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The influence of inhibitors of poly (ADP-ribose) polymerase on X-ray-induced potentially lethal damage repair

D M Brown, J W Evans, J M Brown
1984 The British journal of cancer. Supplement  
Inhibition of repair of X-ray-induced potentially lethal damage (PLD) could enhance the curability of radioresistant tumours. We have studied the effect of inhibitors of the enzyme poly (ADP-ribose) polymerase on X-ray PLD repair. Four classes of inhibitors are known: aromatic amides (e.g., 3-aminobenzamide), thymidine, nicotinamides and methyl xanthines (e.g., caffeine). Plateau-phase Chinese hamster ovary (HA-1) cultures were exposed to 10mM concentrations of thymidine, nicotinamide,
more » ... otinamide, 3-aminobenzamide (3-ABA) and caffeine prior to irradiation to 12 Gy in air, and then incubated with drug at 37 degrees C for varying times (0-6 h) prior to subculture. Irradiated cells without drug exhibited a 5-6 fold increase in survival over the 6 h period compared to cultures plated immediately after irradiation. Although none of the compounds proved cytotoxic to unirradiated controls over the 6.5 h exposure, all of the compounds except thymidine reduced the capacity of the cells to repair PLD. The order of the inhibitory effect was caffeine greater than 3-ABA greater than nicotinamide, and the inhibition was concentration dependent for nicotinamide and 3-ABA. We also studied the effect of 3-ABA on the radiation response of exponentially growing cells. 5mM 3-ABA for 2 h post-irradiation resulted in a dose-multiplicative sensitization reducing the D0 from 0.88 Gy to 0.69 Gy, indicating an involvement of poly (ADP-ribose) polymerase in the radiosensitivity of exponentially growing as well as plateau-phase cells.
pmid:6320853 pmcid:PMC2149166 fatcat:znensinl5ne65gf7ne2qpjhnui

Hepatic Haemorrhage in the Newborn

J. J. M. Brown
1957 Archives of Disease in Childhood  
doi:10.1136/adc.32.166.480 pmid:13498787 pmcid:PMC2012139 fatcat:edh2uet2bjc3fok3k6vyddbgr4

Some experiences in the treatment of arterial injuries

J J M BROWN
1948 Bristol medico-chirurgical journal (1883)  
Blood-flow through the affected artery continues m mild arterial spasm, minor contusions without thrombosis, arterial haematoma and in aneurysmal varix.  ... 
pmid:18123515 pmcid:PMC5065808 fatcat:jey6q6fbcjesve64q66rpkoz5e

The Laevulose Test in Rheumatic and Choreic Children

M. J. Brown
1929 Archives of Disease in Childhood  
F-rom) the ID)ept. of PP(Idiatrics. Glasgo-w University. and( the Biochemical La<tboratory. floyal Hosital for Sick Chil(dreni, (I'lasgow.) hi a I)aper rCceily I)iil)lished in TIHE ARCHIIVE.s OF DISEAs;E IN CHILDHOOD Traylor Chadwiclk i gave the results of ani investigation of the behaviour of the -vtullose test in the rheumin<atic chil(l. From the results he coiicliided that in certaiin stages of the rheumlatic infection the efficiency of the liver is impaired, andl l he expressed the opinion
more » ... ressed the opinion that this might be (lile to the result of toxic absorption from sonie rheuimatic focuts. In childreni completelv recovered from rheumatism. an(d in those suffering from uincomplicated chorea, he found that the ingestioin of levtlose gave a blood-sugar curve not differing from that obtained in the inormiial individuial. In children presenting active rheumatisin, with or U-ithout heart affectioIl and in the examples of chorea with evidence of carditis there was. on the other hand, an appreciable intolerance to loeviilose as inidicated b)v a rise in the blood sugar. This rise in the blood sugar varied betw-een 18 per cent. anid( 113 per cent., with ani average increase of 49 per cent. A suirvey of the details in Chadwick's paper raises a suspicioin that the dimiinished hepatic efficiency as indicatedl by the lavuilose test is dependent on passixve congestion of the liver seconidarv to cardiac involvement rather thaii oni soniie toxic actioni. Of the number of cases in which there was cardiac involvement 54 per cent. reacted abnormally to lakevulose. If, however, there be excluded the five cases (Nos. 12, 16, 30, 31 and 34), in which the cardiac invol-ement was admittedly transienit, theni the percenitage of abnormial finldinigs in Chadwick's cardiac cases rises to 73. OIn the other hand, of the four rheumatic cases without apparent heart disease, oiily one (No. 11) gave an abniormnal curve. IIn tlhe text of his paper Chad-wick drew attention to the cases with and(i -without heart disease, adl uwhile he remarked that the abnormal blood-sugar curve followving l.mPvulose blears no relatiolnship to the valvular lesioni, he admittedl thcat it (lid bear a certaini relationslhip to the state of tolne, of thle cardiac muiscle. It is, therefore, (lifficult to appreciate oIn what grounids lie bases h1is ultimate (olcluision. that active rheumatism, w%-ith or without heart disease, is accompanied by ati abnormal blood-sugar cuirve after the iIIgestiol) of hevulose. In a previouis commuinicationl2 also published in this Journal, I recorded the resuilts of a studY of the value of the levidlose test as an index of efficiency of thte liver. I concluded that a rise of 30 per cent. in the blood-sugar content after the admninistration of 1ev-ulose should be considered as evidence of hepatic *Thl w-ork wvas carried ouit uinder a. grant from the Medical Research Council on 24 July 2018 by guest. Protected by copyright.
doi:10.1136/adc.4.20.76 pmid:21031753 pmcid:PMC1975031 fatcat:wnjb4mdwhvb6xigiwouxj7mx7m

