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Biomedical subjects

M J Thompson

Publications and source records attributed to M J Thompson.

137 records · Page 8Linked to original sources
PubMed1957

The antiviral action of threo-beta-phenylserine.

L-threo-phenylserine and esters of threo-phenylserine were the most active of a series of compounds tested against influenza A virus in tissue culture. Substitution of the beta-OH or alpha-NH(2) group abolished activity. The activity of phenylserine was reversed competitively by phenylalanine. Phenylserine did not act on free virus or on the adsorption of virus to host cells. It prevented virus growth if added during the first half of the latent period.Phenylalanine appears to be necessary for virus synthesis and can be supplied by phenylalanylglycine or glycylphenylalanine.Phenylserine had no significant activity against ectromelia infections in mice, even when the amino acid content of the livers had been depleted by starvation.

Animals↗
PubMedDate not supplied

24-Methyl-23-dehydrocholesterol: a new sterol intermediate in C-24 demethylation from the nematodes Panagrellus redivivus and Caenorhabditis elegans?

Panagrellus redivivus produced 24-methyl-23-dehydrocholesterol as 4.0% of the 4-desmethylsterols when propagated in a medium containing campesterol as the dietary sterol. The re-examination of previous data revealed that Caenorhabditis elegans produced 1.8% 24-methyl-23-dehydrocholesterol when propagated in medium containing campesterol. 24-Methyl-23-dehydrocholesterol was not detected when the nematodes were propagated in medium containing 22-dihydrobrassicasterol or 24-methylenecholesterol. This may be a result of the greater efficiency of dealkylation of the latter two sterols. This is the first report of the natural occurrence of this sterol in a non-photosynthetic organism, and the first report in organisms that dealkylate 24-alkylsterols.

Acetylation↗
PubMedDate not supplied

Intermediates of stigmasterol metabolism in Spodoptera littoralis.

Stigmasterol-24,28-epoxide, 22E-stigmasta-5,22,24(28E)-trien-3 beta-ol, and 22E-cholesta-5,22,24-trien-3 beta-ol were identified as normal metabolites of [3H]stigmasterol in Spodoptera littoralis larvae. Relative concentrations of all three of these metabolites increased when a diazasterol inhibitor was fed in combination with stigmasterol in the artificial diet. Identification of these sterols as intermediates in the conversion of stigmasterol to cholesterol in this insect indicates that intermediates analogous to fucosterol and fucosterol-24,28-epoxide in the conversion of sitosterol to cholesterol are produced in the metabolism of stigmasterol. This is the first published identification of stigmasterol-24,28-epoxide and 22E-stigmasta-5,22,24(28E)-trien-3 beta-ol as intermediates in this pathway in an insect.

Animals↗
PubMedDate not supplied

Metabolism of [14C]cholesterol to C-20 isomeric [14C]pregn-5-ene-3,20-diols in the tobacco hornworm, Manduca sexta.

After injection into male and female fifth-instar larvae of Manduca sexta, [14C]cholesterol was converted to C21 steroids, [14C]pregn-5-ene-3 beta,20-diols. These metabolites were isolated from 8-day-old pupae and were identified by TLC, HPLC, and GC-MS as the C-20 isomers of pregnene-3 beta,20-diol. They also were isolated from male and female meconium fluid (of 16-day-old pupae) following injection of [14C]cholesterol into 14-day-old pupae.

Animals↗
PubMedDate not supplied

Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152.

Alkylating agents are a group of compounds that have a cytotoxic effect due to their ability to form adducts with DNA. Cells possess the ability to repair this damage via an enzyme, O6-alkylguanine-DNA alkyltransferase (AGT). To study the effect of inhibiting this repair mechanism upon testicular cytotoxicity in BALB/c mice, the AGT inhibitor O6 benzylguanine (O6BG) was used in conjunction with the potential anticancer drug B.4152. Paraffin sections were stained and examined using Chalkley scoring to identify the cells affected by the treatment. Using B.4152 alone the maximal effect upon the spermatogenic tissue was found to be after 32 days. The damage found was minor, with the spermatocytes and spermatids most affected. Using this time point it was found that the combined treatment produced widespread damage, with significant depletion of the majority of spermatogenic cell types. These results therefore, indicate that differentiating spermatogenic cells are normally protected from B.4152 induced damage by AGT, depletion of which significantly potentiates B.4152 toxicity.

Analysis of Variance↗
PubMedDate not supplied

Which thermometer? Factors influencing best choice for intermittent clinical temperature assessment.

The objectives of this study are (a) to review the current technologies, (b) to examine comparative costing data for six selected representative devices, and (c) to discuss the clinical factors related to selection of devices for intermittent temperature measurement. Financial estimates indicate that mercury-in-glass thermometers are the cheapest devices. Compact electronic and chemical (phase change) thermometers are cheaper alternatives than multi-patient contact thermometers requiring probe covers and infrared sensing models, which are commonly adopted in hospitals and clinical practice. However, time required to obtain readings will influence overall costs. Rigorous independent clinical research studies are now needed to establish which of these alternative technologies are 'fit for purpose'. As a minimum they should offer comparable clinical accuracy and reliability to mercury-in-glass and be suitable for most clinical measurement situations. Furthermore any additional costs should bring demonstrable benefits to the patient, user and healthcare system.

Decision Making↗
PubMedDate not supplied

Anti-tumor and anti-vascular effects of the novel tubulin-binding agent combretastatin A-1 phosphate.

The combretastatins are derived from an African medicinal plant Combretum caffrum (Combretaceae). They have previously been shown to be potent inhibitors of microtubule assembly that cause marked haemorrhagic necrosis in murine subcutaneous tumors. Promising clinical trial results with combretastatin A-4 phosphate led to this investigation of the anti-tumor and anti-vascular effects of a close structural analog, combretastatin A-1 phosphate. This compound caused identical disruption of the tubulin cytoskeleton in HUVECs in vitro at similar concentrations and duration of exposure as combretastatin A-4 phosphate. Treatment of a well-vascularised murine colon adenocarcinoma (MAC 29) with an effective dose (150 mg/kg) of combretastatin A-1 phosphate resulted in a dramatic decrease in functional vascular volume 2 hours after administration. Vascular shutdown was complete within 4 hours after treatment apart from in small areas of the tumor periphery. Morphological examination of hepatic deposits of HT29 and DLD-1 human colon tumors in nude mice demonstrated that combretastatin A-1 phosphate displays greater anti-tumor effects than the A-4 analog at the same dose and this order of activity (A-1 > A-4) is mirrored in the subcutaneous site with the same tumor type. In summary, combretastatin A-1 phosphate can exert its anti-tumor action via an anti-vascular mechanism. The results indicate that, despite having similar in vitro anti-tubulin properties, combretastatin A-1 phosphate seems to have greater in vivo anti-tumor activity than combretastatin A-4 phosphate at the same doses and may therefore be more successful in the clinic.

Adenocarcinoma↗