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Biomedical subjects

R M Jones

Publications and source records attributed to R M Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

Anaesthetic organ toxicity: is it really a problem?

The hepatotoxicity of halothane is now well known, but only became apparent after several years of use. The nephrotoxicity of methoxyflurane was not realized immediately, but once identified, led to its withdrawal from use. Therefore, when new agents that appear to offer significant advantages over established drugs become available, exhaustive testing and monitoring is necessary to ensure their safety. Sevoflurane, recently available in the UK and the USA but used for some time in Japan, has been subjected to considerable scrutiny.

Journal Article↗
PubMed1998

Mite allergens: significance of enzymatic activity.

Ten years ago, the cloning and sequencing of a cDNA encoding the group I allergen of house-dust mites unequivocally determined that protein allergens may have biochemical functions in addition to their ability to bind IgE. Since this discovery, several groups have speculated that the biochemical activities of allergens, or substances associated with allergens, may be involved in their immunogenicity or allergenicity. This paper will focus on just one biochemical function, proteolytic activity, and will be illustrated by examples of our own work that we believe support the hypothesis that this category of molecules are endowed with the properties of proallergic adjuvants.

Allergens↗
PubMed1998

One hundred liver resections including comparison to non-resected liver-mobilized patients.

BACKGROUND: Factors of liver resection associated with postoperative recovery and survival, the modalities that affect survival with resected colorectal carcinoma liver metastases, the comparison of liver function of liver-resected to liver-mobilized but not resected patients, and observation of early liver regeneration volume over time have not been studied prospectively. This study aimed to prospectively analyse these factors. METHODS: Data were collected prospectively on 100 consecutive liver resections, and 10 liver-mobilized but not resected patients by the Hepatobiliary Unit, University of Melbourne, Austin Campus. Follow-up of patients was 100%. RESULTS: The factors associated with blood loss were the type of liver resection (P = 0.0001), the length of the operation (P = 0.0001) and a central venous pressure greater than 5 cm of water (P = 0.0008). An inverse correlation existed between blood loss and long-term survival (P = 0.003). The only predictor for a postoperative complication was the length of the operation (P = 0.03): a correlation of moderate significance existed between blood loss and a complication (P = 0.052; confidence interval 0.19-1.17). The 5-year cumulative survival for hepatic resection for colorectal carcinoma Dukes A + B was 55%; there was a significantly better survival of Dukes A + B compared to Dukes C (P = 0.03) and also for those 50 years or older, but this did not depend on whether there were one or more lesions present. Resected patients had a significantly higher alanine transaminase (ALT), total bilirubin and international normalized ratio than non-resected patients, but not albumin, total protein, alkaline phosphatase or aspartate aminotransferase. The serum albumin fall was similar in both groups, which indicated that loss of liver tissue was not the cause. The re-resection rate was 8% without mortality and with low morbidity. Liver volume was restored by 64% (510 +/- 170 cc) by 7 days postoperatively. CONCLUSIONS: Major hepatic resection can be performed with low mortality, morbidity and short hospital stay, with a 5-year survival for colorectal carcinoma better than 50%. Resection needs to be considered more frequently for curative management. Serum albumin fall is not caused by loss of liver tissue and blood loss can be controlled by central venous pressure manipulation and vascular isolation. Re-resection is a safe and rewarding treatment and needs to be planned at the first resection.

Blood Loss, Surgical↗
PubMed1998

The effects of ultraviolet radiation on antibiotic-resistant bacteria in vitro.

