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Biomedical subjects

P M Rogers

Publications and source records attributed to P M Rogers.

14 recordsLinked to original sources

Evaluation of fixed sample-size plans for Plutella xylostella (Lepidoptera: Plutellidae) on broccoli crops in Australia.

Fixed sample-size plans for monitoring Plutella xylostella (L.) (Lepidoptera: Plutellidae) on broccoli and other Brassica vegetable crops are popular in Australia for their simplicity and ease of application. But the sample sizes used are often small, approximately 10-25 plants per crop, and it may be that they fail to provide sufficient information upon which to base pest control decisions. We tested the performance of seven fixed sample-size plans (10, 15, 20, 30, 35, 40, and 45 plants) by resampling a large data set on P. xylostella in commercial broccoli crops. For each sample size, enumerative and presence-absence plans were assessed. The precision of the plans was assessed in terms of the ratio of the standard error to the mean; and at least 45 and 35 samples were necessary for the enumerative and presence-absence plans, respectively, to attain the generally accepted benchmark of < or = 0.3. Sample sizes of 10-20 were highly imprecise. We also assessed the consequences of classifications based on action thresholds (ATs) of 0.2 and 0.8 larvae per plant for the enumerative case, and 0.15 and 0.45 proportion of plants of infested for the presence-absence case. Operating characteristic curves and investigations of the frequency of correct decisions suggest improvements in the performance of plans with increased sample size. In both the enumerative and presence-absence cases, the proportion of incorrect decisions was much higher for the lower of the two ATs assessed, and type II errors (i.e., failure to suggest pest control upon the AT is exceeded) generally accounted for the majority of this error. Type II errors are the most significant from a producer's standpoint. Further consideration is necessary to determine what is an acceptable type II error rate.

Animals↗

Discoloration of a titanium alloy removable partial denture: a clinical report.

With recent advances in dental technology, titanium is currently used for fabrication of crowns, fixed partial dentures, implant frameworks, and removable partial denture frameworks. The use of titanium-aluminum-vanadium (Ti-6Al-4V) alloy assumes that it imparts similar anti-corrosion characteristics to the commercially pure titanium. This clinical report describes a patient who experienced discoloration of a Ti-6Al-4V alloy removable partial denture.

Alloys↗

Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol substituted with two methyl groups alpha to the nitrogen.

N-Acetyl-4-S-cysteaminylphenol 1 is an analogue of a biosynthetic intermediate in the pathway to melanin. It is probably oxidized to an o-quinone which can alkylate cellular nucleophiles resulting in interference with cell growth and proliferation. It is reported to have useful anti-melanoma activity. We previously synthesized a range of analogues of 1 by varying the acyl portion of the amide. A modest increase in melanoma activity against six melanoma cell lines for these analogues could be correlated with increased lipophilicity. Thirteen new analogues of 1 containing two methyl groups at the alpha-position of the amino component and various acyl groups have now been prepared and assessed for anti-melanoma activity against six human melanoma cell lines. Most of the new compounds displayed greater cytotoxicity than the lead compound 1. The highest cytotoxicity against the cell lines was observed for the cyclohexylacetamide 11 followed by the cyclohexylcarboxamide 10 and the 2,2-dimethylpropanamide 6. The IC50 values of the most cytotoxic compound 11 against the cell lines were comparable with those of cisplatin. Small variations in the acyl components of these analogues, such as reducing the ring size, lengthening the carbon chain and reducing the amount of chain branching, resulted in a considerable loss of cytotoxicity. The moderate activity of 6, 10 and 11 against SK-Mel-24 cells (non-tyrosinase containing) and an ovarian cell line suggests that interference with the melanin pathway may not be their only mode of action.

Antineoplastic Agents↗

Synthesis and antimelanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol.