Electric field-directed fibroblast locomotion involves cell surface molecular reorganization and is calcium independent

M. J. Brown
1994 Journal of Cell Biology  
Directional cellular locomotion is thought Address all correspondence to Leslie M. Loew,  ...  Bedlack, J. Pachter, A. Cowan, and J. Watras provided helpful discussions during the course of this investigation. Dr.  ...  Similar results were obtained with the calcium channel antagonist D600 (15 #M) and Nifedipine (15 #M).  ... 
doi:10.1083/jcb.127.1.117 pmid:7929557 pmcid:PMC2120190 fatcat:sfmkxi3pgvefbe2eybjnb5krdu

The Land Question. What to Do

M., J. Brown
1901 All Ireland Review  
J. BROWN. ? Thanks for interesting and illumina ! tive letter. Re the last paragraph?  ...  M. Dear M.?I think you are quite right; some general and clear under standing 'having a reasoanble degree of precisiones?  ... 
doi:10.2307/20545360 fatcat:b3wiexvynjahzgv7d6pxeio5dq

Conscience: the professional and the personal

J. M. BROWN
1996 Journal of Nursing Management  
BROWN Ba, Ma, MSc Senior Lecturer in Philosophy, School of History, Philosophy and Politics, University of Ulster at Coleraine, N. Ireland, UK Correspondence J. M.  ...  Brown School of History, Philosophy and Politics University of Ulster at Coleraine Cromore Road Coleraine N. Ireland BT52 1SA UK BROWN J.  ... 
doi:10.1111/j.1365-2834.1996.tb00046.x pmid:8705077 fatcat:uhm4cnsczndpbho65aa4x3d3ju

Regional variation in kwongan in the central wheatbelt of south-western Australia

J. M. BROWN
1989 Austral ecology (Print)  
M. (1981) An ecological analysis of kwongan vegetation south of Eneabba, Western Australia. Aust. J. Ecol. 6, 423-38. Hopkins A. J. M., Brown J. M. & Goodsell J.  ...  There was an increase in the number of species 350 J. M. Brown _— Group Il Group IVS.  ... 
doi:10.1111/j.1442-9993.1989.tb01443.x fatcat:nwuxqz7nrbgwdaxde7z44pgu2i

Ins and Outs of Aldosterone-Producing Adenomas of the Adrenal: From Channelopathy to Common Curable Cause of Hypertension

M. J. Brown
2013 Hypertension  
Brown is a Senior Investigator of the National Institute of Health Research.  ...  Not only is this a molecular target of our most widely used drug class, the L-type Ca 2+ channel blockers, but these Brown Ins and Outs of Aldosterone-Producing Adenomas 25 drugs sometimes completely normalize  ... 
doi:10.1161/hypertensionaha.113.01833 pmid:24082060 fatcat:bll7obsrajcthguo3ypkm5sro4

Lesions of the anterior urethra in infancy and childhood

J J M BROWN
1956 Proceedings of the Royal Society of Medicine  
J. J. Mason Brown said in discussion that most of the questions were concerned with enuresis of which he had little experience. In his hospital they had a physician who was very interested in  ...  J. P. Mitchell or myself. A total of 331 enuretic children have been examined and a further 98, who were not enuretic, had a cystoscopy done as part of the investigation of various other conditions.  ...  ., and BAND, D. (1946) J. ment. Sci., 92, 324. Mr. D.  ... 
pmid:13379428 pmcid:PMC1889250 fatcat:64ja55lv7vfglieogxcl2hnpca

Small intestine obstruction in the newly born

J J M BROWN
1957 Annals of the Royal College of Surgeons of England  
M. Mackay's case.) Fig. 6 . 6 Lateral radiograph showing mottled appearance of bubbles of gas intermingled with abnormal meconium in meconium ileus. . 7.  ...  The only surprising point is that it took ten years for the symptoms to arise, for previously I recorded (Mason Brown, 1952) a similar but more severe syndrome following lateral anastomosis after resection  ... 
pmid:13425266 pmcid:PMC2413473 fatcat:vzu4elthxjbutkyjdprcf2bwia

To (ss) block or better block?

