Role of protein kinase C in regulating smooth muscle electrical and contractile activity: the effect of phorbol ester

The effects of protein kinase C activation by 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) on the functions of guinea-pig smooth muscle taenia coli have been studied, using double-sucrose-gap method. A 15-20-min treatment of the muscle with 2 X 10(-8) M TPA caused a progressing inhibition of spontaneous electrical activity and mechanical tension, suppression of post-hyperpolarizing electrical and contractile "off-responses", a decrease in the number of action potentials during superthreshold membrane depolarization, depression of electrical and mechanical responses induced by acetylcholine, histamine, bradykinin mediators. The treatment of pre-depolarized (140 mM kappa+) muscle with 2.10(-8) TPA has led to a considerable reduction in contractile responses induced by the above mediators. The results obtained indicate that protein kinase C is capable of regulating both voltage-sensitive and receptor-operated ionic channels in smooth muscle cells.     

Effect of dibunol and isoptin on the creatine kinase and myoglobin content of the blood serum in dogs undergoing postischemic coronary reperfusion

The effect of an antioxidant dibunol and calcium antagonist verapamil on postperfusion release of myoglobin (Mb) and MB-creatine kinase (MB-CK) has been assessed in 30 dogs with experimental coronary occlusive myocardial infarction. It has been shown that reperfusion after 3-hour ischemia does not only accelerate the release of intracellular proteins, but also leads to pronounced myoglobinemia and blood enzymes. In postischemic blood flow recovery with combined dibunol and verapamil preliminary injections, an almost threefold decrease in MB-CK and Mb blood content, as compared to "reperfusion" indexes, was observed by the 10th minute of reperfusion.     

Rescue of developmental lens abnormalities in chimaeras of noncataractous and congenital cataractous mice

In the study of the lens of a congenital cataractous mouse mutant (CAT), it has been shown that a loss of growth regulation at the cellular level causes gross lens abnormalities. The phenotypic characteristics of the cataractous mouse lens are similar to those seen in human congenital cataract and thus serves as a model system for medical research. In this present investigation, we have demonstrated that the abnormalities of the congenital cataractous lens can be rescued by forming chimaeras between DBA/2 (a noncataractous strain of mouse) and the CAT mutant. This report describes the histological, cellular and biochemical analysis of the resultant chimaeric eyes, and discusses possible mechanisms by which these results were achieved.     

Nuclear DNA analysis of koilocytic and premalignant lesions of the uterine cervix.

Cervical biopsy samples were taken from 79 patients who had various grades of cervical intraepithelial neoplasia or who showed evidence, in the form of koilocytosis, of human papillomavirus infection of the uterine cervix and from 10 women with normal cervices. The DNA content of the cells in the samples was analysed by flow cytometry. Analysis of the data obtained showed that the biopsy samples from women with cervical intraepithelial neoplasia and human papillomavirus lesions contained significantly more dividing cells (31.2% of cells from human papillomavirus lesions with no cervical intraepithelial neoplasia and 33.06%, 29.89%, and 31.76% of cells from cervical intraepithelial neoplasia grades I, II, and III, respectively) than those from women with normal cervices (21.6%). The proportion of aneuploid samples from the group who showed evidence of human papillomavirus infection only (18.2%) did not differ significantly from the group with cervical intraepithelial neoplasia grade III (21.2%). Aneuploidy and an increased rate of cellular proliferation are recognised characteristics of malignancy. These results therefore support the view that human papillomavirus plays an important part in the aetiology of cervical carcinoma and are relevant to the clinical management of patients.     

Hydrolysis of N3-methyl-2'-deoxycytidine: model compound for reactivity of protonated cytosine residues in DNA

Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2'-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.     

Characterization of aminoalkylimidazol-4-one mutagens from liquid-reflux models

A new class of low molecular weight, aminomethylimidazol-4-one (IQ-"like") mutagens have been produced by the reaction of creatinine with the amino acid L-threonine, in liquid-reflux models, mimicking cooking, of diethylene glycol:5% distilled water (2 h at 150 degrees C). Two mutagens, 2-amino-1-methyl-5-propylideneimidazol-4-one (AMPI) and 2-amino-5-ethylidene-1-methylimidazol-4-one (AEMI) were isolated and characterized by UV absorption spectra, mass spectra, and 1H-NMR. The mutagen AEMI was identical to that obtained from the reaction of creatinine with acetaldehyde. These mutagens were positive in all IQ-sensitive Ames tester strains and were not inactivated by acidic nitrosation at pH 1.0. Products displaying mutagenicity were also obtained by refluxing creatinine with other hydroxyamino acids such as L-serine, L-homoserine, and L-4-amino-3-hydroxybutyric acid, and aldehydes such as glyoxal, methylglyoxal, glycolaldehyde, but not formaldehyde. Simple model systems such as creatinine and acetaldehyde may be useful in more clearly defining the exact mechanism of formation of IQ-type mutagens (aminomethylimidazo-quinolines and -quinoxalines) produced during cooking, as well as in screening for potential inhibitors of IQ-type mutagen formation, and elucidating the mechanism of such inhibition.     

Induction of specific-locus and dominant lethal mutations in male mice by chlormethine

Chlormethine (WHO), a nitrogen mustard (2,2'-dichloro-N-methyldiethylamine), induces dominant lethal and specific-locus mutations in spermatozoa and spermatids of mice.     

Palaeosols in Westphalian Coal-bearing and red-bed sequences, central and northern England

Westphalian A-C coal-bearing strata and red-beds in the Pennine Basin of Central and Northern England contain a wide variety of palaeosols. In coal-bearing facies associations alluvial, gley, semi-gley, organic and rare well-drained palaeosols reflect the predominance of poor drainage conditions during deposition. In red-beds more evolved ferruginous and ferallitic palaeosols testify to free drainage conditions during deposition. Catenary relationships can be inferred between most of the palaeosols in both facies associations, providing further information on the palaeogeomorphology of the depositional systems, and assisting in the understanding of the environments and conditions of coal seam formation.