Photodynamic therapy--achievements and prospects.
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Humans↗
Biomedical subjects
S B Brown
Publications and source records attributed to S B Brown.
The distribution of porphyrins with different tumour localising ability among human plasma proteins.
The distribution among the main fractions of human plasma lipoproteins of a number of porphyrins with different tumour localising ability has been determined by means of ultracentrifugation. A main trend is that the fraction of the dyes that are bound to low density lipoprotein (LDL) increases, and the fraction bound to HSA decreases with decreasing polarity of the dyes. An asymmetric charge distribution, such as in TPPS2a, favours LDL-binding more than expected on the basis of lipophilicity. No correlation between the known tumour localising ability of the drugs tested in the present work and their relative affinity for LDL was found. One of the best tumour localisers reported in the literature, TPPS4, hardly binds to LDL, while Hp and Pp, which are commonly considered inefficient tumour localisers, do have a significant affinity for LDL. On the other hand, the LDL binding capacity for a drug is suggested to be a good index for cellular uptake. Such an index does not necessarily imply that the actual uptake occurs by the LDL pathway.
Blood Proteins↗
Mouse skin photosensitivity with dihaematoporphyrin ether (DHE) and aluminium sulphonated phthalocyanine (AlSPc): a comparative study.
Skin photosensitivity of sun exposed sites is the major side effect of dihaematoporphyrin ether (DHE) photodynamic therapy (PDT). Reports of severe oedema and erythema have generally been anecdotal. We have studied aluminium sulphonated phthalocyanine (AlSPc) as a potential photosensitiser for PDT. In this paper we report our work comparing the skin photosensitivity reactions of DHE and AlSPc. We have studied: (i) the time course of the skin reactions, (ii) the effect of increasing time from administration of photosensitiser to irradiation, (iii) drug-skin reaction dose response. Groups of Skh I female hairless albino mice were given an intravenous bolus dose of either 0.9% saline solution, AlSPc or DHE (Photofrin II). Drug doses ranged from 0.5 to 50 mg/kg. At times ranging from 1 h to 1 month animals were irradiated with a range of doses of solar simulated radiation (SSR). The skin reaction was observed over a 2 week period. DHE reactions were always more severe than those with AlSPc. Peak skin reaction was seen at 3 h for DHE and 6 h for AlSPc. DHE reactions were still visible 2 weeks after irradiation whereas the AlSPc reaction disappeared by 48 h. Irradiation evoked a reaction up to 2 months after administration of DHE but only up to 2 weeks with AlSPc. The mean SSR dose at which a skin reaction was seen decreased with increasing dose of both agents. The rate of decrease was slower with AlSPc than DHE. This study suggests that in PDT, AlSPc will cause much less skin photosensitivity than DHE.
Animals↗
Conformational analysis of thioredoxin using organoarsenical reagents as probes. A time-resolved fluorescence anisotropy and size exclusion chromatography study.
Reduced thioredoxin was subjected to chemical modification studies employing organoarsenical reagents specific for "spatially close" thiols. Modification was monitored by the loss in the free thiol content, by the percent incorporation of radiolabelled organoarsenical reagents, and by observing the changes in the amounts of the various thioredoxins by size exclusion chromatography. The rate of modification depends upon the polarity, rigidity, and size of the reagents. Small nonpolar organoarsenical reagents readily modified reduced thioredoxin, whereas polar and large reagents do not. Modifications resulted in the formation of stable 15-membered cyclodithioarsenite ring structures with no apparent changes in the secondary structure of the protein. Modification was reversed by the extrusion of the arsenical moiety by addition of 2,3-dimercaptopropanol. We have further characterized the oxidized, reduced, and modified thioredoxins by size exclusion chromatography and fluorescence anisotropy decay measurements. Both techniques show an increase in the hydrated volume of the protein upon reduction. Upon modification, the hydrodynamic volume of the protein further swells. Fluorescence anisotropy decay reveals that with modification there is loosening of the protein so that a "domain" containing the fluorophores can relax independently of the whole protein structure.
