Delayed diagnosis of malignant tumours missed at laparoscopic cholecystectomy.
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Adenocarcinoma↗
Biomedical subjects
A R Morgan
Publications and source records attributed to A R Morgan.
Ogilvie's syndrome: a new approach to an old problem.
PURPOSE: This study was designed to determine the value of intravenous neostigmine in achieving adequate colonic decompression in patients with Ogilvie's syndrome. METHODS: A prospective study was undertaken in 12 consecutive patients (median age, 60 (range, 38-98) years) with contrast enema-proven Ogilvie's syndrome (median duration, four (range, two-nine) days) RESULTS: Satisfactory clinical decompression of large bowel distention was attained in 11 patients, although one required colectomy for subsequent recurrence and ischemia. CONCLUSION: These results support the theory that many cases of Ogilvie's syndrome are the result of excessive large bowel parasympathetic suppression rather than sympathetic overactivity.
Adult↗
Binding of etiopurpurin to human plasma proteins. Delivery in cremophor EL and dimethyl sulphoxide. III.
Binding of the photosensitizer etiopurpurin (ET2) to human plasma was assessed, using conditions that would yield a high percentage of ET2 in the form of LDL-bound monomers which may favor photosensitizer tumor localization. Two delivery systems, Cremophor EL (CRM) and dimethyl sulphoxide (DMSO), were used. The binding of ET2 to CRM-modified lipoproteins was compared to the binding of the dye to the native proteins using delivery in DMSO. Plasma-bound monomers and unbound high density aggregates were shown to coexist. The density and rate of formation of the dye aggregates were correlated. The aggregates formed by delivery in DMSO could be partially converted into plasma-bound monomeric ET2. There was no mode-delivery-effect upon the distribution of monomeric ET2 among the plasma proteins. 70% of monomeric ET2 was bound to LDL and most of the remainder to HDL. In delivery in DMSO the yield of LDL-bound dye monomers (up to 30% of added ET2) increased with decreasing concentration of ET2 in the delivery solution and with increasing time of incubation (< or = 48 hr). Long incubation also induced changes in the densities of LDL and HDL. The yields of LDL-bound monomers (up to 40%) increased with increasing concentration of CRM-bound ET2. High yields of LDL-bound monomers were obtained using both modes of delivery. Although the aggregates associated with the two modes of delivery had different properties. The change in lipoprotein composition might be involved in the conversion of aggregates into plasma-bound monomers.
Adsorption↗
Three-stranded (triplex) DNAs (RNAs): do they have a role in biology?
The first triplexes were homopolymer mixtures, e.g. dTn.dAn.dTn. More complex triplexes could be made on the basis that the base triads [symbol: see text] and [symbol: see text] containing Watson-Crick and Hoogsteen base pairs are isomorphous and so could be expected to give regular triple helices. It follows that such triplexes can only be formed from asymmetric DNAs with pyrimidines (Yn) in one strand and purines (Rn) in the complementary strand. Such triplexes Yn.Rn.Yn are formed with the above rules for pairing of triads with the Hoogsteen C protonated, [symbol: see text]. There are also triplexes built on the theme Yn.Rn.Rn (with triads T:A:A and [symbol: see text]). Here the triads are nearly isomorphous. Recently other triplexes without isomorphous triads at all have been obtained. Also RecA protein can promote triplex formation between a duplex DNA of any sequence and an homologous single-stranded DNA. The latter triplex is evidently important in recombination. The other possible roles for triplexes include transcriptional control, and roles in origins of replication and DNA condensation.
Base Sequence↗
Evolution of severe aphasia in the first two years post onset.
In this longitudinal recovery study of severe aphasia, subjects were tested five times at 6-month intervals with the Boston Assessment of Severe Aphasia (BASA), for a period of 2 years post onset. The majority of subjects had global aphasia (n = 17), but five had severe Wernicke's aphasia, and two had other varieties of severe aphasia. Significant improvements in communicative functions were noted for up to 18 months post onset, but the greatest improvement occurred in the first 6 months post onset. Most subjects did not change aphasia classification during the 2-year period. Initial individual BASA cluster (subtest) scores were less accurate than the 6-month scores in the prediction of later BASA Total scores. Cluster scores obtained at 6 months post onset could reliably predict BASA Total scores at 24 months post onset.