N-Acetyl-4-S-cysteaminylphenol (1) has been shown by Jimbow and co-workers to possess useful antimelanoma activity. It is an analogue of a biosynthetic intermediate in the pathway to melanin and probably acts as a prodrug, being oxidized to an o-quinone which reacts with essential enzymes containing sulphydryl groups resulting in interference with cell growth and proliferation. We have synthesized a range of analogues of 1 by varying the acyl portion of the amide with the intention of increasing the lipophilicity of the compounds. A modest increase in melanoma activity against six melanoma cell lines for these analogues could be correlated with increased lipophilicity. The most active of these compounds, N-[2-[(4-hydroxyphenyl)thiol]ethyl]cyclohexanecarboxamide (9), showed promising selectivity (lack of cytotoxicity) on the non-melanotic cell line SK-Mel-24 and on an ovarian cell line. A significant improvement in antimelanoma activity was observed with a new type of analogue containing three carbon atoms between the sulphur and nitrogen. The most active of these new analogues, N-[3-[(4-hydroxyphenyl)-thiolpropyl]-1-cyclohexanecarboxamide (15), had activity comparable to cisplatin against several cell lines and low cytotoxicity towards the non-melanotic cell line.

Antineoplastic Agents↗

DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90.

BACKGROUND: To our knowledge, 17-allylamino,17-demethoxygeldanamycin (17AAG) is the first inhibitor of heat shock protein 90 (Hsp90) to enter a phase I clinical trial in cancer. Inhibition of Hsp90, a chaperone protein (a protein that helps other proteins avoid misfolding pathways that produce inactive or aggregated states), leads to depletion of important oncogenic proteins, including Raf-1 and mutant p53 (also known as TP53). Given its ansamycin benzoquinone structure, we questioned whether the antitumor activity of 17AAG was affected by expression of the NQO1 gene, which encodes the quinone-metabolizing enzyme DT-diaphorase. METHODS: The antitumor activity of 17AAG and other Hsp90 inhibitors was determined by use of a sulforhodamine B-based cell growth inhibition assay in culture and by the arrest of xenograft tumor growth in nude mice. DT-diaphorase activity was determined by use of a spectrophotometric assay, and protein expression was determined by means of western immunoblotting. RESULTS: In two independent in vitro human tumor cell panels, we observed a positive relationship between DT-diaphorase expression level and growth inhibition by 17AAG. Stable, high-level expression of the active NQO1 gene transfected into the DT-diaphorase-deficient (by NQO1 mutation) BE human colon carcinoma cell line resulted in a 32-fold increase in 17AAG growth-inhibition activity. Increased sensitivity to 17AAG in the transfected cell line was also confirmed in xenografts. The extent of depletion of Raf-1 and mutant p53 protein confirmed that the Hsp90 inhibition mechanism was maintained in cells with high and low levels of DT-diaphorase. 17AAG was shown to be a substrate for purified human DT-diaphorase. CONCLUSION: These results suggest that the antitumor activity and possibly the toxicologic properties of 17AAG in humans may be influenced by the expression of DT-diaphorase. Careful monitoring for NQO1 polymorphism and the level of tumor DT-diaphorase activity is therefore recommended in clinical trials with 17AAG.

Antibiotics, Antineoplastic↗

A review of ultrasound-guided percutaneous biopsy of the gastrointestinal tract in HIV-infected patients.

OBJECTIVE: To illustrate the use of percutaneous ultrasound-guided biopsy of the gastrointestinal tract in HIV-infected patients to obtain a tissue diagnosis. DESIGN: The technique was used in relation to relevant clinical situations in which a diagnosis may have only been reached by open biopsy. METHOD: Three HIV-infected patients with suspected gastrointestinal tract lesions underwent percutaneous ultrasound-guided biopsy under local anaesthetic. RESULTS: A tissue diagnosis was made in each case resulting in initiation or continuation of appropriate therapy and avoided the need for open biopsy under general anaesthetic. CONCLUSION: Although the number of patients undergoing the procedure in this series was small, the technique has so far been shown to be safe and effective with few complications.

AIDS-Related Opportunistic Infections↗

Report of EPFA/NIBSC workshop 'nucleic acid amplification tests (NAT) for the detection of blood-borne viruses' held on 31 October 1996 in Amsterdam, The Netherlands.