Wound infections produced by antibiotic-resistant bacterial strains are particularly difficult to manage. This study examined the effectiveness of ultraviolet (UV) light treatment in killing antibiotic-resistant strains of Staphylococcus aureus and Enterococcus faecalis in vitro. Between 2 and 5 replications of each organism at 10(8) organisms/ml were prepared and plated on sheep blood agar medium and treated with UV light (254 nm, 15.54 mW/cm2 output). Irradiation times were 0, 2, 5, 8, 15, 30, 45, 60, 90 or 120 seconds. Bacterial cultures were then incubated at 35 degrees C for 24 hours. Kill rates were 99.9 percent for the methicillin-resistant strain of S. aureus (MRSA) at 5, 8, 15, 30, 45, 60 seconds and 100 percent at 90 and 120 seconds. Kill rates were 99.9 percent at 5, 8, 15, 30 seconds for vancomycin-resistant E. faecalis (VRE) and 100 percent at 45, 60, 90, 120 seconds. Similar results were found with UV light treatment of the antibiotic-susceptible strains of S. aureus and E. faecalis. A significant difference in kill rates at 30 seconds of UV exposure was detected between the antibiotic-resistant strain of S. aureus and the antibiotic-resistant strain of E. faecalis (Student's t test, p < 0.01). Significant differences were also detected in the kill rates at 30 second exposure times for the antibiotic-susceptible strains of S. aureus and E. faecalis. These findings suggest that the Enterococcal bacteria is more susceptible to the killing effects of UV. This data also suggests that UV light at 254 nm is bactericidal for antibiotic-resistant strains of S. aureus and E. faecalis at times as short as 5 seconds and that the enterococcal bacteria is more susceptible to the killing effects of UV. With recommended patient treatment times for infected wounds being significantly longer than 5 seconds, this data indicates that patient treatment times need to be re-examined.

Cross Infection↗
PubMed1997

Resolution of gas exchange abnormalities and intrapulmonary shunting following liver transplantation.

This prospective study evaluated pulmonary gas exchange in patients with severe liver disease, its relationship to intrapulmonary shunting, and its response to liver transplantation. Detailed clinical examinations, chest radiographs, and arterial blood gas estimations were performed on 74 consecutive patients before and after liver transplantation. Fifty percent of the 74 patients had a widened alveolar-arterial (A-a) oxygen gradient (> 15 mm Hg) and 45% a reduced PaCO2 (< 35 mm Hg). Twenty-two percent were hypoxemic (PaO2 < 80 mm Hg). Following transplantation mean PaO2 increased (pre-89 +/- 14 vs. post-94 +/- 8 mm Hg; P = .014) and A-a oxygen gradient decreased (pre-16 +/- 14 vs. post-8 +/- 9 mm Hg; P < .001), despite an increase in PaCO2 (pre-36 +/- 5 vs. post-39 +/- 4; P < .001). To examine this improvement in oxygen exchange further, a subgroup of 26 consecutive patients, with no obvious cardiorespiratory cause for abnormal gas exchange underwent, pre- and post-operative spirometry, measurement of carbon monoxide diffusion capacity (DLCO), intrapulmonary shunt estimations (100% oxygen technique), and echocardiography. In this subgroup, 23% were hypoxemic, 54% had a widened A-a oxygen gradient, and 85% had increased intrapulmonary shunting (> 5%) before transplantation. There was a significant correlation between the degree of pre-transplantation intrapulmonary shunting and A-a oxygen gradient (P < .01). Nineteen of the 22 patients with increased shunting improved following transplantation and improved A-a oxygen gradient correlated well with the reduction in shunting (P < .005). DLCO was reduced in 69% of these patients with a mean value of 73% of predicted. However, the post-transplantation mean DLCO did not increase despite the improvement in oxygen exchange. In conclusion, gas exchange abnormalities are common in patients with severe liver disease but these usually resolve post-transplantation. Intrapulmonary shunting is a major determinant of abnormal oxygen uptake in transplant candidates without evidence of cardiorespiratory disease. Finally, the mechanism for the reduced DLCO is unclear but appears different to that responsible for intrapulmonary shunting and abnormal oxygen exchange.

Adult↗
PubMed1997

Assignment of the human gene encoding eukaryotic initiation factor 4E (EIF4E) to the region q21-25 on chromosome 4.

We recently cloned genomic sequences containing the promoter region for the messenger RNA cap binding protein (eIF4E). As the rate-limiting step in translation, eukaryotic initiation factor 4E is important in cellular growth control. Using oligonucleotide primers specific for the promoter region in polymerase chain reactions (PCR), we amplified the human gene in a chromosome 4-specific human/rodent somatic cell panel. This panel mapped single copy genomic sequences for eIF4E in the region 4q21 to 4q25.

Animals↗
PubMed1997

Identification and mechanism of formation of potentially genotoxic metabolites of tamoxifen: study by LC-MS/MS.