Adult↗
The distribution of the tumour photosensitizers Zn(II)-phthalocyanine and Sn(IV)-etiopurpurin among rabbit plasma proteins.
Zn-phthalocyanine (ZnPc) and Sn-etiopurpurin (SnET2) incorporated in unilamellar liposomes or solubilized in a Cremophor-EL emulsion have been incubated in vitro with rabbit plasma or intravenously administered to rabbits. Ultracentrifugation and chromatographic analysis of the plasma showed that ZnPc and SnET2 are mainly released to lipoproteins; within the lipoprotein family, both dyes are preferentially bound by low-density (LDL) and high-density (HDL) lipoproteins. The amount of dye bound with these two lipoprotein classes was related to their relative concentration in the plasma; in most cases a larger amount of photosensitizer was bound to HDL as compared to LDL on a protein concentration basis.
1,2-Dipalmitoylphosphatidylcholine↗
Base alterations in yeast induced by alkylating agents with differing Swain-Scott substrate constants.
The base alterations induced by four alkylating agents, methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), N-nitroso-N-methylurea (MNU), and N-nitroso-N-ethylurea (ENU), have been determined at the URA3 locus in the yeast Saccharomyces cerevisiae. The mutagen treatment was carried out on yeast cells in the logarithmic phase of growth. The mutants were selected by their resistance to 7.3 mM-5-fluoroorotic acid at pH 3.8. DNA sequence analysis was carried out by the dideoxy chain termination method. The alkylating agents were selected for their widely differing Swain-Scott substrate constants (s values), which are as follows: MMS, s = 0.83; EMS, s = 0.67; MNU, s = 0.42; ENU, s = 0.26. A higher s value is correlated with a higher ratio of 7-alkylguanine to O6-alkylguanine in native DNA in vitro. 125 forward mutations from URA3----ura3 were sequenced with marked differences in the mutational spectra being observed as the s value changed. Five hotspots were recorded for the four alkylating agents. They were all G.C----A.T transition mutations. There was one common hotspot for all of them; there were two additional ones for the two ethylating agents (ENU and EMS) and two different ones for MNU. Four of the five hotspots have the 5'-GG-3' sequence with the 3'-guanine mutated. It was seen that MMS, which has the highest Swain-Scott substrate constant, yielded the widest array of mutational types. As the substrate constants decreased, the types of mutations became more and more restricted to the G.C----A.T transitions and the A.T----T.A transversions. The transitions are consistent with the concept that mutations arise from O6-alkylation of guanine and alkylation of thymine. The transversions are consistent with the notion of N1-alkylation of adenosine or adenylic acid.
Alkylating Agents↗
Observations on the synthesis and in vivo photodynamic activity of some benzochlorins.
An improved synthesis of benzochlorins is reported. Demetallation of the meso-hydroxymethylvinyl derivative of octaethylporphyrin, followed by treatment with sulfuric acid results in cyclization to generate the corresponding octaethylbenzochlorin in high yield. Prolonged treatment with acid generates the sulfonated derivative. These sensitizers were shown to be efficient photodynamic agents in vivo. Animals bearing a transplanted N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide induced urothelial tumor were treated with either the benzochlorin or its sulfonated derivative. Irradiation of tumors 24 h later resulted in a significant tumoricidal effect in a short term assay. We conclude that benzochlorins warrant further examination as potential agents for use in photodynamic therapy.
Animals↗
Interaction of recA protein with left-handed Z-DNA.