M. J Brown
1995 BMJ (Clinical Research Edition)  
Thromb Haemost 1995;73:739-42. 9 Morgan M, Downs K, Chesterman CN, Biggs JC. Clinical analysis of 125 patients with the lupus anticoagulant. AustNZJMed 1993;23:151-6.  ... 
doi:10.1136/bmj.311.7007.701 pmid:7549675 pmcid:PMC2550713 fatcat:4oms6c2tzngqpa4sxno5fvkzze

Science, medicine, and the future : Hypertension

M. J Brown
1997 BMJ (Clinical Research Edition)  
Brown, professor of clinical pharmacology mjb14@medschl.  ...  receptor to cortisol Treatment Dexamethasone Amiloride Spironolactone Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge CB2 2QQ Morris J  ... 
doi:10.1136/bmj.314.7089.1258 pmid:9154032 pmcid:PMC2126600 fatcat:d3y7afb2hnam7ip5btm43dblvy

Imaging Tumor Sensitivity to a Bioreductive Prodrug: Two for the Price of One!

J. M. Brown
2012 Clinical Cancer Research  
Hypoxia is an important characteristic of many solid tumors and has a major negative effect on treatment response. A way to combat this is with drugs, called "bioreductive prodrugs", or "hypoxic cytotoxins", that are metabolized under hypoxia to toxic species. However the patients with hypoxic tumors need to be identified. In this issue of Clinical Cancer Research Wang and colleagues (1) report that the hypoxia marker EF5 predicts for the potential antitumor activity of the bioreductive
more » ... ioreductive hypoxia-activated prodrug CEN-209 not only by detecting tumor hypoxia (low oxygen levels) but also by assessing the activity of the enzymes responsible for reducing the prodrug to its cytotoxic product under hypoxia. For over 60 years the holy grail of research in radiation oncology has been a method to overcome the problem caused by the resistance of the hypoxic cells in tumors to killing by radiation. Many strategies have been tried such as increasing tumor oxygen levels by patients breathing pure oxygen, using densely ionizing radiation such as neutrons whose killing of cells is less dependent on oxygen, and the use of small molecules ("hypoxic cell radiosensitizers") that substitute for oxygen in the free radical reaction that makes permanent the radiation-induced radical damage to DNA. Though each of these strategies only imperfectly combats the hypoxia problem, the sum total of the clinical trials demonstrates that modifiers of tumor hypoxia produce a highly significant, though modest, improvement in local tumor control and patient survival when combined with radiotherapy (2). However, perhaps the most promising strategy in recent years has been the development of agents that can actually exploit the fact that tumors are usually more hypoxic than normal tissues by selectively killing the hypoxic tumor cells (3). One such drug, a benzotriazine di-N-oxide, tirapazamine (TPZ), has a very high selectivity for killing hypoxic cells (with drug levels needed to kill hypoxic cells typically only 1% or less of those needed to kill aerobic cells) and has been tested in several clinical trials. However, the recent report of a large randomized multicenter phase III trial of TPZ combined with radiotherapy for head and neck cancer reported no benefit (4), though part of this could be attributed to major deficiencies in treatment in a subset of patients (5). Meanwhile, further drug development by the team led by Wilson and Hay in Auckland, NZ, has identified analogs of TPZ that are less toxic and that are superior to Research. on April 13, 2017.
doi:10.1158/1078-0432.ccr-11-3267 pmid:22317761 fatcat:hslmzgm4bjbwnn35ehxcbjxjwy

Hepatic Efficiency: The Value of the Haemoclastic and the Laevulose Tests in Childhood

M. J. Brown
1928 Archives of Disease in Childhood  
Summary of Results in Group J.  ...  10,200 9,800 +21% in 20 min. 12 5 yrs. 10,200 12,400 11,600 10,800 +21%o in 10 min. 13 6 yrs. 9,800 11,200 8,200 8,400 +14% in 10 min. |_______ i_______________ -16% in 20 m  ... 
doi:10.1136/adc.3.14.81 pmid:21031721 pmcid:PMC1974995 fatcat:hsfkzmaxv5au3kff2jps4ovepy
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