On-line high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI MS) and tandem mass spectrometry (MS/MS) have been applied to the study of tamoxifen metabolism in liver microsomes and to the identification of potentially genotoxic metabolites. The results showed that the hydroxylated derivatives, including 4-hydroxytamoxifen and alpha-hydroxytamoxifen are detoxication metabolites, while arene oxides, their free radical precursors or metabolic intermediates, are the most probable species involved in DNA-adduct formation.

Chromatography, High Pressure Liquid↗
PubMed1997

Peroxidase activation of 4-hydroxytamoxifen to free radicals detected by EPR spectroscopy.

4-Hydroxytamoxifen is a major metabolite of the antiestrogenic drug tamoxifen used in the treatment of women with breast cancer. 4-Hydroxytamoxifen is broken down by a horseradish peroxidase/H2O2 system very much more rapidly than tamoxifen and causes much greater DNA damage determined by 32P-postlabelling. EPR spin trapping of 4-hydroxytamoxifen reaction products in the presence of the free radical trap 5,5-dimethyl-1-pyrroline N-oxide, together with glutathione as a hydrogen donor, resulted in the generation of a species with the characteristics of the glutathione thiyl radical (aN approximately 15.3 G, aH approximately 16.2 G). Support for the creation of thiyl radicals comes from the close to stoichiometric time dependent formation of glutathione disulfide concomitant with the loss of glutathione. Similar results were obtained using 4-hydroxytoremifene but no radical formation or glutathione loss could be detected using 3-hydroxytamoxifen (droloxifene). On-line LC-ESI MS analysis of the incubation products from 4-hydroxytamoxifen has identified three products with a protonated molecular mass of 773, consistent with the formation of dimers of 4-hydroxytamoxifen. The role that radical mechanisms have in the carcinogenic effects of tamoxifen in the endometrium or other target organs of women taking this drug remains to be established.

DNA Adducts↗
PubMed1997

Heterogeneous proteolytic specificity and activity of the house dust mite proteinase allergen Der p I.

BACKGROUND: Exposure of the skin or respiratory tract to proteinases is frequently associated with allergic sensitization. This is of particular significance in the domestic indoor environment where the proteolytic activity of Der p I, the group I allergen of the house dust mite Dermatophagoides pteronyssinus, may influence the allergenicity of mites. Using class-specific proteinase inhibitors and active-site affinity chromatography, we have previously shown that Der p I exhibits a mixed cysteine-serine proteinase activity. Measurement of the amount of cleavage, however, did not determine whether the inhibitors used were targeting exactly the same proteolytic mechanism. OBJECTIVE: To resolve this issue, we have examined whether the cleavage specificity of the cysteine and serine proteinase activities of Der p I was the same. METHODS: HPLC and mass spectrometry were used to analyse and identify the products of a Der p I-digested peptide substrate and thus identify the peptide bonds cleaved. RESULTS: Der p I cleaves different peptide bonds, depending upon the class of proteolytic mechanism used. In the model peptide substrate insulin B chain, the cysteine and serine proteinase activities of Der p I showed preference for glutamic acid and arginine respectively in the P1 position. CONCLUSION: These data suggest the existence of more than one mechanistic form of the allergen immunologically identified as Der p I. If proteolytic activity is indeed a function of allergenicity, this information may have important implications for the pathogenicity of Der p I and the ability of innate antiproteinase defences in the respiratory tract to prevent immune sensitization.

Allergens↗
PubMed1997

Effects of toothbrush design and brushing proficiency on plaque removal.

A single-blind, short-term cross-over clinical trial compared the plaque removal performance of three commercially available manual toothbrushes. A sample of 25 dental hygiene students, 19 to 42 years old, served as participants. On 3 separate occasions, participants were instructed to refrain from toothbrushing or flossing for 24 hours before clinical trials. A prebrushing plaque index using disclosing solution was performed on each participant. One of the 3 test brushes was then randomly dispensed to each participant, and they were allowed to brush for 90 seconds without the aid of a mirror. A postbrushing plaque index was then performed on each participant. This procedure was repeated 2 more times at 2-week intervals so that each participant was tested with all 3 toothbrushes. Previous studies of this kind using random participant samples have suggested that brush design does indeed affect the efficacy of plaque removal. This study used participants who were well versed on efficient toothbrushing technique to determine if improved brushing skills would overshadow advantages in toothbrush design. No significant differences in performance were detected between the test brushes for any of the three scored areas.

