Biomedical subjects

R Quinn

Publications and source records attributed to R Quinn.

43 records · Page 3Linked to original sources

PubMedDate not supplied

The disposition of 6-deoxyacyclovir, a xanthine oxidase-activated prodrug of acyclovir, in the isolated perfused rat liver.

The antiviral drug, acyclovir, has been used in the treatment of chronic type B hepatitis. High serum concentrations of acyclovir are required to achieve inhibition of hepatitis B viral replication. Because only 15 to 20% of an oral dose is absorbed, it is necessary to administer acyclovir by intravenous infusion. 6-Deoxyacyclovir, an analog of acyclovir, is well absorbed when given orally, and is converted to acyclovir by xanthine oxidase which is present in the gut and liver. This study has examined the hepatic disposition of 6-deoxyacyclovir in a 100 ml recirculating (12 ml per min) perfused rat liver system. Following administration of a bolus dose of 5 mumoles 6-deoxyacyclovir to the reservoir, perfusate concentrations of 6-deoxyacyclovir declined monoexponentially, as the metabolite acyclovir appeared in the perfusate. Addition of the xanthine oxidase inhibitor allopurinol (5 mg) to the perfusate reservoir prior to the administration of 6-deoxyacyclovir resulted in impaired hepatic metabolism of 6-deoxyacyclovir, as demonstrated by a 47% reduction in systemic clearance rate (4.5 +/- 0.4 to 2.4 +/- 0.9 ml per min; p less than 0.05) (mean +/- S.E., n = 6) and a 1.8-fold increase in terminal elimination half-life of 6-deoxyacyclovir (23.5 +/- 2.7 to 42.7 +/- 4.1 min; p less than 0.05), accompanied by a 30% reduction in appearance of acyclovir. The efficient hepatic conversion of 6-deoxyacyclovir to the active antiviral drug, acyclovir, provides a rationale for trials of oral 6-deoxyacyclovir in the treatment of chronic type B hepatitis.

Acyclovir↗

PubMedDate not supplied

Complete structural characterisation of the mammalian and Drosophila TRAF genes: implications for TRAF evolution and the role of RING finger splice variants.

The complete murine TRAF2 gene was obtained using a lambda phage and PCR cloning strategy. The gene was found to consist of ten coding and one 5' non-coding exon spread over 28 kbp of DNA. We also report the basic structure of the human TRAF5 and TRAF6 genes obtained by analysis of the genomic DNA database. Comparison of these three gene structures, along with those previously described for TRAF1, TRAF3 and TRAF4, revealed the evolutionary relationship between the six known mammalian TRAFs. The TRAF1/TRAF2 and TRAF3/TRAF5 gene pairs were found to have arisen from recent independent gene duplications and to share a common ancestral gene. Specific TRAF4 and TRAF6 precursor genes were found to have arisen earlier during evolution, with the divergence of the TRAF6 precursor occuring earliest of all. The Drosophila genome was found to contain three TRAF family genes: dTRAF1, dTRAF6 (dTRAF2) and a previously undescribed member we have designated dTRAF3. TRAF-C domain homology indicated that dTRAF3 is likely to have derived from the common precursor for the TRAF 1, 2, 3 and 5 genes, whilst dTRAF1 and dTRAF6 have derived from the TRAF4 and TRAF6 precursor genes, respectively. The implication of these results for the functional evolution of TRAFs is discussed. Analysis is also presented of the conservation of the TRAF2A molecule, a TRAF2 alternate splice isoform with an extended RING finger domain previously described in mice. TRAF2A was not found to be encoded by the human or rat TRAF2 genes and no other murine TRAF gene was found to produce a similar alternate splice product. We also report that the sequence of murine C57BL/6 TRAF4 differs significantly from the published murine TRAF4 sequence, but appears to represent the actual TRAF4 sequence expressed in many mouse strains.

5' Untranslated Regions↗

PubMedDate not supplied

An electrically powered total artificial heart. Over 1 year survival in the calf.

An electric motor driven orthotopic artificial heart was implanted in a 110 kg female Holstein calf as part of a series of 12 such implants intended to demonstrate the in vivo durability and compatibility of the device. The device uses pusher plates set into motion by a reversing brushless DC motor and roller screw to alternately eject two cylindrical sac type blood pumps. The pumps use Bjork-Shiley Delrindisc convexo-concave or monostrut valves. The left pump provides an 88-90 ml dynamic stroke volume. Woven Dacron grafts and polyurethane coated Dacron/Lycra cuffs are used to attach the device to the major arteries and atria, respectively. A polyurethane conduit and anchoring skin button bring motor wires percutaneously to an extracorporeal controller. The controller provides balanced cardiac output sensitive to atrial or aortic pressures, without operator intervention. The system is hermetically sealed and uses a simple compliance sac to maintain thoracic pressure between the pumps. The calf recovered uneventfully from surgery and thrived thereafter. She was killed on the 388th post-operative day because of worsening cardiac insufficiency. The previous three operative survivors in this series lived 131, 134, and 204 days. These results indicate the device's good potential for durability and body compatibility.

Animals↗

PubMedDate not supplied

Reversible depigmentation of human melanoma cells by halistanol trisulphate, a novel marine sterol.

The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation; HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.

Animals↗

PubMedDate not supplied

Isomers of a marine diterpene distinguish sublines of human melanoma cells on the basis of apoptosis, cell cycle arrest and differentiation markers.

The action of the marine furanoditerpenes, spongiatriol (SP) and episopongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors.

Antigens, Neoplasm↗

PubMedDate not supplied

Pigmented skin tumors.

Explore the source record for details and available documents.

Basal Cell Carcinoma↗

PubMedDate not supplied

How much of a general practitioner's prescribing is outside his/her control?

OBJECTIVE: To analyse and quantify that portion of one General Practioner's prescribing that is outside his/her control. DESIGN: Detailed analysis of one General Practioner's General Medical Services prescribing over a three month period during 1996. SETTING: A Group Practice in Sligo, Ireland. MAIN OUTCOME MEASURES: The number and cost of items outside the General Practitioner's control expressed as a percentage of his total General Medical Services prescribing. The source of these items, and whether they are newly prescribed items or not. RESULTS: 12.8% numerically and 23.8%, costwise, of items prescribed by one GMS General Practitioner were found to be outside his control. Of these items, psychiatric outpatient consultations and medical in-patient discharges account for 22.8% and 18.4% numerically, respectively, and 25.7% and 22.6% costwise, respectively of the total numbers of items and costs outside his control. CONCLUSIONS: A relatively small proportion of items of a General Practitioners prescribing accounting for a disproportionately large amount of the costs are outside his control.

Drug Costs↗