Bradykinin B2 receptors and coupling mechanisms in the smooth muscle of the guinea-pig taenia caeci.

1. In the smooth muscle of the guinea-pig taenia caeci, bradykinin produces a relaxation followed by a contraction. In the presence of hexamethonium and guanethidine, both these phases of the response were insensitive to tetrodotoxin (100 nM), omega-conotoxin GVIA (100 nM) and ibuprofen (1 microM), suggesting that they are due to a direct action on the smooth muscle.

Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons.

The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans.

P53 expression in end-stage squamous-cell carcinoma of the head and neck prior to chemotherapy treatment - expression correlates with a very poor clinical outcome.

p53 expression was assessed immunohistochemically in 24 'end stage disease' patients with squamous cell carcinoma of the head and neck, prior to selection for a chemotherapy trial. Twelve patients were assigned to each arm of the trial; cisplatinum arm or the cisplatinum and nifedipine arm. p53 expression was assessed using the CM-1 antibody in specimens from biopsies or surgically removed tissue at the time these patients were assessed as end stage disease.

Over-expression of p53-protein and cigarette-smoking in bronchial-carcinoma.

A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and over-expression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti-p53 protein antibodies PAb1801, DO7 and CM1, over-expression was demonstrable in 13 of 59 tissue biopsy specimens from a series of patients with newly-diagnosed primary bronchial carcinoma from whom accurate data on smoking history had been obtained prior to bronchoscopy. There was a statistically significant relationship between over-expression and total exposure to cigarette smoke (p53-positive, median 46 pack-years; p53-negative, median 32 pack-years; P<0.

Exposure to cigarette smoke and expression of the protein encoded by the p53 gene in bronchial carcinoma.

Mutation of the onco-suppressor gene encoding the protein known as p53 may cause synthesis of a mutant p53 protein which can bind to and inactivate its wild-type equivalent. This protein is detectable in many malignant neoplasms, including bronchial carcinoma, and has been associated with cigarette smoking. Of 59 tissue biopsy specimens of primary bronchial malignancies immunolabeled for p53 by the avidin-biotin technique using the antibodies PAb 1801, CM1, and D07, 13 (22%) expressed the protein.

Atraumatic quantitation of cerebral perfusion in cats by 19F magnetic resonance imaging.

We have noninvasively produced low-resolution, quantitative nuclear magnetic resonance images of cerebral blood flow in 2-ml voxels in eight cats. Typical signal-to-noise of 4 to 1 was obtained in cerebral voxels in 16.5-s epochs.

Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxy guanosines.

A series of four isomeric 2'- and 6'-fluorocarbocyclic guanosine analogues have been prepared and evaluated as potential anti-herpes agents. The racemic 2' beta-fluoro isomer 2-amino-1,9-dihydro- 9-[(1 alpha, 2 alpha, 3 beta, 4 alpha)-2-fluoro-3-hydroxy-4- (hydroxymethyl)cyclopentyl]-6H-purin-6-one (11a, C-AFG) and its 2' alpha-fluoro epimer 11b plus the chiral 6' beta-fluoro isomer 2-amino-1,9-dihydro-9-[[1S-(1 alpha, 2 alpha, 3 alpha, 4 beta)]- 2-fluoro-4-hydroxy-3-(hydroxymethyl)cyclopentyl]-6H-purine-6-one (11c) and its 6' alpha-fluoro epimer 11d were prepared from their respective fluoro amino diol hydrochlorides (6a,d). For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha- D-arabinofuranosyl bromide followed by base hydrolysis.

c-myc oncoprotein in bronchial carcinoma: expression in all major morphological types.

We have studied the prevalence of a 62 kd protein product of the c-myc oncogene in tissue biopsies from 79 primary bronchial carcinomata using the monoclonal antibody Myc 1-9E10 and the avidin-biotin complex (ABC) technique. This oncoprotein was strongly expressed in 43% of 37 squamous lesions, 29% of 14 adenocarcinomata, 42% of 7 non-small cell lesions not further classifiable and 19% of 21 small cell neoplasms, all of classical morphology. There was no statistical difference between groups in the prevalence of its expression, nor was it related to survival.

Fluorocarbon-23 measure of cat cerebral blood flow by nuclear magnetic resonance.

We employed fluorocarbon-23 (trifluoromethane) as a nuclear magnetic resonance gaseous indicator of cerebral blood flow in seven cats. Pulsed inhalation of this indicator and switching between two coils allowed the acquisition of both an arterial input and a cerebral response function, making possible multicompartmental curve fits to cerebral uptake and clearance data. The brain:blood partition coefficient for trifluoromethane was 0.

Cerebral blood flow measured by NMR indicator dilution in cats.

We developed techniques to assess the utility of a nuclear magnetic resonance (NMR) indicator for cerebral blood flow studies in cats, using Freon-22 for the first candidate. A PIN-diode-switched NMR experiment allowed the acquisition of an arterial as well as a cerebral fluorine-19 signal proportional to concentration vs. time in a 1.

The effects of delaying reward on choice preference in rats with hippocampal or selective septal lesions.

Two experiments are reported in which rats were trained to choose one of two goal arms in a Y-maze, for water reward. In one arm, the rats always received water (the continuously reinforced-CRF-arm). In the other arm the rats only sometimes received water (the partially reinforced-PRF-arm).