The 3rd annual European Plasma Fractionators Association/National Institut of Biological Standard and Control (EPFA/NIBSC) meeting provided a forum for regulators, blood product and test kit manufacturers and organisations developing standards to present and discuss their latest data. The main conclusions were as follows. There has been substantial progress during the last year in the development of NAT technology specifically for improving the safety of blood products though there is an urgent need for the development of international reference materials. The technology is not yet sufficiently developed to be used as a routine screening test though testing of plasma pools for hepatitis C virus may be achieved within a year. Introduction of testing should not result in the creation of dual standards for plasma derived and cellular products. Once the technology is fully developed it could significantly improve the safety of all blood products, particularly those derived from starting materials with a high incidence of viral markers.

Blood↗

Transport of cisplatin and bis-acetato-ammine-dichlorocyclohexylamine Platinum(IV) (JM216) in human ovarian carcinoma cell lines: identification of a plasma membrane protein associated with cisplatin resistance.

The mechanisms by which cis-diamminedichloroplatinum(II) (cisplatin) is transported across the plasma membrane (i.e., passive diffusion versus active transport) were investigated in the 41M and CH1 human ovarian carcinoma cell lines and their acquired cisplatin-resistant variants 41McisR6 and CH1cisR6, respectively. Intracellular cisplatin accumulation was significantly reduced (4.0 +/- 1.7-fold) in the parental 41M line at 4 degrees C when compared to incubations at 37 degrees C. However, no significant differences in platinum uptake were observed in the 41McisR6 and in the CH1 pair of lines at 4 degrees C versus 37 degrees C. Similarly, in the presence of ouabain (an inhibitor of Na+,K+-ATPase), there was a marked reduction (2.0 +/- 0.4-fold) in drug accumulation in the sensitive 41M cells only, and no changes in drug uptake were observed in the other cell lines in the absence or presence of ouabain. Platinum accumulation was significantly enhanced in all cell lines in the presence of metabolic inhibitors (NaF and NaN3). These results suggest that in the parental 41M cell line, cisplatin transport may occur via passive diffusion and active/facilitated transport, whereas in the resistant 41McisR6 variant, cisplatin enters cells by passive diffusion only. The orally active drug bis-acetato-ammine-dichloro-cyclohexylamine platinum(IV) (JM216) is a lipophilic platinum(IV) complex that has been shown to circumvent cisplatin resistance in the 41McisR6 by increasing drug uptake. Across the entire range of concentrations used (5-50 microm), intracellular accumulation of JM216 was significantly reduced in 41M and 41McisR6 cells (3.5 +/- 0.7-fold; P < 0.01), and in CH1 and CH1cisR6 cells (14.2 +/- 6.0-fold; p < 0.01) at 4 degrees C when compared to incubations at 37 degrees C. No significant difference in JM216 uptake was observed in the 41M pair of lines in the absence or presence of ouabain. Additional studies have revealed that the fold reduction observed in cis-ammine(cyclohexylamine)dichloroplatinum(II) (JM118) accumulation in the 41M and 41McisR6 cells at 4 degrees C (3.7 +/- 1.9) reflects similar fold reductions to those observed with JM216 uptake at 4 degrees C. These results suggest that the mechanism of JM216 transport across cell membranes is through passive diffusion, predominantly as a result of its enhanced lipophilicity. Notably, an overexpression of a Mr 36,000 plasma membrane protein was observed in the 41McisR variants when compared to the sensitive 41M line. Increased levels of this Mr 36,000 protein may relate to the observed reduction in active transport of cisplatin in the 41McisR6 variant. Tyrosine phosphorylation of the Mr 36,000 protein appeared to be greater in the resistant 41McisR6 variant than in the parental 41M line. In addition, the constitutive levels of the Mr 36,000 protein in the CH1 pair of lines and in two acquired JM216-resistant variants (41M/JM216R and CH1/JM216R), where resistance in these cell lines is not mediated through reduced drug uptake, were similar to those observed in their respective parental lines. These results suggest that the overexpression of this Mr 36,000 protein in the acquired cisplatin-resistant subline 41McisR6 may play a significant role in cisplatin uptake in resistant cells exhibiting reduced drug accumulation as a major mechanism of cisplatin resistance.

Antineoplastic Agents↗