The inotropic vasodilator, ICI 153,110, a phosphodiesterase inhibitor intended for the treatment of congestive heart failure, was administered to Alderley Park Wistar-derived rats for periods of up to 182 days. Treatment produced hypertrophy of salivary glands, hyperplasia of intestinal mucosa, and dacryoadenitis of the harderian gland. As the functions of these glandular tissues can be modified by factors which alter cyclic nucleotide metabolism, it is postulated that the glandular alterations produced by ICI 153,110 occurred as a result of phosphodiesterase inhibition.

The histologic appearance and cytochemical characteristics of foci of hepatic cellular alteration, hepatic nodules, and hepatocellular carcinomas occurring in male Sprague-Dawley rats treated with the hypolipidemic agent clofibrate (CAS: 637-07-0), with phenobarbital (CAS: 50-06-6), or with diethylnitrosamine [(DENA) CAS: 55-18-5] followed by phenobarbital were studied after treatment periods from 1 month to 2 years. Rats treated with clofibrate revealed foci of cellular alteration that were more often basophilic and occurred slightly sooner (wk 42) than those in untreated controls (wk 60). Of 36 rats that had received 68 or more weeks of continuous clofibrate, 19 had hepatic nodules. Of the 11 nodules examined cytochemically, none was gamma-glutamyltransferase (gamma-GT) positive and 2 were positive to glucose-6-phosphate dehydrogenase (G-6-PD) under oxygen. In rats withdrawn from clofibrate for 16-18 weeks after 68-95 weeks of clofibrate, 0 of 14 had nodules. In several of these rats zones of hepatic scarring were observed, suggesting the reversibility of the nodules. Phenobarbital alone had little effect on the incidence of foci of cellular alteration, although the number of gamma-GT-positive foci was increased. DENA followed by phenobarbital led to the early appearance of foci of cellular alteration (from wk 4), of nodules (from wk 13), and of hepatocellular carcinomas (from wk 26). gamma-GT activity was raised in most of these nodules and carcinomas, while G-6-PD activity was raised in only 3 of 9 nodules but in all 9 carcinomas examined. DENA-phenobarbital given for 13 or 26 weeks followed by withdrawal of phenobarbital for 28 and 26 weeks, respectively, produced an essentially similar pattern of lesions. In view of the growing recognition of the nonspecificity gamma-GT as a marker of carcinogen-initiated foci, the value of G-6-PD (under oxygen) as a marker merits further investigation.

Wheat-germ lectin peroxidase conjugate was used to stain the liver of normal rats and rats given α-naphthylisothiocyanate (ANIT). Changes in patterns in bile duct and canalicular staining were compatible with the hypothesis that cell damage caused by ANIT is essentially restricted to bile ducts.

We have explored the merit of a simultaneous study of sialomucin content and carcinoembryonic antigen (CEA) expression in the identification of early malignancy in adenomas. One hundred and thirteen colorectal adenomas were investigated by histochemical and immunocytochemical techniques. We compared adenomas from ‘high risk’ patients having synchronous carcinoma and ‘low risk’ groups with incidental polyps only. Twenty‐three metaplastic and eight inflammatory polyps were also included. Our data suggest that size and dysplasia are not always closely related and that synchronous adenomas seem to carry a higher malignant potential than incidental polyps irrespective of size. The degree of O‐acylation of sialic acids appears to be a sensitive indicator of early malignant change: loss of O‐acylation was seen in all 11 adenomas with highly atypical foci (‘focal carcinoma’) but noted in only four of the remaining polyps with lower grade dysplasia ( P < 0.005). By contrast the intensity of staining for CEA was a gradual phenomenon and showed no statistically significant increase with the onset of malignancy. Inflammatory polyps showed staining characteristics similar to normal mucosa. Metaplastic polyps, however, revealed increased expression of CEA and reduced O‐acylation with increased size which may reflect a disorder of growth and differentiation. Finally, by comparing these profiles of staining with those of normal mucosa,‘transitional’ mucosa adjacent to carcinoma and carcinoma, we further illustrate a progression of changes occurring in colonic mucosa in carcinogenesis.

The ultrastructural features of a spontaneous malignant fibrous histiocytoma and three malignant histiocytomas in Sprague-Dawley rats are described. The ultrastructural features of the malignant histiocytomas (or histiocytic sarcomas) support origin from cells of the monocyte series. The histogenesis of more fibrous tumors (fibrous histiocytomas) remains uncertain.

The mucosa in 100 segments of colon and rectum resected for cancer were examined using light microscopy and histochemical techniques. The extent of abnormal or transitional mucosa was defined for each case. Transitional mucosa was present in 93 of 95 adenocarcinomas and one malignant melanoma. The average total length of transitional change was 3.4 cm the maximum length was 19.5 cm. An inverse correlation was observed between the survival and the length of transitional mucosa around locally invasive (Dukes' B) carcinomas (P = 0.005). This may be related to increased amounts of sialic acid in transitional mucosa and the ability of sialic acid to depress tumor immunogenicity. The raised levels of sialic acids in transitional mucosa may have practical value in assessment of prognosis in colorectal cancer.

Cross sections, polarisations and analysing powers are presented for the elastic and inelastic scattering of 30.4 MeV polarised protons by 12C(Q = 0.0, − 4.44, −7.65, −9.64 MeV), 13C(Q = 0.0, −3.09 MeV), 16O (Q = 0.0, −8.87 MeV) and 54Fe (Q = 0.0, −1.41 MeV). Conventional optical model analyses of the elastic scattering are presented. The inelastic scattering data are analysed using a microscopic model employing shell-model wave functions, together with an effective interaction; also, a macroscopic collective model is applied where appropriate.

Experimental differential cross sections and asymmetries were measured for proton inelastic scattering at 30.3 MeV from strongly excited 2+ states in 54, 56Fe, 58Ni and 120Sn and 3− states in 58Ni, 120Sn and 208Pb. A coupled-channels analysis was performed using both the collective and shell-model descriptions of the nuclei. A good fit was obtained to all the data with the vibrational model when the whole optical potential was deformed; the deformation parameters deduced here are in agreement with those reported elsewhere. A microscopic description of the interaction using effective nucleon-nucleon forces was less successful and some aspects of the problem are discussed.

For proton-oxygen elastic scattering measurements are presented of differential cross sections at eight energies between 19.8 and 30.5 MeV, polarization at 19.8, 20.4, 20.8, 21.4, 22.1 and 30.3 MeV and the integrated excitation function at backward angles from 16.0 MeV to 30.6 MeV. The latter shows anomalies at Ep = 17.6, 20.4, 21.8, 23.3, 26.7 and 28.4 MeV. The data are analysed in terms of optical-model plus compound-nucleus-scattering amplitudes. A fit to experimental results is presented assuming contributions from four resonances at energies 17.6, 20.4, 26.7 and 28.4 MeV with Jπ assignment 52t-, 32−(32+), and 32− and 52−, respectively.

Polarizations and cross sections at 30.3 MeV are presented for 11B(p, p) and 11B(p, p′) exciting the 2.14 and 4.46 MeV states. For the 2.14 MeV state the results are compared with coupled-channels calculations using shell-model nuclear wave functions. Poor agreement is found for a wide range of nucleon-nucleon forces. For the 4.46 MeV state, a model involving coupling of a p32 hole to states of 12C is investigated.