Exercise: the right prescription in practice.
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Biomedical subjects
Publications and source records attributed to R Jaques.
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The mutator (RER(+)) phenotype has been shown to be a mutational mechanism for tumour-suppressor-gene inactivation in colorectal cancer. A group of 60 prostate-carcinoma patients was studied to determine the frequency, intratumour distribution and timing of mutator phenotype in this cancer. Ten microsatellite loci were analyzed in 172 carcinoma foci (CF) and in 57 associated non-cancerous prostate tissues, including 31 areas of prostate intra-epithelial neoplasia (PIN) and 26 non-dysplastic areas with glandular hyperplasia (HP). We detected lesions with the RER(+) phenotype in 42% (25/60) of the prostate tumours. Clonal foci with RER(+) phenotype were detected at similar frequencies in pre-cancereous PIN (16%, 5/31) as in associated carcinoma foci (22%, 37/172), but were detected in only one of the 26 non-dysplastic prostate tissues studied (4%). Thus, clonal RER(+) foci were significantly more frequent in CF than in HP (p < 0.05). MI itself was significantly more frequent in CF (53%, p < 0.0001) and in PIN (35%, p < 0.05) than in HP (12%). Furthermore, 5 PIN harboured microsatellite mutations also detected in the associated cancer. Our overall results therefore strongly suggest that the mutator phenotype may occur as an early event in prostate tumorigenesis.
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DNA sequencing of the HindIII-P fragment of the baculovirus Autographa californica nuclear polyhedrosis virus downstream of a major late protein, p10, revealed the presence of an open reading frame (ORF) 1935 nucleotides in length and in opposite polarity to p10. The gene product is considered essential for virus virulence in Trichoplusia ni larvae since infection with occlusion bodies from a mutant, Ac228z, in which portions of adjacent carboxy-termini from peptides p74 and p10 were deleted, failed to kill larvae, whereas virus with deletions in p10 alone were as infectious to larvae as wild-type virus. The ORF has the potential to code for a polypeptide of 645 amino acid residues (Mr 73,819) and was designated p74. Time course analysis of RNA from infected cells using primer extension assays suggested that the gene's promoter was weak and was most active at 16-20 hr postinfection. The transcription initiation site of the RNA was located at -90/-91 bases upstream of the start codon. The p74 gene was cloned into a baculovirus expression vector and a recombinant virus was produced which overexpressed the p74 protein.
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Diclofenac sodium (Voltaren) is a non-steroid anti-inflammatory agent of a new chemical structure, which is animal experiments shows a high degree of anti inflammatory, analgesic, and antipyretic activity in various pharmacological models. It inhibits prostaglandin biosynthesis in vitro and in vivo, and this inhibitory effect at least partly explains the mechanism of action of the preparation. In animal experiments diclofenac sodium is characterised by a broad therapeutic range. Also, its gastrointestinal tolerability is better than that of other highly effective non-steroid anti-inflammatory agents. Two of the metabolites produced during the biotransformation of diclofenac sodium in man are also biologically active. The activity of these two metabolites, however, is very much weaker than that of unchanged diclofenac sodium and is comparable to that of phenylbutazone.
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Methionine-enkephalin and leucine-enkephalin (m-enk and 1-enk) as well as D-Ala2-methionine-enkephalin amide have been shown to antagonize contractions of the isolated guinea-pig intestine elicited by PGE1, the last mentioned being the most potent of the three. The inhibitory effect of these pentapeptides is abolished by naloxone.
The histamine-liberating properties of a synthetic polypeptide (an a synthetic polypeptide (an alkylprolyl derivative of beta1-19-corticotrophin) were investigated under a variety of experimental conditions. It was found to be more potent in this respect than Compound 48/80, Melittin and Triton X-100. The degree of cell destruction observed in conjunction with the release of histamine induced by C 44 680-Ba suggests that the mode of action of the substance more closely resembles that of Compound 48/80 than that of Triton.
Ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside (RBGF) the active substance of Glyvenol displays a unique spectrum of activities. It possesses anti-inflammatory, mild analgesic, antitoxic, wound-healing, fibrinolysis-promoting, anti-arthrotic, amine-release-inhibitory, membrane-stabilizing and venotropic properties. Unlike corticosteroids or nonsteroidal anti-inflammatory agents, TBGF dose not exert untoward effects on the gastrointestinal system, the connective tissue or the body's defence systems. In addition, TBGF does not affect the prostaglandin-synthetase system. TBGF thus seems to share the positive pharmacological properties ascribed to glucocorticoids and non-steroidal anti-inflammatory agents, yet is free from the undesirable effects of both.
Candida albicans produced chlamydospores after 24 h in the dark at 27 degrees C, but the process was inhibited under adequate irradiation of light. The in vivo absorption spectra showed a main peak at 414 nm, and less important peaks at 430, 446, 477, 519, 549 and 560 nm. No bands were detected beyond 600 nm. A total inhibition of chlamydosporulation occurred at 414 nm (monochromatic light) for an initial energy of 2,000 ergs cm-2 s-1. A 4,000 ergs cm-2 s-1 irradiation energy was necessary to observe a marked inhibition at 460, 500 and 530 nm (les chlamydospores and/or immaturity); this energy must be raised to 300,000 ergs cm-2 s-1 to observe a similar effect at 575 and 630 nm. Biological activity spectra were in full concordance with absorption spectra at 414 nm; no interpretation of absorption band at 460 nm is given, but total or partial inhibition could be explained by modulation of protoporphyrin activity.
Thiol-group reactive agents [alloxan, N-ethyimaleimide (NEM), ethacrynic acid, p-chlormercuribenzoate (PCMB)] were shown to induce a writhing syndrome in mice and rats when injected i.p. in appropriate dosage. Non-steroidal anti-inflammatory agents, narcotic analgesics and also psychotropic drugs inhibit the syndrome elicited in rats by ethacrynic acid. Rats pretreated with cysteine i.p. show a greatly reduced nociceptive response to ethacrynic acid or alloxan.
In the isolated rat uterus, mescaline induces contractions that are notably antagonized by catecholamines, by beta-adrenergic stimulants and certain beta-adrenergic blocking agents as well as by chlorpromazine, amitriptyline and methysergide.
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