Alkylation↗
Percutaneous transluminal aortic angioplasty: techniques and results.
Percutaneous transluminal angioplasty of the infrarenal abdominal aorta has been reported by a few authors. In the present series, aortic stenoses in 32 patients were treated with various percutaneous angioplasty techniques. Isolated aortic stenoses and primary aortic stenoses extending into the iliac arteries were successfully dilated. The initial success rate was 100%, without evidence of rupture, thrombosis, dissection, or distal embolization. In only three of the 28 patients who returned for follow-up did symptoms recur or noninvasive vascular laboratory indexes deteriorate (mean follow-up, 25 months). Percutaneous transluminal aortic angioplasty has proved safe and efficacious in the treatment of atherosclerotic aortic stenoses.
Adult↗
Lymphoceles: percutaneous treatment with povidone-iodine sclerosis.
Although percutaneous procedures have gained a degree of acceptance for treatment of lymphoceles, success rates for aspiration and drainage have been less than optimal. The authors investigated transcatheter sclerosis of pelvic lymphoceles with povidone-iodine as a method to increase the success rate of percutaneous management. Eight patients with a total of nine pelvic lymphoceles were treated with this method. Eight of the nine lymphoceles (89%) resolved without complications. Four patients had undergone lymphadenectomy and four, renal transplantation. The duration of catheter drainage ranged from 15 to 37 days. Four of the lymphoceles were found to be infected at initial drainage, but this did not alter the amount of time the catheter was left in place. One lymphocele failed to heal with sclerotherapy and required internal drainage. The early results with transcatheter povidone-iodine sclerosis of postoperative lymphoceles are encouraging and warrant further evaluation.
Humans↗
The effect of gabaculine on tetrapyrrole biosynthesis and heterotrophic growth in Cyanidium caldarium.
Pigment synthesis in four strains of the unicellular red alga Cyanidium caldarium with different pigment-synthesizing patterns was inhibited in the presence of gabaculine (3-amino-2,3-dihydrobenzoic acid). Parallel inhibition of light-induced chlorophyll and phycocyanin synthesis was observed in strain III-D-2, which only synthesizes pigments in the light. Similar parallel inhibition was observed in the dark in mutant CPD, which is able to synthesize chlorophyll and phycocyanin in the absence of light. Inhibition of pigment synthesis in all strains was overcome by addition of 5-aminolaevulinic acid. Inhibition of phycocyanin synthesis in mutant GGB (unable to synthesize chlorophyll) and inhibition of chlorophyll synthesis in mutant III-C (unable to synthesize phycocyanin) were also observed. Gabaculine also inhibited the heterotrophic growth of C. caldarium in the dark. However, inhibition was overcome after an extended lag period, following which cell growth proceeded at a similar rate to that of control cells not exposed to gabaculine. Heterotrophic growth in cells pre-exposed to gabaculine was not inhibited by subsequent exposure. Possible mechanisms for this adaptation are discussed.
Aminolevulinic Acid↗
Structural comparison between oxidized and reduced Escherichia coli thioredoxin. Proton NMR and CD studies.