The ability of recA protein to interact with a Z-DNA polymer, Br-poly(dG-dC), or M13 bacteriophage single-stranded DNA was investigated. RecA protein binds more avidly to Z-DNA than to single-stranded DNA in the absence of a nucleotide cofactor. This binding pattern changes in the presence of adenosine 5'-(gamma-thio)triphosphate (ATP[S]), however, such that the binding to Z-DNA decreases while binding to single-stranded DNA increases roughly 2-fold. When present together, the two forms of DNA compete with each other in the presence of ATP[S]. Experiments involving recA protein binding to recombinant plasmids showed neither a preferential binding of recA protein to the plasmid containing Z-DNA nor a similar effect of ATP[S] to that observed with the Z-DNA polymer. In contrast, maximal binding was obtained with a plasmid (linear or supercoiled) containing a polypurine.polypyrimidine insert, thus suggesting that recA protein displays sequence preferences in its interaction with DNA. The results of the present study provide no evidence that recA protein specifically interacts with or stabilizes the Z-DNA insert of a recombinant plasmid in the left-handed conformation.
Adenosine Triphosphate↗
An assay for proteinases and their inhibitors based on DNA/ethidium bromide fluorescence.
Proteinases and their inhibitors have become the subject of intense research interest recently, since they control a multitude of very important biological processes, from the development of lambda phage to hypertension in humans. We have developed a simple and sensitive assay for detecting the activity of proteinases and of their proteinase inhibitors. The assay is based on ethidium bromide fluorescence, according to the following principles: (i) Ethidium bromide increases its fluorescence by 25-fold when it intercalates between base pairs of double-stranded DNA. (ii) Histones prevent this large increase in fluorescence by binding with high affinity to DNA thus blocking ethidium bromide intercalation. (iii) A proteinase that digests histones will make more DNA available for ethidium bromide intercalation, thereby producing an increase of fluorescence. Proteinase activity can easily be determined, in the presence of a DNA/histone complex, from the rate of ethidium fluorescence increase. In contrast, activity of a proteinase inhibitor is quantitated by the inhibition of fluorescence gain in the presence of a known amount of proteinase. This assay is rapid, simple, inexpensive, and, at the same time, accurate and sensitive enough to allow quantitation of nanogram amounts of various broad-specificity proteinases and their inhibitors. We show some possible applications of the assay (i) in testing column fractions during protein purifications, (ii) quantitation of alpha 1-antitrypsin in human serum, and (iii) detection of proteinase activity in cell extracts.
DNA↗
Photophysics and photochemistry of new verdin compounds.
Five different verdins, including one zinc metal chelate, were examined by laser flash techniques. Triplet molar absorption coefficients, triplet and singlet oxygen quantum yields and triplet lifetimes were determined. Zinc methyl pyroverdin (ZNMPV), copro II verdin trimethyl ester (CVTME) and deuteroverdin methyl ester (DVME) have the highest triplet and singlet oxygen quantum yields. ZNMPV and CVTME have the longest triplet lifetimes. Our data are consistent with singlet oxygen as the primary modality for phototherapy and it is suggested that DVME and CVTME may be useful agents.
Lasers↗
Synthesis and in vivo photodynamic activity of some bacteriochlorin derivatives against bladder tumors in rodents.
Bacteriochlorins have been suggested as potential photosensitizers for use in photodynamic therapy. We have shown that bacteriochlorin-like macrocycles can be generated through cyclization of either 5,10- or 5,15-bis[(ethoxycarbonyl)vinyl]porphyrins; however, the resulting products are rapidly decomposed on exposure to air. More stable systems can be generated by Diels-Alder reactions between dienophiles such as dimethyl acetylenedicarboxylate or tetracyanoethylene, and vinylporphyrinones. Although spectroscopic properties of these latter products resemble those of porphyrinones rather than bacteriochlorins, in vivo studies using the N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced rat bladder tumor (AY-27) transplanted into Fisher CDF (F344)/CrlBr rats demonstrated a powerful photodynamic response.
Animals↗
Fluorometric assays for DNA topoisomerases and topoisomerase-targeted drugs: quantitation of catalytic activity and DNA cleavage.