Adult↗
PubMed1996

Activity of doramectin against nematode and arthropod parasites of swine.

The efficacy of doramectin, a novel avermectin, was assessed against both naturally-acquired and experimentally-induced infections of gastrointestinal roundworms, lungworms, kidneyworms, lice and mites in studies conducted across North America and Europe. Twenty-two studies evaluated efficacy against fourth larval and adult stages of the following nematode species: Hyostrongylus rubidus, Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus. Efficacy was evaluated against the louse Haematopinus suis in six studies and against the mite Sarcoptes scabiei in four studies. A common study design was employed for each study type. In all studies, animals were allotted at random to a doramectin-treated or a saline-treated group. The doramectin-treated group received the drug at 300 micrograms kg-1 by intramuscular injection while the saline-treated group received saline by the same route. In the nematode studies, worm burdens were determined for each animal at slaughter 14-16 days after treatment. Efficacy against each nematode species/stage was assessed on the basis of percentage reduction in geometric mean worm burden in doramectin-treated animals compared with saline-treated controls. In louse and mite studies, counts were made immediately before treatment and then at weekly intervals for four weeks. Efficacy was based on a comparison of the level of infestation on the day of treatment with that on the last day of test. Data from individual studies were combined to derive a single estimate of efficacy against each of the parasite species represented in the study program. Efficacy of doramectin was 98% or greater against all nematode species except T. suis for which the efficacy was 87% and 79% against adult and fourth larval stage, respectively. Efficacy was 100% against both Haematopinus suis and Sarcoptes scabiei.

Animals↗
PubMed1996

High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50. p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83%) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67%) harbored homozygous deletions, 5 (21%) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.

Blotting, Southern↗
PubMed1996

On-line high-performance liquid chromatographic-electrospray ionization mass spectrometric method for the study of tamoxifen metabolism.

An on-line high-performance liquid chromatographic (HPLC)-electrospray ionization mass spectrometric (ESI-MS) method has been developed and optimized for the study of tamoxifen metabolism. Metabolism in mouse liver microsomes was chosen to demonstrate the applicability and superiority of the method, since mice metabolize tamoxifen faster and produce more metabolites than rats or humans. Mouse liver microsomal preparations were incubated with tamoxifen in the presence of NADPH and MgCl2. The metabolites formed were separated and analyzed by the optimized HPLC-ESI-MS system. The separation was performed on a Res Elute-BD column (5 microns particle size, 250 x 4.6 mm I.D.) with 70% (v/v) methanol in 0.5 M ammonium acetate as the mobile phase. A total of eleven metabolites have been detected, some of which have not been previously reported. The metabolites identified are: tamoxifen N-oxide, N-desmethyltamoxifen, 4-hydroxytamoxifen, 4'-hydroxytamoxifen, 4-hydroxytamoxifen N-oxide, 4'-hydroxytamoxifen N-oxide, 4-hydroxy-N-desmethylamoxifen, 4'-hydroxy-N-desmethyltamoxifen, 3,4-dihydroxytamoxifen, 3,4-epoxytamoxifen and 3,4-epoxytamoxifen N-oxide.

Animals↗
PubMed1996

Subcellular location of the tetrapyrrole synthesis enzyme porphobilinogen deaminase in higher plants: an immunological investigation.

A recombinant plasmid, pArab8, harbouring the cDNA encoding the mature form of the tetrapyrrole synthesis enzyme porphobilinogen deaminase (EC 4.3.1.8; also known as hydroxymethylbilane synthase) from Arabidopsis thaliana (L.) Heynh. has been constructed, and used to transform Escherichia coli. The porphobilinogen deaminase protein from Arabidopsis was overexpressed in this strain, and purified to homogeneity (3000-fold) with a yield of 20%. Antibodies were raised against the purified plant enzyme, and used in Western blot analysis, immunoprecipitation of enzyme activity and immuno-gold electron microscopy. The results indicate that the enzyme is confined to plastids in both leaves and roots. The implications of this finding for plant tetrapyrrole synthesis are discussed.

Animals↗