Escherichia coli thioredoxin (Mr 11,700) usually functions as a hydrogen carrier protein that undergoes reversible oxidation/reduction reactions of its active-site disulfide linkage. By use of a number of assigned and identified resonances in one- and two-dimensional 1H NMR spectra, the two forms of the protein have been compared. Only groups that are relatively close to the active-site Cys-32, Cys-35 linkage such as Trp-28, Trp-31, Phe-27, Ala-29, and Val-25 undergo substantial changes in their 1H NMR chemical shift upon reduction. Various residues that are further removed from the active site, like Tyr-49, Tyr-70, His-6, Phe-12, Phe-81, and Phe-102, appear to be little affected (less than 0.02 ppm) by the reduction, suggesting that the rest of the protein structure is not much affected. Thus, the structural changes that occur upon reduction appear to be localized to the disulfide-containing turn and the central strand of the twisted beta-sheet that directly leads to this turn. Notwithstanding the apparent similarity in the secondary and tertiary structures of the oxidized and reduced forms of the protein, the thermal stability of the protein decreases by 10 degrees C upon the reduction of the single disulfide. This was found by both 1H NMR and near- and far-ultraviolet circular dichroism studies. Oxidized thioredoxin was also more resistant to alkaline denaturation. Furthermore, the exchange rate of the relatively stable slow-exchanging backbone amide protons that are part of the core of the twisted five-stranded beta-sheet of thioredoxin increases substantially after reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacterial Proteins↗
Spectroscopic characterization of thioredoxin covalently modified with monofunctional organoarsenical reagents.
Thioredoxin upon reduction with mercaptoethylamine was subjected to covalent modification by the monofunctional organoarsenical reagents H2NPhAsO and HO(CH2)4AsCl2. The degree of modification was monitored by the percentage loss in free thiol content as measured by the reaction with the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid). The modification results in the formation of a stable 15-membered cyclic dithioarsenite ring that readily extrudes the arsenic moiety upon the addition of 2,3-dimercaptopropanol. The conformational effects of this modification were monitored by steady-state fluorescence and circular dichroism. On the basis of circular dichroic spectra, it appeared that the protein experiences no significant backbone conformational change from this modification. The degree of conformational change was found to be within the range observed upon reduction of the oxidized thioredoxin. Steady-state fluorescence revealed that the arsenicals caused strong quenching of the tryptophan fluorescence. Stern-Volmer titrations revealed that the quenching was a function of both the nature of the organic group and its covalent attachment to the "spatially close" thiols. The analysis of the spectroscopic results obtained with the arsenical reagents provides further insight into the nature of the conformational change that has been observed upon reduction of thioredoxin.
Arsenicals↗
The preparation of radiolabelled porphyrins and their use in studies of photodynamic therapy.
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Carbon Radioisotopes↗
Tracheobronchial stenosis in infants: successful balloon dilation therapy.
Four infants with congenital or acquired tracheobronchial stenosis were successfully treated with angioplasty balloon catheter dilation. The technical details and complications of these procedures are described. The authors believe balloon dilation therapy should be considered as the initial form of therapy for tracheal stenosis in infants, even in the presence of complex stenotic lesions.
Bronchial Diseases↗
Theoretical prediction and experimental measurement of the bile-pigment isomer pattern obtained from degradation of catalase haem.
Degradation in vitro of the haem in catalase by a 'coupled oxidation' reaction yields products in which approx. 45% of the haem groups have been cleaved at the alpha-methene bridge, 55% at the beta-bridge and a trace at the delta-bridge. Molecular-mechanics calculations with the three-dimensional structural co-ordinates of catalase shows that these proportions of products can be accounted for by the relative accessibility of the four methene bridges to a haem-linked oxygen molecule, thus further confirming Brown's [(1976) Biochem. J. 159, 23-27] hypothesis that the first stage of haem catabolism in vivo is selective attack by haem-bound oxygen, with selectivity conferred by the surrounding protein moiety.
Animals↗
A protocol for estimation of cortisol plasma clearance in acid-exposed rainbow trout (Salmo gairdneri).
