine the comparative value and roles of the pp65 antigenaemia assay and DNA PCR in the management of CMV disease, especially with regard to the use of primary prophylaxis and pre-emptive therapy.

AIDS-Related Opportunistic Infections↗

Reconstitution of native-like nucleosome core particles from reversed-phase-HPLC-fractionated histones.

We have reconstituted nucleosome core particles from reversed-phase-HPLC-purified chicken erythrocyte core histones and 145 bp random-sequence DNA fragments. Characterization of the resulting nucleoprotein complexes by sedimentation velocity, CD and DNase I footprinting showed that they are structurally indistinguishable from native nucleosome core particles. Furthermore, we have shown that the ability to reproduce these native-like structural features in these reconstituted nucleosome core particles is basically independent of the biological source or the method used (i.e. salt versus acid) for the extraction of histones before their HPLC fractionation. The usefulness and relevance of this approach for the reconstitution of native-like chromatin structures from histone types (histone variants/post-translationally modified histones), which are usually available only in relatively small amounts, is discussed.

Animals↗

The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.

Large-scale systematic sequencing has generally depended on the availability of an ordered library of large-insert bacterial or viral genomic clones for the organism under study. The generation of these large insert libraries, and the location of each clone on a genome map, is a laborious and time-consuming process. In an effort to overcome these problems, several groups have successfully demonstrated the viability of the whole-genome random 'shotgun' method in large-scale sequencing of both viruses and prokaryotes. Here we report the sequence of Saccharomyces cerevisiae chromosome IX, determined in part by a whole-chromosome 'shotgun', and describe the particular difficulties encountered in the random 'shotgun' sequencing of an entire eukaryotic chromosome. Analysis of this sequence shows that chromosome IX contains 221 open reading frames (ORFs), of which approximately 30% have been sequenced previously. This chromosome shows features typical of a small Saccharomyces cerevisiae chromosome.

Base Composition↗

The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.

Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed thousands of new predicted genes and allowed analysis of long-range features of chromosomal organization. Generally, genes and predicted genes seem to be distributed evenly throughout the genome, having no overall preference for DNA strand. Apart from the smaller chromosomes, which can have substantially lower gene density in their telomeric regions, there is a consistent average of one open reading frame (ORF) approximately every two kilobases. However, one of the most surprising findings for a eukaryote with approximately 6,000 genes was the amount of apparent redundancy in its genome. This redundancy occurs both between individual ORFs and over more extensive chromosome regions, which have been duplicated preserving gene order and orientation. Here we report the entire nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae chromosome, and demonstrate that its features and organization are consistent with those observed for other S. cerevisiae chromosomes. Analysis revealed 459 ORFs, 284 have not been identified previously. Both intra- and interchromosomal duplications of regions of this chromosome have occurred.

Base Composition↗

Histopathological changes in Yucatan minipig skin following challenge with sulphur mustard. A sequential study of the first 24 hours following challenge.

Sulphur mustard (HD) or "mustard gas' is a potent vesicant chemical warfare agent whose biological effects in man have been well documented. The histopathological features of the developing cutaneous HD lesion in female Yucatan minipigs up to 24 hours post exposure are reported. Following challenge with HD vapour at a concentration of 12.0 mumol/cm2 a sequence of ultrastructural changes to keratinocytes occurred which were initially seen in the stratum basale. Condensation of nuclear heterochromatin and loss of euchromatin was accompanied by cytoplasmic swelling and culminated in focal epidermal necrosis which was evident at 24 h after the challenge. The melanocyte appeared to be the cell type most sensitive to HD challenge with a loss of cytoplasmic electron density in areas of the cytoplasm immediately surrounding the melanosomes, chromatin condensation, nuclear membrane blebbing with mitochondrial and generalized cytoplasmic swelling. Isolated complete cell necrosis and disruption were noted as early as 2 h following the challenge with generalized necrosis being seen from 12 h onwards. From 12 h onwards, areas of basement membrane degeneration were also observed. These appeared similar in ultrastructure to that observed in other animal model systems but did not progress to the large blisters so typical of the human lesion. Damage to the upper dermis took the form of an inflammatory response typified by vascular endothelial swelling and vacuolation, dermal oedema and inflammatory cell (mainly neutrophil) infiltration. There was some evidence of transitory epidermal damage outside the prescribed wound area. This finding may be of clinical importance when surgical treatments are being considered.

Animals↗