We report the successful purification of a cloned lysin encoded by the novel Staphylococcus aureus bacteriophage phi MR11. The lysin, designated MV-L, rapidly and completely lysed cells of a number of S. aureus strains tested, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus and a subset of vancomycin-intermediate S. aureus (VISA) in growing conditions. MV-L-mediated killing is specific to S. aureus and not to other species, except for S. simulans. MV-L exerted its staphylocidal effect synergistically with glycopeptide antibiotics against VISA. MV-L efficiently eliminated MRSA that had been artificially inoculated into the nares of mice. The intraperitoneal administration of MV-L also protected mice against MRSA septic death, without any harmful effects. Although MV-L evoked detectable levels of a humoral response in mice, the antibodies did not abolish the bacteriolytic activity. These results indicate that MV-L might be useful as a powerful therapeutic agent against multidrug-resistant S. aureus infections.

Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.

From January 1976 to December 1987, 37 early colorectal cancers of the flat type were treated. Thirty-four of them (91.9%) were not accompanied by adenoma, and were thought to have arisen de novo. There is indeed a de novo route of cancer development in the human large intestine, and cancers de novo merely show polypoid growth. Flat type cancers arising de novo tend to reach deeper layers at an earlier stage than polypoid-type carcinomas in adenoma. Of those with a diameter of less than 10 mm, only 40% stayed in the mucosa. Consequently, advanced cancers cannot be prevented by snare polypectomy alone. More attention should be directed to the discovery of small, flat, nonpolypoid cancers.

In order to search for the histogenesis and progression of colorectal cancer, the background mucosas of 18 patients with a single colorectal cancer, apart from familial adenomatosis coli, were studied by a step sectioning method. Three early minute cancers (3-5 mm in diameter) were detected in the apparently normal mucosa, and two cancers in the adenoma (focal cancer in adenomatous polyp). The three early cancers had no evidence of preexisting adenoma, so they were considered to be de novo cancers. In form they were depressed, flat, and slightly elevated. In humans, de novo cancer has an important significance in histogenesis and treatment of colorectal cancer. Clinically, it is also important to recognize the early phase of colorectal cancer in flat type as well as polypoid type.

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