The cortisol metabolic clearance rate (MCR) and degradation rate (DR) were determined in acid (H2SO4)-stressed and control rainbow trout (260 g) cannulated via the dorsal aorta. Recovery from catheterization, as judged by plasma cortisol, glucose, protein, and packed cell volume (PCV), was complete by 6 days. However, serial blood sampling increased plasma cortisol. Furthermore, although no major or consistent diel change in plasma cortisol occurred in terminally sampled free-swimming control trout, fluctuations were observed in serially bled catheterized trout. These findings preclude cortisol MCR estimation by any serial sampling method. Although plasma cortisol was temporarily elevated by constant infusion (70 microliter hr-1) of saline:ethanol vehicle, a satisfactory protocol was established for determining cortisol MCR by infusion of labeled cortisol to constant plasma specific activity. The MCR for control trout in water, pH 7.7, for 7 days was 30.3 +/- 4.2 ml hr-1 100 g-1, which did not differ from that of trout in water, pH 5.0. However, the cortisol DR was greater at pH 5.0 (2.13 +/- 0.46 micrograms hr-1 100 g-1) than at pH 7.7 (0.56 +/- 0.12) due primarily to increased plasma cortisol at pH 5.0.
Animals↗
The angiographic evaluation of lower-extremity arterial disease in the young adult.
The angiographic evaluation of 38 patients younger than 40 years of age with lower-extremity arterial disease is reviewed. Although atherosclerosis was the most common diagnosis, other etiologies included thromboembolism, popliteal artery entrapment, Buerger's disease, collagen vascular disease, and arteritis. The two features of the angiographic workup that proved most helpful in establishing an accurate diagnosis were biplane aortography and runoff exams designed to demonstrate possible popliteal artery entrapment.
Adolescent↗
Observations on the use of the Cope introduction set.
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Dilatation↗
Statistical determinants of success and complications of thrombolytic therapy for arterial occlusion of lower extremity.
In this prospective study, we have documented the limited usefulness of thrombolytic therapy in the management of all patients with arterial occlusion of the lower extremities. We have also emphasized the significant rate of recurrent thrombosis unless an underlying obstructive lesion is corrected surgically after clot dissolution. Because thrombolytic drugs can lyse clots of a duration of several weeks, we recommend consideration of fibrinolytic therapy for subacute graft occlusions and segmental arterial thromboses. In such instances, thrombolysis is likely to reveal a focal underlying lesion that is correctable by a limited anastomotic revision or balloon angioplasty. Without fibrinolytic therapy, these older occlusions generally require more extensive bypass grafting or graft replacement. In contrast, we are less enthusiastic about thrombolytic therapy for distal small vessel thrombosis or embolism because complete clot lysis was achieved in only one of five patients. The primary problems with regional arterial low dosage thrombolytic infusions are bleeding at the angiographic catheter entry site and distal thromboemboli of the lysing clot. These difficulties may discourage wide acceptance of fibrinolytic therapy. However, they can be minimized by careful technique. Although its usefulness is limited and complications are common, catheter directed arterial low dosage thrombolytic therapy can be an important initial step in the diagnosis and treatment of selected arterial occlusion of the lower extremities.
Aorta, Abdominal↗
Mechanism of action of heme oxygenase. A study of heme degradation to bile pigment by 18O labeling.
The formation of bile pigment from heme by a reconstituted heme oxygenase system containing purified bovine spleen heme oxygenase, NADPH-cytochrome P-450 reductase, and biliverdin reductase was studied under an atmosphere containing 18,18O2. The product, bilirubin, was isolated and subjected to mass spectrometry, which revealed incorporation of 18O consistent with a two-molecule mechanism, whereby the product bile pigment contains oxygen atoms derived from two different oxygen molecules.
Animals↗
Formation of bile pigments by coupled oxidation of cobalt-substituted haemoglobin and myoglobin.
Treatment of cobalt-substituted haemoglobin and myoglobin with ascorbate and molecular O2 (coupled oxidation) resulted in biliverdin formation from the cobalt(II) derivatives but not from the cobalt(III) derivatives. This was apparently due to the inability of ascorbate to reduce cobalt(III) haemoproteins. Isomer analysis of the biliverdins produced from coupled oxidation of cobalt(II) oxyhaemoglobin suggested that the orientation of the cobalt protoporphyrin IX in the haem pocket differed slightly from that of the haem in native haemoglobin.
Ascorbic Acid↗