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Biomedical subjects

C Pugh

Publications and source records attributed to C Pugh.

15 recordsLinked to original sources

A new technique for posterior cruciate ligament reconstruction.

We describe a new technique for arthroscopically assisted posterior cruciate ligament reconstruction. We use the TransFix (Arthrex, Naples, FL) pin to provide a single and strong tibial attachment point for the 4-stranded semitendinosus and gracilis tendons. The TransFix technique for anterior cruciate ligament reconstruction has been found to give better initial fixation strength than other techniques using semitendinosus and gracilis grafts, and it provides adequate graft length for secure fixation. Strong and secure graft fixation in knee ligament reconstruction is very important for early and fast rehabilitation.

Accidents, Traffic↗

Selective reduction of 2-

[formula: see text] NaBH4 reduction of 2,5-bis[(4'-(n-alkoxy)benzoyl)oxy]benzaldehydes produces primarily the rearranged phenol, which does not generate liquid crystalline phases when laterally attached to a polymer backbone. Rearrangement is prevented by quenching the intermediate benzyl alkoxide with a weak acid. For example, 2,5-bis[(4'-(methoxy)benzoyl)oxy]benzaldehyde is selectively reduced to 2,5-bis[(4'-(methoxy)benzoyl)oxy]-benzyl alcohol with less than 5% intramolecular transesterification using 2-3 equiv of NaBH4 in the presence of 20-30 equiv of acetic acid (1:10 NaBH4/AcOH).

Journal Article↗

Selective gene transfer into the liver of non-human primates with E1-deleted, E2A-defective, or E1-E4 deleted recombinant adenoviruses.

Preclinical studies were designed to investigate the feasibility and safety of recombinant adenoviruses transduced into the hepatic artery of nonhuman primates. The vectors used are recombinant adenoviruses deleted in E1 and contain either a temperature-sensitive mutation in the E2a gene, which encodes a defective DNA-binding protein at nonpermissive temperatures, or a deletion of the E4 region, including open reading frame (ORF) 6. Six 8- to 10-kg baboons underwent femoral artery cannulation, and angiographic techniques were used to introduce vector selectively into either a portion of the right lobe of the liver via a branch of the right hepatic artery or the common hepatic artery. Necropsies were performed at 4, 29, or 61 days. Serial sequential liver biopsies were performed in the baboons that survived 29 or 61 days. In the 2 baboons with vector transduction into the right hepatic artery, X-Gal histochemical analysis of the liver showed evidence of quantitatively increased gene transfer in the targeted lobe; however, gene transfer was present throughout the liver. Quantitative analysis of histopathology showed that portal inflammation was present throughout both livers transduced with the highest dose of vector. No differences were seen in the level of portal inflammation in targeted and untargeted lobes despite the observed qualitative and quantitative differences in gene expression. Southern blot analysis of total cellular DNA isolated from targeted and nontargeted lobes showed similar levels of viral DNA throughout the liver. Polymerase chain reaction (PCR) analysis was able to detect viral DNA sequence in gonads and brain as well as many other tissues in baboons treated with high-dose vector. In baboons treated with lower doses of an E1-E4 deleted vector expressing the human ornithine transcarbamylase (OTC) gene, DNA was detectable by nested PCR in liver but not gonads at days 29 and 61. The data suggest that intraarterial administration of recombinant adenoviral E1-E4 deleted vector is feasible and safe. At high doses of vector, widespread dissemination of vector DNA is seen. At low doses, hepatic gene transfer is not associated with vector DNA dissemination to gonads.

Adenoviridae↗

Staying healthy while travelling.

By ensuring that the issues raised in this article are appropriately discussed with each traveller at the pre-travel consultation, the chance of staying healthy while travelling is considerably enhanced. If all else fails, the traveller should be well equipped with a first aid medical kit (Table 2) and instructions on how and when to take medications. They should know how to treat travellers diarrhoea, recognise signs and symptoms of malaria and the difference between a bacterial infection and viral infection. Bon voyage!

Accident Prevention↗

Phorbol ester inhibits erythropoietin production in human hepatoma cells (Hep G2).

Using the human hepatoma cell line Hep G2, we have studied a possible role of protein kinase C (PKC) activity for regulation of erythropoietin (EPO) production. During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 microM). The phorbol ester phorbol 12-myristate-13 acetate (PMA) led to a concentration-dependent inhibition of basal and stimulated EPO formation (ED50 10 nM). This decrease of EPO production, which was apparent already after 1 h of incubation with PMA, reached its maximal effect after 24 h and held on for 72 h. It was paralleled by an inhibition of the increase of EPO mRNA levels in response to stimulation. A 24-h preincubation of the cells with PMA (100 nM) virtually blunted the effect of hypoxia on EPO formation. Recovery of EPO synthesis after removal of PMA took 48-72 h. The effect of PMA on EPO production was mimicked by phorbol 12,13-dibutyrate (ED50 1 microM) but not by 4 alpha-phorbol 12,13-didecanoate. The synthetic diacylglycerol analogues oleolyl-acetylglycerol and dioctanoylglycerol (2-200 microM) also had no effect on either basal or stimulated EPO production. Treatment with PMA caused a translocation of the alpha-isoenzyme of PKC from the cytosol to the membrane after 1 h and a disappearance of the membrane-bound form after 24 h of incubation. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two structurally different inhibitors of PKC activity, inhibited basal and stimulated EPO production with ED50 values of 9 nM and 50 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Mouse hepatitis virus A59: mRNA structure and genetic localization of the sequence divergence from hepatotropic strain MHV-3.

The composition and structure of the mouse hepatitis virus (MHV)-specific RNA in actinomycin D-treated, infected L-2 cells were studied. SEven virus-specific RNA species with molecular weights of 0.6 X 10(6), 0.9 X 10(6), 1.2 X 10(6), 1.5 X 10(6), 3.0 X 10(6), 4.0 X 10(6), and 5.4 X 10(6) (equivalent to the viral genome) were detected. T1 oligonucleotide fingerprinting studies suggested that the sequences of each RNA species were totally included within the next large RNa species. The oligonucleotides of each RNA species were mapped on the 60S RNA genome of the virus. Each RNA species contained the oligonucleotides starting from the 3' end of the genome and extending continuously for various lengths in the 3' leads to 5' direction. All of the viral RNA species contained a polyadenylate stretch of 100 to 130 nucleotides and probably identical sequences immediately next to the polyadenylate. These data suggested that the virus-specific RNAs are mRNA's and have a stairlike structure similar to that of infectious bronchitis virus, an avian coronavirus. A proposal is presented, based on the mRNA structure, for the designation of the genes on the MHV genome. Using this proposal, the sequence differences between A59, a weakly pathogenic strain, and MHV-3, a strongly hepatotropic strain, were localized primarily in mRNA's 1 and 3, corresponding t genes A and C.

Animals↗