Efficacy of the anticancer agent cisplatin in the treatment of human cervical squamous carcinoma xenografted in nude mice.

Two human squamous carcinomas of the cervix, established by serial passage in nude mice, are described. The response of the tumours to cis-diamminedichloroplatinum (CDDP) was assessed by comparing tumour weights and by histological observations. Tumours treated with CDDP 10 mg/kg/week for 2 weeks regressed significantly and microscopy revealed extensive degeneration. Treatment with CDDP 5 mg/kg/week produced tumour growth retardation and microscopy showed some degenerative changes, however, viable cells, many of which were mitotic, were evident. There was, therefore, a dose-response relationship. The sensitivity of the tumours to CDDP lends support to its use in humans with this malignancy.

Histochemical localization of acetylcholinesterase in the wall of cardiac blood vessels in the baboon, dog and vervet monkey.

Histochemical methods were used to demonstrate acetylcholinesterase in the wall of cardiac blood vessels in the baboon, dog and vervet monkey. To remove cholinesterase-containing sympathetic nerves, some of the animals were treated with guanethidine for four weeks prior to being sacrificed. In cardiac muscle from the dog and the vervet monkey, cholinergic nerves were histochemically visualized in both small and large vessels. On the other hand, in cardiac muscle from baboons, cholinergic nerves were not seen in branches of the coronary artery with diameters between 0.6 mm to 1 mm and very few fibres were seen around smaller vessels of diameter less than 0.3 mm. The few fibres seen did not appear to penetrate the media of the vessels. These results support physiological findings that the baboon coronary vasculature is not innervated by parasympathetic cholinergic nerves.

The effect of long-term use of cimetidine on the ultrastructure of gastric parietal cells in man.

The effect of long-term cimetidine therapy on the ultrastructure of human parietal cells was investigated in 2 subjects. It was found that after cimetidine therapy for 1 year: (i) the ultrastructural appearance of the parietal cells was normal, and (ii) the parietal cells responded normally to stimulation by pentagastrin. Evidence in favour of a membrane flow mechanism involved in acid secretion is presented.

Ultrastructure of duodenal epithelial cells in patients with active duodenal ulcers and after treatment with cimetidine.

Comparative ultrastructural studies were conducted on biopsy specimens taken under direct vision by endoscopy from the normal duodenum, from the edge of deep and flat duodenal ulcers, and from areas 1 cm away from such ulcers. In addition, the ultrastructure of biopsy tissue from the scar of ulcers which healed after 6 weeks' therapy with the histaminastructural studies of tissue form the edge of both flat and deep duodenal ulcers showed gross pathological changes, particularly with regard to microvilli. Cells from the edge of deep ulcers showed increased secretory activity. Epithelial tissue 1 cm from flat duodenal ulcers exhibited ultrastructural changes far more severe than cells 1 cm from deep duodenal ulcers. The epithelial tissue from the scar area after 6 weeks' treatment appeared capable of regaining a fully functional role, although it was not normal in all specimens.

The effect of acid-stimulating and inhibiting drugs on the ultrastructure of gastric parietal cells in man.

The ultrastructure of the human parietal cell at rest, after stimulation of gastric acid secretion by pentagastrin and after inhibition with propantheline or cimetidine, an H2-receptor antagonist, was studied. On stimulation there was an increase in the total secretory surface area of the gastric gland and canaliculus, with a concomitant decrease in the tubulovesicular system. On inhibition there was a decrease in the secretory surface area and a corresponding increase in the tubulovesicular system. These results are in agreement with other reports and support the hypothesis that during secretion of acid the tubulovesicular system increases the secretory surface by eversion or fusion of the vesicles and tubules with the plasmalemma. On inhibition there is thought to be reformation of the tubulovesicular system by pinocytosis. There is also ultrastructural evidence for the theory of membrane flow between the tubulovesicular system and the microvilli of the canaliculus and gastric lumen. Furthermore, there was an increase in lysosomal activity after the administration of the inhibiting drugs. It is suggested that the increased lysosomal activity could be involved in reducing the quantity of membrane after the membrane flow which occurs on gastric acid inhibition.