We have introduced the novel application of a simple ethidium fluorescence assay, using covalently closed circular DNA, for the study of topoisomerase-targeted drugs. With the specificity of camptothecin for eukaryotic topoisomerases I and of VM26 for eukaryotic topoisomerases II, the two classes of enzymes can be assayed independently in crude extracts and during purification. These assays are fast, sensitive, and quantitative, have a large sample capacity, and eliminate the need for radioactive materials, filters, and agarose gels. We have demonstrated the use of this fluorescence assay to measure the inhibition of the relaxation and supercoiling activities of purified mammalian topoisomerases I and II and bacterial gyrase by nonintercalating drugs. Similarly, the production of drug-induced topoisomerase-mediated cleavable complexes was readily quantitated with both nonintercalating and intercalating drugs. When inhibition and cleavage with VM-26 were measured concurrently as a function of topoisomerase II concentration, a clear inverse relationship between topoisomerase II inhibition and cleavable complex production was observed. When the physiologically relevant salt K+L-glutamate- was used, quantitative relaxation by topoisomerase II was observed up to twice the salt concentration obtained with KCl. The enantiomer K+D-glutamate- gave exactly the same results, indicating that the enhancing role of glutamate- is non-stereospecific.
Amsacrine↗
Interconversion of replication and recombination structures: implications for terminal repeats and concatemers.
Replication and recombination structures can be interconverted by branch-migration. Using this simple concept a novel mechanism is proposed for generating concatemers through an initial single-strand DNA invasion into a duplex. Only DNAs with terminal repeats can form concatemers, and Herpes Simplex Virus DNA replication is considered in detail. The model is more parsimonious than other models such as Watson's for concatemer formation.
Base Sequence↗
Synthesis and in vivo activity of some porphyrindione derivatives with potential in photodynamic therapy.
A number of synthetic bacteriochlorins were prepared from porphyrindiones. The potential of these compounds as sensitizers for photodynamic therapy was examined using the FANFT-induced urothelial cell carcinoma (AY-27) transplanted into rats. In a number of cases, tumor regression was significant following treatment with both drug and light.
Animals↗
Hemodynamic effect of the metallopurpurin SnET2 and light on transplantable FANFT induced bladder tumor.
Changes in blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide induced bladder tumors growing subcutaneously in the flanks of Fischer CDF (F344/CrlBR) rats were measured after photodynamic therapy with the photosensitizer tin (II) etiopurpurin dichloride using the radioactive microsphere technique. As with the other photosensitizers, hematoporphyrin derivative and chloroaluminum tetrasulfophtalocyanine, tin (II) etiopurpurin dichloride and light caused a rapid decrease in tumor blood flow in this tumor model. The decrease in blood flow occurred whether the vehicle for photosensitizer delivery was an emulsion or a liposome. Systemic heparinization of animals prior to light treatment did not alter changes in tumor blood flow.
Animals↗
Diels-Alder adducts of vinyl porphyrins: synthesis and in vivo photodynamic effect against a rat bladder tumor.
Benzoporphyrin derivatives have been proposed as potential photosensitizers for photodynamic therapy. We have prepared a number of benzoporphyrin derivatives and tested their effect, in combination with red light, on the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced rat bladder tumor (AY-27) transplanted into Fischer CDF(F344)/CrlBr rats. Tetracyanoethylene (TCNE) adducts showed very little activity, which may be attributable to their poor tumor uptake or to chemical instability of the adduct under physiological conditions. However, dimethyl acetylenedicarboxylate (DMAD) adducts tested showed greater cytotoxic effect than hematoporphyrin derivative and similar activities to metallopurpurins when tested under the same protocol.
Acetylene↗
Tin etiopurpurin dichloride-sensitized lipid photooxidation of erythrocyte membranes.
Tin(IV) etiopurpurin dichloride (SnET2 x 2Cl) is a photosensitizer which has been shown to be an effective photodynamic agent for the treatment of transplantable animal tumors in vivo. The purpose of this study was to understand the effect of SnET2 x 2Cl on membrane lipid peroxidation. When erythrocyte membranes were exposed to visible light in the presence of SnET2 x 2Cl, lipid peroxidation was observed. An accumulation of lipid hydroperoxides and an increase in lipid fluorescence were also observed. Thin layer chromatography of lipid extracts from photooxidized membrane revealed photoperoxide products derived from phospholipid. Investigations into the mechanism(s) of lipid peroxidation by SnET2 x 2Cl and light-sensitized membranes were also performed. Results indicate that singlet oxygen (1O2) plays a major role in lipid peroxidation.
Animals↗